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Analysis of soil samples from OMRE decommissioning project
In order to establish that the present Organic Moderated Reactor Experiment (OMRE) site does not exceed the criteria for radioactive contamination, samples obtained from the remainder of the facility that was not removed such as soil, concrete pads, various structural materials, and the leach pond area were analyzed to determine their radioactive content. The results of the analyses performed on soil samples are presented. Results of this study indicate that the activity at the OMRE decommissioned area is confined to localized areas (i.e., the leach pond area and reactor area). Comparisons of radionuclide concentrations measured in soil taken from the lip of the leach pond with concentrations in soil obtained outside the Idaho National Engineering Laboratory (INEL) site boundaries indicate that the concentration in the soil at the edge of the leach pond is at background levels. The vertical augering technique was determined to be the best approach for obtaining shallow soil samples at the INEL. Selection of this technique was based on ease of operation and analytical results. Less area is disturbed per sample than with the horizontal trenching and coring techniques. The radionuclide analysis of the samples shows the existence of a few regions in the reactor and leach pond areas that were still above INEL release criteria. These regions have been or are being further decontaminated
Neuromuscular synaptic transmission in aged ganglioside-deficient mice
Gangliosides are sialylated glycosphingolipids that are present in high density on neuronal membranes, especially at synapses, where they are assumed to play functional or modulating roles. Mice lacking GM2/GD2-synthase express only the simple gangliosides GD3 and GM3 and develop progressive motor behaviour deficits upon ageing, apparently due to failing complex ganglioside-dependent maintenance and/or repair processes or, alternatively, toxic GM3/GD3 accumulation. We investigated the function of neuromuscular junctions (NMJs) of aged (>9 month-old) GM2/GD2-synthase null-mutant mice, because synaptic dysfunction might develop with age and could potentially contribute to the late-onset motor phenotype. In addition, we studied NMJs of old mice lacking GD3-synthase (expressing only O- and a-series gangliosides), which do not show an overt neurological phenotype but may develop subclinical synaptic deficits. Detailed electrophysiological analyses showed subtle changes in presynaptic neurotransmitter release. Acetylcholine release at 40 Hz nerve stimulation at aged GM2/GD2-synthase null-mutant NMJs ran down slightly more pronounced than at wild-type NMJs, and spontaneous acetylcholine release rate at GD3-synthase null-mutant NMJs was somewhat higher than at wild-type, selectively at 25 degrees C bath temperature. Interestingly, we observed faster kinetics of postsynaptic electrophysiological responses at aged GD3-synthase null-mutant NMJs, not previously seen by us at NMJs of young GD3-synthase null-mutants or other types of (aged or young) ganglioside-deficient mice. These kinetic changes might reflect a change in postsynaptic acetylcholine receptor behaviour. Our data indicate that it is highly unlikely that transmission failure at NMJs contributes to the progressive motor defects of aged GM2/GD2-synthase null-mutants and that, despite some kinetic changes of synaptic signals, neuromuscular transmission remains successful in aged GD3-synthase null-mutant mice. Apparently, mutual redundancy of the different gangliosides in supporting presynaptic function, as observed previously by us in young mice, remains adequate upon ageing or, alternatively, gangliosides have only relatively little direct impact on neuromuscular synaptic function, even in aged mice. (C) 2009 Elsevier Inc. All rights reserve
Agr quorum sensing influences the Wood-Ljungdahl pathway in Clostridium autoethanogenum
Acetogenic bacteria are capable of fermenting CO2 and carbon monoxide containing waste-gases into a range of platform chemicals and fuels. Despite major advances in genetic engineering and improving these biocatalysts, several important physiological functions remain elusive. Among these is quorum sensing, a bacterial communication mechanism known to coordinate gene expression in response to cell population density. Two putative agr systems have been identified in the genome of Clostridium autoethanogenum suggesting bacterial communication via autoinducing signal molecules. Signal molecule-encoding agrD1 and agrD2 genes were targeted for in-frame deletion. During heterotrophic growth on fructose as a carbon and energy source, single deletions of either gene did not produce an observable phenotype. However, when both genes were simultaneously inactivated, final product concentrations in the double mutant shifted to a 1.5:1 ratio of ethanol:acetate, compared to a 0.2:1 ratio observed in the wild type control, making ethanol the dominant fermentation product. Moreover, CO2 re-assimilation was also notably reduced in both hetero- and autotrophic growth conditions. These findings were supported through comparative proteomics, which showed lower expression of carbon monoxide dehydrogenase, formate dehydrogenase A and hydrogenases in the ∆agrD1∆agrD2 double mutant, but higher levels of putative alcohol and aldehyde dehydrogenases and bacterial micro-compartment proteins. These findings suggest that Agr quorum sensing, and by inference, cell density play a role in carbon resource management and use of the Wood-Ljungdahl pathway as an electron sink
The influence of νh11/2 occupancy on the magnetic moments of collective 21+ states in A∼100 fission fragments
AbstractThe magnetic moments of Iπ=21+ states in even–even A∼100 fission fragments have been measured using the Gammasphere array, using the technique of time-integral perturbed angular correlations. The data are interpreted within the context of the interacting boson model (IBA2) leading to the suggestion of a strong νh11/2 component in the deformed 21+ states of this region
Familial Occurrence of Multiple Sclerosis with Thyroid Disease and Systemic Lupus Erythematosus
Multiple sclerosis (MS) has some features which suggest it is an autoimmune disease. Autoimmune diseases frequently occur in families, and patients and families often have more than one type of autoimmune disease. However, there are few reports of MS occurring in patients or families with other autoimmune conditions. It is difficult to make a separate diagnosis of MS in a patient who has a systemic autoimmune disease such as systemic lupus erythematosus (SLE) or Sjogren's syndrome, because these diseases can affect the nervous system directly. However, it is possible to make independent diagnoses of MS and an autoimmune disease confined to another single organ in the same patient, or diagnoses of MS and SLE (or other autoimmune diseases) in different family members. Here we describe clinically definite MS in 2 sisters, one of whom had Graves' disease, and the other of whom had a daughter with SLE and with a high titre of anti-thyroid antibodies. Other female family members over 4 generations had histories of thyroid disease, MS and Addison's disease. Available family members were HLA typed. The MS patients were positive for HLA DR2. All but one of the affected family members were related to the proband on the maternal side, and all of these affected females shared an HLA haplotype. However, this haplotype was also present in unaffected individuals. Thus HLA type alone cannot account for the familial occurrence of these disorders. We conclude that, in this family, MS, like autoimmune thyroid disease and SLE, may be an autoimmune disease developing in genetically predisposed individuals
Launch of the Space experiment PAMELA
PAMELA is a satellite borne experiment designed to study with great accuracy
cosmic rays of galactic, solar, and trapped nature in a wide energy range
protons: 80 MeV-700 GeV, electrons 50 MeV-400 GeV). Main objective is the study
of the antimatter component: antiprotons (80 MeV-190 GeV), positrons (50
MeV-270 GeV) and search for antimatter with a precision of the order of 10^-8).
The experiment, housed on board the Russian Resurs-DK1 satellite, was launched
on June, 15, 2006 in a 350*600 km orbit with an inclination of 70 degrees. The
detector is composed of a series of scintillator counters arranged at the
extremities of a permanent magnet spectrometer to provide charge,
Time-of-Flight and rigidity information. Lepton/hadron identification is
performed by a Silicon-Tungsten calorimeter and a Neutron detector placed at
the bottom of the device. An Anticounter system is used offline to reject false
triggers coming from the satellite. In self-trigger mode the Calorimeter, the
neutron detector and a shower tail catcher are capable of an independent
measure of the lepton component up to 2 TeV. In this work we describe the
experiment, its scientific objectives and the performance in the first months
after launch.Comment: Accepted for publication on Advances in Space Researc
A phase 2, open‐label study of single‐dose dupilumab in children aged 6 months to <6 years with severe uncontrolled atopic dermatitis: pharmacokinetics, safety and efficacy
Background
Dupilumab has demonstrated efficacy and acceptable safety in adults and children (aged 6–17 years) with moderate-to-severe atopic dermatitis (AD), but effective systemic therapy with a favorable risk–benefit profile in younger children remains a significant unmet need.
Objectives
To determine the pharmacokinetics, safety and efficacy of single-dose dupilumab in children with severe AD aged ≥6 months to <6 years.
Methods
This open-label, multicenter, phase 2, sequential, two-age cohort, two-dose level study (LIBERTY AD PRE-SCHOOL; NCT03346434) included an initial cohort of older children aged ≥2 to <6 years, followed by a younger cohort aged ≥6 months to <2 years. Pharmacokinetic sampling, safety monitoring and efficacy assessments were performed during the 4-week period after a single subcutaneous injection of dupilumab, in two sequential dosing groups (3 mg/kg, then 6 mg/kg). The use of standardized, low-to-medium potency topical corticosteroids was allowed.
Results
Forty patients were enrolled (20/age cohort, 10/dose level within a cohort) between December 20, 2017 and July 22, 2019. Within each age cohort, pharmacokinetic exposures after a single injection of dupilumab increased in a greater than dose-proportional manner. At week 3, treatment with 3 and 6 mg/kg dupilumab reduced scores of mean Eczema Area and Severity Index by −44.6% and −49.7% (older cohort) and −42.7% and −38.8% (younger cohort), and mean Peak Pruritus NRS scores by −22.9% and −44.7% (older cohort) and −11.1% and −18.2% (younger cohort), respectively. At week 4, improvements in most efficacy outcomes diminished in both age groups, particularly with the lower dose. The safety profile was comparable to that seen in adults, adolescents and children.
Conclusions
Single-dose dupilumab was generally well tolerated and substantially reduced clinical signs/symptoms of AD. Slightly better responses were seen in older than younger children. The pharmacokinetics of dupilumab were non-linear, consistent with previous studies in adults and adolescents
Triaxial strongly deformed bands in Tm160,161
High-spin states in Tm160,161 were populated using the Te128(Cl37, 5n and 4n) reactions at a beam energy of 170 MeV. Emitted γ rays were detected in the Gammasphere spectrometer. Two rotational bands with high moments of inertia were discovered, one assigned to Tm160, while the other tentatively assigned to Tm161. These sequences display features similar to bands observed in neighboring Er, Tm, Yb, and Lu nuclei which have been discussed in terms of triaxial strongly deformed structures. Cranked Nilsson Strutinsky calculations have been performed that predict well-deformed triaxial shapes at high spin in Tm160,161
Superdeformed band in 155Dy: Where does the "island" of superdeformation end?
A superdeformed band of 15 transitions has been found in the 155Dy nucleus. The measurement was performed with a backed target and the large deformation was inferred from the measured Doppler shifts. The new band displays an intensity pattern much different from typical superdeformed bands in this mass region. The dynamic moment of inertia is essentially identical to that of band 1 in 153Dy and is somewhat larger than those of the yrast superdeformed bands in 152, 154Dy, suggesting that the associated configuration has an additional N = 7, j15/2 intruder orbital occupied with respect to the 154Dy core
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