A functional Na(+)/K(+)-ATPase consists of a catalytic α subunit and a regulatory β subunit. Four α isoforms of the Na(+)/K(+)-ATPase are found in mammals, each with a unique expression pattern and ...catalytic activity. The α2 isoform, encoded by the ATP1A2 gene, is primarily found in the central nervous system (CNS) and in heart-, skeletal- and smooth muscle tissues. In the CNS, the α2 isoform is mainly expressed in glial cells. In particular, the α2 isoform is found in astrocytes, important for astrocytic K(+) clearance and, consequently, the indirect uptake of neurotransmitters. Both processes are essential for proper brain activity, and autosomal dominantly mutations in the ATP1A2 gene cause the neurological disorder Familial hemiplegic migraine type 2 (FHM2). FHM2 is a severe subtype of migraine with aura including temporary numbness or weakness, and affecting only one side of the body. FHM2 patients often suffer from neurological comorbidities such as seizures, sensory disturbances, cognitive impairment, and psychiatric manifestations. The functional consequences of FHM2 disease mutations leads to a partial or complete loss of function of pump activity; however, a clear phenotype-genotype correlation has yet to be elucidated. Gene-modified mouse models targeting the Atp1a2 gene have proved instrumental in the understanding of the pathology of FHM2. Several Atp1a2 knockout (KO) mice targeting different exons have been reported. Homozygous Atp1a2 KO mice die shortly after birth due to respiratory malfunction resulting from abnormal Cl(-) homeostasis in brainstem neurons. Heterozygous KO mice are viable, but display altered behavior and neurological deficits such as altered spatial learning, decreased motor activity and enhanced fear/anxiety compared to wild type mice. FHM2 knock-in (KI) mouse models carrying the human in vivo disease mutations W887R and G301R have also been reported. Both models display altered cortical spreading depression (CSD) and point to deficits in the glutamatergic system as the main underlying mechanism of FHM2.
Migraine is a complex brain disorder, and understanding the complexity of this prevalent disease could improve quality of life for millions of people. Familial Hemiplegic Migraine type 2 (FHM2) is a ...subtype of migraine with aura and co-morbidities like epilepsy/seizures, cognitive impairments and psychiatric manifestations, such as obsessive-compulsive disorder (OCD). FHM2 disease-mutations locate to the ATP1A2 gene encoding the astrocyte-located α2-isoform of the sodium-potassium pump (α2Na(+)/K(+)-ATPase). We show that knock-in mice heterozygous for the FHM2-associated G301R-mutation (α2(+/G301R)) phenocopy several FHM2-relevant disease traits e.g., by mimicking mood depression and OCD. In vitro studies showed impaired glutamate uptake in hippocampal mixed astrocyte-neuron cultures from α2(G301R/G301R) E17 embryonic mice, and moreover, induction of cortical spreading depression (CSD) resulted in reduced recovery in α2(+/G301R) male mice. Moreover, NMDA-type glutamate receptor antagonists or progestin-only treatment reverted specific α2(+/G301R) behavioral phenotypes. Our findings demonstrate that studies of an in vivo relevant FHM2 disease knock-in mouse model provide a link between the female sex hormone cycle and the glutamate system and a link to co-morbid psychiatric manifestations of FHM2.
The response of the EJ 299-33 plastic scintillator to energetic charged nuclear particles ranging from isotopes of hydrogen to isotopes of carbon has been determined over a wide energy range using a ...complex experimental setup and nuclear reactions induced by a 20AMeV carbon beam on an aluminum target. A strong pulse-shape dependence of the generated light bursts on the impinging particle specie is observed, which makes this scintillator suitable, among other things, for neutron vs.γ-ray identification. Fit formulas are proposed for the normalized light output as a function of particle energy for eleven isotopes of elements ranging from hydrogen to carbon.
The response of the EJ 299-33 plastic scintillator to energetic charged nuclear particles ranging from isotopes of hydrogen to carbon-12 has been analyzed in terms of Birks׳ semi-empirical approach ...over the wide range of particle energies from 2 to 20AMeV. It was found that while the original two-parameter scaling involving Birks׳ composite quenching parameter kB and an overall conversion efficiency parameter S may be applicable to select sets of particles, a more universal fit would still require individual scintillation efficiencies Sx for individual particle species and more than just one value of the composite Birks׳ constant kB.
Detecting emitted radiation from nuclear processes such as reactions and radioactive decay allows for probes of the not-so-well-understood nuclear interaction, a residual of the strong interaction ...which acts on quarks and gluons rather than protons and neutrons. Employing multidetector systems as opposed to single-detector systems increases the breadth of studies, which can be performed both by increasing the overall efficiency and by using time-correlated measurement techniques. With multidetector systems, however, comes an increase in complexity, size, power consumption, and cost for data acquisition systems, which can process and perform logical operations on raw signals. To combat this in the Nuclear Science Laboratory, Simon Fraser University, Burnaby, BC, Canada, real-time event filtering has been implemented using a user programmable logic module called XLM72S. The logic module provides 72 emitter-coupled logic ports, configurable quartetwise as inputs or outputs, an on-board 80-MHz clock, four digital clock managers capable of synthesizing additional clock frequencies, and two serial peripheral interface memories. In the current setup, the XLM72S allows for simultaneous and computer controlled logic to be performed on up to 20 Compton suppressed spectrometers (CSSs) used for the detection of gamma rays from nuclear decays, as well as up to four auxiliary signals used for filtering events, which have coincident particle emission. The XLM72S module has been implemented and tested for a system containing five CSSs and a charged particle detector, demonstrating its effectiveness at performing logic in real time for anticoincident Compton suppression and coincidence multifold events.
Summary
We examined bone densitometric data in a four-year follow-up period before and after the cure of CS. Plasma cortisol concentrations were similar, but the duration of estimated glucocorticoid ...excess was longer in patients with prevalent bone fractures compared to those without fractures. After therapy of CS, bone area, BMC and BMD increased significantly at the LS and femur during follow-up, but they decreased at the forearm, suggesting redistribution of bone minerals from the peripheral to the axial skeleton.
Introduction
Only a few studies report the changes in bone mineral density (BMD) after the cure of Cushing’s syndrome (CS).
Methods
Forty-one patients with Cushing’s disease, 21 patients with adrenal CS and 6 patients with ectopic CS were prospectively enrolled. BMD, bone mineral content (BMC) and bone area were measured by DXA.
Results
No significant correlations were found between serum cortisol concentrations and baseline bone densitometric data. After successful therapy of CS, bone area and BMD increased significantly at the lumbar spine (LS) and femur during follow-up, but they decreased at the forearm. The progressive increase in BMC at the LS had a significant negative correlation with the change of the BMC of radius in the first and second follow-up years. The change in the body mass index was an independent predictor for changes in BMC both at the LS and at the forearm at the second year of remission.
Conclusions
The regional differences and the time-dependent changes of BMC suggest that the source of marked increase in axial BMC after the cure of CS is, at least partly, due to the redistribution of bone minerals from the peripheral to the axial skeleton.
A novel prompt decay mode of highly excited nuclear systems is shown to set in with necessity as a certain critical excitation energy per nucleon is reached. It is driven by a peculiar, open-ended ...type of spinodal instability, unique to self-bound open systems, and consists in parts of the system undergoing spontaneous indefinite thermal expansion ending in vaporization into the surrounding open space. The mode, named here spinodal vaporization, is distinctly different from all known decay modes of excited nuclei and faces no competition from the latter. It sets a natural upper limit for the excitation energy that can be thermalized by compound nuclear systems, while setting also a limit to the applicability of thermodynamics to the description of highly excited nuclear systems.
Background
Late-night salivary cortisol level is one of the first-line tests recommended by the Endocrine Society for the diagnosis of endogenous hypercortisolism. Most routine laboratories measure ...cortisol levels using immunoassay tests which fail to determine low cortisol levels accurately due to the numerous interfering substances. A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method with simple and rapid sample preparation was developed for the simultaneous measurement of cortisol and cortisone and its performance in the diagnosis of endogenous hypercortisolism was evaluated.
Methods
324 late-night saliva samples were analyzed from which 272 samples were derived from patients with a suspected diagnosis of endogenous hypercortisolism. Salivary cortisol levels were assayed using an electrochemiluminescent immunoassay (ECLIA, Cortisol II, Roche), and simultaneous measurement of cortisol and cortisone was performed using an LC–MS/MS method.
Results
A strong correlation between cortisol results measured using ECLIA and LC–MS/MS (
r
2
= 0.892) was demonstrated. Receiver operating characteristics (ROC) analysis showed good diagnostic performance of cortisol and cortisone levels assayed using LC–MS/MS method and for cortisol measured using ECLIA.
Conclusions
Late-night salivary cortisol and cortisone are useful parameters for the diagnosis of hypercortisolism. Using samples obtained from patients where the diagnosis of hypercortisolism is extremely challenging cut-off values for midnight salivary cortisol and cortisone measured by LC–MS/MS method were established.
De-excitation modes of compound systems 118Ba and 134Ba' produced respectively in the 78Kr+40Ca and 86Kr+48Ca collisions at 10 A.MeV' are investigated. In particular' the competition between the ...various disintegration decay paths of medium mass compound nuclei' formed by fusion processes and the isospin (related to N/Z) of the entrance channel influence on the decay process' are studied. Data were taken at the INFN-Laboratori Nazionali del Sud (LNS) in ISODEC experiment' by using the CHIMERA array. The experiment complements and improves the previous experiment performed at GANIL where the same mechanisms were studied at lower excitation energies. The results show the presence of a relaxed component in the reaction mechanism' evident staggering effects in the Z distributions' as well as different isotopic composition and neutron enrichment for the reaction products in the two systems.
Mass and atomic-number identification (ID) of reaction products is a fundamental requirement of any nuclear reaction study. An effective particle-ID method is demonstrated, based on pulse shape ...analysis/discrimination (PSD) applied to large-area, single-element silicon detectors. This technique uses commercial electronic modules and achieves atomic number resolution rivaling that typically obtained with multi-element (/spl Delta/E-E) detector telescopes. The method is applied to the CHIMERA detector system without compromising its time-of-flight (TOF) resolution. In-beam tests of the PSD method have been performed with large-area, 300-/spl mu/m thick CHIMERA silicon detectors, measuring particles from the /sup 19/F+/sup 12/C reaction at Tandem energies. Performance of a simple PSD set up is discussed, for front and rear particle injection.
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