Upregulated expression of oncomodulin, the beta isoform of parvalbumin, in perikarya and axons in the diencephalon of parvalbumin knockout mice

The calcium-binding proteins parvalbumin, calbindin D-28k, calretinin and calcineurin are present in subsets of GABAergic gigantic calyciform presynaptic terminals of the reticular thalamic nucleus (RTN). Previously it was hypothesized that GABA and calcium-binding proteins including parvalbumin are not only colocalized in the same neuron subpopulation, but that GABA synthesis and parvalbumin expression could be also genetically regulated by a common mechanism. Moreover, parvalbumin expression levels could influence GABA synthesis. For this, we analyzed GABA immunoreactivity in RTN gigantic calyciform presynaptic terminals of parvalbumin–deficient (PV−/−) mice. With respect to GABA immunoreactivity we found no differences compared to wild–type animals. However, using a polyclonal parvalbumin antibody raised against full-length rat muscle parvalbumin on brain sections of PV−/− mice, we observed paradoxical parvalbumin immunoreactivity in partly varicose axons in the diencephalon, mainly in the lamina medullaris externa surrounding the thalamus. A detailed immunohistochemical, biochemical and molecular biological analysis revealed this immunoreactivity to be the result of an upregulation of oncomodulin (OM), the mammalian beta isoform of parvalbumin in PV−/− mice. In addition, OM was present in a sparse subpopulation of neurons in the thalamus and in the dentate gyrus. OM expression has not been observed before in neurons of the mammalian brain; its expression was restricted to outer hair cells in the organ of Corti. Our results indicate that the absence of parvalbumin has no major effect on the GABA-synthesizing system in RTN presynaptic terminals excluding a direct effect of parvalbumin on this regulation. However, a likely homeostatic mechanism is induced resulting in the upregulation of OM in selected axons and neuronal perikarya. Our results warrant further detailed investigations on the putative role of OM in the brain

Hall effect in quasi one-dimensional organic conductors

We study the Hall effect in a system of weakly coupled Luttinger Liquid chains, using a Memory function approach to compute the Hall constant in the presence of umklapp scattering along the chains. In this approximation, the Hall constant decomposes into two terms: a high-frequency term and a Memory function term. For the case of zero umklapp scattering, where the Memory function vanishes, the Hall constant is simply the band value, in agreement with former results in a similar model with no dissipation along the chains. With umklapp scattering along the chains, we find a power-law temperature dependance of the Hall constant. We discuss the applications to quasi 1D organic conductors at high temperatures.Comment: Proceedings of the ISCOM conference "Sixth International Symposium on Crystalline Organic Metals, Superconductors, and Ferromagnets", Key West, Florida, USA (Sept. 2005), to be plublished in the Journal of Low Temperature Physic

Getting It on Record: Issues and Strategies for Ethnographic Practice in Recording Studios

The recording studio has been somewhat neglected as a site for ethnographic fieldwork in the field of ethno-musicology and, moreover, the majority of published studies tend to overlook the specific concerns faced by the researcher within these contexts. Music recording studios can be places of creativity, artistry, and collaboration, but they often also involve challenging, intimidating, and fractious relations. Given that recording studios are, first and foremost, concerned with documenting musicians’ performances, we discuss the concerns of getting studio interactions “on record” in terms of access, social relations, and methods of data collection. This article reflects on some of the issues we faced when conducting our fieldwork within British music recording facilities and makes suggestions based on strategies that we employed to address these issues

Optimal Respiratory Syncytial Virus intervention programmes using Nirsevimab in England and Wales

Introduction: Respiratory Syncytial Virus (RSV) is a major cause of acute lower respiratory tract infections (ALRI) in infants. There are no licensed vaccines and only one monoclonal antibody available to protect infants from disease. A new and potentially longer-lasting monoclonal antibody, Nirsevimab, showed promising results in phase IIb/III trials. We evaluate the cost-effectiveness of Nirsevimab intervention programmes in England and Wales. Methods: We used a dynamic model for RSV transmission, calibrated to data from England and Wales. We considered a suite of potential Nirsevimab programmes, including administration to all neonates (year-round); only neonates born during the RSV season (seasonal); or neonates born during the RSV season plus infants less than six months old before the start of the RSV season (seasonal + catch-up). Results: If administered seasonally to all infants at birth, we found that Nirsevimab would have to be priced at £63 or less per dose for at least 50% certainty that it could cost-effectively replace the current Palivizumab programme, using an ICER threshold of £20,000/QALY. An extended seasonal programme which includes a pre-season catch-up becomes the optimal strategy at a purchasing price of £32/dose or less for at least 50% certainty. At a purchasing price per dose of £5-32, the annual implementation costs of a seasonal programme could be as high as £2 million before a switch to a year-round strategy would be optimal. Discussion: Nirsevimab has the potential to be cost-effective in England and Wales not only for use in high-risk infants

The SS-diagnostic -- an a posteriori error assessment for single-reference coupled-cluster methods

We propose a novel a posteriori error assessment for the single-reference coupled-cluster (SRCC) method called the $S$-diagnostic. We provide a derivation of the $S$-diagnostic that is rooted in the mathematical analysis of different SRCC variants. We numerically scrutinized the $S$-diagnostic, testing its performance for (1) geometry optimizations, (2) electronic correlation simulations of systems with varying numerical difficulty, and (3) the square-planar copper complexes [CuCl$_4$]$^{2-}$, [Cu(NH$_3$)$_4$]$^{2+}$, and [Cu(H$_2$O)$_4$]$^{2+}$. Throughout the numerical investigations, the $S$-diagnostic is compared to other SRCC diagnostic procedures, that is, the $T_1$, $D_1$, and $D_2$ diagnostics as well as different indices of multi-determinantal and multi-reference character in coupled-cluster theory. Our numerical investigations show that the $S$-diagnostic outperforms the $T_1$, $D_1$, and $D_2$ diagnostics and is comparable to the indices of multi-determinantal and multi-reference character in coupled-cluster theory in their individual fields of applicability. The experiments investigating the performance of the $S$-diagnostic for geometry optimizations using SRCC reveal that the $S$-diagnostic correlates well with different error measures at a high level of statistical relevance. The experiments investigating the performance of the $S$-diagnostic for electronic correlation simulations show that the $S$-diagnostic correctly predicts strong multi-reference regimes. The $S$-diagnostic moreover correctly detects the successful SRCC computations for [CuCl$_4$]$^{2-}$, [Cu(NH$_3$)$_4$]$^{2+}$, and [Cu(H$_2$O)$_4$]$^{2+}$, which have been known to be misdiagnosed by $T_1$ and $D_1$ diagnostics in the past. This shows that the $S$-diagnostic is a promising candidate for an a posteriori diagnostic for SRCC calculations

Age-related microvascular degeneration in the human cerebral periventricular white matter

Clinical studies have identified white matter (WM) lesions as hyperintensive regions in the MRI images of elderly patients. Since a cerebrovascular origin was attributed to such lesions, the present analysis set out to define the microvascular histopathologic changes in the periventricular WM in the aged. Post-mortem samples of the frontal, parietal, and occipital periventricular WM of 40-90-year-old subjects were prepared for quantitative light and electron microscopy. Light microscopic examination revealed microvascular fibrohyalinosis as the most common type of microvascular damage in the elderly. Ultrastructural analysis identified the microvascular thickening as collagen deposits affecting the basement membrane. The vascular density did not correlate with the age. The basement membrane pathology significantly increased, while the number of intact microvessels gradually decreased, with advancing age in the frontal and occipital WM. Finally, peripheral atherosclerosis coincided with massive microvascular fibrosis, particularly in the frontal WM. Our results demonstrate an age-related microvascular degeneration in the periventricular WM, which may contribute to the development of WM lesions by hindering a sufficient supply of nutrients to the affected WM sites. Furthermore, the data accord with previous observations identifying the frontal lobe as the site at which WM vulnerability is most pronounced. Finally, atherosclerosis in large, peripheral vessels is considered to be a predictive marker of microvascular pathology in the WM.</p

Innovative interstellar explorer

An interstellar "precursor" mission has been under discussion in the scientific community for at least 30 years. Fundamental scientific questions about the interaction of the Sun with the interstellar medium can only be answered with in situ measurements that such a mission can provide. The Innovative Interstellar Explorer (IIE) and its use of Radioisotope Electric Propulsion (REP) is being studied under a NASA "Vision Mission" grant. Speed is provided by a combination of a high-energy launch, using current launch vehicle technology, a Jupiter gravity assist, and long-term, low-thrust, continuous acceleration provided by an ion thruster running off electricity provided by advanced radioisotope electric generators. A payload of ten instruments with an aggregate mass of ~35 kg and requiring ~30 W has been carefully chosen to address the compelling science questions. The nominal 20-day launch window opens on 22 October 2014 followed by a Jupiter gravity assist on 5 February 2016. The REP system accelerates the spacecraft to a "burnout" speed of 7.8 AU per year at 104 AU on 13 October 2032 (Voyager 1's current speed is ~3.6 AU/yr). The spacecraft will return at least 500 bits per second from at least 200 AU ~30 years after launch. Additional (backup) launch opportunities occur every 13 months to early 2018. In addition to addressing basic heliospheric science, the mission will ensure continued information on the far-heliospheric galactic cosmic ray population after the Voyagers have fallen silent and as the era of human Mars exploration begins

String breaking by dynamical fermions in three-dimensional lattice QCD

The first observation is made of hadronic string breaking due to dynamical fermions in zero temperature lattice QCD. The simulations are done for SU(2) color in three dimensions, with two flavors of staggered fermions. The results have clear implications for the large scale simulations that are being done to search (so far, without success) for string breaking in four-dimensional QCD. In particular, string breaking is readily observed using only Wilson loops to excite a static quark-antiquark pair. Improved actions on coarse lattices are used, providing an extremely efficient means to access the quark separations and propagation times at which string breaking occurs.Comment: Revised version to appear in Physical Review D, has additional discussion of the results, additional references, modified title, larger figure

Reactive Hall constant of Strongly Correlated Electrons

The zero-temperature Hall response within tight-binding models of correlated electrons is studied. Using the linear response theory and a linearization in the magnetic field B, a general relation for the reactive (zero frequency) Hall constant in the fast (transport) limit is derived, involving only matrix elements between the lowest excited states at B=0; for noninteracting fermions, the Boltzmann expression is reproduced. For a Fermi liquid with a well defined Fermi surface and linear gapless excitations an analogous expression is found more generally. In the specific case of quasi-one-dimensional correlated systems a relation of $R^0_H$ to the charge stiffness D is recovered. Similar analysis is performed and discussed for D and the compressibility.Comment: 8 pages, submitted to Phys.Rev.