Analysis of charged particle emission sources and coalescence in E/A = 61 MeV 36^{36}Ar + 27^{27}Al, 112^{112}Sn and 124^{124}Sn collisions

Single-particle kinetic energy spectra and two-particle small angle correlations of protons ($p$), deuterons ($d$) and tritons ($t$) have been measured simultaneously in 61A MeV $^{36}$Ar + $^{27}$Al, $^{112}$Sn and $^{124}$Sn collisions. Characteristics of the emission sources have been derived from a ``source identification plot'' ($\beta_{source}$--$E_{CM}$ plot), constructed from the single-particle invariant spectra, and compared to the complementary results from two-particle correlation functions. Furthermore, the source identification plot has been used to determine the conditions when the coalescence mechanism can be applied for composite particles. In our data, this is the case only for the Ar + Al reaction, where $p$, $d$ and $t$ are found to originate from a common source of emission (from the overlap region between target and projectile). In this case, the coalescence model parameter, $\tilde{p}_0$ -- the radius of the complex particle emission source in momentum space, has been analyzed.Comment: 20 pages, 5 figures, submitted to Nuclear Physics

The complement: a solution to liquid drop finite size effects in phase transitions

The effects of the finite size of a liquid drop undergoing a phase transition are described in terms of the complement, the largest (but still mesoscopic) drop representing the liquid in equilibrium with the vapor. Vapor cluster concentrations, pressure and density from fixed mean density lattice gas (Ising) model calculations are explained in terms of the complement. Accounting for this finite size effect is key to determining the infinite nuclear matter phase diagram from experimental data.Comment: Four two column pages, four figures, two tables; accepted for publication in PR

Quantum-Statistical Correlations and Single Particle Distributions for Slowly Expanding Systems with Temperature Profile

Competition among particle evaporation, temperature gradient and flow is investigated in a phenomenological manner, based on a simultaneous analysis of quantum statistical correlations and momentum distributions for a non-relativistic, spherically symmetric, three-dimensionally expanding, finite source. The parameters of the model emission function are constrained by fits to neutron and proton momentum distributions and correlation functions in intermediate energy heavy-ion collisions. The temperature gradient is related to the momentum dependence of the radius parameters of the two-particle correlation function, as well as to the momentum-dependent temperature parameter of the single particle spectrum, while a long duration of particle evaporation is found to be responsible for the low relative momentum behavior of the two-particle correlations.Comment: 20 pages + 5 ps figures, ReVTeX, uses psfig.sty, the description is extended to include final state interactions, phenomenological evaporation and to fit intermediate energy heavy ion proton and neutron spectrum and correlation dat

The tau tubulin kinases TTBK1/2 promote accumulation of pathological TDP-43

Pathological aggregates of phosphorylated TDP-43 characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), two devastating groups of neurodegenerative disease. Kinase hyperactivity may be a consistent feature of ALS and FTLD-TDP, as phosphorylated TDP-43 is not observed in the absence of neurodegeneration. By examining changes in TDP-43 phosphorylation state, we have identified kinases controlling TDP-43 phosphorylation in a C. elegans model of ALS. In this kinome-wide survey, we identified homologs of the tau tubulin kinases 1 and 2 (TTBK1 and TTBK2), which were also identified in a prior screen for kinase modifiers of TDP-43 behavioral phenotypes. Using refined methodology, we demonstrate TTBK1 and TTBK2 directly phosphorylate TDP-43 in vitro and promote TDP-43 phosphorylation in mammalian cultured cells. TTBK1/2 overexpression drives phosphorylation and relocalization of TDP-43 from the nucleus to cytoplasmic inclusions reminiscent of neuropathologic changes in disease states. Furthermore, protein levels of TTBK1 and TTBK2 are increased in frontal cortex of FTLD-TDP patients, and TTBK1 and TTBK2 co-localize with TDP-43 inclusions in ALS spinal cord. These kinases may represent attractive targets for therapeutic intervention for TDP-43 proteinopathies such as ALS and FTLD-TDP

Upper Limit on the Prompt Muon Flux Derived from the LVD Underground Experiment

We present the analysis of the muon events with all muon multiplicities collected during 21804 hours of operation of the first LVD tower. The measured depth-angular distribution of muon intensities has been used to obtain the normalization factor, A, the power index, gamma, of the primary all-nucleon spectrum and the ratio, R_c, of prompt muon flux to that of pi-mesons - the main parameters which determine the spectrum of cosmic ray muons at the sea level. The value of gamma = 2.77 +/- 0.05 (68% C.L.) and R_c < 2.0 x 10^-3 (95% C.L.) have been obtained. The upper limit to the prompt muon flux favours the models of charm production based on QGSM and the dual parton model.Comment: 10 pages, 4 figures, RevTex. To appear in Phys. Rev.

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Context Dependent Neuroprotective Properties of Prion Protein (Prp)

Although it has been known for more than twenty years that an aberrant conformation of the prion protein (PrP) is the causative agent in prion diseases, the role of PrP in normal biology is undetermined. Numerous studies have suggested a protective function for PrP, including protection from ischemic and excitotoxic lesions and several apoptotic insults. On the other hand, many observations have suggested the contrary, linking changes in PrP localization or domain structure—independent of infectious prion conformation—to severe neuronal damage. Surprisingly, a recent report suggests that PrP is a receptor for toxic oligomeric species of a-β, a pathogenic fragment of the amyloid precursor protein, and likely contributes to disease pathogenesis of Alzheimer’s disease. We sought to access the role of PrP in diverse neurological disorders. First, we confirmed that PrP confers protection against ischemic damage using an acute stroke model, a well characterized association. After ischemic insult, PrP knockouts had dramatically increased infarct volumes and decreased behavioral performance compared to controls. To examine the potential of PrP’s neuroprotective or neurotoxic properties in the context of other pathologies, we deleted PrP from several transgenic models of neurodegenerative disease. Deletion of PrP did not substantially alter the disease phenotypes of mouse models of Parkinson’s disease or tauopathy. Deletion of PrP in one of two Huntington’s disease models tested, R6/2, modestly slowed motor deterioration as measured on an accelerating rotarod but otherwise did not alter other major features of the disease. Finally, transgenic overexpression of PrP did not exacerbate the Huntington’s motor phenotype. These results suggest that PrP has a context-dependent neuroprotective function and does not broadly contribute to the disease models tested herein.Ellison Medical FoundationWhitaker Health Sciences Fund Fellowshi

Prion Seeding Activities of Mouse Scrapie Strains with Divergent PrPSc Protease Sensitivities and Amyloid Plaque Content Using RT-QuIC and eQuIC

Different transmissible spongiform encephalopathy (TSE)-associated forms of prion protein (e.g. PrPSc) can vary markedly in ultrastructure and biochemical characteristics, but each is propagated in the host. PrPSc propagation involves conversion from its normal isoform, PrPC, by a seeded or templated polymerization mechanism. Such a mechanism is also the basis of the RT-QuIC and eQuIC prion assays which use recombinant PrP (rPrPSen) as a substrate. These ultrasensitive detection assays have been developed for TSE prions of several host species and sample tissues, but not for murine models which are central to TSE pathogenesis research. Here we have adapted RT-QuIC and eQuIC to various murine prions and evaluated how seeding activity depends on glycophosphatidylinositol (GPI) anchoring and the abundance of amyloid plaques and protease-resistant PrPSc (PrPRes). Scrapie brain dilutions up to 10-8 and 10-13 were detected by RT-QuIC and eQuIC, respectively. Comparisons of scrapie-affected wild-type mice and transgenic mice expressing GPI anchorless PrP showed that, although similar concentrations of seeding activity accumulated in brain, the heavily amyloid-laden anchorless mouse tissue seeded more rapid reactions. Next we compared seeding activities in the brains of mice with similar infectivity titers, but widely divergent PrPRes levels. For this purpose we compared the 263K and 139A scrapie strains in transgenic mice expressing P101L PrPC. Although the brains of 263K-affected mice had no immunoblot-detectable PrPRes, RT-QuIC indicated that seeding activity was comparable to that associated with a high-PrPRes strain, 139A. Thus, in this comparison, RT-QuIC seeding activity correlated more closely with infectivity than with PrPRes levels. We also found that eQuIC, which incorporates a PrPSc immunoprecipitation step, detected seeding activity in plasma from wild-type and anchorless PrP transgenic mice inoculated with 22L, 79A and/or RML scrapie strains. Overall, we conclude that these new mouse-adapted prion seeding assays detect diverse types of PrPSc

Muon `Depth -- Intensity' Relation Measured by LVD Underground Experiment and Cosmic-Ray Muon Spectrum at Sea Level

We present the analysis of the muon events with all muon multiplicities collected during 21804 hours of operation of the first LVD tower. The measured angular distribution of muon intensity has been converted to the `depth -- vertical intensity' relation in the depth range from 3 to 12 km w.e.. The analysis of this relation allowed to derive the power index, $\gamma$, of the primary all-nucleon spectrum: $\gamma=2.78 \pm 0.05$. The `depth -- vertical intensity' relation has been converted to standard rock and the comparison with the data of other experiments has been done. We present also the derived vertical muon spectrum at sea level.Comment: 7 pages, 3 figures, to be published on Phys. Rev.

Hearsay Exceptions: Adjusting the Ratio of Intuition to Psychological Science

Myers explores hearsay exeptions by examining three exceptions: excited utterances, statements for purposes of diagnosis or treatment, and the residual hearsay exception. The focus is child declarants, and these exceptions play key roles in child abuse litigation