Correlation functions and emission time sequence of light charged particles from projectile-like fragment source in E/A = 44 and 77 MeV 40Ar + 27Al collisions

Two-particle correlation functions, involving protons, deuterons, tritons, and alpha-particles, have been measured at very forward angles (0.7 deg < theta_lab < 7 deg), in order to study projectile-like fragment (PLF) emission in E/A = 44 and 77 MeV 40Ar + 27Al collisions. Peaks, originating from resonance decays, are larger at E/A = 44 than at 77 MeV. This reflects the larger relative importance of independently emitted light particles, as compared to two-particle decay from unstable fragments, at the higher beam energy. The time sequence of the light charged particles, emitted from the PLF, has been deduced from particle-velocity-gated correlation functions (discarding the contribution from resonance decays). Alpha-particles are found to have an average emission time shorter than protons but longer than tritons and deuterons.Comment: 18 pages, 5 figures, submitted to Nuclear Physics

Secondary structure prediction for RNA binding domain in RNP proteins identifies βαβ as the main structural motif

AbstractIn eukaryotic cells transcript processing is strictly dependent upon binding of specific proteins. Nuclear RNA binding proteins share a common domain, which is involved in RNA binding. In order to characterize RNP-RNA interactions we have performed a secondary structure prediction based both on statistical algorithms and comparative analysis of different proteins. A high conservation for secondary structure propensity between different RNPs was observed

A Three-Dimensional Code for Muon Propagation through the Rock: MUSIC

We present a new three-dimensional Monte-Carlo code MUSIC (MUon SImulation Code) for muon propagation through the rock. All processes of muon interaction with matter with high energy loss (including the knock-on electron production) are treated as stochastic processes. The angular deviation and lateral displacement of muons due to multiple scattering, as well as bremsstrahlung, pair production and inelastic scattering are taken into account. The code has been applied to obtain the energy distribution and angular and lateral deviations of single muons at different depths underground. The muon multiplicity distributions obtained with MUSIC and CORSIKA (Extensive Air Shower simulation code) are also presented. We discuss the systematic uncertainties of the results due to different muon bremsstrahlung cross-sections.Comment: 24 pages, 11 Postscript figures, LaTeX, to be published in Astroparticle Physic

Pathological phosphorylation of tau and TDP-43 by TTBK1 and TTBK2 drives neurodegeneration

BACKGROUND: Progressive neuron loss in the frontal and temporal lobes of the cerebral cortex typifies frontotemporal lobar degeneration (FTLD). FTLD sub types are classified on the basis of neuronal aggregated protein deposits, typically containing either aberrantly phosphorylated TDP-43 or tau. Our recent work demonstrated that tau tubulin kinases 1 and 2 (TTBK1/2) robustly phosphorylate TDP-43 and co-localize with phosphorylated TDP-43 in human postmortem neurons from FTLD patients. Both TTBK1 and TTBK2 were initially identified as tau kinases and TTBK1 has been shown to phosphorylate tau epitopes commonly observed in Alzheimer's disease and other tauopathies. METHODS: To further elucidate how TTBK1/2 activity contributes to both TDP-43 and tau phosphorylation in the context of the neurodegeneration seen in FTLD, we examined the consequences of elevated human TTBK1/2 kinase expression in transgenic animal models of disease. RESULTS: We show that C. elegans co-expressing tau/TTBK1 tau/TTBK2, or TDP-43/TTBK1 transgenes in combination exhibit synergistic exacerbation of behavioral abnormalities and increased pathological protein phosphorylation. We also show that C. elegans co-expressing tau/TTBK1 or tau/TTBK2 transgenes in combination exhibit aberrant neuronal architecture and neuron loss. Surprisingly, the TTBK2/TDP-43 transgenic combination showed no exacerbation of TDP-43 proteinopathy related phenotypes. Additionally, we observed elevated TTBK1/2 protein expression in cortical and hippocampal neurons of FTLD-tau and FTLD-TDP cases relative to normal controls. CONCLUSIONS: Our findings suggest a possible etiology for the two most common FTLD subtypes through a kinase activation driven mechanism of neurodegeneration

Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation

Alzheimer's disease (AD) and other neurodegenerative disorders are associated with the cytoplasmic aggregation of microtubule-associated protein tau. Recent evidence supports transcellular transfer of tau misfolding (seeding) as the mechanism of spread within an affected brain, a process reminiscent of viral infection. However, whereas microbial pathogens can be recognized as nonself by immune receptors, misfolded protein assemblies evade detection, as they are host-derived. Here, we show that when misfolded tau assemblies enter the cell, they can be detected and neutralized via a danger response mediated by tau-associated antibodies and the cytosolic Fc receptor tripartite motif protein 21 (TRIM21). We developed fluorescent, morphology-based seeding assays that allow the formation of pathological tau aggregates to be measured in situ within 24 h in the presence of picomolar concentrations of tau seeds. We found that anti-tau antibodies accompany tau seeds into the cell, where they recruit TRIM21 shortly after entry. After binding, TRIM21 neutralizes tau seeds through the activity of the proteasome and the AAA ATPase p97/VCP in a similar manner to infectious viruses. These results establish that intracellular antiviral immunity can be redirected against host-origin endopathogens involved in neurodegeneration

Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP

Stop codon mutations in the gene encoding the prion protein (PRNP) are very rare and have thus far only been described in two patients with prion protein cerebral amyloid angiopathy (PrP-CAA). In this report, we describe the clinical, histopathological and pathological prion protein (PrPSc) characteristics of two Dutch patients carrying novel adjacent stop codon mutations in the C-terminal part of PRNP, resulting in either case in hereditary prion protein amyloidoses, but with strikingly different clinicopathological phenotypes. The patient with the shortest disease duration (27 months) carried a Y226X mutation and showed PrP-CAA without any neurofibrillary lesions, whereas the patient with the longest disease duration (72 months) had a Q227X mutation and showed an unusual Gerstmann-Sträussler-Scheinker disease phenotype with numerous cerebral multicentric amyloid plaques and severe neurofibrillary lesions without PrP-CAA. Western blot analysis in the patient with the Q227X mutation demonstrated the presence of a 7 kDa unglycosylated PrPSc fragment truncated at both the N- and C-terminal ends. Our observations expand the spectrum of clinicopathological phenotypes associated with PRNP mutations and show that a single tyrosine residue difference in the PrP C-terminus may significantly affect the site of amyloid deposition and the overall phenotypic expression of the prion disease. Furthermore, it confirms that the absence of the glycosylphosphatidylinositol anchor in PrP predisposes to amyloid plaque formation

Multi-imaging investigation to evaluate the relationship between serum cystatin c and features of atherosclerosis in Non-ST-Segment elevation acute coronary syndrome

Objectives: High cystatin C(CysC) levels are associated with impaired cardiovascular outcome. Whether CysC levels are independently related to the atherosclerosis burden is still controversial. Methods: We enrolled 31 non-ST-segment elevation acute coronary syndrome patients undergoing percutaneous coronary intervention. Patients were divided into 2 groups on the basis of median value of serum CysC. Using the high CysC group as a dependent variable, univariable and multivariable analyses were used to evaluate the association between CysC and three different features of atherosclerosis: 1) coronary plaque vulnerability as assessed by optical coherence tomography (OCT), 2) coronary artery calcium (CAC) by means of computed tomography scan, and 3) aortic wall metabolic activity, as assessed using 18 F-Fluorodeoxyglucose-positron emission tomography ( 18 F-FDG-PET). Results: After univariable and multivariable analyses, 18 F-FDG uptake in the descending aorta (DA) was independently associated with a low level of CysC [(Odds Ratio = 0.02; 95%CI 0.0004-0.89; p = 0.044; 18 F-FDG uptake measured as averaged maximum target to blood ratio); (Odds Ratio = 0.89; 95%CI 0.82-0.98, p = 0.025; 18 F-FDG uptake measured as number of active slices)]. No trend was found for the association between CysC and characteristics of OCT-assessed coronary plaque vulnerability or CAC score. Conclusions: In patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), 18 F-FDG uptake in the DA was associated with a low level of serum CysC. There was no relation between CysC levels and OCT-assessed coronary plaque vulnerability or CAC score. These findings suggest that high levels of CysC may not be considered as independent markers of atherosclerosis

Modelling the freezing and thawing behaviour of saturated soils

This thesis presents an investigation of the thermo / hydro / mechanical behaviour of saturated soils with cryogenic suction effects. The flow relationships accommodate a number of mechanisms: i) heat transfer by conduction, convection, and latent heat transfer and ii) moisture transfer in the liquid phase due to pressure head, elevation head, and thermal gradients. The mechanical behaviour of the soil is modelled by an elasto-plastic work hardening modified Cam- Clay constitutive model. A numerical solution for the theoretical formulation is presented. Standard finite element methods are used for spatial discretisation and finite difference methods are used for temporal discretisation. Verification of the model is achieved by means of programme of tests to check the following cryogenic components i) coupled thermo-hydraulic response, ii) deformation behaviour of the fully coupled thermo-hydro-mechanical model, iii) transient coupled liquid flow and deformation behaviour, and iv) latent heat of fusion. Validation focused on the impact of the cryogenic related processes included within the proposed theoretical formulation. In particular the development of ice lenses and the movement of moisture under cryogenic suction were investigated. The performance of the proposed model with respect to a number of variables was subsequently explored in order to determine their effect on the magnitude and growth of ice lenses in a freezing soil. The model was then applied to a large scale freezing experiment, namely a fully coupled thermo / hydro / mechanical simulation. The simulated results show a good correlation with the experimental results by predicting the patterns and trends of experimentally observed behaviour and the cryogenic processes that occur during the freezing and thawing of frost susceptible soils. It was therefore concluded that the proposed model is capable of providing a good representation of the fully coupled THM behaviour of saturated soils with cryogenic effects.EThOS - Electronic Theses Online ServiceGBUnited Kingdo