Density-matrix formalism with three-body ground-state correlations

A density-matrix formalism which includes the effects of three-body ground- state correlations is applied to the standard Lipkin model. The reason to consider the complicated three-body correlations is that the truncation scheme of reduced density matrices up to the two-body level does not give satisfactory results to the standard Lipkin model. It is shown that inclusion of the three-body correlations drastically improves the properties of the ground states and excited states. It is pointed out that lack of mean-field effects in the standard Lipkin model enhances the relative importance of the three-body ground-state correlations. Formal aspects of the density-matrix formalism such as a relation to the variational principle and the stability condition of the ground state are also discussed. It is pointed out that the three-body ground-state correlations are necessary to satisfy the stability condition

Fully-Renormalized QRPA fulfills Ikeda sum rule exactly

The renormalized quasiparticle-RPA is reformulated for even-even nuclei using restrictions imposed by the commutativity of the phonon creation operator with the total particle number operator. This new version, Fully-Renormalized QRPA (FR-QRPA), is free from the spurious low-energy solutions. Analytical proof is given that the Ikeda sum rule is fullfiled within the FR-QRPA.Comment: 9 page

Double quantum dot turnstile as an electron spin entangler

We study the conditions for a double quantum dot system to work as a reliable electron spin entangler, and the efficiency of a beam splitter as a detector for the resulting entangled electron pairs. In particular, we focus on the relative strengths of the tunneling matrix elements, the applied bias and gate voltage, the necessity of time-dependent input/output barriers, and the consequence of considering wavepacket states for the electrons as they leave the double dot to enter the beam splitter. We show that a double quantum dot turnstile is, in principle, an efficient electron spin entangler or entanglement filter because of the exchange coupling between the dots and the tunable input/output potential barriers, provided certain conditions are satisfied in the experimental set-up.Comment: published version; minor error correcte

Fibrin(ogen) engagement of S. aureus promotes the host antimicrobial response and suppression of microbe dissemination following peritoneal infection

The blood-clotting protein fibrin(ogen) plays a critical role in host defense against invading pathogens, particularly against peritoneal infection by the Gram-positive microbe Staphylococcus aureus. Here, we tested the hypothesis that direct binding between fibrin(ogen) and S. aureus is a component of the primary host antimicrobial response mechanism and prevention of secondary microbe dissemination from the peritoneal cavity. To establish a model system, we showed that fibrinogen isolated from FibγΔ5 mice, which express a mutant form lacking the final 5 amino acids of the fibrinogen γ chain (termed fibrinogenγΔ5), did not support S. aureus adherence when immobilized and clumping when in suspension. In contrast, purified wildtype fibrinogen supported robust adhesion and clumping that was largely dependent on S. aureus expression of the receptor clumping factor A (ClfA). Following peritoneal infection with S. aureus USA300, FibγΔ5 mice displayed worse survival compared to WT mice coupled to reduced bacterial killing within the peritoneal cavity and increased dissemination of the microbes into circulation and distant organs. The failure of acute bacterial killing, but not enhanced dissemination, was partially recapitulated by mice infected with S. aureus USA300 lacking ClfA. Fibrin polymer formation and coagulation transglutaminase Factor XIII each contributed to killing of the microbes within the peritoneal cavity, but only elimination of polymer formation enhanced systemic dissemination. Host macrophage depletion or selective elimination of the fibrin(ogen) β2-integrin binding motif both compromised local bacterial killing and enhanced S. aureus systemic dissemination, suggesting fibrin polymer formation in and of itself was not sufficient to retain S. aureus within the peritoneal cavity. Collectively, these findings suggest that following peritoneal infection, the binding of S. aureus to stabilized fibrin matrices promotes a local, macrophage-mediated antimicrobial response essential for prevention of microbe dissemination and downstream host mortality

Terrestrial habitat requirements of nesting freshwater turtles

Because particular life history traits affect species vulnerability to development pressures, cross-species summaries of life history traits are useful for generating management guidelines. Conservation of aquatic turtles, many members of which are regionally or globally imperiled, requires knowing the extent of upland habitat used for nesting. Therefore, we compiled distances that nests and gravid females had been observed from wetlands. Based on records of \u3e 8000 nests and gravid female records compiled for 31 species in the United States and Canada, the distances that encompass 95% of nests vary dramatically among genera and populations, from just 8 m for Malaclemys to nearly 1400 m for Trachemys. Widths of core areas to encompass varying fractions of nesting populations (based on mean maxima across all genera) were estimated as: 50% coverage = 93 m, 75% = 154 m, 90% = 198 m, 95% = 232 m, 100% = 942 m. Approximately 6–98 m is required to encompass each consecutive 10% segment of a nesting population up to 90% coverage; thereafter, ca. 424 m is required to encompass the remaining 10%. Many genera require modest terrestrial areas (\u3c200 m zones) for 95% nest coverage (Actinemys, Apalone, Chelydra, Chrysemys, Clemmys, Glyptemys, Graptemys, Macrochelys, Malaclemys, Pseudemys, Sternotherus), whereas other genera require larger zones (Deirochelys, Emydoidea, Kinosternon, Trachemys). Our results represent planning targets for conserving sufficient areas of uplands around wetlands to ensure protection of turtle nesting sites, migrating adult female turtles, and dispersing turtle hatchlings

Task swapping networks in distributed systems

In this paper we propose task swapping networks for task reassignments by using task swappings in distributed systems. Some classes of task reassignments are achieved by using iterative local task swappings between software agents in distributed systems. We use group-theoretic methods to find a minimum-length sequence of adjacent task swappings needed from a source task assignment to a target task assignment in a task swapping network of several well-known topologies.Comment: This is a preprint of a paper whose final and definite form is published in: Int. J. Comput. Math. 90 (2013), 2221-2243 (DOI: 10.1080/00207160.2013.772985

Neuronal pentraxin 2 : a synapse-derived CSF biomarker in genetic frontotemporal dementia

Introduction: Synapse dysfunction is emerging as an early pathological event in frontotemporal dementia (FTD), however biomarkers are lacking. We aimed to investigate the value of cerebrospinal fluid (CSF) neuronal pentraxins (NPTXs), a family of proteins involved in homeostatic synapse plasticity, as novel biomarkers in genetic FTD. Methods: We included 106 presymptomatic and 54 symptomatic carriers of a pathogenic mutation in GRN, C9orf72 or MAPT, and 70 healthy non-carriers participating in the Genetic Frontotemporal dementia Initiative (GENFI), all of whom had at least one CSF sample. We measured CSF concentrations of NPTX2 using an in-house ELISA, and NPTX1 and NPTX receptor (NPTXR) by Western blot. We correlated NPTX2 with corresponding clinical and neuroimaging datasets as well as with CSF neurofilament light chain (NfL) using linear regression analyses. Results: Symptomatic mutation carriers had lower NPTX2 concentrations (median 643 pg/mL, IQR (301-872)) than presymptomatic carriers (1003 pg/mL (624-1358), p<0.001) and non-carriers (990 pg/mL (597-1373), p<0.001) (corrected for age). Similar results were found for NPTX1 and NPTXR. Among mutation carriers, NPTX2 concentration correlated with several clinical disease severity measures, NfL and grey matter volume of the frontal, temporal and parietal lobes, insula and whole brain. NPTX2 predicted subsequent decline in phonemic verbal fluency and Clinical Dementia Rating scale plus FTD modules. In longitudinal CSF samples, available in 13 subjects, NPTX2 decreased around symptom onset and in the symptomatic stage. Discussion: We conclude that NPTX2 is a promising synapse-derived disease progression biomarker in genetic FTD

Age at symptom onset and death and disease duration in genetic frontotemporal dementia : an international retrospective cohort study

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49\ub75 years (SD 10\ub70; onset) and 58\ub75 years (11\ub73; death) in the MAPT group, 58\ub72 years (9\ub78; onset) and 65\ub73 years (10\ub79; death) in the C9orf72 group, and 61\ub73 years (8\ub78; onset) and 68\ub78 years (9\ub77; death) in the GRN group. Mean disease duration was 6\ub74 years (SD 4\ub79) in the C9orf72 group, 7\ub71 years (3\ub79) in the GRN group, and 9\ub73 years (6\ub74) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0\ub745 between individual and parental age at onset, r=0\ub763 between individual and mean family age at onset, r=0\ub758 between individual and parental age at death, and r=0\ub769 between individual and mean family age at death) than in either the C9orf72 group (r=0\ub732 individual and parental age at onset, r=0\ub736 individual and mean family age at onset, r=0\ub738 individual and parental age at death, and r=0\ub740 individual and mean family age at death) or the GRN group (r=0\ub722 individual and parental age at onset, r=0\ub718 individual and mean family age at onset, r=0\ub722 individual and parental age at death, and r=0\ub732 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35\u201362, for age at onset; 61%, 47\u201373, for age at death), and even more by family membership (66%, 56\u201375, for age at onset; 74%, 65\u201382, for age at death). In the GRN group, only 2% (0\u201310) of the variability of age at onset and 9% (3\u201321) of that of age of death was explained by the specific mutation, whereas 14% (9\u201322) of the variability of age at onset and 20% (12\u201330) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11\u201326) of the variability of age at onset and 19% (12\u201329) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates. Funding: UK Medical Research Council, National Institute for Health Research, and Alzheimer's Society

[Accepted Manuscript] Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study.

Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. Serial T1-weighed magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point. Atrophy increased after the change-point, which occurred 1-1.5 years (assuming a single step change in atrophy rate) or 3-8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change-point. Atrophy rates are pathologically increased up to seven years before "expected onset". During this period, atrophy rates may be useful for inclusion and tracking of disease progression