Spreading with immunization in high dimensions

We investigate a model of epidemic spreading with partial immunization which is controlled by two probabilities, namely, for first infections, $p_0$, and reinfections, $p$. When the two probabilities are equal, the model reduces to directed percolation, while for perfect immunization one obtains the general epidemic process belonging to the universality class of dynamical percolation. We focus on the critical behavior in the vicinity of the directed percolation point, especially in high dimensions $d>2$. It is argued that the clusters of immune sites are compact for $d\leq 4$. This observation implies that a recently introduced scaling argument, suggesting a stretched exponential decay of the survival probability for $p=p_c$, $p_0\ll p_c$ in one spatial dimension, where $p_c$ denotes the critical threshold for directed percolation, should apply in any dimension $d \leq 3$ and maybe for $d=4$ as well. Moreover, we show that the phase transition line, connecting the critical points of directed percolation and of dynamical percolation, terminates in the critical point of directed percolation with vanishing slope for $d<4$ and with finite slope for $d\geq 4$. Furthermore, an exponent is identified for the temporal correlation length for the case of $p=p_c$ and $p_0=p_c-\epsilon$, $\epsilon\ll 1$, which is different from the exponent $\nu_\parallel$ of directed percolation. We also improve numerical estimates of several critical parameters and exponents, especially for dynamical percolation in $d=4,5$.Comment: LaTeX, IOP-style, 18 pages, 9 eps figures, minor changes, additional reference

Yang-Lee zeros for a nonequilibrium phase transition

Equilibrium systems which exhibit a phase transition can be studied by investigating the complex zeros of the partition function. This method, pioneered by Yang and Lee, has been widely used in equilibrium statistical physics. We show that an analogous treatment is possible for a nonequilibrium phase transition into an absorbing state. By investigating the complex zeros of the survival probability of directed percolation processes we demonstrate that the zeros provide information about universal properties. Moreover we identify certain non-trivial points where the survival probability for bond percolation can be computed exactly.Comment: LaTeX, IOP-style, 13 pages, 10 eps figure

Comparative physical-tribological properties of anti-friction ion-plasma Ti-C-Mo-S coating on VT6 alloy or 20X13 and 40X steels

Results of comparative tests mechanical and tribological properties of solid antifriction Ti-C-Mo-S coating, deposited by magnetron-plasma combined sputtering method on substrates of VT6 titanium alloy, 40X and 20X13 hardened steels are provided. Coating is sputtered using the same conditions and technological regimes on substrates of different materials. However, the friction tests results showed significant difference in tribological characteristics of coating depending on type of material used for substrate, first of all by wear-resistance ability. Authors suppose that this is due to difference between physical properties such as composition and structure of substrate materials that determines hardness and coating adhesion to surface

Comparative physical-tribological properties of anti-friction ion-plasma Ti-C-Mo-S coating on VT6 alloy or 20X13 and 40X steels

Results of comparative tests mechanical and tribological properties of solid antifriction Ti-C-Mo-S coating, deposited by magnetron-plasma combined sputtering method on substrates of VT6 titanium alloy, 40X and 20X13 hardened steels are provided. Coating is sputtered using the same conditions and technological regimes on substrates of different materials. However, the friction tests results showed significant difference in tribological characteristics of coating depending on type of material used for substrate, first of all by wear-resistance ability. Authors suppose that this is due to difference between physical properties such as composition and structure of substrate materials that determines hardness and coating adhesion to surface

Proteomic Analysis of Hippocampal Dentate Granule Cells in Frontotemporal Lobar Degeneration: Application of Laser Capture Technology

Frontotemporal lobar degeneration (FTLD) is the most common cause of dementia with pre-senile onset, accounting for as many as 20% of cases. A common subset of FTLD cases is characterized by the presence of ubiquitinated inclusions in vulnerable neurons (FTLD-U). While the pathophysiological mechanisms underlying neurodegeneration in FTLD-U have not yet been elucidated, the presence of inclusions in this disease indicates enhanced aggregation of one or several proteins. Moreover, these inclusions suggest altered expression, processing, or degradation of proteins during FTLD-U pathogenesis. Thus, one approach to understanding disease mechanisms is to delineate the molecular changes in protein composition in FTLD-U brain. Using a combined approach consisting of laser capture microdissection (LCM) and high-resolution liquid chromatography-tandem mass spectrometry (LC–MS/MS), we identified 1252 proteins in hippocampal dentate granule cells excised from three post-mortem FTLD-U and three unaffected control cases processed in parallel. Additionally, we employed a labeling-free quantification technique to compare the abundance of the identified proteins between FTLD-U and control cases. Quantification revealed 54 proteins with selective enrichment in FTLD-U, including TAR–DNA binding protein 43 (TDP-43), a recently identified component of ubiquitinated inclusions. Moreover, 19 proteins were selectively decreased in FTLD-U. Subsequent immunohistochemical analysis of TDP-43 and three additional protein candidates suggests that our proteomic profiling of FTLD-U dentate granule cells reveals both inclusion-associated proteins and non-aggregated disease-specific proteins. Application of LCM is a valuable tool in the molecular analysis of complex tissues, and its application in the proteomic characterization of neurodegenerative disorders such as FTLD-U may be used to identify proteins altered in disease

Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age

In advanced age, some individuals maintain a stable cognitive trajectory while others experience a rapid decline. Such variation in cognitive trajectory is only partially explained by traditional neurodegenerative pathologies. Hence, to identify new processes underlying variation in cognitive trajectory, we perform an unbiased proteome-wide association study of cognitive trajectory in a discovery (n = 104) and replication cohort (n = 39) of initially cognitively unimpaired, longitudinally assessed older-adult brain donors. We find 579 proteins associated with cognitive trajectory after meta-analysis. Notably, we present evidence for increased neuronal mitochondrial activities in cognitive stability regardless of the burden of traditional neuropathologies. Furthermore, we provide additional evidence for increased synaptic abundance and decreased inflammation and apoptosis in cognitive stability. Importantly, we nominate proteins associated with cognitive trajectory, particularly the 38 proteins that act independently of neuropathologies and are also hub proteins of protein co-expression networks, as promising targets for future mechanistic studies of cognitive trajectory.Accelerating Medicine Partnership for AD [U01AG046161, U01 AG061357]; Emory Alzheimer's Disease Research Center [P50 AG025688]; NINDS Emory Neuroscience Core [P30 NS055077]; intramural program of the National Institute on Aging (NIA); Alzheimer's Association; Alzheimer's Research UK; Michael J. Fox Foundation for Parkinson's Research; Weston Brain Institute Biomarkers Across Neurodegenerative Diseases Grant [11060]; National Institute of Neurological Disorders and Stroke [U24 NS072026]; National Institute on Aging [P30 AG19610]; Arizona Department of Health Services [211002]; Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]; [R01 AG056533]; [R01 AG053960]; [U01 MH115484]; [I01 BX003853]; [IK2 BX001820]; [R01 AG061800]; [R01 AG057911]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Demagnetization via Nucleation of the Nonequilibrium Metastable Phase in a Model of Disorder

We study both analytically and numerically metastability and nucleation in a two-dimensional nonequilibrium Ising ferromagnet. Canonical equilibrium is dynamically impeded by a weak random perturbation which models homogeneous disorder of undetermined source. We present a simple theoretical description, in perfect agreement with Monte Carlo simulations, assuming that the decay of the nonequilibrium metastable state is due, as in equilibrium, to the competition between the surface and the bulk. This suggests one to accept a nonequilibrium "free-energy" at a mesoscopic/cluster level, and it ensues a nonequilibrium "surface tension" with some peculiar low-T behavior. We illustrate the occurrence of intriguing nonequilibrium phenomena, including: (i) Noise-enhanced stabilization of nonequilibrium metastable states; (ii) reentrance of the limit of metastability under strong nonequilibrium conditions; and (iii) resonant propagation of domain walls. The cooperative behavior of our system may also be understood in terms of a Langevin equation with additive and multiplicative noises. We also studied metastability in the case of open boundaries as it may correspond to a magnetic nanoparticle. We then observe burst-like relaxation at low T, triggered by the additional surface randomness, with scale-free avalanches which closely resemble the type of relaxation reported for many complex systems. We show that this results from the superposition of many demagnetization events, each with a well- defined scale which is determined by the curvature of the domain wall at which it originates. This is an example of (apparent) scale invariance in a nonequilibrium setting which is not to be associated with any familiar kind of criticality.Comment: 26 pages, 22 figure

Single-molecule experiments in biological physics: methods and applications

I review single-molecule experiments (SME) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SME it is possible to: manipulate molecules one at a time and measure distributions describing molecular properties; characterize the kinetics of biomolecular reactions and; detect molecular intermediates. SME provide the additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SME it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level emphasizing the importance of SME to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SME from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOT), magnetic tweezers (MT), biomembrane force probe (BFP) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation), proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SME to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.Comment: Latex, 60 pages, 12 figures, Topical Review for J. Phys. C (Cond. Matt

U1 small nuclear ribonucleoproteins (snRNPs) aggregate in Alzheimer’s disease due to autosomal dominant genetic mutations and trisomy 21

BACKGROUND: We recently identified U1 small nuclear ribonucleoprotein (snRNP) tangle-like aggregates and RNA splicing abnormalities in sporadic Alzheimer’s disease (AD). However little is known about snRNP biology in early onset AD due to autosomal dominant genetic mutations or trisomy 21 in Down syndrome. Therefore we investigated snRNP biochemical and pathologic features in these disorders. FINDINGS: We performed quantitative proteomics and immunohistochemistry in postmortem brain from genetic AD cases. Electron microscopy was used to characterize ultrastructural features of pathologic aggregates. U1-70k and other snRNPs were biochemically enriched in the insoluble fraction of human brain from subjects with presenilin 1 (PS1) mutations. Aggregates of U1 snRNP-immunoreactivity formed cytoplasmic tangle-like structures in cortex of AD subjects with PS1 and amyloid precursor protein (APP) mutations as well as trisomy 21. Ultrastructural analysis with electron microscopy in an APP mutation case demonstrated snRNP immunogold labeling of paired helical filaments (PHF). CONCLUSIONS: These studies identify U1 snRNP pathologic changes in brain of early onset genetic forms of AD. Since dominant genetic mutations and trisomy 21 result in dysfunctional amyloid processing, the findings suggest that aberrant β-amyloid processing may influence U1 snRNP aggregate formation