Proteinopathy, oxidative stress and mitochondrial dysfunction: cross talk in alzheimer’s disease and parkinson’s disease

Alzheimer's disease and Parkinson's disease are two common neurodegenerative diseases of the elderly people that have devastating effects in terms of morbidity and mortality. The predominant form of the disease in either case is sporadic with uncertain etiology. The clinical features of Parkinson's disease are primarily motor deficits, while the patients of Alzheimer's disease present with dementia and cognitive impairment. Though neuronal death is a common element in both the disorders, the postmortem histopathology of the brain is very characteristic in each case and different from each other. In terms of molecular pathogenesis, however, both the diseases have a significant commonality, and proteinopathy (abnormal accumulation of misfolded proteins), mitochondrial dysfunction and oxidative stress are the cardinal features in either case. These three damage mechanisms work in concert, reinforcing each other to drive the pathology in the aging brain for both the diseases; very interestingly, the nature of interactions among these three damage mechanisms is very similar in both the diseases, and this review attempts to highlight these aspects. In the case of Alzheimer's disease, the peptide amyloid beta (A beta) is responsible for the proteinopathy, while alpha-synuclein plays a similar role in Parkinson's disease. The expression levels of these two proteins and their aggregation processes are modulated by reactive oxygen radicals and transition metal ions in a similar manner. In turn, these proteins - as oligomers or in aggregated forms - cause mitochondrial impairment by apparently following similar mechanisms. Understanding the common nature of these interactions may, therefore, help us to identify putative neuroprotective strategies that would be beneficial in both the clinical conditions

International shocks and growth in emerging markets

The paper provides evidence on the extent and channels of transmission of international shocks on the economic growth of emerging markets. Using a block dynamic factor model, the shocks are decomposed into four components; a general global component, an activity based component, a financial component and a commodity price component. Using a sample of 75 emerging markets over the period 1992–2009, the paper finds that the average effect of international shocks on emerging markets' growth over the entire sample period is negligible, which supports the classic view of isolated, de-coupled emerging markets. However, there is considerable variation both over time, over cross-section and across factors. When we split our sample by time period, we find greater effect of the international factors on the emerging markets' growth during 2002–2009 period. There is evidence which suggests that sensitivity to international shocks has increased over time and at the country level these sensitivities are more pronounced. Although the drivers of integration vary as does the sensitivity to alternative sources of shocks, we find that certain emerging markets have become considerably more integrated with the global economy than others. Overall, there is evidence of a significant impact on the economic growth of some emerging markets of the international shock caused by the global financial crisis

Shape-invariant quantum Hamiltonian with position-dependent effective mass through second order supersymmetry

Second order supersymmetric approach is taken to the system describing motion of a quantum particle in a potential endowed with position-dependent effective mass. It is shown that the intertwining relations between second order partner Hamiltonians may be exploited to obtain a simple shape-invariant condition. Indeed a novel relation between potential and mass functions is derived, which leads to a class of exactly solvable model. As an illustration of our procedure, two examples are given for which one obtains whole spectra algebraically. Both shape-invariant potentials exhibit harmonic-oscillator-like or singular-oscillator-like spectra depending on the values of the shape-invariant parameter.Comment: 16 pages, 5 figs; Present e-mail of AG: [email protected]

Time lower bounds for nonadaptive turnstile streaming algorithms

We say a turnstile streaming algorithm is "non-adaptive" if, during updates, the memory cells written and read depend only on the index being updated and random coins tossed at the beginning of the stream (and not on the memory contents of the algorithm). Memory cells read during queries may be decided upon adaptively. All known turnstile streaming algorithms in the literature are non-adaptive. We prove the first non-trivial update time lower bounds for both randomized and deterministic turnstile streaming algorithms, which hold when the algorithms are non-adaptive. While there has been abundant success in proving space lower bounds, there have been no non-trivial update time lower bounds in the turnstile model. Our lower bounds hold against classically studied problems such as heavy hitters, point query, entropy estimation, and moment estimation. In some cases of deterministic algorithms, our lower bounds nearly match known upper bounds

On Deterministic Sketching and Streaming for Sparse Recovery and Norm Estimation

We study classic streaming and sparse recovery problems using deterministic linear sketches, including l1/l1 and linf/l1 sparse recovery problems (the latter also being known as l1-heavy hitters), norm estimation, and approximate inner product. We focus on devising a fixed matrix A in R^{m x n} and a deterministic recovery/estimation procedure which work for all possible input vectors simultaneously. Our results improve upon existing work, the following being our main contributions: * A proof that linf/l1 sparse recovery and inner product estimation are equivalent, and that incoherent matrices can be used to solve both problems. Our upper bound for the number of measurements is m=O(eps^{-2}*min{log n, (log n / log(1/eps))^2}). We can also obtain fast sketching and recovery algorithms by making use of the Fast Johnson-Lindenstrauss transform. Both our running times and number of measurements improve upon previous work. We can also obtain better error guarantees than previous work in terms of a smaller tail of the input vector. * A new lower bound for the number of linear measurements required to solve l1/l1 sparse recovery. We show Omega(k/eps^2 + klog(n/k)/eps) measurements are required to recover an x' with |x - x'|_1 <= (1+eps)|x_{tail(k)}|_1, where x_{tail(k)} is x projected onto all but its largest k coordinates in magnitude. * A tight bound of m = Theta(eps^{-2}log(eps^2 n)) on the number of measurements required to solve deterministic norm estimation, i.e., to recover |x|_2 +/- eps|x|_1. For all the problems we study, tight bounds are already known for the randomized complexity from previous work, except in the case of l1/l1 sparse recovery, where a nearly tight bound is known. Our work thus aims to study the deterministic complexities of these problems

Computing Inferences for Large-Scale Continuous-Time Markov Chains by Combining Lumping with Imprecision

If the state space of a homogeneous continuous-time Markov chain is too large, making inferences - here limited to determining marginal or limit expectations - becomes computationally infeasible. Fortunately, the state space of such a chain is usually too detailed for the inferences we are interested in, in the sense that a less detailed - smaller - state space suffices to unambiguously formalise the inference. However, in general this so-called lumped state space inhibits computing exact inferences because the corresponding dynamics are unknown and/or intractable to obtain. We address this issue by considering an imprecise continuous-time Markov chain. In this way, we are able to provide guaranteed lower and upper bounds for the inferences of interest, without suffering from the curse of dimensionality.Comment: 9th International Conference on Soft Methods in Probability and Statistics (SMPS 2018

Phosphorylation of pRb: mechanism for RB pathway inactivation in MYCN-amplified retinoblastoma.

A small, but unique subgroup of retinoblastoma has been identified with no detectable mutation in the retinoblastoma gene (RB1) and with high levels of MYCN gene amplification. This manuscript investigated alternate pathways of inactivating pRb, the encoded protein in these tumors. We analyzed the mutation status of the RB1 gene and MYCN copy number in a series of 245 unilateral retinoblastomas, and the phosphorylation status of pRb in a subset of five tumors using immunohistochemistry. There were 203 tumors with two mutations in RB1 (RB1(-/-) , 83%), 29 with one (RB1(+/-) , 12%) and 13 with no detectable mutations (RB1(+/+) , 5%). Eighteen tumors carried MYCN amplification between 29 and 110 copies: 12 had two (RB1(-/-) ) or one RB1 (RB1(+/-) ) mutations, while six had no mutations (RB1(+/+) ). Immunohistochemical staining of tumor sections with antibodies against pRb and phosphorylated Rb (ppRb) displayed high levels of pRb and ppRb in both RB1(+/+) and RB1(+/-) tumors with MYCN amplification compared to no expression of these proteins in a classic RB1(-/-) , MYCN-low tumor. These results establish that high MYCN amplification can be present in retinoblastoma with or without coding sequence mutations in the RB1 gene. The functional state of pRb is inferred to be inactive due to phosphorylation of pRb in the MYCN-amplified retinoblastoma without coding sequence mutations. This makes inactivation of RB1 by gene mutation or its protein product, pRb, by protein phosphorylation, a necessary condition for initiating retinoblastoma tumorigenesis, independent of MYCN amplification

The fractional porous medium equation on the hyperbolic space

We consider a nonlinear degenerate parabolic equation of porous medium type, whose diffusion is driven by the (spectral) fractional Laplacian on the hyperbolic space. We provide existence results for solutions, in an appropriate weak sense, for data belonging either to the usual Lp spaces or to larger (weighted) spaces determined either in terms of a ground state of the laplacian, or of the (fractional) Green’s function. For such solutions, we also prove different kind of smoothing effects, in the form of quantitative L1- L∞ estimates. To the best of our knowledge, this seems the first time in which the fractional porous medium equation has been treated on non-compact, geometrically non-trivial examples