Increased oxidative stress, inflammation, and glutamate: Potential preventive and therapeutic targets for hearing disorders.

Hearing disorders constitute one of the major health concerns in the USA. Decades of basic and clinical studies have identified numerous ototoxic agents and investigated their modes of action on the inner ear, utilizing tissue culture as well as animal and human models. Current preventive and therapeutic approaches are considered unsatisfactory. Therefore, additional modalities should be developed. Many studies suggest that increased levels of oxidative stress, chronic inflammation, and glutamate play an important role in the initiation and progression of damage to the inner ear leading to hearing impairments. To prevent these cellular deficits, antioxidants, anti-inflammatory agents, and antagonists of glutamate receptor have been used individually or in combination with limited success. It is essential, therefore, to simultaneously enhance the levels of antioxidant enzymes by activating the Nrf2 (a nuclear transcriptional factor) pathway, dietary and endogenous antioxidant compounds, and B12-vitamins in order to reduce the levels of oxidative stress, chronic inflammation, and glutamate at the same time. This review presents evidence to show that increased levels of these cellular metabolites, biochemical or factors are involved in the pathogenesis of cochlea leading to hearing impairments. It presents scientific rationale for the use of a mixture of micronutrients that may decrease the levels of oxidative damage, chronic inflammation, and glutamate at the same time. The benefits for using oral administration of proposed micronutrient mixture in humans are presented. Animal and limited human studies indirectly suggest that orally administered micronutrients can accumulate in the inner ear. Therefore, this route of administration may be useful in prevention, and in combination with standard care, in improved management of hearing problems following exposure to well-recognized and studied ototoxic agents, such as noise, cisplatin, aminoglycoside antibiotics, and advanced age

Oxidative and Inflammatory Events in Prion Diseases: Can They Be Therapeutic Targets?

Prion diseases are a group of incurable infectious terminal neurodegenerative diseases caused by the aggregated misfolded PrPsc in selected mammals including humans. The complex physical interaction between normal prion protein PrPc and infectious PrPsc causes conformational change from the α- helix structure of PrPc to the β-sheet structure of PrPsc, and this process is repeated. Increased oxidative stress is one of the factors that facilitate the conversion of PrPc to PrPsc. This overview presents evidence to show that increased oxidative stress and inflammation are involved in the progression of this disease. Evidence is given for the participation of redoxsensitive metals Cu and Fe with PrPsc inducing oxidative stress by disturbing the homeostasis of these metals. The fact that some antioxidants block the toxicity of misfolded PrPc peptide supports the role of oxidative stress in prion disease. After exogenous infection in mice, PrPsc enters the follicular dendritic cells where PrPsc replicates before neuroinvasion where they continue to replicate and cause inflammation leading to neurodegeneration. Therefore, reducing levels of oxidative stress and inflammation may decrease the rate of the progression of this disease. It may be an important order to reduce oxidative stress and inflammation at the same time. This may be achieved by increasing the levels of antioxidant enzymes by activating the Nrf2 pathway together with simultaneous administration of dietary and endogenous antioxidants. It is proposed that a mixture of micronutrients could enable these concurrent events thereby reducing the progression of human prion disease

Colourings of cubic graphs inducing isomorphic monochromatic subgraphs

A $k$-bisection of a bridgeless cubic graph $G$ is a $2$-colouring of its vertex set such that the colour classes have the same cardinality and all connected components in the two subgraphs induced by the colour classes (monochromatic components in what follows) have order at most $k$. Ban and Linial conjectured that every bridgeless cubic graph admits a $2$-bisection except for the Petersen graph. A similar problem for the edge set of cubic graphs has been studied: Wormald conjectured that every cubic graph $G$ with $|E(G)| \equiv 0 \pmod 2$ has a $2$-edge colouring such that the two monochromatic subgraphs are isomorphic linear forests (i.e. a forest whose components are paths). Finally, Ando conjectured that every cubic graph admits a bisection such that the two induced monochromatic subgraphs are isomorphic. In this paper, we give a detailed insight into the conjectures of Ban-Linial and Wormald and provide evidence of a strong relation of both of them with Ando's conjecture. Furthermore, we also give computational and theoretical evidence in their support. As a result, we pose some open problems stronger than the above mentioned conjectures. Moreover, we prove Ban-Linial's conjecture for cubic cycle permutation graphs. As a by-product of studying $2$-edge colourings of cubic graphs having linear forests as monochromatic components, we also give a negative answer to a problem posed by Jackson and Wormald about certain decompositions of cubic graphs into linear forests.Comment: 33 pages; submitted for publicatio

Logarithmic corrections in the free energy of monomer-dimer model on plane lattices with free boundaries

Using exact computations we study the classical hard-core monomer-dimer models on m x n plane lattice strips with free boundaries. For an arbitrary number v of monomers (or vacancies), we found a logarithmic correction term in the finite-size correction of the free energy. The coefficient of the logarithmic correction term depends on the number of monomers present (v) and the parity of the width n of the lattice strip: the coefficient equals to v when n is odd, and v/2 when n is even. The results are generalizations of the previous results for a single monomer in an otherwise fully packed lattice of dimers.Comment: 4 pages, 2 figure

Telomere shortening during aging: Attenuation by antioxidants and anti-inflammatory agents.

Telomeres are a repeated sequence -of bases found at the ends of chromosomes. In humans, this sequence is TTAGGG, which is repeated over 2000 times. Telomeres protect the ends chromosomes from fusion with nearby chromosomes, and allow effective replication of DNA. Each time a cell divides, 25-200 base pairs are lost from the terminal sequence of chromosomes. By becoming truncated during cell division, telomeres protect essential genes from being shortened and thus inactivated. In addition, telomeres are sensitive to inflammation and oxidative stress, which can further promote telomere shortening. Reduction in the length of telomeres leads to the cessation of cell division and thus cellular senescence and apoptosis. This review discusses evidence for the role of oxidative stress and inflammation in regulating the length of telomeres in mammalian cells during senescence. Evidence is presented suggesting that antioxidants and anti-inflammatories can reduce the pace of shortening of telomere length during aging. The distinctive properties of transformed cells suggest that treatment with such materials will have a deleterious rather than a protective effect on such abnormal cells

Parameterized Study of the Test Cover Problem

We carry out a systematic study of a natural covering problem, used for identification across several areas, in the realm of parameterized complexity. In the {\sc Test Cover} problem we are given a set $[n]=\{1,...,n\}$ of items together with a collection, $\cal T$, of distinct subsets of these items called tests. We assume that $\cal T$ is a test cover, i.e., for each pair of items there is a test in $\cal T$ containing exactly one of these items. The objective is to find a minimum size subcollection of $\cal T$, which is still a test cover. The generic parameterized version of {\sc Test Cover} is denoted by $p(k,n,|{\cal T}|)$-{\sc Test Cover}. Here, we are given $([n],\cal{T})$ and a positive integer parameter $k$ as input and the objective is to decide whether there is a test cover of size at most $p(k,n,|{\cal T}|)$. We study four parameterizations for {\sc Test Cover} and obtain the following: (a) $k$-{\sc Test Cover}, and $(n-k)$-{\sc Test Cover} are fixed-parameter tractable (FPT). (b) $(|{\cal T}|-k)$-{\sc Test Cover} and $(\log n+k)$-{\sc Test Cover} are W[1]-hard. Thus, it is unlikely that these problems are FPT

Association study of suicidal behavior and affective disorders with a genetic polymorphism in ABCG1, a positional candidate on chromosome 21q22.3

The gene that codes for the ABC transporter ABCG1 is located in a chromosomal susceptibility region (21q22.3) for affective disorders. Genetic variations in ABCG1 have been associated with affective disorders in Japanese males. In this study, we investigated the distribution of a G2457A polymorphism in patients with affective disorders, suicide attempters with various psychiatric diagnoses and healthy subjects, We initially found a trend towards a modest association with affective disorders in males (p = 0.046 for allele frequencies and p = 0.046 for AA versus GG). We conducted a replication study with independent patients and controls, There was no association with affective disorders, either in the replication or in the combined group, Furthermore, we found no association with suicidal behavior, These findings do not support the hypothesis that ABCG1 is a susceptibility gene for affective disorders or suicidal behavior. Copyright (C) 2000 S. Karger AG, Basel

Fundamental Cycles and Graph Embeddings

In this paper we present a new Good Characterization of maximum genus of a graph which makes a common generalization of the works of Xuong, Liu, and Fu et al. Based on this, we find a new polynomially bounded algorithm to find the maximum genus of a graph

The Discovery of Cherenkov Radiation and its use in the detection of extensive air showers

Cascades of charged particles are created when high-energy cosmic rays enter the earth's atmosphere: these 'extensive air-showers' are studied to gain information on the energy spectrum, arrival direction distribution and mass composition of the particles above 1014 eV where direct observations using instruments carried by balloons or satellites become impractical. Detection of light in the visible and ultra-violet ranges of the electromagnetic spectrum plays a key role in this work, the two processes involved being the emission of Cherenkov light and the production of fluorescence radiation. In this paper I will outline some of the history of the discovery of the Cherenkov process and describe the use to which it has been put in the study of extensive air-showers at ground level.Comment: To appear in Proceedings of CRIS2010: Cosmic Ray International Seminar on '100 years of Cosmic Rays: from Pioneering Experiments to Physics in Space