BACKGROUND Given the slow and variable clinical course of Alzheimer disease, very large and extended clinical trials are needed to identify a beneficial clinical effect of disease-modifying treatments. Therefore, biomarkers are essential to prove that an anti-β-amyloid (Aβ) drug candidate affects both Aβ metabolism and plaque load as well as downstream pathogenic mechanisms. OBJECTIVE To eval...

Pseudo orthogonal bases are a certain type of frames proposed in the engineering field, whose concept is equivalent to a tight frame with frame bound 1 in the frame terminology. This paper shows that pseudo orthogonal bases play an essential role in neural network learning. One of the most important issues in neural network learning is “what training data provides the optimal generalization cap...

Pseudo orthogonal bases are a certain type of frames proposed in the engineering field, whose concept is equivalent to a normalized tight frame in the frame terminology. This paper shows that pseudo orthogonal bases play an essential role in neural network learning. One of the most important issues in neural network learning is “what training data provides the optimal generalization capability?...

Neurofibrillary pathology [paired helical filaments (PHFs)] formed by the microtubule-associated protein tau in a hyperphosphorylated form is a major hallmark of Alzheimer's disease and related disorders. The process of tau phosphorylation, thought to be of critical importance for PHF formation, and its potential link to neurodegeneration, however, is not understood very well, mostly because of...

Asymptotics of the normalizing constant are computed for a class of one parameter exponential families on permutations which include Mallows models with Spearmans’s Footrule and Spearman’s Rank Correlation Statistic. The MLE and a computable approximation of the MLE are shown to be consistent. The pseudo-likelihood estimator of Besag is shown to be √ n-consistent. An iterative algorithm (IPFP) ...

The abnormally hyperphosphorylated tau is thought to be implicated in diabetes-associated cognitive deficits. The role of mammalian target of rapamycin (mTOR) / S6 kinase (S6K) signalling in the formation of tau hyperphosphorylation has been previously studied. Caveolin-1 (Cav-1), the essential structure protein of caveolae, promotes neuronal survival and growth, and inhibits glucose metabolism...

Objective(s):Breast cancer is an important leading cause of death from cancer. Stathmin and tau proteins are regulators of cell motility, and their overexpression is associated with the progression and bad prognosis of breast cancer. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is the potential inhibitor of tau protein in neurons. This study determines the effect of memantine ...

Objective(s):Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. One of the hallmarks of AD is an abnormal accumulation of fibril forms of tau protein which is known as a microtubule associated protein. In this regard, inhibition of tau aggregation has been documented to be a potent therapeutic approach in AD and tauopathies. Unfortunately, the available syntheti...

Tau protein, found in both neuronal and non-neuronal cells, forms aggregates in neurons that constitutes one of the hallmarks of Alzheimer's disease (AD). For nearly four decades, research efforts have focused more on tau's role in physiology and pathology in the context of the microtubules, even though, for over three decades, tau has been localised in the nucleus and the nucleolus. Its nuclea...

Regulated protein degradation by the proteasome plays an essential role in the enhancement and suppression of signaling pathways in the nervous system. Proteasome-associated factors are pivotal in ensuring appropriate protein degradation, and we have previously demonstrated that alterations in one of these factors, the proteasomal deubiquitinating enzyme ubiquitin-specific protease 14 (Usp14), ...