Role of the ubiquitin proteasome system in Alzheimer's disease

Though Alzheimer's disease (AD) is a syndrome with well-defined clinical and neuropathological manifestations, an array of molecular defects underlies its pathology. A role for the ubiquitin proteasome system (UPS) was suspected in the pathogenesis of AD since the presence of ubiquitin immunoreactivity in AD-related neuronal inclusions, such as neurofibrillary tangles, is seen in all AD cases. Recent studies have indicated that components of the UPS could be linked to the early phase of AD, which is marked by synaptic dysfunction, as well as to the late stages of the disease, characterized by neurodegeneration. Insoluble protein aggregates in the brain of AD patients could result from malfunction or overload of the UPS, or from structural changes in the protein substrates, which prevent their recognition and degradation by the UPS. Defective proteolysis could cause the synaptic dysfunction observed early in AD since the UPS is known to play a role in the normal functioning of synapses. In this review, we discuss recent observations on possible links between the UPS and AD, and the potential for utilizing UPS components as targets for treatment of this disease

Cystatin C based eGFR - for early detection of diabetic kidney disease

Background: Diabetic kidney disease is the leading cause of premature death in young diabetic patients. Detection of diabetic kidney disease as early as possible in the disease process currently offers the best chance of delaying or possibly preventing progression to end-stage renal disease. The present study was aimed to evaluate utility of serum cystatin C based eGFR for early diagnosis of diabetic kidney disease.Methods: Diagnosed patients of type 2 diabetes mellitus having frank proteinuria were excluded. Patients without proteinuria were tested for microalbuminuria.  50 patients having microalbuminuria were tested for 24 hour urine creatinine, serum creatinine and serum cystatin C. Both cystatin C based eGFR and eGFR by Cockcroft and Gault equation were compared with standard GFR by 24 hour urine Creatinine clearance respectively.Results: There was statistically significant positive correlation between cystatin C based eGFR and standard GFR by 24 hr Creatinine clearance (r=0.87). For eGFR by Cockcroft-Gault equation, it was 0.36 (r=0.36).Conclusions: The results of this study suggest that serum cystatin C based eGFR  measurement is a useful, practical tool for the evaluation of renal involvement in the course of diabetes. As serum creatinine values are affected by many factors like age, sex, muscle mass and diet, serum cystatin C based eGFR estimation offers a hope that diabetic kidney disease can be well prevented with appropriate interventions

Complex Energy Spectrum and Time Evolution of QBIC States in a Two-Channel Quantum wire with an Adatom Impurity

We provide detailed analysis of the complex energy eigenvalue spectrum for a two-channel quantum wire with an attached adatom impurity. The study is based on our previous work [Phys. Rev. Lett. 99, 210404 (2007)], in which we presented the quasi-bound states in continuum (or QBIC states). These are resonant states with very long lifetimes that form as a result of two overlapping continuous energy bands one of which, at least, has a divergent van Hove singularity at the band edge. We provide analysis of the full energy spectrum for all solutions, including the QBIC states, and obtain an expansion for the complex eigenvalue of the QBIC state. We show that it has a small decay rate of the order $g^6$, where $g$ is the coupling constant. As a result of this expansion, we find that this state is a non-analytic effect resulting from the van Hove singularity; it cannot be predicted from the ordinary perturbation analysis that relies on Fermi's golden rule. We will also numerically demonstrate the time evolution of the QBIC state using the effective potential method in order to show the stability of the QBIC wave function in comparison with that of the other eigenstates.Comment: Around 20 pages, 50 total figure

Hamilton's theory of turns generalized to Sp(2,R)

We present a generalization of Hamilton's geometric theory of turns, originally invented for SU(2), to the noncompact group Sp(2,R) relevant in a variety of physical applications

Free Space Optical Communications: An Overview

Bridging the so-called “last mile” in communication networks has revived keen interest in free-Space Optics (FSO), also known as fiber-free or fiberless optics, which is a technology that transports data via laser technology. It is a line-of-sight technology that currently enables optical transmission up to 2.5 Gbps of data, voice and video through the air at long distances (4km), allowing optical connectivity without deploying fiber-optic cable or securing spectrum licenses. It is moving closer to being a realistic alternative to laying fiber in access networks. This paper presents an introduction to FSO and the current state of its technology

Master analytic representations and unified representation theory of certain orthogonal and pseudo-orthogonal groups

The representation theory of the groups SO(5),SO(4, 1),SO(6) and SO(5, 1) is studied using the method of Master Analytic Representations (MAR). It is shown that a single analytic expression for the matrix elements of the generators of SO(n+1) and SO(n, 1) in an SO(n) basis yields all the unitary representations (for n=4,5); and that the compact and non-compact groups have essentially the same analytic representation. Once the MAR of a group is worked out, the search for the unitary irreducible representations is reduced to a purely arithmetic operation. The utmost care has been exercised to conduct the discussions at an elementary level: knowledge of simple angular momentum theory is the only prerequisite

PCR Based Genotyping of Lulu Cattle of Nepal for A1, A2 Type Beta-caseins

Lulu is an indigenous breed of cattle (Bos taurus) found in high altitude regions of western Nepal. Population of Lulu cattle has been declining due to introgression with other exotic breeds to increase milk productivity. Here we aimed at finding potential approach for conserving Lulu cattle and its assets by studying the milk contents and investigating which variant of beta-casein protein is present in this breed. Beta caseins are an abundant protein in cow milk with A1 and A2 being the most common genetic variants of this protein. Consumption of A1 type of milk has numerous health-related complications whereas A2 type of milk has numerous human health promoting factors. We used restriction fragment length polymorphism (RFLP) for determining the A1 and A2 variant of beta casein in Lulu cattle. For performing DNA extraction, we collected (n = 18) blood samples of Lulu from Mustang and (n=17) Nepal Agriculture research council farm. The amplified fragments in 3% agarose at 251bp and 213bp respectively confirmed the presence of both A1 and A2 gene in Lulu; however, A2 was of greater abundance. Our study indicated that Lulu has A2 variant of beta-casein predominantly. The gene frequency of A1A1 is 0, A1A2 is 0.06 and A2A2 is 0.94. We further found that the allele frequency of A1 and A2 is 0.03 and 0.97 respectively. We designed special primer for sequencing CSN2 genes since A2 type beta casein gene was predominantly seen on Lulu. The sequencing result further supports our RFLP result as most of our samples have “C” nucleotide SNP in amplified CSN2 gene sequence. The Chi-square value of the current study is 0.04 which supports Hardy-Weinberg equilibrium inferring that Lulu cattle are still in the pure state, where there is no genetic introgression with the exotic breed for the sake of improvement of productivity

Pipelining in multi-query optimization

AbstractDatabase systems frequently have to execute a set of related queries, which share several common subexpressions. Multi-query optimization exploits this, by finding evaluation plans that share common results. Current approaches to multi-query optimization assume that common subexpressions are materialized. Significant performance benefits can be had if common subexpressions are pipelined to their uses, without being materialized. However, plans with pipelining may not always be realizable with limited buffer space, as we show. We present a general model for schedules with pipelining, and present a necessary and sufficient condition for determining validity of a schedule under our model. We show that finding a valid schedule with minimum cost is NP-hard. We present a greedy heuristic for finding good schedules. Finally, we present a performance study that shows the benefit of our algorithms on batches of queries from the TPCD benchmark

Guaranteeing Envy-Freeness under Generalized Assignment Constraints

We study fair division of goods under the broad class of generalized assignment constraints. In this constraint framework, the sizes and values of the goods are agent-specific, and one needs to allocate the goods among the agents fairly while further ensuring that each agent receives a bundle of total size at most the corresponding budget of the agent. Since, in such a constraint setting, it may not always be feasible to partition all the goods among the agents, we conform -- as in recent works -- to the construct of charity to designate the set of unassigned goods. For this allocation framework, we obtain existential and computational guarantees for envy-free (appropriately defined) allocation of divisible and indivisible goods, respectively, among agents with individual, additive valuations for the goods. We deem allocations to be fair by evaluating envy only with respect to feasible subsets. In particular, an allocation is said to be feasibly envy-free (FEF) iff each agent prefers its bundle over every (budget) feasible subset within any other agent's bundle (and within the charity). The current work establishes that, for divisible goods, FEF allocations are guaranteed to exist and can be computed efficiently under generalized assignment constraints. In the context of indivisible goods, FEF allocations do not necessarily exist, and hence, we consider the fairness notion of feasible envy-freeness up to any good (FEFx). We show that, under generalized assignment constraints, an FEFx allocation of indivisible goods always exists. In fact, our FEFx result resolves open problems posed in prior works. Further, for indivisible goods and under generalized assignment constraints, we provide a pseudo-polynomial time algorithm for computing FEFx allocations, and a fully polynomial-time approximation scheme (FPTAS) for computing approximate FEFx allocations.Comment: 29 page