Diabetes-Related Ankyrin Repeat Protein (DARP/Ankrd23) Modifies Glucose Homeostasis by Modulating AMPK Activity in Skeletal Muscle.

Skeletal muscle is the major site for glucose disposal, the impairment of which closely associates with the glucose intolerance in diabetic patients. Diabetes-related ankyrin repeat protein (DARP/Ankrd23) is a member of muscle ankyrin repeat proteins, whose expression is enhanced in the skeletal muscle under diabetic conditions; however, its role in energy metabolism remains poorly understood. Here we report a novel role of DARP in the regulation of glucose homeostasis through modulating AMP-activated protein kinase (AMPK) activity. DARP is highly preferentially expressed in skeletal muscle, and its expression was substantially upregulated during myotube differentiation of C2C12 myoblasts. Interestingly, DARP-/- mice demonstrated better glucose tolerance despite similar body weight, while their insulin sensitivity did not differ from that in wildtype mice. We found that phosphorylation of AMPK, which mediates insulin-independent glucose uptake, in skeletal muscle was significantly enhanced in DARP-/- mice compared to that in wildtype mice. Gene silencing of DARP in C2C12 myotubes enhanced AMPK phosphorylation, whereas overexpression of DARP in C2C12 myoblasts reduced it. Moreover, DARP-silencing increased glucose uptake and oxidation in myotubes, which was abrogated by the treatment with AICAR, an AMPK activator. Of note, improved glucose tolerance in DARP-/- mice was abolished when mice were treated with AICAR. Mechanistically, gene silencing of DARP enhanced protein expression of LKB1 that is a major upstream kinase for AMPK in myotubes in vitro and the skeletal muscle in vivo. Together with the altered expression under diabetic conditions, our data strongly suggest that DARP plays an important role in the regulation of glucose homeostasis under physiological and pathological conditions, and thus DARP is a new therapeutic target for the treatment of diabetes mellitus

Improving DRAM Performance by Parallelizing Refreshes with Accesses

Modern DRAM cells are periodically refreshed to prevent data loss due to leakage. Commodity DDR DRAM refreshes cells at the rank level. This degrades performance significantly because it prevents an entire rank from serving memory requests while being refreshed. DRAM designed for mobile platforms, LPDDR DRAM, supports an enhanced mode, called per-bank refresh, that refreshes cells at the bank level. This enables a bank to be accessed while another in the same rank is being refreshed, alleviating part of the negative performance impact of refreshes. However, there are two shortcomings of per-bank refresh. First, the per-bank refresh scheduling scheme does not exploit the full potential of overlapping refreshes with accesses across banks because it restricts the banks to be refreshed in a sequential round-robin order. Second, accesses to a bank that is being refreshed have to wait. To mitigate the negative performance impact of DRAM refresh, we propose two complementary mechanisms, DARP (Dynamic Access Refresh Parallelization) and SARP (Subarray Access Refresh Parallelization). The goal is to address the drawbacks of per-bank refresh by building more efficient techniques to parallelize refreshes and accesses within DRAM. First, instead of issuing per-bank refreshes in a round-robin order, DARP issues per-bank refreshes to idle banks in an out-of-order manner. Furthermore, DARP schedules refreshes during intervals when a batch of writes are draining to DRAM. Second, SARP exploits the existence of mostly-independent subarrays within a bank. With minor modifications to DRAM organization, it allows a bank to serve memory accesses to an idle subarray while another subarray is being refreshed. Extensive evaluations show that our mechanisms improve system performance and energy efficiency compared to state-of-the-art refresh policies and the benefit increases as DRAM density increases.Comment: The original paper published in the International Symposium on High-Performance Computer Architecture (HPCA) contains an error. The arxiv version has an erratum that describes the error and the fix for i

An Alternative Public Health Vision for a National Drug Strategy: Treatment Works

This article returns to a war waged virtually throughout this century--a war between the theories of punishment and rehabilitation in curtailing the drug epidemic. Today, the terms of the war are recast as supply-side policies based upon law enforcement; destroying crops in source countries; interdiction and increased sentencing; and demand reduction based upon prevention, education, and treatment. The war on drugs has reached a feverish pitch. New policies and statutes have tightened the grip of supply-side policies, with images of battle and hate mongering which go beyond the vilified drug lords and governments which harbor them, to the middle men, the dealers, and even the users. First this article reviews the set of current and proposed federal policies designed to punish users and to hold them strictly accountable for their addiction. Second, it proposes an alternative public health strategy for controlling the drug epidemic based upon social science research. Third, in demonstrating the efficacy and cost effectiveness of prevention and treatment, the article sets the parameters of a public health agenda in curtailing the drug epidemic

Housing Typology of Pune (A Case Study from Nal stop to Chandni Chowk, Pune)

This paper aims to discuss the various types of housing systems in Pune that is traditional, planned and unplanned in a way the city evolved. Further going to details of traditional system that includes the Wadas and chawls of Pune followed by planned unit development including residential bungalows or detached housing, town housing or row housing, apartments and mixed use housing. It also discusses how the typologies are somehow interconnected and also deals with slums or the informal housing types. This paper looks at the choice and appropriateness of different housing typologies[1], considerations given to the availability, cost of land, socio-economic profile of end-users and thus, enhancing their general wellbeing

On green routing and scheduling problem

The vehicle routing and scheduling problem has been studied with much interest within the last four decades. In this paper, some of the existing literature dealing with routing and scheduling problems with environmental issues is reviewed, and a description is provided of the problems that have been investigated and how they are treated using combinatorial optimization tools

A Multi-robot Coverage Path Planning Algorithm Based on Improved DARP Algorithm

The research on multi-robot coverage path planning (CPP) has been attracting more and more attention. In order to achieve efficient coverage, this paper proposes an improved DARP coverage algorithm. The improved DARP algorithm based on A* algorithm is used to assign tasks to robots and then combined with STC algorithm based on Up-First algorithm to achieve full coverage of the task area. Compared with the initial DARP algorithm, this algorithm has higher efficiency and higher coverage rate