Scalable Peer-to-Peer Indexing with Constant State

We present a distributed indexing scheme for peer to peer networks. Past work on distributed indexing traded off fast search times with non-constant degree topologies or network-unfriendly behavior such as flooding. In contrast, the scheme we present optimizes all three of these performance measures. That is, we provide logarithmic round searches while maintaining connections to a fixed number of peers and avoiding network flooding. In comparison to the well known scheme Chord, we provide competitive constant factors. Finally, we observe that arbitrary linear speedups are possible and discuss both a general brute force approach and specific economical optimizations

Fast Approximate Reconciliation of Set Differences

We present new, simple, efficient data structures for approximate reconciliation of set differences, a useful standalone primitive for peer-to-peer networks and a natural subroutine in methods for exact reconciliation. In the approximate reconciliation problem, peers A and B respectively have subsets of elements SA and SB of a large universe U. Peer A wishes to send a short message M to peer B with the goal that B should use M to determine as many elements in the set SB–SA as possible. To avoid the expense of round trip communication times, we focus on the situation where a single message M is sent. We motivate the performance tradeoffs between message size, accuracy and computation time for this problem with a straightforward approach using Bloom filters. We then introduce approximation reconciliation trees, a more computationally efficient solution that combines techniques from Patricia tries, Merkle trees, and Bloom filters. We present an analysis of approximation reconciliation trees and provide experimental results comparing the various methods proposed for approximate reconciliation.National Science Foundation (ANI-0093296, ANI-9986397, CCR-0118701, CCR-0121154); Alfred P. Sloan Research Fellowshi

Simple Load Balancing for Distributed Hash Tables

Distributed hash tables have recently become a useful building block for a variety of distributed applications. However, current schemes based upon consistent hashing require both considerable implementation complexity and substantial storage overhead to achieve desired load balancing goals. We argue in this paper that these goals can b e achieved more simply and more cost-effectively. First, we suggest the direct application of the "power of two choices" paradigm, whereby an item is stored at the less loaded of two (or more) random alternatives. We then consider how associating a small constant number of hash values with a key can naturally b e extended to support other load balancing methods, including load-stealing or load-shedding schemes, as well as providing natural fault-tolerance mechanisms

A Pragmatic Approach to DHT Adoption

Despite the peer-to-peer community's obvious wish to have its systems adopted, specific mechanisms to facilitate incremental adoption have not yet received the same level of attention as the many other practical concerns associated with these systems. This paper argues that ease of adoption should be elevated to a first-class concern and accordingly presents HOLD, a front-end to existing DHTs that is optimized for incremental adoption. Specifically, HOLD is backwards-compatible: it leverages DNS to provide a key-based routing service to existing Internet hosts without requiring them to install any software. This paper also presents applications that could benefit from HOLD as well as the trade-offs that accompany HOLD. Early implementation experience suggests that HOLD is practical

Program representation size in an intermediate language with intersection and union types

The CIL compiler for core Standard ML compiles whole programs using a novel typed intermediate language (TIL) with intersection and union types and flow labels on both terms and types. The CIL term representation duplicates portions of the program where intersection types are introduced and union types are eliminated. This duplication makes it easier to represent type information and to introduce customized data representations. However, duplication incurs compile-time space costs that are potentially much greater than are incurred in TILs employing type-level abstraction or quantification. In this paper, we present empirical data on the compile-time space costs of using CIL as an intermediate language. The data shows that these costs can be made tractable by using sufficiently fine-grained flow analyses together with standard hash-consing techniques. The data also suggests that non-duplicating formulations of intersection (and union) types would not achieve significantly better space complexity.National Science Foundation (CCR-9417382, CISE/CCR ESS 9806747); Sun grant (EDUD-7826-990410-US); Faculty Fellowship of the Carroll School of Management, Boston College; U.K. Engineering and Physical Sciences Research Council (GR/L 36963, GR/L 15685

Byzantine Agreement Given Partial Broadcast

This paper considers unconditionally secure protocols for reliable broadcast among a set of n players, where up to t of the players can be corrupted by a (Byzantine) adversary but the remaining h = n - t players remain honest. In the standard model with a complete, synchronous network of bilateral authenticated communication channels among the players, broadcast is achievable if and only if 2n/h < 3. We show that, by extending this model by the existence of partial broadcast channels among subsets of b players, global broadcast can be achieved if and only if the number h of honest players satisfies 2n/h < b + 1. Achievability is demonstrated by protocols with communication and computation complexities polynomial in the size of the network, i.e., in the number of partial broadcast channels. A respective characterization for the related consensus problem is also give

Oncostatin m is produced in adipose tissue and is regulated in conditions of obesity and type 2 diabetes

CONTEXT: Adipose tissue is a highly active endocrine organ that secretes many factors that affect other tissues and whole-body metabolism. Adipocytes are responsive to several glycoprotein 130 (gp130) cytokines, some of which have been targeted as potential antiobesity therapeutics. OBJECTIVE: Oncostatin M (OSM) is a gp130 family member known to inhibit adipocyte differentiation in vitro, but its effects on other adipocyte properties are not characterized. The expression of OSM in white adipose tissue (WAT) has not been evaluated in the context of obesity. Thus, our objective was to examine the expression of adipose tissue OSM in obese animals and humans. DESIGN: OSM expression was examined in adipose tissues from mice with diet-induced and genetic obesity and in obese humans as well as in fractionated adipose tissue from mice. Murine adipocytes were used to examine OSM receptor expression and the effects of OSM on adipocytes, including the secretion of factors such as plasminogen activator inhibitor 1 and IL-6, which are implicated in metabolic diseases. RESULTS: OSM expression is increased in rodent and human obesity/type 2 diabetes mellitus. In humans, OSM levels correlate with body weight and insulin and are inversely correlated with glucose disposal rate as measured by hyperinsulinemic-euglycemic clamp. OSM is not produced from the adipocytes in WAT but derives from cells in the stromovascular fraction, including F4/80(+) macrophages. The specific receptor of OSM, OSM receptor-β, is expressed in adipocytes and adipose tissue and increased in both rodent models of obesity examined. OSM acts on adipocytes to induce the expression and secretion of plasminogen activator inhibitor 1 and IL-6. CONCLUSIONS: These data indicate that WAT macrophages are a source of OSM and that OSM levels are significantly induced in murine and human obesity/type 2 diabetes mellitus. These studies suggest that OSM produced from immune cells in WAT acts in a paracrine manner on adipocytes to promote a proinflammatory phenotype in adipose tissue

Treatment With Treprostinil and Metformin Normalizes Hyperglycemia and Improves Cardiac Function in Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction

Objective: Pulmonary hypertension (PH) due to left heart disease (group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide; however, at present, there is no proven effective therapy available for its treatment. PH-HFpEF is associated with insulin resistance and features of metabolic syndrome. The stable prostacyclin analog, treprostinil, is an effective and widely used Food and Drug Administration-approved drug for the treatment of pulmonary arterial hypertension. While the effect of treprostinil on metabolic syndrome is unknown, a recent study suggests that the prostacyclin analog beraprost can improve glucose intolerance and insulin sensitivity. We sought to evaluate the effectiveness of treprostinil in the treatment of metabolic syndrome-associated PH-HFpEF. Approach and Results: Treprostinil treatment was given to mice with mild metabolic syndrome-associated PH-HFpEF induced by high-fat diet and to SU5416/obese ZSF1 rats, a model created by the treatment of rats with a more profound metabolic syndrome due to double leptin receptor defect (obese ZSF1) with a vascular endothelial growth factor receptor blocker SU5416. In high-fat diet-exposed mice, chronic treatment with treprostinil reduced hyperglycemia and pulmonary hypertension. In SU5416/Obese ZSF1 rats, treprostinil improved hyperglycemia with similar efficacy to that of metformin (a first-line drug for type 2 diabetes mellitus); the glucose-lowering effect of treprostinil was further potentiated by the combined treatment with metformin. Early treatment with treprostinil in SU5416/Obese ZSF1 rats lowered pulmonary pressures, and a late treatment with treprostinil together with metformin improved pulmonary artery acceleration time to ejection time ratio and tricuspid annular plane systolic excursion with AMPK (AMP-activated protein kinase) activation in skeletal muscle and the right ventricle. Conclusions: Our data suggest a potential use of treprostinil as an early treatment for mild metabolic syndrome-associated PH-HFpEF and that combined treatment with treprostinil and metformin may improve hyperglycemia and cardiac function in a more severe disease

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead