bluuebunny/crossref_metadata_2025 huggingface dataset:
Empirical analysis of overheads in cluster environments
Authors: Schmidt Brian K. , Sunderam Vaidy S.
Published: November 2006

In concurrent computing environments based on heterogeneous processing elements interconnected by general‐purpose networks, several classes of overheads contribute to lowered performance. The most obvious limitations are network throughput and latency, but certain other factors also play a significant role. In an attempt to gain some insight into the nature of these overheads, and to propose strategies to alleviate them, empirical measurements of native communication performance as well as application execution performance were conducted, using the PVM network computing system. These experiments and our analyses have identified load imbalance, the parallelism model adopted, communication delay and throughput, and within‐host overheads as the primary factors affecting performance in cluster environments. Interestingly, we find that agenda parallelism and load balancing strategies contribute significantly more to better performance than improved communications or system tuning. Drawing general conclusions on how these inefficiencies may be overcome is inadvisable because of the tremendous variability of many parameters in general purpose network environments; we therefore propose several potential approaches, including model selection criteria, partitioning strategies, and software system heuristics, to reduce overheads and enhance performance in network based environments.
Solving an advection‐diffusion problem on the connection machine
Authors: Berggren Martin
Published: November 2006

An algorithm is presented that solves a linear advection‐diffusion problem using a least‐squares formulation and a conjugate gradient method to solve the corresponding minimization problem. An implementation in CM‐Fortran on a Thinking Machines CM‐2 is compared with a serial implementation on an IBM RS6000. The maximum speed‐up obtained is a factor of 70. For fine grids, the CPU time scales almost ideally when the number of processors is increased from 4096 to 8192.
High‐performance emulation of hierarchical structures on hypercube supercomputers
Authors: Ziavras Sotirios G. , Shah Devenkumar P.
Published: November 2006

The problem or emulating multilevel structures on hypercube supercomputers is studied in the paper. The frequently used pyramid belongs to the class of multilevel structures. Several algorithms have been published in the literature for the emulation of pyramids by hypercubes. The paper extends the most important of these algorithms to make them applicable for multilevel structures. Results for the Connection Machine system CM‐2 with 16,384 processors are presented and comparative analysis of the new algorithms is carried out. It is shown that very often higher performance can be obtained for multilevel structures other than the pyramid.
Fast multilevel implementation of recursive spectral bisection for partitioning unstructured problems
Authors: Barnard Stephen T. , Simon Horst D.
Published: November 2006

If problems involving unstructured meshes are to be solved efficiently on distributed‐memory parallel computers, the meshes must be partitioned and distributed across processors in a way that balances the computational load and minimizes communication. The recursive spectral bisection method (RSB) has been shown to be very effective for such partitioning problems compared to alternative methods, but RSB in its simplest form is expensive. Here a multilevel version of RSB is introduced that attains about an order‐of‐magnitude improvement in run time on typical examples.
Do hypercubes sort faster than tree machines?
Authors: Hansen Per Brinch
Published: November 2006

We develop a balanced, parallel quicksort algorithm for a hypercube and compare it with a similar algorithm for a binary tree machine. The performance of the hypercube algorithm is measured on a Computing Surface.
SuperPascal—a publication language for parallel scientific computing
Authors: Hansen Per Brinch
Published: November 2006

Parallel computers will not become widely used until scientists and engineers adopt a common programming language for publication of parallel scientific algorithms. This paper describes the publication language SuperPascal by examples. SuperPascal extends Pascal with deterministic statements for parallel processes and synchronous message communication. The language permits unrestricted combinations of recursive procedures and parallel statements. SuperPascal omits ambiguous and insecure features of Pascal. Restrictions on the use of variables enable a single‐pass compiler to check that parallel processes are disjoint, even if the processes use procedures with global variables. A portable implementation of SuperPascal has been developed on a Sun workstation under Unix.
Parallel search for the interpretation of aerial images
Authors: Narayanan P. J. , Davis Larry S.
Published: November 2006

In this paper, we present a parallel search scheme for model‐based interpretation of aerial images, following a focus‐of‐attention paradigm. Interpretation is performed using the gray level image of an aerial scene and its segmentation into connected components of almost constant gray level. Candidate objects are generated from the window as connected combinations of its components. Each candidate is matched against the model by checking if the model constraints are satisfied by the parameters computed from the region. The problem of candidate generation and matching is posed as searching in the space of combinations of connected components in the image, with finding an (optimally) successful region as the goal. Our implementation exploits parallelism at multiple levels by parallelizing the management of the open list and other control tasks as well as the task of model matching. We discuss and present the implementation of the interpretation system on a Connection Machine CM‐2. The implementation reported a successful match in a few hundred milliseconds whenever they existed.
Parallel dynamic programming and ship voyage management
Authors: Barber Christine , Sen Pratyush , Downie Martin
Published: November 2006

The paper is concerned with the design and implementation of a parallel dynamic programming algorithm for use in ship voyage management The basic concepts are presented in terms of a simple model for weather routing. Other factors involved in voyage management, and their inclusion in a more comprehensive algorithm, are also discussed. The algorithms have been developed and implemented using a transputer‐based distributed‐memory parallel machine using the high‐level communication harness CS Tools. Trial calculations over grids of up to 282 nodes have been carried out and the results are presented. Good speed‐ups for the calculations have been attained, and the factors affecting the efficiency of the parallel computations are reviewed. These trial calculations indicate that a ship voyage management system based on parallel dynamic programming is likely to be beneficial.
Fault tolerance in the execution of remote jobs on idling workstations
Authors: Yang Cul‐Qing , Qu Yaoshuang
Published: November 2006

Many workstation‐based distributed systems allow programs to be executed on remote idling machines for effective utilization of system resources. Usually, the control policies in these systems force a remote job be discontinued by the arrival of local jobs to guarantee the autonomy of individual workstations. Therefore, one special concern in the design of such systems is the fault‐tolerant aspects for the execution of remote jobs. In the paper we discuss two control policies of workstation‐based distributed systems, checkpointing and non‐checkpointing policy, which support fault‐tolerant execution of remote jobs on idling workstations. An analytical analysis on the reliability and mean turnaround time of the execution of remote jobs are conducted for both control policies. The optimal time interval between checkpoints in the checkpointing policy is formulated based on the given reliability and overhead of the system. In addition, several sample results derived from these analyses are compared with the outcome of corresponding simulation programs. Some observations of fault‐tolerant features of each control policy are thereupon presented as guidelines for the future development of such workstation‐based distributed systems.
Processing recursive queries on transputers
Authors: Shao J. , Bell D. A. , Hull M. E. C.
Published: November 2006

There is a perceived need within the database community to extend the traditional relational database systems so as to accommodate applications which are deductive in nature. One major problem involved in such an extension is the efficient processing of recursive queries. To this end, parallel processing is expected to play an important role. While substantial work has been done in devising strategies for processing recursive queries in parallel, it is perhaps surprising that little has been reported on the implementation and the run‐time performance of these strategies. In the paper we report our experience of implementing a pipelined evaluation strategy on transputers. A wide range of queries, database structures and architectural configurations are considered as benchmarks in this study. The performance is studied in terms of both speed‐up factors and communication costs. The experimental results show the potential of processing recursive queries in parallel, and provide insight into the usefulness of using transputers for such applications.
Compile‐time scheduling of multithread data localities on multiple vector processors
Authors: Chang Chih‐Yung , Sheu Jang‐Ping
Published: November 2006

A large class of loop programs applied in solving differential equations, Fourier transforms, image processing and neural processing can be translated or rewritten into a vector execution form with a π‐block dependence graph. In the paper we propose a multithreading strategy to partition such vectorized loops into multithread execution form. Each partitioned thread consists of instances of statements with localities in vector registers. The multithreading scheme gives a novel combination of loop unrolling, statement instances reordering, index shifting, vector register reuse exploiting and multithreading. For some cases of loop program with π‐block dependence graph, experimental results show that our scheme assists vector compilers of the Convex C38 series to reduce the number of memory accesses and synchronizations among CPUs.
Run‐time issues in program partitioning on distributed memory systems
Authors: Pande Santosh , Agrawal Dharma P.
Published: November 2006

Our earlier work reported a Threshold Scheduling Method for compile‐time mapping of functional parallism on distributed‐memory systems. The work reported in this paper discusses run‐time issues in efficiently supporting the functional parallism with minimal overheads, through a combination of compile‐time and run‐time ownership analysis.

At compile time, the code generation phase determines whether a local copy of a live definition of a variable needed by a task is available on a given processor, through an ownership analysis. In case ownership cannot be resolved at compile time, an appropriate code is generated to perform analysis at run time. The code generation is carried out so that all the processors carry the same copy of the compiled program with the individual processor's code being isolated and the universally owned code being replicated on all processors to minimize run‐time overheads. The run‐time system maintains the static and dynamic ownerships at every processor to avoid communication overhead on ownership information.

We demonstrate the approach by incorporating it in the compiler for targeting a parallel functional language, Sisal (streams and iterations in single assignment language), to Intel Touchstone i860 systems. Several benchmarks demonstrate the viability of the approach.
A framework for partitioning parallel computations in heterogeneous environments
Authors: Weissman Jon B. , Grimshaw Andrew S.
Published: November 2006

In the paper we present a framework for partitioning data parallel computations across a heterogeneous metasystem at runtime. The framework is guided by program and resource information which is made available to the system. Three difficult problems are handled by the framework: processor selection, task placement and heterogeneous data domain decomposition. Solving each of these problems contributes to reduced elapsed time. In particular, processor selection determines the best grain size at which to run the computation, task placement reduces communication cost, and data domain decomposition achieves processor load balance. We present results which indicate that excellent performance is achievable using the framework. The paper extends our earlier work on partitioning data parallel computations across a single‐level network of heterogeneous workstations.
A compendium of processor allocation strategies for two‐dimensional mesh connected systems
Authors: Melhart Bonnie E. , Morgenstern Craig A. , Nute Tom
Published: November 2006

Multiple processor systems are an integral part of today's high‐performance computing environment. Such systems are often configured as a two‐dimensional grid of processors called a mesh. Tasks compete for rectangular submeshes of this mesh. The choice of submesh allocation strategy can significantly affect the level of processor utilization and a task's waiting time. In addition, the execution speed of various allocation algorithms varies widely, which can further affect system performance. This paper describes and categorizes several submesh allocation strategies, including a previously unreported method that is superior to other methods in terms of execution speed. The paper includes results of simulation studies used to compare the performance characteristics of the most efficient allocation strategies in each category.
Enhancement of Photocurrent Generation by Honeycomb Structures in Organic Thin Films
Authors: Heng Liping , Zhai Jin , Zhao Yong , Xu Jinjie , Sheng Xianliang , Jiang Lei
Published: November 2006

A light‐emitting poly (distyryldimethylbenzene‐co‐triethylene glycol) rod–coil block copolymer was used to fabricate films with three‐dimensionally ordered honeycomb structures by the breath‐figure method. Photocurrent generation and photovoltaic performance are studied, and the dependence of photocurrent on applied electric field is investigated. Introducing the ordered porous structure significantly improves the photoelectric conversion behavior, because porous structures not only enhance the light‐harvesting efficiency but also benefit charge separation and charge transfer. This phenomenon may have great prospects for enhancing the photovoltaic behavior of organic thin‐film devices.
Release from Silica SBA‐3‐like Mesoporous Fibers: Cross‐Wall Transport and External Diffusion Barrier
Authors: Stempniewicz Magdalena , Rohwerder Michael , Marlow Frank
Published: November 2006

The transport of guest molecules between adjacent pore channels (cross‐wall transport) is the limiting factor in the release of guest molecules from SBA‐3‐like fibers. This specific mode of diffusion is identified by microscopic observation and studied quantitatively in a UV/Vis‐monitored release experiment. Analysis of release curves reveals that the external particle surface offers resistance to the guest molecules passing through it (external diffusion barrier). This barrier is native to as‐synthesized fibers and can be effectively modified to slow down the release. Extremely effective slowdown is achieved by deposition of a nanometer‐thick layer of sodium silicate, that is, the guest molecules are then safely stored in the particles.
The apoptosis of blood polymorphonuclear leukocytes in sickle cell disease
Authors: Ozdogu Hakan , Boga Can , Sozer Oktay , Sezgin Nurzen , Kizilkilic Ebru , Maytalman Erkan , Yalcintas Defne
Published: November 2006

Background:

The apoptosis of human polymorphonuclear leukocytes (PMNs) in patients with sickle cell disease (SCD) is not well understood. The goal of this study was to examine the apoptosis of PMNs in patients with SCD and in controls.

Methods:

Flow cytometric quantitation of PMN apoptosis was performed in 17 patients during and after sickle cell vasoocclusive crisis and in 17 healthy volunteers. Plasma nitric oxide concentrations were also measured in patients with SCD.

Results:

The mean of annexin‐V and annexin‐V/PI staining (early and late apoptotic cells) increased to a greater degree in patients with SCD than in healthy controls for patients with SCD during and after vasoocclusive crisis. The mean of PI staining showing dead cells was higher only in patients after SCD crisis than in healthy controls. In the SCD groups during and after vasoocclusive crisis, there was no difference between PMN apoptosis levels. Furthermore, plasma nitric oxide concentrations were not correlated with PMN apoptosis.

Conclusions:

There was an evidence that the alteration of blood PMN apoptosis could contribute to the pathogenetic mechanisms of vasoocclusion in patients with SCD. This can be attributed to the effects of numerous inflammatory mediators rather than simply the effects of nitric oxide. © 2006 International Society for Analytical Cytology
Metabolic syndrome: a wake‐up call
Authors: Rendell Marc , Gurwitz David
Published: November 2006

Metabolic Syndrome, already affecting over 40% of the US population over the age of 60, is fast becoming “the plague of the 21st century” in developed nations. The time has come for health system policymakers to prioritize the fight against Metabolic Syndrome and its associated morbidity. We need an aggressive effort and funding for better early diagnosis, educational programs and assistance for lifestyle changes, basic research, as well as novel drug development programs. Failing in this effort, we are doomed to witness further increases in morbidity from associated diseases, ranging from type 2 diabetes to coronary heart disease and stroke, with these events taking place at younger ages. The cost to society is projected to be so high that it justifies an effort at least similar in magnitude to past and current drives for fighting cancer, drug abuse, and AIDS. Sadly, it seems that so far we have fallen behind in our battle against Metabolic Syndrome. We call upon government and industry leaders to wake up and engage the fight against Metabolic Syndrome and its associated diseases. The clock is ticking and the cost to society is escalating. Drug Dev. Res. 67:535–538, 2006. © 2006 Wiley‐Liss, Inc.
Trends and opportunities in the metabolic syndrome
Authors: “Wick” Johnson John H.
Published: November 2006

Metabolic Syndrome consists of a multifactoral set of indications and, unfortunately, definitions. There is, at present, no consensus definition for Metabolic Syndrome and physicians who recognize the syndrome use different definitions. Some of the major stakeholder associations do not believe that Metabolic Syndrome is an approvable indication and no regulatory agency has weighed in on the matter. This has been the cause of confusion among many physicians resulting in different emphasis on intervention. However, there is close agreement between physicians surveyed in major markets as to the top three indications. The largest unmet medical need among these indications is obesity and obesity represents the largest opportunity. However, any single NCE or combination of existing drugs that can treat 3 indications will be a major advance. Any therapy will be an intervention and will have to have a very clean safety profile. Morbidity and mortality studies with existing therapies and combinations will be needed to establish outcomes. Drug Dev. Res. 67:539–544, 2006. © 2006 Wiley‐Liss, Inc.
Management of type 2 diabetes: the role of incretin mimetics
Authors: Holcombe John H. , Kim Dennis D. , Stonehouse Anthony H. , Kendall David M.
Published: November 2006

Current strategies for the treatment of type 2 diabetes target deficient insulin secretion and insulin resistance, but have not been shown to correct the progressive β–cell dysfunction characteristic of the disease. Traditionally, type 2 diabetes is treated in a stepwise manner with medical nutrition therapy, oral anti–diabetes therapies, and ultimately exogenous insulin. These therapies improve glycemic control, but are unable to prevent or delay either deterioration in glucose control or the decline of β–cell function. Despite the use of current anti–diabetes therapies, patients with type 2 diabetes are likely to experience deteriorating glycemic control and substantial weight gain. In addition to these issues, patients treated with insulin secretogogues such as sulfonylureas and exogenous insulin are subject to an increased risk of hypoglycemia. Moreover, insulin–based therapies do not fully address the complex hormonal irregularities, such as glucagon hypersecretion, that characterize type 2 diabetes. In view of the drawbacks associated with current treatment strategies, new therapies are being developed that may provide more durable glycemic control with associated reductions in body weight. These new therapies include the incretin mimetics, agents that share many of the glucoregulatory effects of the incretin hormones such as glucagon–like peptide–1 (GLP–1). Leveraging the physiological functions of incretin hormones such as GLP–1 may potentially benefit the ever growing number of patients with type 2 diabetes. Drug Dev. Res. 67:545–552, 2006. © 2006 Wiley‐Liss, Inc.
Tissue‐specific glucocorticoid excess in the metabolic syndrome: 11β‐HSD1 as a therapeutic target
Authors: Wang Minghan
Published: November 2006

Systemic glucocorticoid excess is linked to the development of the metabolic syndrome, a group of metabolic disorders including central obesity and insulin resistance. 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) converts the inert cortisone to the active cortisol in target tissues. The increased expression of 11β‐HSD1 in the adipose tissue of obese subjects suggests that there could be glucocorticoid excess at the tissue level, which is likely to be involved in the development of the metabolic syndrome. 11β‐HSD1 inhibitors have been under development as a potential therapy for the treatment of the metabolic syndrome. With the current progress, the future prospects of 11β‐HSD1 inhibitors are encouraging for providing beneficial metabolic effects. Drug Dev. Res. 67:567–569, 2006. © 2006 Wiley‐Liss, Inc.
Glucocorticoids in type 2 diabetes mellitus and the metabolic syndrome
Authors: Welles Bernice
Published: November 2006

While glucocorticoids were originally named for their role in glucose metabolism, their role in many aspects of resting and stress‐related homeostasis has been elucidated. An accumulation of evidence linking abnormal glucocorticoid metabolism to both type 2 diabetes and metabolic syndrome has led to a search for therapeutic agents that lower levels of cortisol, the principal active glucocorticoid in humans, and/or that block the effects of cortisol excess. Several promising approaches are currently under investigation and some compounds have reached early stage clinical development. A popular approach is the inhibition of the enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), which regenerates the active cortisol from cortisone, its inactive form. This approach still awaits clinical proof of concept. Other therapeutic approaches include blockade at the level of the glucocorticoid receptor and inhibition of adrenal cortisol synthesis. Ketoconazole and metyrapone, inhibitors of 11β hydroxylase, the terminal step in adrenal cortisol synthesis, are frequently used to effect pharmacologic adrenalectomy in patients with Cushing's syndrome, a disorder caused by a marked elevation in levels of cortisol. The 2S,4R enantiomer of ketoconazole, which may be safer than racemic ketoconazole, is currently being tested in a phase‐2 clinical trial in patients with type 2 diabetes, many of whom have one or more co‐morbidities frequently associated with the metabolic syndrome. Given the central role that cortisol appears to play in the development of the metabolic syndrome, it is likely that a single agent may treat multiple components of this syndrome. Drug Dev. Res. 67:570–573, 2006. © 2006 Wiley‐Liss, Inc.
Today's challenges and tomorrow's opportunities: ligands to peroxisome proliferator‐activated receptors as therapies for type 2 diabetes and the metabolic syndrome
Authors: Miller Anne Reifel
Published: November 2006

For over a decade, scientists have been investigating the sub‐family of nuclear hormone receptors known as the peroxisome proliferator‐activated receptors (PPARs) as potential targets for improved therapies for type 2 diabetes (T2D). Initial efforts focused on compounds with the thiazolidinedione (TZD) structure, synthesizing compounds based on structural differences followed by testing in rodent models without knowing the molecular target. Once the receptor for the TZDs was identified as PPARγ, more extensive efforts began to identify and develop improved versions of the TZDs. Many biotechnology and pharmaceutical companies using this information established assays that were used in high through‐put screening efforts to identify compounds with greater affinity and selectivity to the receptor. Surprising, these extensive efforts have not led to improved therapies but, in fact, have identified molecules with improved efficacy but with more severe and diverse liabilities. Today, scientists continue to pursue the PPAR subfamily as a target for advanced treatments for T2D and the metabolic syndrome. New approaches include selective PPAR modulators, expansion into the PPARα and PPARδ subtypes, and partial agonists with dual or pan PPAR properties. These drug discovery efforts will continue, as T2D and the associated metabolic diseases become severe medical problems in nations worldwide. Eventually, new and improved therapies will emerge based on the extensive preclinical and clinical knowledge that has accumulated from research and discovery on PPARs by dedicated and thoughtful scientists in search of improved therapies for people with T2D. Drug Dev. Res. 67:574–578, 2006. © 2006 Wiley‐Liss, Inc.
Activation of PPARγ by Sartans
Authors: Erbe David V. , Gartrell Katherine , Will Sarah , Perreault Mylene , Wang Suyue , Tobin James F.
Published: November 2006

The physiological links between abnormalities in glucose regulation and blood pressure provide novel means to treat patients with the Metabolic Syndrome. In fact, recent data indicate that ATR1 antagonists may also improve insulin resistance. We explored one proposed explanation for these effects, namely activation of the PPARγ nuclear hormone receptor. These studies should guide further efforts to develop agents to treat hypertension and insulin resistance. Drug Dev. Res. 67:579–581, 2006. © 2006 Wiley‐Liss, Inc.
Postprandial hyperglycemia: Why do we care about it? What should we do?
Authors: Rendell Marc S.
Published: November 2006

There is increasing evidence that elevated postprandial plasma glucose (PPG) exerts a more deleterious effect on the vascular system than elevation of fasting plasma glucose (FPG). In particular, individuals with normal FPG but impaired glucose tolerance (IGT) have significantly increased risk of cardiovascular events. With the recognition of the importance of PPG and the availability of new pharmacologic options, management of diabetes will shift to greater attention to PPG levels. There are many approaches to reduction of PPG; dietary management and promotion of exercise are very effective. Sulfonylureas, meglitinides, metformin, thiazolidinediones, and disaccharidase inhibitors all counteract PPG elevation. The development of glucagon‐like peptide‐1 (GLP‐1) agonists such as exendin and dipeptidyl peptidase IV inhibitors offers a new approach to suppression of PPG elevation. New semisynthetic insulin analogues permit a more aggressive response to post‐prandial glucose elevation, with lower risk of hypoglycemia, than with regular insulin. The advent of accurate continuous glucose monitoring will facilitate the treatment of post‐prandial hyperglycemia. Drug Dev. Res. 67:582–586, 2006. © 2006 Wiley‐Liss, Inc.
The importance of postprandial glucose concentration: lessons learned from diabetes and pregnancy
Authors: Jovanovic Lois
Published: November 2006

Pregnancy may be considered as a model for the importance of postprandial hyperglycemia on the risk of complications in diabetic subjects in the non‐pregnant state. Although pregnancy is only 9 months, the accelerated growth of the fetus is very sensitive to glucose variability and may be similar to a “life time” of struggle for survival. The toxicity due to hyperglycemia during pregnancy manifests itself by fetal overgrowth secondary to maternal overnourishment to the fetus. Glucose is the main nutrient that passes to the fetus by facilitated diffusion. Thus, maternal hyperglycemia results in a big baby who is also sick secondary to fetal hyperinsulinemia and the resultant metabolic aberrancy. In addition, if the fetus has inherited the type 2 diabetes gene or genes, then the fetal adiposity tends to be accrual of visceral fat, an abnormal distribution of fat in utero that increases the risk of subsequent type 2 diabetes in the child if the baby survives the insult. Studies have shown that the maternal postprandial glucose concentration is the most important variable associated with fetal overgrowth. The studies that support the importance of maternal postprandial glucose concentrations as the primary risk factor in fetopathy and this discussion suggests that these observations may extrapolate to the non‐pregnant person with diabetes and are presented in this review. Drug Dev. Res. 67:591–594, 2006. © 2006 Wiley‐Liss, Inc.
The metabolic syndrome and the clinician
Authors: Einhorn Daniel
Published: November 2006

The diagnosis of the Metabolic Syndrome is somewhat controversial, with many definitions and some arguments as to the need for a diagnosis. From the viewpoint of clinical medicine, however, the concept is highly useful in organizing our interest in prevention of the consequences of this condition. Drug Dev. Res. 600–601, 2006. © 2006 Wiley‐Liss, Inc.
Metabolic syndrome and higher risk of maternal placental syndromes and cardiovascular disease
Authors: Ray Joel G.
Published: November 2006

Maternal placental syndromes (MPS), including the hypertensive disorders of pregnancy and abruption or infarction of the placenta, likely originate from diseased placental vessels. MPS is more common in women who exhibit the metabolic syndrome and classic risk factors for cardiovascular disease, including obesity, pre‐pregnancy hypertension, diabetes mellitus, and dyslipidemia. The link between the MPS and premature cardiovascular disease is likely mediated by a woman's metabolic syndrome profile, thus providing an early opportunity for the prevention of cardiovascular disease in women through dietary and lifestyle modifications. Drug Dev. Res. 67:607–611, 2006. © 2006 Wiley‐Liss, Inc.
Syndrome Zzzzzzzzz: the overlap between snoring, sleep apnea, and metabolic syndrome
Authors: Grunstein Ronald R.
Published: November 2006

Obstructive sleep apnea (OSA) is a common medical condition strongly associated with central obesity. There is increasing evidence that OSA is an independent risk factor for impaired cardiovascular health but the strong association between OSA and central obesity has confounded cross‐sectional studies. Large‐scale OSA treatment intervention studies are needed to investigate cardiovascular endpoints in these patients and OSA needs to be an outcome variable for clinical trails in weight loss. Drug Dev. Res. 67:616–618, 2006. © 2006 Wiley‐Liss, Inc.
The metabolic syndrome: linking oxidative stress and inflammation to obesity, type 2 diabetes, and the syndrome
Authors: Dandona Paresh , Ghanim Husam , Mohanty Priya , Chaudhuri Ajay
Published: November 2006

Metabolic syndrome defined by a cluster of clinical features increases the risk of cardiovascular disease and type 2 diabetes mellitus. The original hypothesis linking this syndrome to these diseases was based on insulin resistance and the effect of hyperinsulinemia on atherogenesis. However, inflammatory processes have now been linked to the pathogenesis of atherosclerosis and insulin resistance. Novel data have shown the effect of macronutrients on inflammatory mediators and the anti‐inflammatory effects of insulin that is secreted in response to food intake. This review attempts to provide an alternative explanation for the pathogenesis of the metabolic syndrome and the increase in risk of cardiovascular disease and diabetes on the basis of these findings. Drug Dev. Res. 67:619–626, 2006. © 2006 Wiley‐Liss, Inc.
Stearoyl‐CoA desaturase: a new therapeutic target of liver steatosis
Authors: Dobrzyn Pawel , Dobrzyn Agnieszka
Published: November 2006

Stearoyl‐CoA desaturase (SCD) is the rate limiting enzyme catalyzing the biosynthesis of monounsaturated fatty acids, mainly oleate and palmitoleoate, which are used as substrates for the synthesis of triglycerides, wax esters, cholesterol esters, and phospholipids. Recent studies have shown that SCD1, the main SCD isoform expressed in liver, is a key player in the regulation of lipid metabolism. SCD1 deficient mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet‐induced obesity and liver steatosis. SCD1 was found to be specifically repressed during leptin‐mediated weight loss and leptin‐deficient ob/ob mice lacking SCD1 showed markedly reduced adiposity, despite higher food intake. In addition, SCD1 deficiency completely corrects the hypometabolic phenotype and hepatic steatosis of ob/ob mice, and attenuates fasting‐induced liver steatosis in peroxisome proliferator‐activated receptor‐α – deficient mice. Consequently, increased SCD activity has been found in humans and animals which accumulate significant amounts of lipids in liver, whereas SCD1 deficiency ameliorates both high‐fat diet induced and genetically induced hepatic steatosis. Much evidence indicates that the direct anti‐steatotic effect of SCD1 deficiency stems from increased fatty acid oxidation and reduced lipid synthesis. In this review we discuss our current understanding of the role of SCD1 in regulation of hepatic lipid partitioning and test the hypothesis that pharmacological manipulation of SCD might be of benefit in the treatment of non‐alcoholic fatty liver disease. Drug Dev. Res. 67:643–650, 2006. © 2006 Wiley‐Liss, Inc.
Viral infections as potential triggers of type 1 diabetes
Authors: van der Werf Nienke , Kroese Frans G.M. , Rozing Jan , Hillebrands Jan‐Luuk
Published: November 2006

During the last decades, the incidence of type 1 diabetes (T1D) has increased significantly, reaching percentages of 3% annually worldwide. This increase suggests that besides genetical factors environmental perturbations (including viral infections) are also involved in the pathogenesis of T1D. T1D has been associated with viral infections including enteroviruses, rubella, mumps, rotavirus, parvovirus and cytomegalovirus (CMV). Although correlations between clinical presentation with T1D and the occurrence of a viral infection that precedes the development of overt disease have been recognized, causalities between viruses and the diabetogenic process are still elusive and difficult to prove in humans. The use of experimental animal models is therefore indispensable, and indeed more insight in the mechanism by which viruses can modulate diabetogenesis has been provided by studies in rodent models for T1D such as the biobreeding (BB) rat, nonobese diabetic (NOD) mouse or specific transgenic mouse strains. Data from experimental animals as well as in vitro studies indicate that various viruses are clearly able to modulate the development of T1D via different mechanisms, including direct β‐cell lysis, bystander activation of autoreactive T cells, loss of regulatory T cells and molecular mimicry. Data obtained in rodents and in vitro systems have improved our insight in the possible role of viral infections in the pathogenesis of human T1D. Future studies will hopefully reveal which human viruses are causally involved in the induction of T1D and this knowledge may provide directions on how to deal with viral infections in diabetes‐susceptible individuals in order to delay or even prevent the diabetogenic process. Copyright © 2007 John Wiley & Sons, Ltd.
Slow versus fast proteins in the stimulation of beta‐cell response and the activation of the entero‐insular axis in type 2 diabetes
Authors: Tessari Paolo , Kiwanuka Edward , Cristini Michela , Zaramella Michela , Enslen Marc , Zurlo Corinna , Garcia‐Rodenas Clara
Published: November 2006

Background

We tested whether ingestion of whey protein can induce greater post‐prandial amino acid (AA) levels in the plasma and a higher beta‐cell response than casein ingestion in type 2 diabetes mellitus patients.

Methods

The study was designed as a double‐blind, randomized, and controlled cross‐over clinical trial. Twelve post‐absorptive type 2 diabetic subjects who were withdrawn from their usual hypoglycemic therapy were studied. A medium calorie (≈6 kcal/kg BW), high protein (≈50% of total kcal) mixed meal, containing whey protein, casein, or a free amino acid (FREE AA) mixture matching the casein AA composition, was randomly administered on three different occasions.

Results

Following ingestion of whey protein, plasma concentrations of total, branched chain, and essential AA were 25–50% greater than after ingestion of casein (p < 0.0001), and were similar to those observed after the FREE AA meal. With whey protein, C‐peptide, insulin, and pro‐insulin concentrations were greater by 12–40% (p < 0.02 or less) than with casein, and similar to those with FREE AA. Glucagon‐like polypeptide 1 (GLP‐1) response tended to be lower with casein than with whey protein. Glucose‐dependent insulinotropic polypeptide (GIP) response was greater with either whey protein or casein than with FREE AA. Post‐prandial glucose concentrations were similar after whey protein and casein ingestion, but lower after the FREE AA meal.

Conclusions

In type 2 diabetes, the ingestion of a fast‐absorbable protein results in a greater post‐prandial aminoacidemia and a higher beta‐cell secretion than the ingestion of a ‘slow’ protein. Whether these changes can be maintained chronically in combination with hypoglycemic therapy, possibly also resulting in better glycemic control, remains to be established. Copyright © 2006 John Wiley & Sons, Ltd.
The C‐peptide fragment EVARQ reduces glomerular hyperfiltration in streptozotocin‐induced diabetic rats
Authors: Nordquist Lina , Moe Erika , Sjöquist Mats
Published: November 2006

Background

Initially, diabetes is commonly associated with an increased glomerular filtration rate (GFR), a potential mechanism involved in the progression of diabetic nephropathy. Several studies have reported reno‐protective effects of C‐peptide. C‐peptide reduces diabetes‐induced hyperfiltration, as well as renal hypertrophy and albuminuria. In order to gain further understanding of these effects, it is very important to localize the active sites within the C‐peptide molecule. This study was designed to elucidate the effects of the C‐peptide fragment EVARQ on kidney function, blood pressure and blood glucose levels in diabetic rats in vivo.

Methods

The study was performed on adult inactin‐anaesthetized male Sprague‐Dawley rats. Two weeks prior to the experiment, diabetes was induced by a single intravenous injection of streptozotocin (55 mg/kg BW). After recovery and recording of baseline values, vehicle, C‐peptide (50 pmol · kg BW−1·h−1) or EVARQ (500 pmol·kg BW−1·h−1) was continuously administered for a total of 100 min.

Results

Before substance administration, all diabetic groups displayed a pronounced hyperfiltration as compared to the control rats. Continuous administration of both C‐peptide and EVARQ reduced the diabetes‐induced hyperfiltration within an hour. Furthermore, blood pressure was only reduced in diabetic rats that were given C‐peptide, whereas the blood glucose decreased in the diabetic groups that were given either C‐peptide or EVARQ.

Conclusions

The present study shows that administration of the C‐peptide fragment EVARQ has similar effects on GFR and blood glucose levels as the intact C‐peptide molecule, suggesting at least one active site within this region. Copyright © 2007 John Wiley & Sons, Ltd.
Chordin affects pronephros development in Xenopus embryos by anteriorizing presomitic mesoderm
Authors: Mitchell Tracy , Jones Elizabeth A. , Weeks Daniel L. , Sheets Michael D.
Published: November 2006

Spemann's organizer emits signals that pattern the mesodermal germ layer during Xenopus embryogenesis. In a previous study, we demonstrated that FGFR1 activity within the organizer is required for the production of both the somitic muscle‐ and pronephros‐patterning signals by the organizer and the expression of chordin, an organizer‐specific secreted protein (Mitchell and Sheets [2001] Dev. Biol. 237:295–305). Studies from others in both chicken and Xenopus embryos provide compelling evidence that pronephros forms by means of secondary induction signals emitted from anterior somites (Seufert et al. [1999] Dev. Biol. 215:233–242; Mauch et al. [2000] Dev. Biol. 220:62–75). Here we provide several lines of evidence in support of the hypothesis that chordin influences pronephros development by directing the formation of anterior somites. Chordin mRNA was absent in ultraviolet (UV) ‐irradiated embryos lacking pronepheros (average DAI<2) but was always found in UV‐irradiated embryos that retain pronepheros (average DAI>2). Furthermore, ectopic expression of chordin in embryos and in tissue explants leads to the formation of anterior somites and pronephros. In these experiments, pronephros was only observed in association with muscle. Chordin diverted somatic muscle cells to more anterior positions within the somite file in chordin‐induced secondary trunks and induced the expression of the anterior myogenic gene myf5. Finally, depletion of chordin mRNA with DEED antisense oligonucleotides substantially reduced somitic muscle and pronephric tubule and duct formation in whole embryos. These data and previous studies on ectoderm and endoderm (Sasai et al. [1995] Nature 377:757) support the idea that chordin functions as an anteriorizing signal in patterning the germ layers during vertebrate embryogenesis. Our data support the hypothesis that chordin directs the formation of anterior somites that in turn are necessary for pronephros development. Developmental Dynamics 236:251–261, 2007. © 2006 Wiley‐Liss, Inc.
Storage space saving and error avoidance of passive delay variation measurement employing a hash‐based technique for IP networks
Authors: Ohta Satoru
Published: November 2006

Delay variation of packets is a significant performance measure in IP networks. Both active and passive measurements can evaluate delay variation. Among these, passive measurement is more advantageous because it can monitor the performance experienced by users without disturbing network load. Meanwhile, a shortcoming of using passive measurement is an extremely large storage space required to record packets and timestamps. This problem is solved by feeding a portion of each packet to a hash function as its input and recording the output to identify the packet. Since the data length of the hash function output is very short, such an approach effectively decreases the storage space. However, this approach still needs a considerably large storage space to record time‐stamps. Additionally, the collisions among hash output values may bring unacceptable measurement errors. This paper proposes a method to decrease the storage space required to record timestamps for hash‐based delay variation measurement. This decrease is achieved by a variable length coding of timestamps. The paper also presents methods to avoid measurement errors brought by hash value collisions. Through experiments, it is shown that the proposed techniques correctly measure delay variation as well as effectively reduce the storage space. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 90(3): 21–32, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20328
Optical/electrical two‐step heterodyne technique for 60‐GHz Radio‐On‐Fiber downlink
Authors: Taniguchi Tomohiro , Sakurai Naoya , Kumozaki Kiyomi
Published: November 2006

In order to economically realize a Gbit/s class downlink using 60‐GHz millimeter waves, the authors have previously proposed an optical/electrical two‐step heterodyne system, based on the Radio‐On‐Fiber (ROF) transmission technique, in which millimeter‐wave filters at the wireless base station and a millimeter‐wave local oscillator at the wireless terminal are unnecessary. In this paper, for four types of three‐wave/four‐wave optical transmission method realizing the proposed scheme, the CNR of the IF signals obtained at the wireless terminal is analyzed and an optimization method is found for optical power distribution to each of multiple wavelength optical signals. The analytical results are compared to show that the scheme for generating three‐wave millimeter‐wave signals from four‐wave optical signals has excellent characteristics for application to either a feed or a nonfeed base station. At the wireless terminal, deterioration can be reduced to about 6.5 dB and about 4.8 dB in comparison with the conventional scheme using a millimeter‐wave local oscillator. Further, the output from a single optical source is optically modulated with two‐wave 30‐GHz‐band signals, and then the above optical transmission system generating the four optical signals is used for generation of the 1.0 Gbit/s‐BPSK millimeter‐wave/IF signal and for demodulation by synchronous detection. It is demonstrated that a BER of less than 10−9can be obtained for a PD input optical power of −11 dBm even in 10‐km SMF transmission. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 90(3): 9–20, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20337
Residual capacity estimation of stationary lithium‐ion secondary battery based on its discharge voltage characteristics
Authors: Matsushima Toshio
Published: November 2006

The relationship between the residual capacity and the discharge voltage of a lithium‐ion secondary battery having sufficient capacity to be used as a backup power supply in telecommunication applications is described. From results of high‐temperature accelerated deterioration tests conducted on lithium‐ion secondary cells, a drop in not only the capacity but also the discharge duration and the discharge voltage was observed, and a fixed relationship was found between the drop in discharge voltage and the residual capacity. This relationship was confirmed not only for single cells, but also for a multicell battery composed of 14 cells which was periodically discharged while being maintained at a floating charge. The possibility of estimating the residual capacity of lithium‐ion secondary cells and batteries from a voltage measurement obtained in constant‐current discharging was confirmed. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 90(3): 1–8, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20355