bluuebunny/crossref_metadata_2025 huggingface dataset:
Disjunctive image computation for software verification
Authors: Wang Chao , Yang Zijiang , Ivančić Franjo , Gupta Aarti
Published: June 2007

Existing BDD-based symbolic algorithms designed for hardware designs do not perform well on software programs. We propose novel techniques based on unique characteristics of software programs. Our algorithm divides an image computation step into a disjunctive set of easier ones that can be performed in isolation. We use hypergraph partitioning to minimize the number of live variables in each disjunctive component, and variable scopes to simplify transition relations and reachable state subsets. Our experiments on nontrivial C programs show that BDD-based symbolic algorithms can directly handle software models with a much larger number of state variables than for hardware designs.
Transition-overhead-aware voltage scheduling for fixed-priority real-time systems
Authors: Mochocki Bren , Hu Xiaobo Sharon , Quan Gang
Published: June 2007

Time transition overhead is a critical problem for hard real-time systems that employ dynamic voltage scaling (DVS) for power and energy management. While it is a common practice of much previous work to ignore transition overhead, these algorithms cannot guarantee deadlines and/or are less effective in saving energy when transition overhead is significant and not appropriately dealt with. In this article we introduce two techniques, one offline and one online, to correctly account for transition overhead in preemptive fixed-priority real-time systems. We present several DVS scheduling algorithms that implement these methods that can guarantee task deadlines under arbitrarily large transition time overheads and reduce energy consumption by as much as 40% when compared to previous methods.
Forming N-detection test sets without test generation
Authors: Pomeranz Irith , Reddy Sudhakar M.
Published: June 2007

We describe a procedure for forming
n
-detection test sets for
n
>1 without applying a test generation procedure to target faults. The proposed procedure accepts a one-detection test set. It extracts test cubes for target faults from the one-detection test set, and merges the test cubes to obtain new test vectors. By extracting and merging different test cubes in different iterations of this process, an
n
-detection test set is obtained. Merging of test cubes does not require test generation or fault simulation. Fault simulation is required for extracting test cubes for target faults. We demonstrate that the resulting test set is as effective in detecting untargeted faults as an
n
-detection test set generated by a deterministic test generation procedure. We also discuss the application of the proposed procedure starting from a random test set (instead of a one-detection test set).
Computational approaches to temporal sampling of video sequences
Authors: Liu Tiecheng , Kender John R.
Published: June 2007

Video key frame extraction is one of the most important research problems for video summarization, indexing, and retrieval. For a variety of applications such as ubiquitous media access and video streaming, the temporal boundaries between video key frames are required for synchronizing visual content with audio. In this article, we define temporal video sampling as a unified process of extracting video key frames and computing their temporal boundaries, and formulate it as an optimization problem. We first provide an optimal approach that minimizes temporal video sampling error using a dynamic programming process. The optimal approach retrieves a key frame hierarchy and all temporal boundaries in
O
(
n
4
) time and
O
(
n
2
) space. To further reduce computational complexity, we also provide a suboptimal greedy algorithm that exploits the data structure of a binary heap and uses a novel “look-ahead” computational technique, enabling all levels of key frames to be extracted with an average-case computational time of
O
(
n log n
) and memory usage of
O
(
n
). Both the optimal and the greedy methods are free of parameters, thus avoiding the threshold-selection problem that exists in other approaches. We empirically compare the proposed optimal and greedy methods with several existing methods in terms of video sampling error, computational cost, and subjective quality. An evaluation of eight videos of different genres shows that the greedy approach achieves performance very close to that of the optimal approach while drastically reducing computational cost, making it suitable for processing long video sequences in large video databases.
ACM established to develop communication about computing
Authors: Longo Bernadette
Published: June 2007

Sixty years ago most computer scientists worked in a vacuum, unaware of the projects their peers around the U.S. were exploring. Sharing research was key to furthering the field, most agreed, but what vehicle could best serve as a conduit for communication?
Edmund Berkeley and the origins of ACM
Authors: Akera Atsushi
Published: June 2007

A fascination with computing machinery, and a desire to explore this emerging field with mathematicians, engineers, computer manufacturers, and others, inspired E.C. Berkeley to help create a hub for these common interests to connect.
Not only digital
Authors: Care Charles
Published: June 2007

When analog and digital were in flux, ACM provided a forum---as well as publications and conferences---to explore both sides.
The ACM and IEEE-CS guidelines for undergraduate CS education
Authors: Hemmendinger David
Published: June 2007

ACM curriculum recommendations have been instrumental over the last 40 years in defining what is taught at educational institutions around the world.
Universal accessibility as a multimodal design issue
Authors: Obrenovic Zeljko , Abascal Julio , Starcevic Dusan
Published: June 2007

Creating adaptable solutions to address diverse users and situations.
The whitewater process
Authors: Harris Michael , Aebischer Kris , Klaus Tim
Published: June 2007

Small software development companies need it to ensure they stay on course and are able to respond to the market's ebbs and flows.
The right place at the right time
Authors: Goodell Geoffrey , Syverson Paul
Published: June 2007

Examining the use of network location in authentication and abuse prevention.
Concurrent programming without locks
Authors: Fraser Keir , Harris Tim
Published: June 2007

Mutual exclusion locks remain the
de facto
mechanism for concurrency control on shared-memory data structures. However, their apparent simplicity is deceptive: It is hard to design scalable locking strategies because locks can harbor problems such as priority inversion, deadlock, and convoying. Furthermore, scalable lock-based systems are not readily composable when building compound operations. In looking for solutions to these problems, interest has developed in
nonblocking
systems which have promised scalability and robustness by eschewing mutual exclusion while still ensuring safety. However, existing techniques for building nonblocking systems are rarely suitable for practical use, imposing substantial storage overheads, serializing nonconflicting operations, or requiring instructions not readily available on today's CPUs.

In this article we present three APIs which make it easier to develop nonblocking implementations of arbitrary data structures. The first API is a
multiword compare-and-swap
operation (MCAS) which atomically updates a set of memory locations. This can be used to advance a data structure from one consistent state to another. The second API is a
word-based software transactional memory
(WSTM) which can allow sequential code to be reused more directly than with MCAS and which provides better scalability when locations are being read rather than being updated. The third API is an
object-based software transactional memory
(OSTM). OSTM allows a simpler implementation than WSTM, but at the cost of reengineering the code to use OSTM objects.

We present practical implementations of all three of these APIs, built from operations available across all of today's major CPU families. We illustrate the use of these APIs by using them to build highly concurrent skip lists and red-black trees. We compare the performance of the resulting implementations against one another and against high-performance lock-based systems. These results demonstrate that it is possible to build useful nonblocking data structures with performance comparable to, or better than, sophisticated lock-based designs.
Characterization of national Web domains
Authors: Baeza-Yates Ricardo , Castillo Carlos , Efthimiadis Efthimis N.
Published: June 2007

During the last few years, several studies on the characterization of the public Web space of various national domains have been published. The pages of a country are an interesting set for studying the characteristics of the Web because at the same time these are diverse (as they are written by several authors) and yet rather similar (as they share a common geographical, historical and cultural context).

This article discusses the methodologies used for presenting the results of Web characterization studies, including the granularity at which different aspects are presented, and a separation of concerns between contents, links, and technologies. Based on this, we present a side-by-side comparison of the results of 12 Web characterization studies, comprising over 120 million pages from 24 countries. The comparison unveils similarities and differences between the collections and sheds light on how certain results of a single Web characterization study on a sample may be valid in the context of the full Web.
Supporting ad-hoc resource sharing on the Web
Authors: Zhou Jing , Hall Wendy , De Roure David C. , Dialani Vijay K.
Published: June 2007

The key element to support ad-hoc resource sharing on the Web is to discover resources of interest. The hypermedia paradigm provides a way of overlaying a set of resources with additional information in the form of links to help people find other resources. However, existing hypermedia approaches primarily develop mechanisms to enable resource sharing in a fairly static, centralized way. Recent developments in distributed computing, on the other hand, introduced peer-to-peer (P2P) computing that is notable for employing distributed resources to perform a critical function in a more dynamic and ad-hoc scenario. We investigate the feasibility and potential benefits of bringing together the P2P paradigm with the concept of hypermedia link services to implement ad-hoc resource sharing on the Web. This is accomplished by utilizing a web-based Distributed Dynamic Link Service (DDLS) as a testbed and addressing the issues arising from the design, implementation, and enhancement of the service. Our experimental result reveals the behavior and performance of the semantics-based resource discovery in DDLS and demonstrates that the proposed enhancing technique for DDLS, topology reorganization, is appropriate and efficient.
Sharing the cost more efficiently
Authors: Becchetti L. , Könemann J. , Leonardi S. , Páal M.
Published: June 2007

In the
multicommodity rent-or-buy
(MROB) network design problems, we are given a network together with a set of
k
terminal pairs (
s
1
,
t
1
), …, (
s

k

,
t

k

. The goal is to provision the network so that a given amount of flow can be shipped between
s

i

and
t

i

for all 1 ≤
i
≤
k
simultaneously. In order to provision the network, one can either
rent
capacity on edges at some cost per unit of flow, or
buy
them at some larger fixed cost. Bought edges have no incremental, flow-dependent cost. The overall objective is to minimize the total provisioning cost.

Recently, Gupta et al. [2003a] presented a 12-approximation for the MROB problem. Their algroithm chooses a subset of the terminal pairs in the graph at random and then buys the edges of an approximate Steiner forest for these pairs. This technique had previously been introduced [Gupta et al. 2003b] for the single-sink rent-or-buy network design problem.

In this article we give a 6.828-approximation for the MROB problem by refining the algorithm of Gupta et al. and simplifying their analysis. The improvement in our article is based on a more careful adaptation and simplified analysis of the primal-dual algorithm for the Steiner forest problem due to Agrawal et al. [1995]. Our result significantly reduces the gap between the single-sink and multisink case.
Combinatorial testing
Authors: Krishnan R. , Krishna S. Murali , Nandhan P. Siva
Published: June 2007

Combinatorial testing methods address generation of test cases for problems involving multiple parameters and combinations. The Orthogonal Array Based Testing Strategy (OATS) is one such combinatorial testing method, a systematic, statistical way of testing pair-wise interactions. It provides representative (uniformly distributed) coverage of all variable pair combinations. This makes the technique particularly useful for testing of software, wherever there is combinatorial explosion: a. In system testing for handling feature interactions b. In integration testing components c. It is also quite useful for testing products with a large number of configuration possibilities.

One of the fundamental assumptions behind OATS approach is that a subset covering all pair-wise combinations will be more effective than a randomly selected subset. OATS provides a means to select a minimal test set that guarantees testing the pair-wise combinations of all the selected variables. Covering pair-wise combinations has been reported to be very effective in the literature. Successful use of this technique, with 50% effort saving and improved testing with a factor of 2.6 is reported in the literature.

In this paper, we report on the in-house web-based application that we designed and implemented to support customized version of OATS and our experience in piloting and getting this method used in projects. In the in-house tool we have introduced a number of additional features, that help in generation and post processing of test-cases. We have also designed a supporting process for using this method, and we discuss the steps in this process in the paper. We share details on application in feature testing of a mobile phone application. This method has also been successfully used in designing feature interaction test cases and for augmenting the regression suite to increase coverage.
Hybrid multi-core architecture for boosting single-threaded performance
Authors: Yan Jun , Zhang Wei
Published: June 2007

The scaling of technology and the diminishing return of complicated uniprocessors have driven the industry towards multicore processors. While multithreaded applications can naturally leverage the enhanced throughput of multi-core processors, a large number of important applications are single-threaded, which cannot automatically harness the potential of multi-core processors. In this paper, we propose a compiler-driven heterogeneous multicore architecture, consisting of tightly-integrated VLIW (Very Long Instruction Word) and superscalar processors on a single chip, to automatically boost the performance of single-threaded applications without compromising the capability to support multithreaded programs. In the proposed multi-core architecture, while the high-performance VLIW core is used to run code segments with high instruction-level parallelism (ILP) extracted by the compiler; the superscalar core can be exploited to deal with the runtime events that are typically difficult for the VLIW core to handle, such as L2 cache misses. Our initial experimental results by running the preexecution thread on the superscalar core to mitigate the L2 cache misses of the main thread on the VLIW core indicate that the proposed VLIW/superscalar multi-core processor can automatically improve the performance of single-threaded general-purpose applications by up to 40.8%.
From chaos to QoS
Authors: Guo Fei , Kannan Hari , Zhao Li , Illikkal Ramesh , Iyer Ravi , Newell Don , Solihin Yan , Kozyrakis Christos
Published: June 2007

As more and more cores are enabled on the die of future CMP platforms, we expect that several diverse workloads will run simultaneously on the platform. A key example of this trend is the growth of virtualization usage models. When multiple virtual machines or applications or threads run simultaneously, the quality of service (QoS) that the platform provides to each individual thread is non-deterministic today. This occurs because the simultaneously running threads place very different demands on the shared resources (cache space, memory bandwidth, etc) in the platform and in most cases contend with each other. In this paper, we first present case studies that show how this results in non-deterministic performance. Unlike the compute resources managed through scheduling, platform resource allocation to individual threads cannot be controlled today. In order to provide better determinism and QoS, we then examine resource management mechanisms and present QoS-aware architectures and execution environments. The main contribution of this paper is the architecture feasibility analysis through prototypes that allow experimentation with QoS-Aware execution environments and architectural resources. We describe these QoS prototypes and then present preliminary case studies of multi-tasking and virtualization usage models sharing one critical CMP resource (last-level cache). We then demonstrate how proper management of the cache resource can provide service differentiation and deterministic performance behavior when running disparate workloads in future CMP platforms.
Subroutine profiling results for the CPU2006 benchmarks
Authors: Weicker Reinhold P. , Henning John L.
Published: June 2007

Subroutine profiling is a well-known performance tool. For application or system programmers, it determines "hot spots" where the program spends most of its time, and where careful rewriting can most help performance. For compiler authors, it can give information about programming style in such hot spots, and can indicate where compiler improvements may be useful. For hardware designers and analysts, it can be the starting point to explain performance behavior.
Calendar
Authors: Stanik John
Published: June 2007

NSDI (Usenix Symposium on Networked Systems Design and Implementation) Gelato ICE (Itanium Conference and Expo) April 15-18, 2007 San Jose, California
Foreword
Authors: Harchol-Balter Mor
Published: June 2007

I would like to introduce this issue by telling a story. Sometime back in 1997, I wrote a paper on a new idea for improving the response times of http requests at a Web server. The idea was to schedule the HTTP requests so as to favor requests for small files, in accordance with the well-known scheduling policy Shortest Remaining Processing Time (SRPT). The paper was rejected, for many reasons, but the review that stuck in my mind was the one that said,
"Why is this person writing about scheduling? Scheduling is dead."
According to this reviewer, everything that would ever be known about scheduling was already described in the beautiful
Theory of Scheduling
book, written in 1967, by Conway, Maxwell, and Miller.
Beyond processor sharing
Authors: Aalto Samuli , Ayesta Urtzi , Borst Sem , Misra Vishal , Núñez-Queija Rudesindo
Published: June 2007

While the (Egalitarian) Processor-Sharing (PS) discipline offers crucial insights in the performance of fair resource allocation mechanisms, it is inherently limited in analyzing and designing differentiated scheduling algorithms such as Weighted Fair Queueing and Weighted Round-Robin. The Discriminatory Processor-Sharing (DPS) and Generalized Processor-Sharing (GPS) disciplines have emerged as natural generalizations for modeling the performance of such service differentiation mechanisms. A further extension of the ordinary PS policy is the Multilevel Processor-Sharing (MLPS) discipline, which has captured a pivotal role in the analysis, design and implementation of size-based scheduling strategies. We review various key results for DPS, GPS and MLPS models, highlighting to what extent these disciplines inherit desirable properties from ordinary PS or are capable of delivering service differentiation.
Competitive online scheduling for server systems
Authors: Pruhs Kirk
Published: June 2007

Our goal here is to illustrate the competitive online scheduling research community's approach to online server scheduling problems by enumerating some of the results obtained for problems related to response and slowdown, and by explaining some of the standard analysis techniques.
Compiler support for the Fortran 2003 standard
Authors: Chivers Ian D. , Sleightholme Jane
Published: June 2007

This article looks at compiler support for new features in the Fortran 2003 standard. The basis for the entries in the list of features was a report by John Reid.
The new features of Fortran 2003
Authors: Reid John
Published: June 2007

The aim of this paper is to summarize the new features of the Fortran 2003 standard (WG5 2004). We take as our starting point Fortran 95 plus the two official extensions (Cohen 2001, Reid 2001) that have been published as Type 2 Technical Reports (TRs). These provide features for

• Allocatable dummy arguments and type components, and

• Support for the five exceptions of the IEEE Floating Point Standard (IEEE 1989) and for other features of this Standard.
What happened to pastry
Authors: Herbert Andrew
Published: June 2007

This paper describes how Microsoft Research goes about the process of technology transfer, using the experience of transferring the MS Pastry Distributed Hash Table and its applications as an example.
The Farsite project
Authors: Bolosky William J. , Douceur John R. , Howell Jon
Published: June 2007

The Farsite file system is a storage service that runs on the desktop computers of a large organization and provides the semantics of a central NTFS file server. The motivation behind the Farsite project was to harness the unused storage and network resources of desktop computers to provide a service that is reliable, available, and secure despite the fact that it runs on machines that are unreliable, often unavailable, and of limited security. A main premise of the project has been that building a scalable system requires more than scalable algorithms: To be scalable in a practical sense, a distributed system targeting 10
5
nodes must tolerate a significant (and never-zero) rate of machine failure, a small number of malicious participants, and a substantial number of opportunistic participants. It also must automatically adapt to the arrival and departure of machines and changes in machine availability, and it must be able to autonomically repartition its data and metadata as necessary to balance load and alleviate hotspots. We describe the history of the project, including its multiple versions of major system components, the unique programming style and software-engineering environment we created to facilitate development, our distributed debugging framework, and our experiences with formal system specification. We also report on the lessons we learned during this development.
Web science
Authors: Shneiderman Ben
Published: June 2007

Here's how it can awaken computer science to the interdisciplinary possibilities of the Web's socially embedded computing technology.
A solution to an open problem by Knuth
Authors: Pager David
Published: June 2007

In Knuth [2] the problem of minimizing the number of sets of states required for his parsing algorithm is raised as an open question. We solve this problem by showing it is equivalent to that of finding the minimal representation for an incompletely specified finite automaton. A solution may thus be obtained using the known methods of the latter. This result may be viewed in contrast to Pager [8] and [9] where it is shown that it is not generally possible to make optimizations of this kind.
A portable computer security workshop
Authors: Wagner Paul J. , Phillips Andrew T.
Published: June 2007

We have developed a computer security workshop designed to instruct post-secondary instructors who want to start a course or laboratory exercise sequence in computer security. This workshop has also been used to provide computer security education to IT professionals and students. It is effective in communicating basic computer security principles as well as an understanding of some of the significant tools and techniques in this area. Evaluations of the workshop have been very positive; we will offer the workshop locally, regionally, and nationally in the next year. The materials from this workshop are available at http://clics.cs.uwec.edu/workshopmaterials.htm.
The effect of training on the expression of mitochondrial biogenesis- and apoptosis-related proteins in skeletal muscle of patients with mtDNA defects
Authors: Adhihetty Peter J. , Taivassalo Tanja , Haller Ronald G. , Walkinshaw Donald R. , Hood David A.
Published: June 2007

Mitochondrial myopathy patients (MMPs) have impaired oxidative phosphorylation and exercise intolerance. Endurance training of MMPs improves exercise tolerance, but also increases mutational load. To assess the regulation of mitochondrial content in MMPs, we measured proteins involved in 1) biogenesis, 2) oxidative stress, and 3) apoptosis in MMPs and healthy controls (HCs) both before and after endurance training. Before training, MMPs had a greater mitochondrial content, along with a 1.4-fold ( P < 0.05) higher expression of the biogenesis regulator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). The DNA repair enzyme 8-oxoguanine DNA glycolase-1 (OGG-1), the antioxidant manganese superoxide dismutase (MnSOD), and the apoptotic proteins AIF and Bcl-2 were higher in MMPs compared with HCs. Aconitase, an enzyme sensitive to oxidative stress, was 52% lower ( P < 0.05) in MMPs when calculated based on an estimate of mitochondrial volume and oxidative stress-induced protein modifications tended to be higher in MMPs compared with HCs. Endurance training (ET) induced increases in mitochondrial content in both HC subjects and MMPs, but there was no effect of training on the regulatory proteins Tfam or PGC-1α. In MMPs, training induced a selective reduction of OGG-1, an increase in MnSOD, and a reduction in aconitase activity. Thus, before training, MMPs exhibited an adaptive response of nuclear proteins indicative of a compensatory increase in mitochondrial content. Following training, several parallel adaptations occurred in MMPs and HCs, which may contribute to previously observed functional improvements of exercise in MMPs. However, our results indicate that muscle from MMPs may be exposed to greater levels of oxidative stress during the course of training. Further investigation is required to evaluate the long-term benefits of endurance training as a therapeutic intervention for mitochondrial myopathy patients.
LCAT-null mice develop improved hepatic insulin sensitivity through altered regulation of transcription factors and suppressors of cytokine signaling
Authors: Li Lixin , Naples Mark , Song Hui , Yuan Ronghua , Ye Feilu , Shafi Sharmi , Adeli Khosrow , Ng Dominic S.
Published: June 2007

We previously reported that LCAT-deficient mice develop not only low HDL-cholesterol but also hypertriglyceridemia, hepatic triglyceride (TG) overproduction, and, unexpectedly, improved hepatic insulin sensitivity and reduced hepatic TG content. Here, we examined the mechanistic links underlying this apparent paradox. The LDL receptor-deficient (Ldlr)−/−×Lcat−/−mouse model and age- and sex-matched Ldlr−/−×Lcat+/+littermates, both in C57Bl/6 background, were employed. Studies of hepatic insulin signal transduction showed an upregulation of hepatic Irs2 mRNA level (5.3-fold, P = 0.02), IRS-2 protein mass level (1.5-fold, P = 0.009) and pIRS-2 (1.8-fold. P = 0.02) in the Ldlr−/−×Lcat−/−mice. There was a 1.2-fold increase in pAkt ( P = 0.03) with a nonsignificant change in total Akt. We observed a significant shift in its downstream transcription factor FoxO-1 to the cytosolic compartment (2.3-fold increase in cytosolic/nuclear ratio, P = 0.04). We also observed a significant 3.1-fold increase in nuclear abundance of FoxA-2 mass ( P = 0.017) and a 1.5-fold upregulation of its coactivator PGC-1β ( P = 0.002), the coordinated actions of which promotes hepatic TG production and β-oxidation. Increased hepatic insulin signaling in the Ldlr−/−×Lcat−/−mice was associated with an upregulation of the Tcfe3 gene (1.7-fold, P = 0.024), a selective downregulation of the Socs-1 gene by 60% ( P = 0.01), and no change in PTP-1B protein mass. These data suggest that LCAT deficiency induces complex alterations in hepatic signal transduction cascades, which explain, at least in part, the observed enhanced insulin signaling in association with hepatic TG overproduction and reduced hepatic TG content.
Acute effect of insulin on nitric oxide synthesis in humans: a precursor-product isotopic study
Authors: Tessari Paolo , Coracina Anna , Puricelli Lucia , Vettore Monica , Cosma Alessandra , Millioni Renato , Cecchet Diego , Avogaro Angelo , Tiengo Antonio , Kiwanuka Edward
Published: June 2007

Nitric oxide (NO) is a key regulatory molecule with wide vascular, cellular, and metabolic effects. Insulin affects NO synthesis in vitro. No data exist on the acute effect of insulin on NO kinetics in vivo. By employing a precursor-product tracer method in humans, we have directly estimated the acute effect of insulin on intravascular NOx(i.e., the NO oxidation products) fractional (FSR) and absolute (ASR) synthesis rates in vivo. Nine healthy male volunteers were infused iv with l-[15N2-guanidino]arginine ([15N2]arginine) for 6 h. Timed measurements of15NOxand [15N2]arginine enrichments in whole blood were performed in the first 3 h in the fasting state and then following a 3-h euglycemic-hyperinsulinemic clamp (with plasma insulin raised to ≈1,000 pmol/l). In the last 60 min of each experimental period, at ≈steady-state arginine enrichment, a linear increase of15NOxenrichment (mean r = 0.9) was detected in both experimental periods. In the fasting state, NOxFSR was 27.4 ± 4.3%/day, whereas ASR was 0.97 ± 0.36 mmol/day, accounting for 0.69 ± 0.27% of arginine flux. Following hyperinsulinemia, both FSR and ASR of NOxincreased (FSR by ≈50%, to 42.4 ± 6.7%/day, P < 0.005; ASR by ≈25%, to 1.22 ± 0.41 mmol/day, P = 0.002), despite a ≈20–30% decrease of arginine flux and concentration. The fraction of arginine flux used for NOxsynthesis was doubled, to 1.13 ± 0.35% ( P < 0.003). In conclusion, whole body NOxsynthesis can be directly measured over a short observation time with stable isotope methods in humans. Insulin acutely stimulates NOxsynthesis from arginine.
Long-term testosterone supplementation augments overnight growth hormone secretion in healthy older men
Authors: Muniyappa Ranganath , Sorkin John D. , Veldhuis Johannes D. , Harman S. Mitchell , Münzer Thomas , Bhasin Shalender , Blackman Marc R.
Published: June 2007

Circulating testosterone (T) and GH/IGF-I are diminished in healthy aging men. Short-term administration of high doses of T augments GH secretion in older men. However, effects of long-term, low-dose T supplementation on GH secretion are unknown. Our objective was to evaluate effects of long-term, low-dose T administration on nocturnal GH secretory dynamics and AM concentrations of IGF-I and IGFBP-3 in healthy older men (65–88 yr, n = 34) with low-normal T and IGF-I. In a double-masked, placebo-controlled, randomized study we assessed effects of low-dose T supplementation (100 mg im every 2 wk) for 26 wk on nocturnal GH secretory dynamics [8 PM to 8 AM, Q20 min sampling, analyzed by multiparameter deconvolution and approximate entropy (ApEn) algorithms]. The results were that T administration increased serum total T by 33% ( P = 0.004) and E2 by 31% ( P = 0.009) and decreased SHBG by 17% ( P = 0.002) vs. placebo. T supplementation increased nocturnal integrated GH concentrations by 60% ( P = 0.02) and pulsatile GH secretion by 79% ( P = 0.05), primarily due to a twofold increase in GH secretory burst mass ( P = 0.02) and a 1.9-fold increase in basal GH secretion rate ( P = 0.05) vs. placebo. There were no significant changes in GH burst frequency or orderliness of GH release (ApEn). IGF-I levels increased by 22% ( P = 0.02), with no significant change in IGFBP-3 levels after T vs. placebo. We conclude that low-dose T supplementation for 26 wk increases spontaneous nocturnal GH secretion and morning serum IGF-I concentrations in healthy older men.
TLRs in the Gut.IV. Negative regulation of Toll-like receptors and intestinal homeostasis: addition by subtraction
Authors: Shibolet Oren , Podolsky Daniel K.
Published: June 2007

Toll-like receptors (TLRs) are a family of transmembrane proteins that recognize conserved molecular motifs on microorganisms. Ligand binding to TLRs initiates signaling cascades that activate NF-κB, MAPK, and interferon response factors. These culminate in cellular responses including activation of antimicrobial killing mechanisms, production of cytokines and chemokines, maturation of antigen presenting cells, and the recruitment of the adaptive immune response. Intestinal epithelial cells represent a unique population of cells that exist in direct contact with a biomass of bacteria. Initiation of TLR signaling is tightly regulated because prolonged and excessive activation of TLRs can lead to uncontrolled inflammation detrimental to the host. Varied mechanisms appear to contribute to control of TLR activation in the intestinal epithelium. These include the collective effects of several negative regulators that include IRAK-M, TOLLIP, SIGIRR, A20, Nod2, and PPARγ. However, it remains to be determined whether they comprise the entire spectrum of negative control mechanisms and how they are bypassed to trigger activation during challenge by pathogens.
Contributions of glucokinase and phosphofructokinase-2/fructose bisphosphatase-2 to the elevated glycolysis in hepatocytes from Zuckerfa/farats
Authors: Payne Victoria A. , Arden Catherine , Lange Alex J. , Agius Loranne
Published: June 2007

The insulin-resistant Zucker fa/fa rat has elevated hepatic glycolysis and activities of glucokinase and phosphofructokinase-2/fructose bisphosphatase-2 (PFK2). The latter catalyzes the formation and degradation of fructose-2,6-bisphosphate (fructose-2,6-P2) and is a glucokinase-binding protein. The contributions of glucokinase and PFK2 to the elevated glycolysis in fa/fa hepatocytes were determined by overexpressing these enzymes individually or in combination. Metabolic control analysis was used to determine enzyme coefficients on glycolysis and metabolite concentrations. Glucokinase had a high control coefficient on glycolysis in all hormonal conditions tested, whereas PFK2 had significant control only in the presence of glucagon, which phosphorylates PFK2 and suppresses glycolysis. Despite the high control strength of glucokinase, the elevated glycolysis in fa/fa hepatocytes could not be explained by the elevated glucokinase activity alone. In hepatocytes from fa/fa rats, glucokinase translocation between the nucleus and the cytoplasm was refractory to glucose but responsive to glucagon. Expression of a kinase-active PFK2 variant reversed the glucagon effect on glucokinase translocation and glucose phosphorylation, confirming the role for PFK2 in sequestering glucokinase in the cytoplasm. Glucokinase had a high control on glucose-6-phosphate content; however, like PFK2, it had a relative modest effect on the fructose-2,6-P2content. However, combined overexpression of glucokinase and PFK2 had a synergistic effect on fructose-2,6-P2levels, suggesting that interaction of these enzymes may be a prerequisite for formation of fructose-2,6-P2. Cumulatively, this study provides support for coordinate roles for glucokinase and PFK2 in the elevated hepatic glycolysis in fa/fa rats.
Altered basal and stimulated accumbens dopamine release in obese OLETF rats as a function of age and diabetic status
Authors: Anderzhanova Elmira , Covasa Mihai , Hajnal Andras
Published: June 2007

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat lacking the CCK-1 receptor is hyperphagic, prefers palatable and high-calorie meals, and gradually develops obesity and type 2 diabetes. To determine dopamine levels in this strain, we used in vivo quantitative (no net flux) microdialysis at three different ages representing nondiabetic (8 wk), prediabetic (18 wk), and diabetic (56 wk) stages in OLETF and age-matched lean Long-Evans Tokushima Otsuka (LETO) controls. Results showed significantly elevated basal dopamine levels in the caudomedial nucleus accumbens of OLETF rats compared with LETO at younger ages (8 wk: 20.10 ± 5.61 nM vs. 15.85 ± 5.63 nM; 18 wk: 7.37 ± 3.71 nM vs. 4.75 ± 1.25 nM, means ± SD). In contrast, at 56 wk of age, a profound decline in extracellular dopamine concentrations was seen in both strains with a tendency for a greater effect in OLETF rats (1.78 ± 0.40 nM vs. 2.39 ± 0.42 nM). Further, extracellular fraction, an index for reuptake, was higher in 56-wk-old OLETF compared with LETO (0.648 ± 0.049 vs. 0.526 ± 0.057). Potassium-stimulated dopamine efflux revealed an increased capacity of vesicular pool in OLETF rats compared with LETO across all age groups with an accentuated strain difference at 56 wk. These findings demonstrate altered striatal dopamine functions (i.e., increased stimulated release and uptake) in obese OLETF rat. This could be due to the lack of functional CCK-1 receptors, or metabolic and hormonal factors associated with the development of obesity and insulin resistance, or both.
Cellular and subcellular distribution of the type-2 vasopressin receptor in the kidney
Authors: Fenton Robert A. , Brønd Lone , Nielsen Søren , Praetorius Jeppe
Published: June 2007

Arginine vasopressin (AVP) is essential for maintaining body fluid homeostasis. The antidiuretic effects of AVP are initialized by binding of AVP to the type-2 vasopressin receptor (V2R) in the kidney collecting duct (CD), resulting in the exocytic insertion of aquaporin-2 (AQP-2) water channels into the apical plasma membrane. In this study, we describe the generation and characterization of a polyclonal antibody targeted against the NH2terminus of the rat V2R. HEK-293 cells overexpressing the rat, mouse, or human V2R showed strong intracellular immunolabeling. Additionally, immunostaining of M-1 kidney cells expressing a V2R-green fluorescent protein (GFP) fusion construct showed colocalization between GFP and antibody-specific V2R labeling. Immunoblots of rat kidney showed 43- and 47-kDa proteins in all zones that were both reduced to 34-kDa by N-glycosidase F. Protein solubilization with nonionic detergents or the use of homobifunctional cross-linkers demonstrated that the rat V2R exists as a protein complex in native kidney. Immunohistochemistry of rat and mouse kidney revealed abundant labeling of the CD. Double-labeling confocal immunofluorescence microscopy [using distal convoluted tubule/connecting tubule (CNT)-specific marker calbindin and CNT/CD-specific marker AQP-2] showed V2R labeling in both CD and CNT. There was a complete absence of labeling in vascular structures and other renal tubules, including the thick ascending limb (TAL), although RT-PCR of microdissected tubules showed expression of V2R mRNA in TAL. Confocal microscopy demonstrated that at the subcellular level, V2R labeling was predominantly intracellular in normal kidneys, although some staining was apparent in basolateral membrane domains. Confocal microscopy of isolated inner medullary collecting duct tubules showed that the V2R is expressed both intracellularly and in basolateral membrane domains.
Biomechanical Models for Radial Distance Determination by the Rat Vibrissal System
Authors: Birdwell J. Alexander , Solomon Joseph H. , Thajchayapong Montakan , Taylor Michael A. , Cheely Matthew , Towal R. Blythe , Conradt Jorg , Hartmann Mitra J. Z.
Published: June 2007

Rats use active, rhythmic movements of their whiskers to acquire tactile information about three-dimensional object features. There are no receptors along the length of the whisker; therefore all tactile information must be mechanically transduced back to receptors at the whisker base. This raises the question: how might the rat determine the radial contact position of an object along the whisker? We developed two complementary biomechanical models that show that the rat could determine radial object distance by monitoring the rate of change of moment (or equivalently, the rate of change of curvature) at the whisker base. The first model is used to explore the effects of taper and inherent whisker curvature on whisker deformation and used to predict the shapes of real rat whiskers during deflections at different radial distances. Predicted shapes closely matched experimental measurements. The second model describes the relationship between radial object distance and the rate of change of moment at the base of a tapered, inherently curved whisker. Together, these models can account for recent recordings showing that some trigeminal ganglion (Vg) neurons encode closer radial distances with increased firing rates. The models also suggest that four and only four physical variables at the whisker base—angular position, angular velocity, moment, and rate of change of moment—are needed to describe the dynamic state of a whisker. We interpret these results in the context of our evolving hypothesis that neural responses in Vg can be represented using a state-encoding scheme that includes combinations of these four variables.
Fgl2deficiency causes neonatal death and cardiac dysfunction during embryonic and postnatal development in mice
Authors: Mu Junwu , Qu Dawei , Bartczak Agata , Phillips M. James , Manuel Justin , He Wei , Koscik Cheryl , Mendicino Michael , Zhang Li , Clark David A. , Grant David R. , Backx Peter H. , Levy Gary A. , Adamson S. Lee
Published: June 2007

We hypothesized that cardiac dysfunction was responsible for the high perinatal lethality that we previously reported in fibrinogen-like protein 2 ( Fgl2) knockout (KO) mice. We therefore used ultrasound biomicroscopy to assess left ventricular (LV) cardiac structure and function during development in Fgl2 KO and wild-type (WT) mice. The only deaths observed between embryonic day (E)8.5 (onset of heart beating) and postnatal day (P)28 (weaning) were within 3 days after birth, when 33% of Fgl2 KO pups died. Histopathology and Doppler assessments suggested that death was due to acute congestive cardiac failure without evidence of valvular or other obvious cardiac structural abnormalities. Heart rates in Fgl2 KO embryos were significantly reduced at E8.5 and E17.5, and irregular heart rhythms were significantly more common in Fgl2 KO (21/26) than WT (2/21) embryos at E13.5. Indexes of systolic and/or diastolic cardiac function were also abnormal in KO mice at E13.5 and E17.5, in postnatal mice studied at P1, and in KO mice surviving to P28. M-mode analysis showed no difference in LV diastolic chamber dimension, although posterior wall thickness was thinner at P7 and P28 in Fgl2 KO mice. We conclude that Fgl2 deficiency is not associated with obvious structural cardiac defects but is associated with a high incidence of neonatal death as well as contractile dysfunction and rhythm abnormalities during embryonic and postnatal development in mice.
Ubiquitin proteasome pathway gene expression varies in rhesus monkey oocytes and embryos of different developmental potential
Authors: Mtango Namdori R. , Latham Keith E.
Published: June 2007

Protein degradation via the ubiquitin-proteasome pathway (UPP) plays a key role in diverse aspects of cell physiology and development. In the early embryo, the UPP may play an important role in the transition from maternal to embryonic control of development. Disruptions in the UPP could thus compromise embryo developmental potential. Additionally, species-specific requirements may dictate diverse patterns of regulation of the UPP components. To investigate the expression of UPP components in a nonhuman primate embryo model, to compare expression between a primate and nonprimate species, and to determine whether disruption of this pathway may contribute to reduced developmental potential, we examined the expression of >50 mRNAs encoding UPP components in rhesus monkey oocytes and embryos. We compared this expression between the rhesus monkey and mouse embryo and between rhesus monkey oocytes and embryos of high, intermediate, and low developmental potential. We report here the temporal patterns of UPP gene expression in oocytes and during preimplantation development, including striking differences between the rhesus monkey and mouse. We also report significant differences in UPP gene expression correlating with oocyte and embryo developmental competence and associated with altered regulation of maternally inherited mRNAs encoding these proteins.
Diameter Control and Photoluminescence of ZnO Nanorods from Trialkylamines
Authors: Andelman Tamar , Gong Yinyan , Neumark Gertrude , O'Brien Stephen
Published: June 2007

A novel solution method to control the diameter of ZnO nanorods is reported. Small diameter (2-3 nm) nanorods were synthesized from trihexylamine, and large diameter (50–80 nm) nanorods were synthesized by increasing the alkyl chain length to tridodecylamine. The defect (green) emission of the photoluminescence (PL) spectra of the nanorods varies with diameter, and can thus be controlled by the diameter control. The small ZnO nanorods have strong green emission, while the large diameter nanorods exhibit a remarkably suppressed green band. We show that this observation supports surface oxygen vacancies as the defect that gives rise to the green emission.
Advances in Contactless Silicon Defect and Impurity Diagnostics Based on Lifetime Spectroscopy and Infrared Imaging
Authors: Schmidt Jan , Pohl Peter , Bothe Karsten , Brendel Rolf
Published: June 2007

This paper gives a review of some recent developments in the field of contactless silicon wafer
characterization techniques based on lifetime spectroscopy and infrared imaging. In the first part of the
contribution, we outline the status of different lifetime spectroscopy approaches suitable for the
identification of impurities in silicon and discuss—in more detail—the technique of temperature- and
injection-dependent lifetime spectroscopy. The second part of the paper focuses on the application
of infrared cameras to analyze spatial inhomogeneities in silicon wafers. By measuring the infrared
signal absorbed or emitted from light-generated free excess carriers, high-resolution recombination
lifetime mappings can be generated within seconds to minutes. In addition, mappings of
non-recombination-active trapping centers can be deduced from injection-dependent infrared lifetime
images. The trap density has been demonstrated to be an important additional parameter in the
characterization and assessment of solar-grade multicrystalline silicon wafers, as areas of increased
trap density tend to deteriorate during solar cell processing.
Genetic Disorders of Surfactant Proteins
Authors: Hamvas Aaron , Cole F. Sessions , Nogee Lawrence M.
Published: June 2007

Inherited disorders of pulmonary surfactant-associated proteins are rare but provide important insights into unique mechanisms of surfactant dysfunction. Recessive loss-of-function mutations in the surfactant protein-B and the ATP-binding cassette family member A3 (ABCA3) genes present as lethal surfactant deficiency in the newborn, whereas other recessive mutations in ABCA3 and dominant mutations in the surfactant protein-C gene result in interstitial lung disease in older infants and children. The molecular basis and the genetic and tissue-based approaches to the evaluation of children suspected of having one of these disorders are discussed.