bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in biomass and production over 53 years in a coastal Piceasitchensis –Tsugaheterophylla forest approaching maturity
Authors: Harcombe P. A. , Harmon Mark E. , Greene Sarah E.
Published: November 2007

Using periodic remeasurements of tagged trees in nine 0.4-ha sample plots in a Piceasitchensis (Bong.) Carr. – Tsugaheterophylla (Raf.) Sarg. forest at Cascade Hand Experimental Forest, Oregon, we calculated that biomass of bolewood increased from 570 Mg•ha−1 at age 85 years to 760 Mg•ha−1 at age 138 years. Net primary production of bolewood declined from 11 to about 6 Mg•ha−1•year−1, and mortality loss increased from 2 to about 6 Mg•ha−1•year−1. Values for 37-year-old plots in the same area were 210–360 Mg•ha−1•year−1 bole biomass, 7–20 Mg•ha−1•year−1 bolewood production, and 0–2 Mg•ha−1•year−1 mortality loss. Indications are that bolewood production and biomass were lower in the older plots when they were 37 years old. In the older plots, biomass did not increase between ages 120 and 138. Of the photosynthate potentially available for bolewood production, some replaces biomass lost via mortality and some is allocated to maintenance (respiration plus allocation to fine roots). We estimate that one-quarter to one-half of the production is lost by mortality, and that mortality loss may thus be an important factor limiting forest biomass accumulation.
Retransformation bias in a stem profile model
Authors: Czaplewski Raymond L. , Bruce David
Published: November 2007

An unbiased profile model, fit to diameter divided by diameter at breast height, overestimated volume of 5.3-m log sections by 0.5 to 3.5%. Another unbiased profile model, fit to squared diameter divided by squared diameter at breast height, underestimated bole diameters by 0.2 to 2.1%. These biases are caused by retransformation of the predicted dependent variable; the degree of retransformation bias depends upon choice of dependent variable in the regression model, variance of its prediction errors, and the bole position of the desired prediction. Retransformation biases were greatest near the merchantable top of large trees. Equations are given that reduce the magnitude of these biases, but accurate variance models are required. Additional biases are identified for more complex transformations of stem profile models.
Combining estimates that are both in error subject to marginal constraints
Authors: Li H. G. , Schreuder H. T. , Scott C. T.
Published: November 2007

Outside estimates with measures of reliability can be combined with existing tabular estimates of resource statistics to produce new, more precise estimates. But cell estimates do not sum to the original marginal or overall totals when this is done. A method is given to adjust the unchanged cell values to maintain additivity. Classical and bootstrap variance estimators are given for the n × 2 case of combining a cell proportion with an outside estimate assumed to be binomially distributed under fixed marginal constraints, and for the n × m case of combining a cell proportion with a binomially distributed outside estimate under no marginal constraints except that the table total is fixed. For a 3 × 2 test case, a bootstrap variance estimator yielded reliable estimates of precision for the adjusted cell proportions in most cases. For the n × m case, a classical variance estimator was more stable than the bootstrap variance estimators and was less biased than the other variance estimators studied.
THE EINSTEIN–YANG–MILLS EQUATIONS FROM BIANCHI IDENTITIES
Authors: BÖHMER CHRISTIAN G. , FABBRI LUCA
Published: November 2007

We suggest a novel extension to the Kaluza–Klein scheme that allows us to obtain consistently all SU (n) Einstein–Yang–Mills theories. This construction is based on allowing the five-dimensional spacetime to carry some nonvanishing torsion; however, the four-dimensional spacetime remains intrinsically torsion-free.
Basinwide stratigraphic synthesis and sequence stratigraphy, upper Pragian, Emsian and Eifelian stages (Lower to Middle Devonian), Appalachian Basin
Authors: Ver Straeten C. A.
Published: November 2007

A new synthesis of the Lower to Middle Devonian (upper Pragian, Emsian and Eifelian) succession across the Appalachian Basin has been developed by high resolution event and sequence stratigraphic analysis. The correlation of numerous marker beds and a hierarchy of cycles in the interval of the Oriskany Sandstone to lower Hamilton Group provide a refined picture of the depositional patterns, faunal changes, formation to member-level (and finer) relationships, and sea-level trends. The succession begins above the Wallbridge Unconformity, or its correlative conformity, which lies beneath the Oriskany Sandstone, not above it as previously thought. The new sequence-stratigraphic framework of Oriskany to lower Hamilton strata comprises nine ‘third order’ stratigraphic sequences (cycles), though an interval of some 25 million years. At a coarse scale, the eustatic Pragian to Eifelian sea-level curve for Euramerica of Johnson
et al.
(1985) shows broad variance with the Appalachian curve, reflecting the regional influence of the Acadian orogeny. However at the finer sequence-scale, the Euramerican sea-level trends are recognizable in the Appalachian Basin succession.
Environmental changes at the Frasnian–Famennian boundary in Central Morocco (Northern Gondwana): integrated rock-magnetic and geochemical studies
Authors: Riquier L. , Averbuch O. , Tribovillard N. , Albani A. E. , Lazreq N. , Chakiri S.
Published: November 2007

Rock magnetic (magnetic susceptibility and hysteresis parameters) and geochemical analyses (major and trace elements) were carried out on whole rock samples of two Frasnian–Famennian boundary sections, Anajdam and Bou-Ounebdou in the Central Morocco (Western Meseta). During the Frasnian, the decreasing trend of the magnetic susceptibility signal, mainly carried by low-coercivity magnetite grains, indicates a gradual reduction of detrital influx. This decrease in detrital input parallels a Frasnian long-term sea-level rise. In the Late Frasnian Kellwasser Horizons, that are classically considered to represent highstand deposits, the magnetic signal exhibits the lowest intensities in connection with maximum diamagnetic contribution of the carbonate fraction. With respect to geochemical data, the two black carbonate-rich Kellwasser Horizons are characterized by noticeable positive anomalies of bottom-water dysoxic proxies and of marine primary productivity markers. Our data thus suggest that in Central Morocco, the Late Frasnian marine environments were marked by a relatively important biogenic productivity favouring the onset of oxygen-depleted conditions during periods of maximum transgression on the continental platforms.
Optimizing indirect branch prediction accuracy in virtual machine interpreters
Authors: Casey Kevin , Ertl M. Anton , Gregg David
Published: November 2007

Interpreters designed for efficiency execute a huge number of indirect branches and can spend more than half of the execution time in indirect branch mispredictions. Branch target buffers (BTBs) are the most widely available form of indirect branch prediction; however, their prediction accuracy for existing interpreters is only 2%--50%. In this article we investigate two methods for improving the prediction accuracy of BTBs for interpreters: replicating virtual machine (VM) instructions and combining sequences of VM instructions into superinstructions. We investigate static (interpreter build-time) and dynamic (interpreter runtime) variants of these techniques and compare them and several combinations of these techniques. To show their generality, we have implemented these optimizations in VMs for both Java and Forth. These techniques can eliminate nearly all of the dispatch branch mispredictions, and have other benefits, resulting in speedups by a factor of up to 4.55 over efficient threaded-code interpreters, and speedups by a factor of up to 1.34 over techniques relying on dynamic superinstructions alone.
ROLAP implementations of the data cube
Authors: Morfonios Konstantinos , Konakas Stratis , Ioannidis Yannis , Kotsis Nikolaos
Published: November 2007

Implementation of the data cube is an important and scientifically interesting issue in On-Line Analytical Processing (OLAP) and has been the subject of a plethora of related publications. Naive implementation methods that compute each node separately and store the result are impractical, since they have exponential time and space complexity with respect to the cube dimensionality. To overcome this drawback, a wide range of methods that provide efficient cube implementation (with respect to both computation and storage) have been proposed, which make use of relational, multidimensional, or graph-based data structures. Furthermore, there are several other methods that compute and store approximate descriptions of data cubes, sacrificing accuracy for condensation. In this article, we focus on Relational-OLAP (ROLAP), following the majority of the efforts so far. We review existing ROLAP methods that implement the data cube and identify six orthogonal parameters/dimensions that characterize them. We place the existing techniques at the appropriate points within the problem space defined by these parameters and identify several clusters that the techniques form with various interesting properties. A careful study of these properties leads to the identification of particularly effective values for the space parameters and indicates the potential for devising new algorithms with better overall performance.
Understanding disk failure rates
Authors: Schroeder Bianca , Gibson Garth A.
Published: November 2007

Component failure in large-scale IT installations is becoming an ever-larger problem as the number of components in a single cluster approaches a million.

This article is an extension of our previous study on disk failures [Schroeder and Gibson 2007] and presents and analyzes field-gathered disk replacement data from a number of large production systems, including high-performance computing sites and internet services sites. More than 110,000 disks are covered by this data, some for an entire lifetime of five years. The data includes drives with SCSI and FC, as well as SATA interfaces. The mean time-to-failure (MTTF) of those drives, as specified in their datasheets, ranges from 1,000,000 to 1,500,000 hours, suggesting a nominal annual failure rate of at most 0.88%.

We find that in the field, annual disk replacement rates typically exceed 1%, with 2--4% common and up to 13% observed on some systems. This suggests that field replacement is a fairly different process than one might predict based on datasheet MTTF.

We also find evidence, based on records of disk replacements in the field, that failure rate is not constant with age, and that rather than a significant infant mortality effect, we see a significant early onset of wear-out degradation. In other words, the replacement rates in our data grew constantly with age, an effect often assumed not to set in until after a nominal lifetime of 5 years.

Interestingly, we observe little difference in replacement rates between SCSI, FC, and SATA drives, potentially an indication that disk-independent factors such as operating conditions affect replacement rates more than component-specific ones. On the other hand, we see only one instance of a customer rejecting an entire population of disks as a bad batch, in this case because of media error rates, and this instance involved SATA disks.

Time between replacement, a proxy for time between failure, is not well modeled by an exponential distribution and exhibits significant levels of correlation, including autocorrelation and long-range dependence.
Optimal multistream sequential prefetching in a shared cache
Authors: Gill Binny S. , Bathen Luis Angel D.
Published: November 2007

Prefetching is a widely used technique in modern data storage systems. We study the most widely used class of prefetching algorithms known as
sequential prefetching
. There are two problems that plague the state-of-the-art sequential prefetching algorithms: (i)
cache pollution
, which occurs when prefetched data replaces more useful prefetched or demand-paged data, and (ii)
prefetch wastage
, which happens when prefetched data is evicted from the cache before it can be used.

A sequential prefetching algorithm can have a fixed or adaptive degree of prefetch and can be either synchronous (when it can prefetch only on a miss) or asynchronous (when it can also prefetch on a hit). To capture these distinctions we define four classes of prefetching algorithms: fixed synchronous (FS), fixed asynchronous (FA), adaptive synchronous (AS), and adaptive asynchronous (AsynchA). We find that the relatively unexplored class of AsynchA algorithms is in fact the most promising for sequential prefetching. We provide a first formal analysis of the criteria necessary for optimal throughput when using an AsynchA algorithm in a cache shared by multiple steady sequential streams. We then provide a simple implementation called AMP (adaptive multistream prefetching) which adapts accordingly, leading to near-optimal performance for any kind of sequential workload and cache size.

Our experimental setup consisted of an IBM xSeries 345 dual processor server running Linux using five SCSI disks. We observe that AMP convincingly outperforms all the contending members of the FA, FS, and AS classes for any number of streams and over all cache sizes. As anecdotal evidence, in an experiment with 100 concurrent sequential streams and varying cache sizes, AMP surpasses the FA, FS, and AS algorithms by 29--172%, 12--24%, and 21--210%, respectively, while outperforming OBL by a factor of 8. Even for complex workloads like SPC1-Read, AMP is consistently the best-performing algorithm. For the SPC2 video-on-demand workload, AMP can sustain at least 25% more streams than the next best algorithm. Furthermore, for a workload consisting of short sequences, where optimality is more elusive, AMP is able to outperform all the other contenders in overall performance.

Finally, we implemented AMP in the state-of-the-art enterprise storage system, the IBM system storage DS8000 series. We demonstrated that AMP dramatically improves performance for common sequential and batch processing workloads and delivers up to a twofold increase in the sequential read capacity.
Level set driven flows
Authors: Acar Rüyam
Published: November 2007

In 2D, incompressible flows, the Stokes equations that represent the dynamics of very viscous flows and vorticity formulation of hydrodynamic equations both reduce to a scalar stream-function representation in terms of elliptic equations. By making use of this simplification and the properties of Fourier space representation of elliptic equations, we use a common spectral method to solve both of these equations. Based on this system of equations, we propose a level set based input description which provides a flexible environment for the user to model a wide range of flows and artistic effects in 2D. This input type allows the modeling of vortex sheet patterns and other complex flows with a very practical approach and chaotic, dynamic flows, even with viscous Stokes equations. A user interface is developed for the level set input which allows the user to draw the strokes or edit the level set data by applying transformation functions or perturbations. To sum up, this model can be used for the simulation of very viscous flows, vorticity dynamics, vortex sheet patterns, turbulent and chaotic flows as well as other artistic effects such as the traditional marbling patterns, with a simple, fast and stable system at high resolutions.
Jeannie
Authors: Hirzel Martin , Grimm Robert
Published: November 2007

Higher-level languages interface with lower-level languages such as C to access platform functionality, reuse legacy libraries, or improve performance. This raises the issue of how to best integrate different languages while also reconciling productivity, safety, portability, and efficiency. This paper presents Jeannie, a new language design for integrating Java with C. In Jeannie, both Javaand C code are nested within each other in the same file and compile down to JNI, the Java platform's standard foreign function interface. By combining the two languages' syntax and semantics, Jeannie eliminates verbose boiler-plate code, enables static error detection across the language boundary, and simplifies dynamic resource management. We describe the Jeannie language and its compiler, while also highlighting lessons from composing two mature programming languages.
Ilea
Authors: Tan Gang , Morrisett Greg
Published: November 2007

Java bug finders perform static analysis to find implementation mistakes that can lead to exploits and failures; Java compilers perform static analysis for optimization.allIf Java programs contain foreign function calls to C libraries, however, static analysis is forced to make either optimistic or pessimistic assumptions about the foreign function calls, since models of the C libraries are typically not available.

We propose ILEA (stands for Inter-LanguagE Analysis), which is a framework that enables existing Java analyses to understand the behavior of C code. Our framework includes: (1) a novel specification language, which extends the Java Virtual Machine Language (JVML) with a few primitives that approximate the effects that the C code might have; (2) an automatic specification extractor, which builds models of the C code. Comparing to other possible specification languages, our language is expressive, yet facilitates construction of automatic specification extractors. Furthermore, because the specification language is based on the JVML, existing Java analyses can be easily migrated to utilize specifications in the language. We also demonstrate the utility of the specifications generated, by modifying an existing non-null analysis to identify null-related bugs in Java applications that contain C libraries. Our preliminary experiments identified dozens of null-related bugs.
Dependent classes
Authors: Gasiunas Vaidas , Mezini Mira , Ostermann Klaus
Published: November 2007

Virtual classes allow nested classes to be refined in subclasses. In this way nested classes can be seen as dependent abstractions of the objects of the enclosing classes. Expressing dependency via nesting, however, has two limitations: Abstractions that depend on more than one object cannot be modeled and a class must know all classes that depend on its objects. This paper presents
dependent classes
, a generalization of virtual classes that expresses similar semantics by parameterization rather than by nesting. This increases expressivity of class variations as well as the flexibility of their modularization. Besides, dependent classes complement multimethods in scenarios where multi-dispatched abstractions rather than multi-dispatched methods are needed. They can also be used to express more precise signatures of multimethods and even extend their dispatch semantics. We present a formal semantics of dependent classes and a machine-checked type soundness proof in Isabelle/HOL [29], the first of this kind for a language with virtual classes and path-dependent types.
The causes of bloat, the limits of health
Authors: Mitchell Nick , Sevitsky Gary
Published: November 2007

Applications often have large runtime memory requirements. In some cases, large memory footprint helps accomplish an important functional, performance, or engineering requirement. A large cache,for example, may ameliorate a pernicious performance problem. In general, however, finding a good balance between memory consumption and other requirements is quite challenging. To do so, the development team must distinguish effective from excessive use of memory.

We introduce
health signatures
to enable these distinctions. Using data from dozens of applications and benchmarks, we show that they provide concise and application-neutral summaries of footprint. We show how to use them to form value judgments about whether a design or implementation choice is good or bad. We show how being independent ofany application eases comparison across disparate implementations. We demonstrate the
asymptotic
nature of memory health: certain designsare limited in the health they can achieve, no matter how much the data size scales up. Finally, we show how to use health signatures to automatically generate formulas that predict this asymptotic behavior, and show how they enable powerful limit studies on memory health.
Living in the comfort zone
Authors: Rinard Martin C.
Published: November 2007

A comfort zone is a tested region of a system's input space within which it has been observed to behave acceptably. To keep systems operating within their comfort zones, we advocate the interposition of
rectifiers
between systems and their input sources. Rectifiers are designed to transform inputs to ensure that they are within the comfort zone before they are presented to the system. Rectifiers enforce a highly constrained input format and, if necessary, discard information to force inputs to conform to this format. Potential benefits of this approach include the elimination of errors and vulnerabilities, the excision of undesirable excess functionality from large, complex systems, and a simplification of the computing environment.

We have developed a rectifier for email messages and used this rectifier to force messages into a specific constrained form. Our results show that this rectifier can successfully produce messages that keep the Pine email client strictly within code previously confirmed (during a small testing and training session) to function acceptably. Our results also show that the rectifier completely eliminates a security vulnerability in the Pine email client. And finally, the rectifier is able to accomplish these goals while still preserving an acceptable amount of information from the original messages.
Confessions of a used programming language salesman
Authors: Meijer Erik
Published: November 2007

For many years I had been fruitlessly trying to sell functional programming and Haskell to solve real world problems such as scripting and data-intensive three-tier distributed web applications. The lack of widespread adoption of Haskell is a real pity. Functional programming concepts are key to curing many of the headaches that plague the majority of programmers, who today are forced to use imperative languages. If the mountain won't come to Mohammed, Mohammed must go to the mountain, and so I left academia to join industry. Instead of trying to convince imperative programmers to forget everything they already know and learn something completely new, I decided to infuse existing imperative object-oriented programming languages with functional programming features. As a result, functional programming has finally reached the masses, except that it is called Visual Basic 9 instead of Haskell 98.
What motivates Wikipedians?
Authors: Nov Oded
Published: November 2007

In order to increase and enhance user-generated content contributions, it is important to understand the factors that lead people to freely share their time and knowledge with others.
Information life cycle management
Authors: Tallon Paul P. , Scannell Richard
Published: November 2007

A new framework, created to enhance information life cycle management by clarifying the relationship between value-at-risk and total cost of ownership, helps IT managers build a winning storage environment.
The impact of size and volatility on IT project performance
Authors: Sauer Chris , Gemino Andrew , Reich Blaize Horner
Published: November 2007

Studying the factors influencing project risk.
Workloads (creation and use)
Authors: Smith Alan Jay
Published: November 2007

Workloads are used to estimate and measure system performance, but the results are only as good as the workloads and models being used.
A "Survivor"-like designer reality show?
Authors: Kowalski Luke
Published: November 2007

Commercial-designer success criteria, an enterprise perspective.
An open source primer
Authors: Dykstra-Erickson Elizabeth , Cheri Yann
Published: November 2007

Design projects come in all sizes. Many interaction designers have responsibility for a part of a larger application; many have sole responsibility for the overall experience of an application; and many have responsibility for the care and nurturing of a user experience, where others are free to chime in and change things. This last point reflects the nature of open source: You never know what someone will think up next, or how someone may change what you have already done.

Working successfully as a designer in an open source project means a huge amount of freedom and a lot of homework. You can do almost anything the technology will permit, because that's the point: It's an open and collaborative environment, where anyone can make a contribution. But it's not without rules, and that's where the homework comes in. For designers, it's imperative to understand where the flexibility lies and where the rules apply.

The articles in this section address project management, licensing options, and some of the community issues around open source software from experts working in this field. We also have a case study from the OpenOffice project and a technical introduction to SMIL, an open format for interactivity. We extend our sincere thanks to all of our contributors, and we hope you enjoy this exploration into open source.
The virtual sandbox
Authors: Junglas Iris A. , Steel Douglas J.
Published: November 2007

Modern virtual environments are three-dimensional, simulated worlds. Inside of them, avatars live the equivalent of a human life: they walk, talk, and interact with other avatars, thus exposing what is considered to be social behavior. As a result, virtual worlds lend themselves to the study of social behaviors in a laboratory setting. In fact, their technical capabilities provide a number of advantages over real life experimental laboratories. On the downside, however, virtual worlds also add complexity to experiments by clouding the identities of the people who "play" the role of their avatars. Despite these issues, virtual environments can contribute to future experimental research by addressing three generic needs that information systems support: increasing social presence, offering an elaborate visualization tool, and providing a safe haven for simulation, exploration, and innovation.
Expressive communication and social conventions in virtual worlds
Authors: Carey John
Published: November 2007

Technological innovation is always social innovation, if the application will be used by people. Yet, many technologies have been introduced with little concern for the social side of the innovation. Virtual worlds are intended to be immersive social experiences that can offer an alternative to face-to-face interactions, as well as provide new forms of human experience. People living in virtual worlds will need a rich array of communication tools if they are to get the kinds of emotional satisfaction that are possible in everyday social exchanges. Expressive communication is one of those tools. Expressive communication includes gestures, tone of voice, body orientation, and other nonverbal signals that are present in face-to-face settings. Two related issues are the sense of space people experience in virtual worlds and the social conventions that govern how people behave. One of our first research tasks will be to collect and analyze research from related areas that can inform us about human factors in virtual worlds. This would include research about videoconferencing, virtual reality, videogames, the Web, and computer mediated communication. Are people communicating effectively and do they feel comfortable in virtual worlds? Have communities emerged and, if so, what is the shape of those communities? In assessing expressive communication, it will be useful to understand how avatars, gestures, and voice are integrated into social interactions, and how these interactions differ from early text-based interactions such as forums.
Generic discrete event simulations using
DEGAS
:
Authors: Pukite Paul , Ludwig Luke
Published: November 2007

This paper describes a powerful Ada pattern which, when integrated with the open-source DEGAS discrete event run-time, allows a developer to write and execute logic design models in a format similar to the VHDL language. The application of this approach to other formulations, including floating-point based simulations, provides a means to establish general design, analysis, and verification strategies to a range of discrete event domains using standard Ada constructs.
Hibachi
Authors: Grosman Tom
Published: November 2007

Hibachi is an open source (EPL), standard, extensible, vendor-neutral Eclipse Ada development environment. Hibachi is currently in the project proposal phase (see http://www.eclipse.org/projects/dev_process/development_process.php, which involves gathering a viable developer/tester/user community around the project and IP rights to any code contributions. When these pieces are in place, the project can be approved by the Eclipse Management Organization (EMO) and begin producing high quality releases available to end users, as well as third party integrators.

As Hibachi project lead, Mr. Grosman has been in touch with the major active Ada development environment vendors (ACT, Aonix, DDC-I, GHS) and they have all expressed interest and a desire to commit resources to making Hibachi a success. In addition, gnuada development team members have also expressed support for Hibachi and a willingness to participate. Mr. Grosman is also in contact with several Universities who will be contributing engineering effort as part of their curricula (master theses), as well as some major industrial partners who are large scale users of Ada and who have expressed interest in contributing development and/or financial resources. Aonix has offered to contribute the source for its Eclipse plugin, AonixADT as a code base for Hibachi. AonixADT currently supports ObjectAda as well as GNAT/gnuada development. Contributions of existing code from other sources are also a possibility depending on the willingness of other potential contributors. Because of these factors, and the encouragement of the Hibachi project mentor Doug Schaefer, CDT project lead, Mr. Grosman has every expectation that the Hibachi proposal will be accepted and that we will be able to produce a plugin with features as outlined in the Hibachi Proposal-http://www.eclipse.org/proposals/adt/. The development plan outlined in the Hibachi proposal indicates that a first useable release of Hibachi will be available in time for SIGAda in November.
Acutely reduced locomotor activity is a major contributor to Western diet-induced obesity in mice
Authors: Bjursell Mikael , Gerdin Anna-Karin , Lelliott Christopher J. , Egecioglu Emil , Elmgren Anders , Törnell Jan , Oscarsson Jan , Bohlooly-Y Mohammad
Published: November 2007

The aim of the present study was to investigate the short- and long-term effects of a high-fat Western diet (WD) on intake, storage, expenditure, and fecal loss of energy as well as effects on locomotor activity and thermogenesis. WD for only 24 h resulted in a marked physiological shift in energy homeostasis, including increased body weight gain, body fat, and energy expenditure (EE) but an acutely lowered locomotor activity. The acute reduction in locomotor activity was observed after only 3–5 h on WD. The energy intake and energy absorption were increased during the first 24 h, lower after 72 h, and normalized between 7 and 14 days on WD compared with mice given chow diet. Core body temperature and EE was increased between 48 and 72 h but normalized after 21 days on WD. These changes paralleled plasma T3 levels and uncoupling protein-1 expression in brown adipose tissue. After 21 days of WD, energy intake and absorption, EE, and body temperature were normalized. In contrast, the locomotor activity was reduced and body weight gain was increased over the entire 21-day study period on WD. Calculations based on the correlation between locomotor activity and EE in 2-h intervals at days 21–23 indicated that a large portion of the higher body weight gain in the WD group could be attributed to the reduced locomotor activity. In summary, an acute and persisting decrease in locomotor activity is most important for the effect of WD on body weight gain and obesity in mice.
Insulin-like growth factor-binding proteins and bone metabolism
Authors: Conover Cheryl A.
Published: November 2007

Insulin-like growth factor-binding proteins (IGFBPs) are important regulators of bone metabolism. However, their precise roles are not fully understood, since IGFBPs can have both enhancing and inhibiting effects on IGF action, depending on context and posttranslational modifications, as well as IGF-independent effects. This review focuses on recent findings from cell culture, rodent models, and clinical studies concerning local IGFBP-2, IGFBP-4, and IGFBP-5 action in bone.
Fractalkine receptor (CX3CR1) inhibition is protective against ischemic acute renal failure in mice
Authors: Oh Dong-Jin , Dursun Belda , He Zhibin , Lu Lawrence , Hoke Thomas S. , Ljubanovic Danica , Faubel Sarah , Edelstein Charles L.
Published: November 2007

Fractalkine (CX3CL1) is expressed on injured endothelial cells and is a potent chemoattractant and adhesion molecule for macrophages carrying the fractalkine receptor (CX3CR1). The aim of this study was to investigate the role of CX3CL1, and its ligand CX3CR1, in ischemic acute renal failure (ARF) in mice. On immunoblotting, CX3CL1 protein expression in the kidney increased markedly in ischemic ARF. On immunofluorescence staining, the intensity of CX3CL1 staining in blood vessels was significantly more prominent in ischemic ARF compared with controls. A specific anti-CX3CR1 antibody (25 μg ip 1 h before induction of ischemia) was functionally and histologically protective against ischemic ARF. CX3CR1 is predominantly expressed on macrophages. Macrophage infiltration in the kidney in ischemic ARF was significantly decreased after anti-CX3CR1 antibody treatment. To determine the role of macrophages in ischemic ARF, macrophages in the kidney were depleted using liposomal-encapsulated clodronate (LEC). LEC resulted in significant functional and histological protection against ischemic ARF. In summary, in ischemic ARF, 1) there is upregulation of CX3CL1 protein in the kidney, specifically in blood vessels; 2) CX3CR1 inhibition using a specific antibody is partially protective and is associated with reduced macrophage infiltration in the kidney; and 3) macrophage depletion in the kidney is protective.
Characterization of Mouse Lumbar Splanchnic and Pelvic Nerve Urinary Bladder Mechanosensory Afferents
Authors: Xu Linjing , Gebhart G. F.
Published: November 2007

Sensory information from the urinary bladder is conveyed via lumbar splanchnic (LSN) and sacral pelvic (PN) nerves to the spinal cord. In the present report we compared the mechanosensitive properties of single afferent fibers in these two pathways using an in vitro mouse bladder preparation. Mechanosensitive primary afferents were recorded from the LSN or PN and distinguished based on their response to receptive field stimulation with different mechanical stimuli: probing (160 mg to 2 g), stretch (1–25 g), and stroking of the urothelium (10–1,000 mg). Four different classes of afferent were recorded from the LSN and PN: serosal, muscular, muscular/urothielial, and urothelial. The LSN contained principally serosal and muscular afferents (97% of the total sample), whereas all four afferent classes of afferent were present in the PN (63% of which were muscular afferents). In addition, the respective proportions and receptive field distributions differed between the two pathways. Both low- and high-threshold stretch-sensitive muscular afferents were present in both pathways, and muscular afferents in the PN were shown to sensitize after exposure to an inflammatory soup cocktail. The LSN and PN pathways contain different populations of mechanosensitive afferents capable of detecting a range of mechanical stimuli and individually tuned to detect the type, magnitude, and duration of the stimulus. This knowledge broadens our understanding of the potential roles these two pathways play in conveying mechanical information from the bladder to the spinal cord.
Advances in IP Micromobility Management Using a Mobility-Aware Routing Protocol
Authors: Georgiades Michael , Chew Kar Ann , Tafazolli Rahim
Published: November 2007

Several micromobility schemes have been proposed to augment Mobile IP and provide a faster and smoother handoff than what is achievable by Mobile IP alone, the majority of which can be categorized into either “network prefix-based” or “host-specific forwarding” mobility management protocols, depending on the routing method used. This letter proposes a mobility-aware routing protocol (MARP) which makes use of both of these routing methods using dynamic IP address allocation. Its performance is evaluated and compared against hierarchical Mobile IP (HMIP) and Cellular IP based on handoff performance, end-to-end delivery delay, and scalability. The results demonstrate that MARP is a more robust, flexible, and scalable micromobility protocol, minimizes session disruption, and offers improvements in handoff performance.
Human Papillomavirus 16/18 E6 Oncoprotein Is Expressed in Lung Cancer and Related with p53 Inactivation
Authors: Cheng Ya-Wen , Wu Ming-Fang , Wang John , Yeh Kun-Tu , Goan Yih-Gang , Chiou Hui-Ling , Chen Chih-Yi , Lee Huei
Published: November 2007

Inactivation of p53 by human papillomavirus 16/18 E6 plays a crucial role in cervical tumorigenesis. To investigate the involvement of HPV16/18 in lung tumorigenesis, the association between HPV16 or HPV18 E6 and p53 protein expression in 122 lung tumors was evaluated by immunohistochemistry, and data showed that HPV16/18 E6 expression correlated inversely with p53 expression, which was further confirmed by tissue in situ immunostaining. Real-time reverse transcription-PCR analysis indicated that E6-positive tumors had lower p21WAF1/CIP1 and mdm2 mRNA levels than E6-negative tumors. To elucidate the role of E6 in p53 inactivation, we successfully established lung adenocarcinoma cell lines with or without HPV16 infection from patients' pleural effusions. Western blotting showed that E6 protein was indeed expressed in HPV16-infected cells and a lower level of p53 protein was observed in E6-positive cells compared with E6-negative cells. Moreover, the levels of p21WAF1/CIP1 and mdm2 mRNA in E6-positive cells were lower than in E6-negative cells. The interaction of E6 with p53 protein was revealed by immunoprecipitation assay showing that p53 could be inactivated by E6 protein. Conversely, p53 proteins and p21WAF1/CIP1 and mdm2 mRNA expressions were restored in E6-knockdown cells by RNA interference compared with control cells. These results reveal that HPV16/18 E6 may be partially involved in p53 inactivation to down-regulate p21WAF1/CIP1 and mdm2 transcription. In conclusion, HPV16/18 E6 is indeed expressed in HPV DNA–positive lung tumors and is involved in p53 inactivation to contributing to HPV-mediated lung tumorigenesis. [Cancer Res 2007;67(22):10686–93]
RNA Interference Inhibition of Matrix Metalloproteinase-1 Prevents Melanoma Metastasis by Reducing Tumor Collagenase Activity and Angiogenesis
Authors: Blackburn Jessica S. , Rhodes C. Harker , Coon Charles I. , Brinckerhoff Constance E.
Published: November 2007

Melanoma incidence is increasing worldwide, and metastatic melanoma is almost completely resistant to every known therapy. New approaches to treating melanoma are urgently needed, and a greater understanding of the biology of melanoma invasion and metastasis will aid in their creation. A high proportion of invasive melanomas have a constitutively active Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) signaling cascade; however, the downstream effectors of ERK signaling that contribute to melanoma invasion and metastasis are unknown. ERK signaling drives the production of the interstitial collagenase matrix metalloproteinase-1 (MMP-1), which is expressed specifically by invasive melanomas. Using short hairpin RNAs (shRNA) to knock down MMP-1 expression in a human melanoma cell line, we investigated the role of MMP-1 in melanoma metastasis in a xenograft model. Knockdown of MMP-1 had no effect on primary tumor growth, but reduction of MMP-1 expression significantly decreased the ability of the melanoma to metastasize from the orthotopic site in the dermis to the lung. Mechanistically, tumor cells expressing MMP-1 shRNAs had diminished collagenase activity, which is required for tumor cell invasion. Additionally, attenuation of MMP-1 expression reduced angiogenesis. These results show, for the first time, that targeted inhibition of MMP-1, a single effector of the Raf/MEK/ERK signaling cascade, prevents the progression of melanoma from a primary to metastatic tumor and, as such, may represent a useful therapeutic tool in controlling this disease. [Cancer Res 2007;67(22):10849–58]
Role of GLI2 Transcription Factor in Growth and Tumorigenicity of Prostate Cells
Authors: Thiyagarajan Saravanan , Bhatia Neehar , Reagan-Shaw Shannon , Cozma Diana , Thomas-Tikhonenko Andrei , Ahmad Nihal , Spiegelman Vladimir S.
Published: November 2007

Aberrant activation of the Hedgehog (Hh) signaling pathway has been reported in various cancer types including prostate cancer. The GLI2 transcription factor is a primary mediator of Hh signaling. However, its relative contribution to development of prostate tumors is poorly understood. To establish the role of GLI2 in maintaining the tumorigenic properties of prostate cancer cells, we developed GLI2-specific small hairpin RNA. Knockdown of GLI2 in these cells resulted in significant down-regulation of the Hh signaling pathway, followed by inhibition of colony formation, anchorage-independent growth, and growth of xenografts in vivo. Conversely, ectopic expression of Gli2 in nontumorigenic prostate epithelial cells resulted in accelerated cell cycle progression, especially transition through G2-M, and augmented proliferation. Altogether, our findings suggest that GLI2 plays a critical role in the malignant phenotype of prostate cancer cells, and GLI2 may potentially become an attractive therapeutic target for the treatment of prostate cancer. [Cancer Res 2007;67(22):10642–6]
Treatment of Invasive Retinoblastoma in a Murine Model Using an Oncolytic Picornavirus
Authors: Wadhwa Lalita , Hurwitz Mary Y. , Chévez-Barrios Patricia , Hurwitz Richard L.
Published: November 2007

Retinoblastoma, the most common intraocular malignancy of childhood, metastasizes by initial invasion of the choroid and the optic nerve. There is no effective treatment for metastatic retinoblastoma, especially when the central nervous system (CNS) is involved, and prevention of this complication is a treatment priority. Seneca Valley Virus (SVV-001) is a conditionally replication-competent picornavirus that is not pathogenic to normal human cells but can kill human retinoblastoma cells in vitro with an IC50 of <1 viral particle (vp) per cell. A xenograft murine model of metastatic retinoblastoma was used to examine the therapeutic potential of SVV-001. Histopathologic analysis of ocular and brain tissues after a single tail vein injection of SVV-001 (1 × 1013 vp/kg) showed effective treatment of choroid and ocular nerve tumor invasion (1 of 20 animals with invasive disease in the treated group versus 7 of 20 animals with invasive disease in the control group; P = 0.017) and prevention of CNS metastasis (0 of 20 animals with CNS metastatic disease in the treated group versus 4 of 20 animals with CNS disease in the control group; P = 0.036). There were no observed adverse events due to the virus in any of the treated animals. SVV-001 may be effective as a treatment of locally invasive and metastatic retinoblastoma. [Cancer Res 2007;67(22):10653–6]
Erlotinib (Tarceva, OSI-774) Antagonizes ATP-Binding Cassette Subfamily B Member 1 and ATP-Binding Cassette Subfamily G Member 2–Mediated Drug Resistance
Authors: Shi Zhi , Peng Xing-Xiang , Kim In-Wha , Shukla Suneet , Si Qiu-Sheng , Robey Robert W. , Bates Susan E. , Shen Tong , Ashby Charles R. , Fu Li-Wu , Ambudkar Suresh V. , Chen Zhe-Sheng
Published: November 2007

It has been reported that gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has the ability to modulate the function of certain ATP-binding cassette (ABC) transporters and to reverse ABC subfamily B member 1 (ABCB1; P-glycoprotein)– and ABC subfamily G member 2 (ABCG2; breast cancer resistance protein/mitoxantrone resistance protein)–mediated multidrug resistance (MDR) in cancer cells. However, it is unknown whether other EGFR TKIs have effects similar to that of gefitinib. In the present study, we have investigated the interaction of another EGFR TKI, erlotinib, with selected ABC drug transporters. Our findings show that erlotinib significantly potentiated the sensitivity of established ABCB1 or ABCG2 substrates and increased the accumulation of paclitaxel or mitoxantrone in ABCB1- or ABCG2-overexpressing cells. Furthermore, erlotinib did not significantly alter the sensitivity of non-ABCB1 or non-ABCG2 substrates in all cells and was unable to reverse MRP1-mediated MDR and had no effect on the parental cells. However, erlotinib remarkably inhibited the transport of E217βG and methotrexate by ABCG2. In addition, the results of ATPase assays show that erlotinib stimulated the ATPase activity of both ABCB1 and ABCG2. Interestingly, erlotinib slightly inhibited the photolabeling of ABCB1 with [125I]iodoarylazidoprazosin (IAAP) at high concentration, but it did not inhibit the photolabeling of ABCG2 with IAAP. Overall, we conclude that erlotinib reverses ABCB1- and ABCG2-mediated MDR in cancer cells through direct inhibition of the drug efflux function of ABCB1 and ABCG2. These findings may be useful for cancer combinational therapy with erlotinib in the clinic. [Cancer Res 2007;67(22):11012–20]