bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and implementation of an efficient wear-leveling algorithm for solid-state-disk microcontrollers
Authors: Chang Li-Pin , Du Chun-Da
Published: August 2010

Solid-state disks (SSDs) are storage devices that emulate hard drives with flash memory. They have been widely deployed in mobile computers as disk drive replacements. Flash memory is organized in terms of erase blocks. With the current technology, a block can reach the end of its lifetime after thousands of erasure operations. Wear leveling is a technique to evenly erase the entire flash memory so that all blocks remain alive as long as possible. This study introduces a new wear-leveling algorithm based the observation that, under a real-life mobile PC's workload, most erasure operations are contributed by a small fraction of blocks. Our key ideas are 1) moving rarely updated data to a block that is extraordinarily worn and 2) avoiding repeatedly involving a block in wear-leveling activities. This study presents a successful implementation of the proposed wear-leveling algorithm using about 200 bytes of RAM in an SSD controller rated at 33 MHz. Evaluation results show that this algorithm achieves even wear of the entire flash memory while reducing the overheads of extra flash-memory operations.
Spatial locality exploitation for runtime reordering of JPEG2000 wavelet data layouts
Authors: Geelen Bert , Ferentinos Vissarion , Catthoor Francky , Lafruit Gauthier , Verkest Diederik , Lauwereins Rudy , Stouraitis Thanos
Published: August 2010

Exploitation of spatial locality is essential for memories to increase the access bandwidth and to reduce the access-related latency and energy per word. Spatial locality exploitation of a kernel can be improved by modifying placement of data in memory, but this may be felt not only by the kernel itself, but also in other application components accessing the same data. Thus care is needed to avoid global miss-rate improvements are thwarted by miss-rate increases in other application components. This article examines application-level miss-rate increases due to handling modified Wavelet Transform data layouts by explicitly reordering at runtime, exploiting the execution order freedom within a reordering buffer when the layout of surrounding components is known. For the JPEG2000 application, taking into account the reordering costs still results in 80% net WT miss-rate gains.
Updating relaxed
K
-d trees
Authors: Duch Amalia , Martínez Conrado
Published: August 2010

In this work we present an in-depth study of randomized relaxed
K
-d trees. It covers two fundamental aspects: the randomized algorithms that allow to preserve the random properties of relaxed
K
-d trees and the mathematical analysis of the expected performance of these algorithms.

In particular, we describe randomized update algorithms for
K
-d trees based on the split and join algorithms of Duch et al. [1998]. We carry out an analysis of the expected cost of all these algorithms, using analytic combinatorics techniques. We show that the average cost of split and join is of the form ζ(
K
) ⋅
n

ϕ(
K
)

+
o
(
n

ϕ(
K
)

), with 1 ≤ ϕ(
K
) < 1.561552813, and we give explicit formulæ for both ζ(
K
) and ϕ(
K
). These results on the average performance of split and join imply that the expected cost of an insertion or a deletion is Θ(
n

ϕ(
K
)−1

) when
K
> 2 and Θ(log
n
) for
K
= 2.
Trading off space for passes in graph streaming problems
Authors: Demetrescu Camil , Finocchi Irene , Ribichini Andrea
Published: August 2010

Data stream processing has recently received increasing attention as a computational paradigm for dealing with massive data sets. Surprisingly, no algorithm with both sublinear space and passes is known for natural graph problems in classical read-only streaming. Motivated by technological factors of modern storage systems, some authors have recently started to investigate the computational power of less restrictive models where writing streams is allowed. In this article, we show that the use of intermediate temporary streams is powerful enough to provide effective space-passes tradeoffs for natural graph problems. In particular, for any space restriction of
s
bits, we show that single-source shortest paths in directed graphs with small positive integer edge weights can be solved in
O
((
n
log
3/2
n
)/√
s
) passes. The result can be generalized to deal with multiple sources within the same bounds. This is the first known streaming algorithm for shortest paths in directed graphs. For undirected connectivity, we devise an
O
((
n
log
n
)/
s
) passes algorithm. Both problems require Ω(
n
/
s
) passes under the restrictions we consider. We also show that the model where intermediate temporary streams are allowed can be strictly more powerful than classical streaming for some problems, while maintaining all of its hardness for others.
Minimum cycle bases
Authors: Mehlhorn Kurt , Michail Dimitrios
Published: August 2010

We consider the problem of computing exact or approximate minimum cycle bases of an undirected (or directed) graph
G
with
m
edges,
n
vertices and nonnegative edge weights. In this problem, a {0, 1} (−1,0,1}) incidence vector is associated with each cycle and the vector space over F
2
(Q) generated by these vectors is the cycle space of
G
. A set of cycles is called a cycle basis of
G
if it forms a basis for its cycle space. A cycle basis where the sum of the weights of the cycles is minimum is called a minimum cycle basis of
G
. Cycle bases of low weight are useful in a number of contexts, for example, the analysis of electrical networks, structural engineering, chemistry, and surface reconstruction.

There exists a set of Θ(
mn
) cycles which is guaranteed to contain a minimum cycle basis. A minimum basis can be extracted by Gaussian elimination. The resulting algorithm [Horton 1987] was the first polynomial-time algorithm. Faster and more complicated algorithms have been found since then.

We present a very simple method for extracting a minimum cycle basis from the candidate set with running time
O
(
m
2
n
), which improves the running time for sparse graphs. Furthermore, in the undirected case by using bit-packing we improve the running time also in the case of dense graphs. For undirected graphs we derive an
O
(
m
2
n
/log
n
+
n
2
m
) algorithm. For directed graphs we get an
O
(
m
3
n
) deterministic and an
O
(
m
2
n
) randomized algorithm.

Our results improve the running times of both exact and approximate algorithms. Finally, we derive a smaller candidate set with size in Ω(
m
) ∩
O
(
mn
).
Optimizing throughput and energy in online deadline scheduling
Authors: Chan Ho-Leung , Chan Joseph Wun-Tat , Lam Tak-Wah , Lee Lap-Kei , Mak Kin-Sum , Wong Prudence W. H.
Published: August 2010

This article extends the study of online algorithms for energy-efficient deadline scheduling to the overloaded setting. Specifically, we consider a processor that can vary its speed between 0 and a maximum speed
T
to minimize its energy usage (the rate is believed to be a cubic function of the speed). As the speed is upper bounded, the processor may be overloaded with jobs and no scheduling algorithms can guarantee to meet the deadlines of all jobs. An optimal schedule is expected to maximize the throughput, and furthermore, its energy usage should be the smallest among all schedules that achieve the maximum throughput. In designing a scheduling algorithm, one has to face the dilemma of selecting more jobs and being conservative in energy usage. If we ignore energy usage, the best possible online algorithm is 4-competitive on throughput [Koren and Shasha 1995]. On the other hand, existing work on energy-efficient scheduling focuses on a setting where the processor speed is unbounded and the concern is on minimizing the energy to complete all jobs;
O
(1)-competitive online algorithms with respect to energy usage have been known [Yao et al. 1995; Bansal et al. 2007a; Li et al. 2006]. This article presents the first online algorithm for the more realistic setting where processor speed is bounded and the system may be overloaded; the algorithm is
O
(1)-competitive on both throughput and energy usage. If the maximum speed of the online scheduler is relaxed slightly to (1+ϵ)
T
for some ϵ > 0, we can improve the competitive ratio on throughput to arbitrarily close to one, while maintaining
O
(1)-competitiveness on energy usage.
Linear-time approximation schemes for clustering problems in any dimensions
Authors: Kumar Amit , Sabharwal Yogish , Sen Sandeep
Published: August 2010

We present a general approach for designing approximation algorithms for a fundamental class of geometric clustering problems in arbitrary dimensions. More specifically, our approach leads to simple randomized algorithms for the
k
-means,
k
-median and discrete
k
-means problems that yield (1+ε) approximations with probability ≥ 1/2 and running times of
O
(2

(
k
/ε)

O
(1)

dn
). These are the first algorithms for these problems whose running times are linear in the size of the input (
nd
for
n
points in
d
dimensions) assuming
k
and ε are fixed. Our method is general enough to be applicable to clustering problems satisfying certain simple properties and is likely to have further applications.
Schema mapping discovery from data instances
Authors: Gottlob Georg , Senellart Pierre
Published: August 2010

We introduce a theoretical framework for discovering relationships between two database instances over distinct and unknown schemata. This framework is grounded in the context of
data exchange
. We formalize the problem of understanding the relationship between two instances as that of obtaining a schema mapping so that a
minimum repair
of this mapping provides a perfect description of the target instance given the source instance. We show that this definition yields “intuitive” results when applied on database instances derived from each other by basic operations. We study the complexity of decision problems related to this optimality notion in the context of different logical languages and show that, even in very restricted cases, the problem is of high complexity.
The nested chinese restaurant process and bayesian nonparametric inference of topic hierarchies
Authors: Blei David M. , Griffiths Thomas L. , Jordan Michael I.
Published: August 2010

We present the nested Chinese restaurant process (nCRP), a stochastic process that assigns probability distributions to ensembles of infinitely deep, infinitely branching trees. We show how this stochastic process can be used as a prior distribution in a Bayesian nonparametric model of document collections. Specifically, we present an application to information retrieval in which documents are modeled as paths down a random tree, and the preferential attachment dynamics of the nCRP leads to clustering of documents according to sharing of topics at multiple levels of abstraction. Given a corpus of documents, a posterior inference algorithm finds an approximation to a posterior distribution over trees, topics and allocations of words to levels of the tree. We demonstrate this algorithm on collections of scientific abstracts from several journals. This model exemplifies a recent trend in statistical machine learning—the use of Bayesian nonparametric methods to infer distributions on flexible data structures.
Tight bounds for clock synchronization
Authors: Lenzen Christoph , Locher Thomas , Wattenhofer Roger
Published: August 2010

We present a novel clock synchronization algorithm and prove tight upper and lower bounds on the worst-case clock skew that may occur between any two participants in any given distributed system. More importantly, the worst-case clock skew between neighboring nodes is (asymptotically) at most a factor of two larger than the best possible bound. While previous results solely focused on the dependency of the skew bounds on the network diameter, we prove that our techniques are optimal also with respect to the maximum clock drift, the uncertainty in message delays, and the imposed bounds on the clock rates. The presented results all hold in a general model where both the clock drifts and the message delays may vary arbitrarily within pre-specified bounds.

Furthermore, our algorithm exhibits a number of other highly desirable properties. First, the algorithm ensures that the clock values remain in an affine linear envelope of real time. A better worst-case bound on the accuracy with respect to real time cannot be achieved in the absence of an external timer. Second, the algorithm minimizes the number and size of messages that need to be exchanged in a given time period. Moreover, only a small number of bits must be stored locally for each neighbor. Finally, our algorithm can easily be adapted for a variety of other prominent synchronization models.
The next 700 data description languages
Authors: Fisher Kathleen , Mandelbaum Yitzhak , Walker David
Published: August 2010

In the spirit of Landin, we present a calculus of dependent types to serve as the semantic foundation for a family of languages called
data description languages
. Such languages, which include pads, datascript, and packettypes, are designed to facilitate programming with
ad hoc data
, that is, data not in well-behaved relational or xml formats. In the calculus, each type describes the physical layout and semantic properties of a data source. In the semantics, we interpret types simultaneously as the in-memory representation of the data described and as parsers for the data source. The parsing functions are robust, automatically detecting and recording errors in the data stream without halting parsing. We show the parsers are type-correct, returning data whose type matches the simple-type interpretation of the specification. We also prove the parsers are “error-correct,” accurately reporting the number of physical and semantic errors that occur in the returned data. We use the calculus to describe the features of various data description languages, and we discuss how we have used the calculus to improve pads.
A constructive proof of the general lovász local lemma
Authors: Moser Robin A. , Tardos Gábor
Published: August 2010

The Lovász Local Lemma discovered by Erdős and Lovász in 1975 is a powerful tool to non-constructively prove the existence of combinatorial objects meeting a prescribed collection of criteria. In 1991, József Beck was the first to demonstrate that a constructive variant can be given under certain more restrictive conditions, starting a whole line of research aimed at improving his algorithm's performance and relaxing its restrictions. In the present article, we improve upon recent findings so as to provide a method for making almost all known applications of the general Local Lemma algorithmic.
A programmable network address translator
Authors: Huang Tzu-Chi , Zeadally Sherali , Chilamkurti Naveen , Shieh Ce-Kuen
Published: August 2010

Network Address Translation (NAT) alleviates the shortage of IPv4 addresses but incurs peer-to-peer communication, application functionality and packet integrity problems. To date, no approach has yet been proposed to solve these three problems. By exploiting mobile agent and active networking technologies, we propose a Programmable Network Address Translation (PNAT) implementation that enables peer-to-peer communication while maintaining application functionality and packet integrity. For peer-to-peer communication, our proposed PNAT approach works for various NAT types (including the Symmetric NAT) with simple APIs supported by our proposed NAT design. For application functionality, the PNAT uses the mobile code to update protocol information in packet payloads according to different application needs. For packet integrity, the PNAT allows applications to delay their data encryption until NAT begins to translate addresses and ports in packet headers. To validate our proposed PNAT approach, we implemented the PNAT design on Windows 2000, and we present an empirical performance evaluation of the implemented design.
Asymptotic robustness of estimators in rare-event simulation
Authors: L'Ecuyer Pierre , Blanchet Jose H. , Tuffin Bruno , Glynn Peter W.
Published: August 2010

The asymptotic robustness of estimators as a function of a rarity parameter, in the context of rare-event simulation, is often qualified by properties such as bounded relative error (BRE) and logarithmic efficiency (LE), also called asymptotic optimality. However, these properties do not suffice to ensure that moments of order higher than one are well estimated. For example, they do not guarantee that the variance of the empirical variance remains under control as a function of the rarity parameter. We study generalizations of the BRE and LE properties that take care of this limitation. They are named bounded relative moment of order
k
(BRM-
k
) and logarithmic efficiency of order
k
(LE-
k
), where k ≥ 1 is an arbitrary real number. We also introduce and examine a stronger notion called vanishing relative centered moment of order
k
, and exhibit examples where it holds. These properties are of interest for various estimators, including the empirical mean and the empirical variance. We develop (sufficient) Lyapunov-type conditions for these properties in a setting where state-dependent importance sampling (IS) is used to estimate first-passage time probabilities. We show how these conditions can guide us in the design of good IS schemes, that enjoy convenient asymptotic robustness properties, in the context of random walks with light-tailed and heavy-tailed increments. As another illustration, we study the hierarchy between these robustness properties (and a few others) for a model of highly reliable Markovian system (HRMS) where the goal is to estimate the failure probability of the system. In this setting, for a popular class of IS schemes, we show that BRM-
k
and LE-
k
are equivalent and that these properties become strictly stronger when
k
increases. We also obtain a necessary and sufficient condition for BRM-
k
in terms of quantities that can be readily computed from the parameters of the model.
Interview with Manolis Tzagarakis
Authors: Atzenbeck Claus
Published: August 2010

Manolis Tzagarakis is a Lecturer at the University of Patras, Greece and a researcher at the Computer Technology Institute. He holds a diploma from the Department of Computer Engineering and Informatics of the University of Patras, and a Ph.D. from the same university. His research interests includes hypermedia, structural computing, Web-technologies and Computer-Supported Collaborative Work. In the context of internationally funded projects, he designed and developed numerous hypermedia systems which resulted in the Callimachus Structural computing environment. He has served as Workshop Chair of ACM Hypertext 2004 and Program Chair of ACM Hypertext 2005. He serves regularly on the conference committee of the ACM Hypertext conference series. His homepage is http://application.econ.upatras.gr/users/tzagara/
"Collaborative tagging as a community-driven approach to knowledge sharing" by Domenico Gendarmi with Jessica Rubart as Coordinator
Authors: Gendarmi Domenico
Published: August 2010

Domenico Gendarmi received his PhD in computer science from the University of Bari, Italy in April 2010. He is currently working as a postdoctoral researcher at Collaborative Development Group of the same University. His recent research activities focus around the Social Web and Global Software Engineering: in particular, how these fields can interact with each other in order to extend knowledge on social aspects of software development, i.e. supporting informal processes in agile and distributed team setting.
Hyperorders and transclusion
Authors: Goulding James , Brailsford Timothy , Ashman Helen
Published: August 2010

ZigZag is a unique hyperstructural paradigm designed by the hypertext pioneer Ted Nelson. It has piqued a lot of interest in the hypertext community in recent years because of its aim of revolutionizing electronic access to information and knowledge bases. In ZigZag information is stored in cells that are arranged into lists organized along unlimited numbers of intersecting sets of associations called dimensions. To this infrastructure a mechanism of transclusion is added, allowing the data stored in cells to span, and hence be utilized, in different contexts. Proponents of ZigZag claim that it is a flexible and universal structure for information representation, and yet the system has not been widely adopted and has been implemented even more rarely. In this paper we address the question of whether there are intrinsic theoretical reasons as to why this is the case.

While the basic features and specifications of ZigZag are well known, we delve in to the less understood area of its theoretical underpinnings to tackle this question. By modeling ZigZag within the framework of set theory we reveal a new class of hyperstructure that contains no referencable link objects whatsoever, instead grouping non-referencable binary associations into disjunct but parallel sets of common semantics (dimensions). We go on to further specialize these "dimensional models" into sets of finite partial functions, which are closed over a single domain, isolating the new class of hyperstructures we are calling hyperorders. This analysis not only sheds light on the benefits and limitations of the ZigZag hypermedia system, but also provides a framework to describe and understand a wider family of possible hyperstructure models of which it is an early example. Characteristics of Zigzag's transclusion mechanisms are also investigated, highlighting a previously unrecognized distinction, and potential irrevocable conflict, between two distinct uses of content reuse: instance and identity transclusion.
The Ages of Stars
Authors: Soderblom David R.
Published: August 2010

The age of an individual star cannot be measured, only estimated through mostly model-dependent or empirical methods, and no single method works well for a broad range of stellar types or for a full range in age. This review presents a summary of the available techniques for age-dating stars and ensembles of stars, their realms of applicability, and their strengths and weaknesses. My emphasis is on low-mass stars because they are present from all epochs of star formation in the Galaxy and because they present both special opportunities and problems. The ages of open clusters are important for understanding the limitations of stellar models and for calibrating empirical age indicators. For individual stars, a hierarchy of quality for the available age-dating methods is described. Although our present ability to determine the ages of even the nearest stars is mediocre, the next few years hold great promise as asteroseismology probes beyond stellar surfaces and starts to provide precise interior properties of stars and as models continue to improve when stressed by better observations.
Cosmic Silicates
Authors: Henning Thomas
Published: August 2010

Silicate dust particles are an important player in the cosmic life cycle of matter. They have been detected in a wide variety of environments, ranging from nearby protoplanetary disks to distant quasars. This review summarizes the fundamental properties of silicates relevant to astronomical observations and processes. It provides a review of our knowledge about cosmic silicates, mostly based on results from IR spectroscopy.
The Birth Environment of the Solar System
Authors: Adams Fred C.
Published: August 2010

This review examines our current understanding of the possible birth environments of our Solar System. Because most stars form within groups and clusters, the question becomes one of determining the nature of the birth aggregate of the Sun. This discussion starts by reviewing Solar System properties that provide constraints on our environmental history. We then outline the range of star-forming environments that are available in the Galaxy and discuss how they affect star and planet formation. The nature of the solar birth cluster is constrained by many physical considerations, including radiation fields provided by the background environment, dynamical scattering interactions, and by the necessity of producing the short-lived radioactive nuclear species inferred from meteoritic measurements. Working scenarios for the solar birth aggregate can be constructed, as discussed herein, although significant uncertainties remain.
Strong Lensing by Galaxies
Authors: Treu Tommaso
Published: August 2010

Strong lensing is a powerful tool to address three major astrophysical issues: understanding the spatial distribution of mass at kiloparsec and subkiloparsec scale, where baryons and dark matter interact to shape galaxies as we see them; determining the overall geometry, content, and kinematics of the Universe; and studying distant galaxies, black holes, and active nuclei that are too small or too faint to be resolved or detected with current instrumentation. After summarizing strong gravitational lensing fundamentals, I present a selection of recent important results. I conclude by discussing the exciting prospects of strong gravitational lensing in the next decade.
A Universal Stellar Initial Mass Function? A Critical Look at Variations
Authors: Bastian Nate , Covey Kevin R. , Meyer Michael R.
Published: August 2010

Whether the stellar initial mass function (IMF) is universal or is instead sensitive to environmental conditions is of critical importance: The IMF influences most observable properties of stellar populations and thus galaxies, and detecting variations in the IMF could provide deep insights into the star formation process. This review critically examines reports of IMF variations, with a view toward whether other explanations are sufficient given the evidence. Studies of the field, young clusters and associations, and old globular clusters suggest that the vast majority were drawn from a universal system IMF: a power law of Salpeter index (Γ = 1.35) above a few solar masses, and a log normal or shallower power law (Γ ∼ 0–0.25) for lower mass stars. The shape and universality of the substellar IMF is still under investigation. Observations of resolved stellar populations and the integrated properties of most galaxies are also consistent with a universal IMF, suggesting no gross variations over much of cosmic time. Indications of “nonstandard” IMFs in specific local and extragalactic environments clearly warrant further study. However, there is no clear evidence that the IMF varies strongly and systematically as a function of initial conditions after the first few generations of stars.
Dark Matter Candidates from Particle Physics and Methods of Detection
Authors: Feng Jonathan L.
Published: August 2010

The identity of dark matter is a question of central importance in both astrophysics and particle physics. In the past, the leading particle candidates were cold and collisionless, and typically predicted missing energy signals at particle colliders. However, recent progress has greatly expanded the list of well-motivated candidates and the possible signatures of dark matter. This review begins with a brief summary of the standard model of particle physics and its outstanding problems. I then discuss several dark matter candidates motivated by these problems, including weakly interacting massive particles (WIMPs), superWIMPs, light gravitinos, hidden dark matter, sterile neutrinos, and axions. For each of these, I critically examine the particle physics motivations and present their expected production mechanisms, basic properties, and implications for direct and indirect detection, particle colliders, and astrophysical observations. Upcoming experiments will discover or exclude many of these candidates, and progress may open up an era of unprecedented synergy between studies of the largest and smallest observable length scales.
Physical Processes in Magnetically Driven Flares on the Sun, Stars, and Young Stellar Objects
Authors: Benz Arnold O. , Güdel Manuel
Published: August 2010

The first flare on the Sun was observed exactly 150 years ago. During most of the long history, only secondary effects have been noticed, so flares remained a riddle. Now the primary flare products, high-energy electrons and ions, can be spatially resolved in hard X-rays (HXRs) and gamma rays on the Sun. Soft X-rays (SXRs) are observed from most stars, including young stellar objects. Structure and bulk motions of the corona are imaged on the Sun in high temperature lines and are inferred from line shifts in stellar coronae. Magnetic reconnection is the trigger for reorganization of the magnetic field into a lower energy configuration. A large fraction of the energy is converted into nonthermal particles that transport the energy to higher density gas, heating it to SXR-emitting temperatures. Flares on young stars are several orders of magnitude more luminous and more frequent; they significantly ionize protoplanetary disks and planetary ionospheres.
Assessing Rainfall Erosivity with Artificial Neural Networks for the Ribeira Valley, Brazil
Authors: Silva Reginald B. , Iori Piero , Armesto Cecilia , Bendini Hugo N.
Published: August 2010

Soil loss is one of the main causes of pauperization and alteration of agricultural soil properties. Various empirical models (e.g., USLE) are used to predict soil losses from climate variables which in general have to be derived from spatial interpolation of point measurements. Alternatively, Artificial Neural Networks may be used as a powerful option to obtain site-specific climate data from independent factors. This study aimed to develop an artificial neural network to estimate rainfall erosivity in the Ribeira Valley and Coastal region of the State of São Paulo. In the development of the Artificial Neural Networks the input variables were latitude, longitude, and annual rainfall and a mathematical equation of the activation function for use in the study area as the output variable. It was found among other things that the Artificial Neural Networks can be used in the interpolation of rainfall erosivity values for the Ribeira Valley and Coastal region of the State of São Paulo to a satisfactory degree of precision in the estimation of erosion. The equation performance has been demonstrated by comparison with the mathematical equation of the activation function adjusted to the specific conditions of the study area.
Testing Gaussianity, Homogeneity, and Isotropy with the Cosmic Microwave Background
Authors: Abramo L. Raul , Pereira Thiago S.
Published: August 2010

We review the basic hypotheses which motivate the statistical framework used
to analyze the cosmic microwave background, and how that framework can be enlarged as we relax those hypotheses. In particular, we try to separate as much as
possible the questions of gaussianity, homogeneity, and isotropy from each other.
We focus both on isotropic estimators of nongaussianity as well as statistically
anisotropic estimators of gaussianity, giving particular emphasis on their signatures and the enhanced “cosmic variances” that become increasingly important
as our putative Universe becomes less symmetric. After reviewing the formalism
behind some simple model‐independent tests, we discuss how these tests can be
applied to CMB data when searching for large‐scale “anomalies”.
The Prevalence of Concha Bullosa and Nasal Septal Deviation and Their Relationship to Maxillary Sinusitis by Volumetric Tomography
Authors: Smith Kyle D. , Edwards Paul C. , Saini Tarnjit S. , Norton Neil S.
Published: August 2010

The objective of this study was to determine the prevalence of concha bullosa and nasal septal deviation and their potential relationships to maxillary sinusitis. 883 CT scans taken at Creighton University School of Dentistry from 2005 to 2008 were retrospectively reviewed for the presence of concha bullosa, nasal septal deviation, and maxillary sinusitis. 67.5% of patients exhibited pneumatization of at least one concha, 19.4% of patients had a deviated septum, and 50.0% had mucosal thickening consistent with maxillary sinusitis. 49.3% of patients who had concha bullosa also had evidence of maxillary sinusitis. Only 19.5% of patients with concha bullosa also had nasal septal deviation, whereas 19.7% of patients with sinusitis also presented with nasal septal deviation. Although concha bullosa is a common occurrence in the nasal cavity, there did not appear to be a statistically significant relationship between the presence of concha bullosa or nasal septal deviation and maxillary sinusitis.
Musculoskeletal Adverse Events Associated with Adjuvant Aromatase Inhibitors
Authors: Khan Qamar J. , O'Dea Anne P. , Sharma Priyanka
Published: August 2010

Musculoskeletal symptoms including arthralgia and myalgia occur frequently in aging women, particularly during the transition to menopause, when plasma estrogens precipitously decline. In postmenopausal women (PMW) with breast cancer, third-generation aromatase inhibitors (AIs) as adjuvant hormonal therapy have proven to be more effective, and to have a more predictable side effect profile, than tamoxifen. However, AIs further reduce plasma estrogens in PMW, exacerbating musculoskeletal symptoms. Clinical trial data have shown significantly higher incidences of arthralgia and myalgia with AIs compared with women on tamoxifen or placebo. Symptoms may be severe enough to significantly affect quality of life; musculoskeletal symptoms are a frequent reason for discontinuing therapy. In many cases, symptoms can be effectively managed with oral analgesics or other strategies. Early recognition and effective management of musculoskeletal symptoms can help maximize treatment compliance, enabling patients to derive optimal benefit from therapy in terms of preventing recurrence.
Boundedness and Global Stability for a Predator‐Prey System with the Beddington‐DeAngelis Functional Response
Authors: Khellaf Wahiba , Hamri Nasreddine
Published: August 2010

We study the qualitative behavior of a class of predator‐prey models with Beddington‐DeAngelis‐type functional response, primarily from the viewpoint of permanence (uniform persistence). The Beddington‐DeAngelis functional response is similar to the Holling type‐II functional response but contains a term describing mutual interference by predators. We establish criteria under which we have boundedness of solutions, existence of an attracting set, and global stability of the coexisting interior equilibrium via Lyapunov function.
Constitutive Rheological Modeling of Flow Serration Behaviour in Metallic Glasses Showing Nanocrystallization during Deformation
Authors: Yousfi M. A. , Hajlaoui K. , Tourki Z. , Yavari A. R.
Published: August 2010

A simple micromechanism-inspired rheological model is developed that incorporates the serrated flow nature of metallic glasses subjected to compressive deformation at room temperatures. The process of propagation and the arrest of shear bands were addressed in this model. Shear-induced nanocrystallisation was believed to be responsible for strain hardening of material within the shear bands. The model is based on the assumption that the behaviour can be decomposed into two resistances acting in parallel: one captures the initial stiffness and shear softening and the second gives the time-shear-temperature hardening of material.
Pharmacokinetic/Pharmacodynamic Modeling Identifies SN30000 and SN29751 as Tirapazamine Analogues with Improved Tissue Penetration and Hypoxic Cell Killing in Tumors
Authors: Hicks Kevin O. , Siim Bronwyn G. , Jaiswal Jagdish K. , Pruijn Frederik B. , Fraser Annie M. , Patel Rita , Hogg Alison , Liyanage H.D. Sarath , Dorie Mary Jo , Brown J. Martin , Denny William A. , Hay Michael P. , Wilson William R.
Published: August 2010

Purpose: Tirapazamine (TPZ) has attractive features for targeting hypoxic cells in tumors but has limited clinical activity, in part because of poor extravascular penetration. Here, we identify improved TPZ analogues by using a spatially resolved pharmacokinetic/pharmacodynamic (SR-PKPD) model that considers tissue penetration explicitly during lead optimization.

Experimental design: The SR-PKPD model was used to guide the progression of 281 TPZ analogues through a hierarchical screen. For compounds exceeding hypoxic selectivity thresholds in single-cell cultures, SR-PKPD model parameters (kinetics of bioreductive metabolism, clonogenic cell killing potency, diffusion coefficients in multicellular layers, and plasma pharmacokinetics at well tolerated doses in mice) were measured to prioritize testing in xenograft models in combination with radiation.

Results: SR-PKPD–guided lead optimization identified SN29751 and SN30000 as the most promising hypoxic cytotoxins from two different structural subseries. Both were reduced to the corresponding 1-oxide selectively under hypoxia by HT29 cells, with an oxygen dependence quantitatively similar to that of TPZ. SN30000, in particular, showed higher hypoxic potency and selectivity than TPZ in tumor cell cultures and faster diffusion through HT29 and SiHa multicellular layers. Both compounds also provided superior plasma PK in mice and rats at equivalent toxicity. In agreement with SR-PKPD predictions, both were more active than TPZ with single dose or fractionated radiation against multiple human tumor xenografts.

Conclusions: SN30000 and SN29751 are improved TPZ analogues with potential for targeting tumor hypoxia in humans. Novel SR-PKPD modeling approaches can be used for lead optimization during anticancer drug development. Clin Cancer Res; 16(20); 4946–57. ©2010 AACR.
Homoarginine, Cardiovascular Risk, and Mortality
Authors: März Winfried , Meinitzer Andreas , Drechsler Christiane , Pilz Stefan , Krane Vera , Kleber Marcus E. , Fischer Joachim , Winkelmann Bernhard R. , Böhm Bernhard O. , Ritz Eberhard , Wanner Christoph
Published: August 2010

Background—

Homoarginine is an amino acid derivative that may increase nitric oxide availability and enhance endothelial function. The effect of the level of homoarginine on cardiovascular outcome and mortality is unknown.

Methods and Results—

We assessed cardiovascular and all-cause mortality according to homoarginine levels in a cohort of 3305 subjects referred for coronary angiography from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study. After investigating the relation of homoarginine with kidney function and markers of endothelial dysfunction, we explored its effects on adverse outcomes in a second high-risk cohort of 1244 patients with type 2 diabetes mellitus receiving maintenance hemodialysis (4D study [Die Deutsche Diabetes Dialyse Studie]). In the LURIC study, mean serum homoarginine levels were 2.6±1.1 μmol/L. During a median follow-up of 7.7 years, 766 patients died. After adjustments for age and sex, patients in the lowest quartile (<1.85 μmol/L) had a >4-fold higher rate of dying of cardiovascular disease (hazard ratio 4.1, 95% confidence interval 3.0 to 5.7) than patients in the highest quartile (>3.1 μmol/L). Lower homoarginine levels were associated with lower estimated glomerular filtration rate and higher levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Hemodialysed patients had lower mean homoarginine levels of 1.2±0.5 μmol/L and experienced a 5-fold increased mortality rate compared with LURIC patients (608 deaths during a median follow-up of 4 years). Homoarginine consistently affected mortality, which was 2-fold higher in 4D study patients in the lowest quartile (<0.87 μmol/L) than in patients in the highest quartile (>1.4 μmol/L).

Conclusions—

Homoarginine levels are independently associated with cardiovascular and all-cause mortality in patients referred for coronary angiography and in patients undergoing hemodialysis. Future studies are needed to elucidate the underlying pathomechanisms.
Background, Incidence, and Predictors of Antiplatelet Therapy Discontinuation During the First Year After Drug-Eluting Stent Implantation
Authors: Ferreira-González Ignacio , Marsal Josep R. , Ribera Aida , Permanyer-Miralda Gaietà , García-Del Blanco Bruno , Martí Gerard , Cascant Purificación , Martín-Yuste Victoria , Brugaletta Salvatore , Sabaté Manuel , Alfonso Fernando , Capote Mari L. , De La Torre Jose M. , Ruíz-Lera Marta , Sanmiguel Dario , Cárdenas Mérida , Pujol Beth , Baz Jose A. , Iñiguez Andrés , Trillo Ramiro , González-Béjar Omar , Casanova Juan , Sánchez-Gila Joaquín , García-Dorado David
Published: August 2010

Background—

Predictors of antiplatelet therapy discontinuation (ATD) during the first year after drug-eluting stent implantation are poorly known.

Methods and Results—

This was a prospective study with 3-, 6-, 9-, and 12-month follow-up of patients receiving at least 1 drug-eluting stent between January and April 2008 in 29 hospitals. Individual- and hospital-level predictors of ATD were assessed by hierarchical-multinomial regression analysis. ATD could be assessed in 1622 candidates for follow-up (82.5%). A total of 234 patients (14.4%) interrupted at least 1 antiplatelet therapy drug, predominantly clopidogrel (n=182, 11.8%). Bleeding events or invasive procedures led to ATD in 109 patients. This was predicted by renal impairment (odds ratio [OR] 2.81, 95% confidence interval [CI] 1.48 to 5.34), prior major hemorrhage (OR 3.77, 95% CI 1.41 to 10.03), and peripheral arterial disease (OR 1.78, 95% CI 1.01 to 3.15). Medical decisions led to ATD in 70 patients; this was predicted by long-term use of anticoagulant therapy (OR 3.88, 95% CI 1.26 to 11.98), undergoing the procedure in a private hospital (OR 13.3, 95% CI 1.69 to 105), and not receiving instructions about medication (OR 2.8, 95% CI 1.23 to 6.36). Thirty-nine patients interrupted ATD on their own initiative, mainly immigrants (OR 3.78, 95% CI 1.2 to 11.98) and consumers of psychotropic drugs (OR 2.58, 95% CI 1.3 to 5.12).

Conclusions—

ATD during the first year after drug-eluting stent implantation is based mainly on patient decision or a medical decision not associated with major bleeding events or major surgical procedures. Individual- and hospital-level variables are important to predict ATD.
Effect of Cardiac Resynchronization Therapy on Reverse Remodeling and Relation to Outcome
Authors: Solomon Scott D. , Foster Elyse , Bourgoun Mikhail , Shah Amil , Viloria Esperanza , Brown Mary W. , Hall W. Jackson , Pfeffer Marc A. , Moss Arthur J.
Published: August 2010

Background—

Cardiac resynchronization therapy (CRT) plus implantation of an implantable cardioverter defibrillator (ICD) reduced the risk of death or heart failure event in patients with mildly symptomatic heart failure, left ventricular dysfunction, and wide QRS complex compared with an ICD only. We assessed echocardiographic changes in patients enrolled in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation Trial: Cardiac Resynchronization Therapy) to evaluate whether the improvement in outcomes with CRT plus an ICD was associated with favorable alterations in cardiac size and function.

Methods and Results—

A total of 1820 patients were randomly assigned to CRT plus an ICD or to an ICD only in a 3:2 ratio. Echocardiographic studies were obtained at baseline and 12 months later in 1372 patients. We compared changes in cardiac size and performance between treatment groups and assessed the relationship between these changes over the first year, as well as subsequent outcomes. Compared with the ICD-only group, the CRT-plus-ICD group had greater improvement in left ventricular end-diastolic volume index (−26.2 versus −7.4 mL/m
2
), left ventricular end-systolic volume index (−28.7 versus −9.1 mL/m
2
), left ventricular ejection fraction (11% versus 3%), left atrial volume index (−11.9 versus −4.7 mL/m
2
), and right ventricular fractional area change (8% versus 5%;
P
<0.001 for all). Improvement in end-diastolic volume at 1 year was predictive of subsequent death or heart failure, with adjustment for baseline covariates and treatment group; each 10% decrease in end-diastolic volume was associated with a 40% reduction in risk (
P
<0.001).

Conclusions—

CRT resulted in significant improvement in cardiac size and performance compared with an ICD-only strategy in patients with mildly symptomatic heart failure. Improvement in these measures accounted for the outcomes benefit.

Clinical Trial Registration Information—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.
Hypertension Induced by the Tyrosine Kinase Inhibitor Sunitinib Is Associated With Increased Circulating Endothelin-1 Levels
Authors: Kappers Mariëtte H.W. , van Esch Joep H.M. , Sluiter Wim , Sleijfer Stefan , Danser A. H. Jan , van den Meiracker Anton H.
Published: August 2010

Angiogenesis inhibition with sunitinib, a multitarget tyrosine kinase inhibitor of the vascular endothelial growth factor receptor, is associated with hypertension and cardiac toxicity, of which the underlying pathophysiological mechanism is unknown. We investigated the effects of sunitinib on blood pressure (BP), its circadian rhythm, and potential mechanisms involved, including the endothelin-1 system, in 15 patients with metastatic renal cell carcinoma or gastrointestinal stromal tumors. In addition, we investigated in rats the effect of sunitinib on BP, serum endothelin-1 levels, coronary microvascular function, cardiac structure, and cardiac mitochondrial function. In patients, BP increased by ≈15 mm Hg, whereas heart rate decreased after 4 weeks of treatment. Furthermore, the nocturnal dipping of BP diminished. Plasma endothelin-1 concentration increased 2-fold (
P
<0.05) and plasma renin decreased (
P
<0.05), whereas plasma catecholamines and renal function remained unchanged. In rats, 8 days of sunitinib administration induced an ≈30-mm Hg rise in BP, an attenuation of the circadian BP rhythm, and a 3-fold rise in serum endothelin-1 and creatinine, of which all but the rise in creatinine reversed after sunitinib withdrawal. Coronary microvascular function studies after 8 days of sunitinib administration showed decreased responses to bradykinin, angiotensin II, and sodium nitroprusside, all normalizing after sunitinib withdrawal. Cardiac structure and cardiac mitochondrial function did not change. In conclusion, sunitinib induces a reversible rise in BP in patients and in rats associated with activation of the endothelin-1 system, suppression of the renin-angiotensin system, and generalized microvascular dysfunction.