bluuebunny/crossref_metadata_2025 huggingface dataset:
FROM DIRAC ACTION TO ELKO ACTION
Authors: HOFF DA SILVA J. M. , DA ROCHA ROLDÃO
Published: July 2009

A fundamental action, representing a mass dimension-transmuting operator between Dirac and ELKO spinor fields, is performed on the Dirac Lagrangian, in order to lead it into the ELKO Lagrangian. Such a dynamical transformation can be seen as a natural extension of the Standard Model that incorporates dark matter fields. The action of the mass dimension-transmuting operator on a Dirac spinor field, that defines and introduces such a mapping, is shown to be a composition of the Dirac operator and the nonunitary transformation that maps Dirac spinor fields into ELKO spinor fields, defined in J. Math. Phys.48, 123517 (2007). This paper gives allowance for ELKO, as a candidate to describe dark matter, to be incorporated in the Standard Model. It is intended to present for the first time, up to our knowledge, the dynamical character of a mapping between Dirac and ELKO spinor fields, transmuting the mass dimension of spin one-half fermionic fields from 3/2 to 1 and from 1 to 3/2.
Chapter 3 Analysis Tools
Authors: Ping Rong-Gang , Mo X. H. , Fu C. D. , He K. L. , Hu J. F. , Huang B. , Qin G. , Sun S. S. , Zheng Y. H. , Liu Beijiang , Xu Min , Zhang Xueyao , Wu Ning , Zheng Hanqing , Asner David
Published: July 2009

The following sections are included:

Monte Carlo Generators

Luminosity Measurements at BES-III

Particle Identification

Kinematic Fitting

Partial Wave Analysis

Dalitz-Plot Analysis Formalism
Chapter 7 Experimental Tests of QCD
Authors: Hu Hai-Ming
Published: July 2009

The following sections are included:

Inclusive Distributions

Exclusive Cross Sections and Form Factors

Multiplicity Distribution

Kinematical and Dynamical Correlations

Topological Event Shapes

Bose-Einstein Correlations (BEC)

Possible Fractal Structure of Final State Phase-Space
Chapter 8 Lineshapes of Charmonium Resonances
Authors: Rong Gang , Zhang Da-Hua
Published: July 2009

The following sections are included:

Resonance Production and 1-- Charmonium States

Key Points for Precision Measurements

An Example for Measuring ψ(2S) and ψ(3770) Parameters

Resonance Measurements at BES-III

Summary
Chapter 24 Charm Baryon Production and Decays
Authors: Cheng Hai-Yang
Published: July 2009

The following sections are included:

Introduction

Production of Charmed Baryons at BES-III

Spectroscopy

Strong Decays

Lifetimes

Hadronic Weak Decays

Semileptonic Decays

Electromagnetic and Weak Radiative Decays
Light Hadron Physics
Authors: Bian Jian-Ming , Bytev Vladimir , Chen Ying , Jin Hong-Ying , Jin Shan , Qin Hu , Shen Xiao-Yan , Wu Ning , Xu Guo-Fa , Zhang Zhen-Xia , Zhao Qiang , Zhemchugov Alexey , Zheng Han-Qing , Zhu Shi-Lin , Zou Bing-Song
Published: July 2009

Our knowledge about the structure of matter and the nature of the interactions between its constituent components follows a hierarchy that closely tracks the evolution of experimental measurements from low to higher and higher energies. For example, with an electron beam of a given energy, one can access the microscopic structure of matter at length scales corresponding to the de-Brogie wave length of the electrons that are being used: λ = 2π × 197.3 Mev · fm /Eγ, were Eγ is the energy of the photon that is exchanged in the experimentally observed process. As the energy of the beams that are available get higher and higher, the sizes of objects that can be probed get smaller and smaller…
ELASTIC ANALYSIS OF A GRIFFITH CRACK IN ICOSAHEDRAL QUASICRYSTAL Al-Pd-Mn QUASICRYSTAL
Authors: ZHU AI-YU , FAN TIAN-YOU
Published: July 2009

The elastic analysis of a Griffith crack in an icosahedral quasicrystal is performed using the general solution and systematic Fourier transform-dual integral equations method, the analytic expressions for the displacement and stress fields are obtained. The asymptotic behavior of the stress field around the crack tip indicates that the stress near the crack tip exhibits the square root singularity. The singularity in the phason stress field arising from those of the phonon and phonon–phason coupling is also discussed. The most important physical quantities of fracture theory, crack stress intensity factor and energy release rate, are determined.
SUPPRESSION OF WEISS OSCILLATIONS IN THE MAGNETOCONDUCTIVITY OF MODULATED GRAPHENE MONOLAYER
Authors: TAHIR M. , SABEEH K.
Published: July 2009

We have investigated the electrical transport properties of Dirac electrons in a monolayer graphene sheet in the presence of both electric and magnetic modulations. The effects of the modulations on quantum transport when they are in phase and out of phase are considered. We present the energy spectrum and the bandwidth of the Dirac electrons in the presence of both the modulations. We determine the σyy component of the magnetoconductivity tensor for this system which is shown to exhibit Weiss oscillations. Asymptotic expressions for σyy are also calculated to better illustrate the effects of in-phase and out-of-phase modulations. We find that the position of the oscillations in magnetoconductivity depends on the relative strength of the two modulations. When the two modulations are out of phase there is a complete suppression of Weiss oscillations for a particular relative strength of the modulations.
PREPARATION OF N-TYPE HIGHER MANGANESE SILICIDE FILMS BY MAGNETRON SPUTTERING
Authors: HOU Q. R. , ZHAO W. , CHEN Y. B. , HE Y. J.
Published: July 2009

N-type polycrystalline higher manganese silicide ( MnSi 1.7) films are prepared on thermally oxidized silicon substrates by magnetron sputtering. MnSi 1.85, Si , and carbon targets are used in the experiments. By co-sputtering of the MnSi 1.85 and Si targets, n-type MnSi 1.7 films are directly obtained. By increasing the Si content to the deposited films, both the Seebeck coefficient and electrical resistivity increase to high values. A Si intermediate layer between the MnSi 1.7 film and substrate plays an important role on the electrical properties of the films. Without the interlayer, the Seebeck coefficient is not stable and the electrical resistivity is higher. For preparation of MnSi 1.7 films by solid phase reaction, a sandwich structure Si / MnSi x/ Si (x < 1.7) and thermal annealing are used. A carbon cap layer is used as a doping source. With the carbon doping, the electrical resistivity of the MnSi 1.7 film decreases, while the Seebeck coefficient increases slightly. For reactive deposition, the MnSi x (x < 1.7) film is directly deposited on the heated substrate with a Si intermediate layer. By using a Si cap layer, a MnSi 1.7 film with a Seebeck coefficient of -292 μ V/K and electrical resistivity of 23 × 10-3 Ω- cm at room temperature is obtained. The power factor reaches 1636 μW/mK2 at 483 K. With such a high power factor, the n-type MnSi 1.7 material may be superior to p-type MnSi 1.7 material for the development of thermoelectric generators. Several smaller (0.036 - 0.099 eV ) and intermediate (0.10 - 0.28 eV ) activation energies are observed from the curves of logarithm of the resistivity versus reciprocal temperature. The larger activation energies (0.35 - 1.1 eV ) are consistent with the reported energy band gaps for higher manganese silicides.
MODELLING VASCULAR MORPHOGENESIS: CURRENT VIEWS ON BLOOD VESSELS DEVELOPMENT
Authors: HERRERO MIGUEL Á. , KÖHN ÁLVARO , PÉREZ-POMARES JOSÉ M.
Published: July 2009

In this work we present a comprehensive account of our current knowledge on vascular morphogenesis, both from a biological and a mathematical point of view. To this end, we first describe the basic steps in the known mechanisms of blood vessel morphogenesis, whose structure, function and unfolding properties are examined. We then provide a wide, although by no means exhaustive, account of mathematical models which are used to describe and discuss particular aspects of the overall biological process considered. We finally summarize the approaches presented, and suggest possible directions for future research. Details about some of the major signalling molecules involved are included in a first Appendix at the end of the paper. A second Appendix provides a brief overview of design principles for vascular nets, a subject that has deserved considerable attention over the years.
UNIFORM CONTROLLABILITY OF A TRANSPORT EQUATION IN ZERO DIFFUSION–DISPERSION LIMIT
Authors: GLASS OLIVIER , GUERRERO SERGIO
Published: July 2009

In this paper, we consider the controllability of a transport equation perturbed by small diffusion and dispersion terms. We prove that for a sufficiently large time, the cost of the null-controllability tends to zero exponentially as the perturbation vanishes. For small times, on the contrary, we prove that this cost grows exponentially.
CONVERGENCE AND ERROR ESTIMATES OF TWO ITERATIVE METHODS FOR THE STRONG SOLUTION OF THE INCOMPRESSIBLE KORTEWEG MODEL
Authors: GUILLÉN-GONZÁLEZ F. , RODRÍGUEZ-BELLIDO M. A.
Published: July 2009

We show the existence of strong solutions for a fluid model with Korteweg tensor, which is obtained as limit of two iterative linear schemes. The different unknowns are sequentially decoupled in the first scheme and in parallel form in the second one. In both cases, the whole sequences are bounded in strong norms and convergent towards the strong solution of the system, by using a generalization of Banach's fixed point theorem. Moreover, we explicit a priori and a posteriori error estimates (respect to the weak norms), which let us to compare both schemes.
SPIN AND ORBITAL ANGULAR MOMENTUM IN THE PROTON
Authors: THOMAS ANTHONY W.
Published: July 2009

Since the announcement of the proton spin crisis by the European Muon Collaboration there has been considerable progress in unravelling the distribution of spin and orbital angular momentum within the proton. We review the current status of the problem, showing that not only have strong upper limits have been placed on the amount of polarized glue in the proton but that the experimental determination of the spin content has become much more precise. It is now clear that the origin of the discrepancy between experiment and the naive expectation of the fraction of spin carried by the quarks and anti-quarks in the proton lies in the non-perturbative structure of the proton. We explain how the features expected in a modern, relativistic and chirally symmetric description of nucleon structure naturally explain the current data. The consequences of this explanation for the presence of orbital angular momentum on quarks and gluons is reviewed and comparison made with recent results from lattice QCD and experimental data.
SIGMA MESON AND PROPERTIES OF NUCLEAR MATTER
Authors: SANTRA A. B. , LOMBARDO U.
Published: July 2009

We have calculated the saturation observables of symmetric nuclear matter and nuclear symmetry energy in the framework of Brueckner-Hartree-Fock (BHF) formalism with Bonn-B potential as two-body interaction, including modification of hadronic parameter inside nuclear medium. We have found that it is possible to understand all the saturation observables of symmetric nuclear matter by incorporating in-medium modification of the parameters of sigma meson alone. Linear density dependent reduction of σ-nucleon coupling constant by about 6.8% and density independent reduction σ-meson mass by about 3.5% is sufficient to understand nuclear matter saturation observables. We find with the calculated symmetry energy that neutron skin thickness of 208Pb is 0.20 fm and the radius of 1.4 solar mass neutron stars as 11.98 ± 0.75 km.
MANY-BODY THEORY OF THE ELECTROWEAK NUCLEAR RESPONSE
Authors: BENHAR OMAR
Published: July 2009

After a brief review of the theoretical description of nuclei based on nonrelativistic many-body theory and realistic hamiltonians, these lectures focus on its application to the analysis of the electroweak response. Special emphasis is given to electron-nucleus scattering, whose experimental study has provided a wealth of information on nuclear structure and dynamics, exposing the limitations of the shell model. The extension of the formalism to the case of neutrino-nucleus interactions, whose quantitative understanding is required to reduce the systematic uncertainty of neutrino oscillation experiments, is also discussed.
WITNESSING THE HADRONIC COLLISION EVENTS AT CLOSE QUARTERS
Authors: JAIN ARUN K. , JOSHI BHUSHAN N.
Published: July 2009

It is seen that in the three body final state of a nucleon knockout reaction the residual nucleus not only bears testimony to the dynamics of the knocked out nucleon before the event but also can testify the happening at the time of the hard collision event. This arises mainly because of the distorting optical potentials of the residual nucleus with the knockout partners. In 40Ca(p, 2p) knockout reaction the optical distortion effects are large enough to be able to differentiate between strong peripheral bruising or the deep interpenetration of the two protons at the time of knockout. Similar effect is witnessed in the proton knockout using pions. Many stronger evidences of the effect of varying behaviour of the knockout vertex exist in the nucleon cluster knockout reactions which were only viewed as unexplained large anomalies. Evidences are provided where the different short distance behaviour of the knockout vertex t -matrix effective interaction produced huge differences in the finite range (FR) distorted wave impulse approximation (DWIA) predictions of various knockout reactions. These observations enhance the possibility of observing the multiquark objects (dibaryons, pentaquark eta.) through nucleon knockout reactions if they are produced at the knockout vertex by the incident hadron beam.
TWIST-THREE DISTRIBUTION AMPLITUDES AND OCTET CURRENT DECAY CONSTANTS OF η AND η': A QCD SUM RULE APPROACH
Authors: SINGH J. P.
Published: July 2009

We investigate twist-three distribution amplitudes (DAs) of η and η' using QCD sum rules. Zeroth moments of light quark DAs of η and η' are evaluated and compared with those found in other approaches. The decay constants of the octet axial vector current in the η and η' system are also estimated.
ASSOCIATED STRANGENESS PHOTOPRODUCTION AT CBELSA/TAPS
Authors:   For the CBELSA/TAPS Collaboration, KLEBER VERA
Published: July 2009

Photoproduction of hyperons provides a key road to a full amplitude analysis. Very significant data have already been reported; major results are discussed here. Recent results obtained at Bonn using the Crystal Barrel/TAPS set up are presented, and future options discussed.
PROBING NUCLEAR DYNAMICS IN REAL-PHOTON EXPERIMENTS
Authors:   for the CLAS Collaboration, ILIEVA YORDANKA
Published: July 2009

Experimental results on the reactions γd → π0d, γd → pn, γ3 He → ppn, and γ3 He → pd obtained in Hall B at Jefferson Lab at photon energies between 0.3 and 3.0 GeV are discussed. The goal of the measurements is to study the transition between long- and short-range nuclear dynamics, as well as more specific dynamical effects, such as manifestations of three-body mechanisms. Conventional nuclear models can describe the data up to a momentum transfer of ~ 1 ( GeV /c)2. All the studied reactions on deuterium clearly show scaling properties consistent with the predictions of the Constituent Counting Rules. The data on 3 He suggest that the favorable energy range for the study of three-body mechanisms is 0.6 - 0.8 GeV .
THE LORENTZ INTEGRAL TRANSFORM (LIT) METHOD
Authors: LEIDEMANN WINFRIED
Published: July 2009

The LIT approach is reviewed both for inclusive and exclusive reactions. It is shown that the method reduces a continuum state problem to a bound-state-like problem, which then can be solved with typical bound-state techniques. The LIT approach opens up the possibility to perform ab initio calculations of reactions also for those particle systems which presently are out of reach in conventional approaches with explicit calculations of many-body continuum wave functions. Various LIT applications are discussed ranging from particle systems with two nucleons up to particle systems with seven nucleons.
Making deterministic signatures quickly
Authors: Ružić Milan
Published: July 2009

We present a new technique of universe reduction. Primary applications are the dictionary problem and the predecessor problem. We give several new results on static dictionaries in different computational models: the word RAM, the practical RAM, and the cache-oblivious model. All algorithms and data structures are deterministic and use linear space. Representative results are: a dictionary with a lookup time ofO(log logn) and construction time ofO(n) on sorted input on a word RAM, and a static predecessor structure for variable- and unbounded length binary strings that in the cache-oblivious model has a query performance ofO(|s|/B+ log |s|) I/Os, for query arguments.
Squarepants in a tree
Authors: Eppstein David
Published: July 2009

We provide efficient constant-factor approximation algorithms for the problems of finding a hierarchical clustering of a point set in any metric space, minimizing the sum of minimimum spanning tree lengths within each cluster, and in the hyperbolic or Euclidean planes, minimizing the sum of cluster perimeters. Our algorithms for the hyperbolic and Euclidean planes can also be used to provide a
pants decomposition
, that is, a set of disjoint simple closed curves partitioning the plane minus the input points into subsets with exactly three boundary components, with approximately minimum total length. In the Euclidean case, these curves are squares; in the hyperbolic case, they combine our Euclidean square pants decomposition with our tree clustering method for general metric spaces.
An
O
(
n
log
n
) approximation scheme for Steiner tree in planar graphs
Authors: Borradaile Glencora , Klein Philip , Mathieu Claire
Published: July 2009

We give a Polynomial-Time Approximation Scheme (PTAS) for the Steiner tree problem in planar graphs. The running time is
O
(
n
log
n
).
Impact of inheritance on vulnerability propagation at design phase
Authors: Agrawal A. , Khan R. A.
Published: July 2009

The design phase of software development provides the foundation for secure software. Reducing vulnerability at this phase minimizes rework in subsequent development phases. Currently, no efficient measure or method is available to reduce this vulnerability. In or-der to address this problem, we have proposed an algorithm to measure vulnerability propagation for an object-oriented design that calculates the Attribute Vulnerability Ratio (AVR).
Evaluating an evolving software component
Authors: Kaur Kuljit , Singh Hardeep
Published: July 2009

Component based development is a reuse based approach in which already existing software components are used to assemble a new application. One of the commonly cited advantages of this approach is that application quality is high because mature components are used in the application. This indicates that as components mature their quality improves. In this paper, we have studied evolution of the design structure of a reusable component using package metrics proposed by Robert Martin. Metric values indicate that internal design of the component has improved over time.
Some issues on scheduling estimation model for object-oriented software projects
Authors: Mishra Alok , Mishra Deepti
Published: July 2009

Object-Oriented (OO) software projects are becoming more popular than structured (functional) technology based projects. Object Technology (OT) offers support to deliver products to market more quickly and to provide high quality with lower maintenance costs. Estimation is an important field of software engineering and there is need for good OO metrics and models for both process and product management. To cut development cost and meet tight deadlines in short staffed software projects, it is essential that managers plan and schedule their projects in a best possible way. To address these issues, we have proposed a model for scheduling estimation by using available OO metrics and affecting factors.
Investigating a new formal model for a library system using B method
Authors: Nami Mohammad Reza , Razavi Hamid , Saeedi Milad , Shahidi Navid
Published: July 2009

The use of formal methods for development of safety-critical sys-tems has motivated researchers to serve them in distributed appli-cations. B method has the precision to support animation and rigorous verification, but requires significant effort in training to overcome the mathematical barrier that many practitioners perce-ive. In this paper, an overview of B method is described including definition, properties, and tools. Then, a new formal model for a library system using B is presented. This formal model can be ex-tended in distributed environments and be integrated with UML as further work.
Predicting software maintenance using fuzzy model
Authors: Singh Yogesh , Bhatia Pradeep Kumar , Sangwan Omprakash
Published: July 2009

Software maintenance is commonly used to refer to the modifications that are made to a software system after its initial release, installed and is operational. There is evidence that maintenance costs exceed 60 percent of the total costs of software. In this paper we have analyzed the major factors that can affect software maintenance and divide them into four categories: Readability of Source Code (RSC), Documentation Quality (DQ), Understandability of Software (UOS), and Average Cyclomatic Complexity (ACC). In our study we have proposed fuzzy model to predict software maintenance using these four factors. The proposed fuzzy model is validated and experimental results indicate that the proposed model is suitable for predicting software maintenance level of the software.
API usability
Authors: Daughtry John M. , Farooq Umer , Myers Brad A. , Stylos Jeffrey
Published: July 2009

The 27th annual International Conference on Human Factors in Computing (CHI) convened in Boston, MA (USA) from April 4-9, 2009. Included in this year's technical program was a special interest group (SIG) meeting on API usability. This report summarizes the SIG, emphasizing the primary takeaways, which include a greater understanding of the types of APIs, case studies, and a place to share our multi-disciplinary results.
Challenges in practice
Authors: Dranidis Dimitris , Masticola Stephen P. , Strooper Paul
Published: July 2009

The Fourth International Workshop on Automation of Software Test (AST 2008) ICSE 2009 expanded previous programs to two days, supported a special theme of Testing Web Services, added a Case Studies from Business and Industry session, and included a charette-style work session. At the workshop, 15 regular papers and 7 short case-study papers were presented in 7 sessions at the workshop. This report summarizes the organization of the workshop as well as the sessions and papers presented, the results of the charette session, attendee feedback, and lessons learned. (This is an updated and expanded version of the workshop summary that was included in the ICSE 2009 proceedings.
Workshop on modeling in software engineering at ICSE 2009
Authors: Baillargeon Robert , France Robert , Zschaler Steffen , Rumpe Bernhard , Völkel Steven , Georg Geri
Published: July 2009

The Modeling in Software Engineering (MiSE) workshop series provides a forum for discussing the challenges associated with modeling software and with incorporating modeling practices into the software development process. The main goal of the series is to further promote cross-fertilization between the modeling communities (e.g., MODELS) and software-engineering communities.

In particular, the workshop provides a medium to exchange innovative technical ideas and experiences related to modeling. The 2009 MiSE workshop provided a venue for presentation and discussion of eleven papers in the five areas of model evolution, domain specific languages, verification and validation, model transformation and state-of-the-art modeling usage in software development. These papers represent a 44% acceptance rate to the workshop. Three posters were also accepted. This report summarizes the discussions and conclusions of the workshop.
Measuring design complexity
Authors: Yadav A. , Khan R. A.
Published: July 2009

Complexity is one of the important attributes of reliability. Higher design complexity increases the probability of error occurrences and decreases reliability of software. Inheritance has been indentified as a key construct to control design complexity. This paper proposes a formula to calculate the overall complexity of design hierarchy caused by inherited methods.
MemTracker
Authors: Venkataramani Guru , Doudalis Ioannis , Solihin Yan , Prvulovic Milos
Published: July 2009

Memory bugs are a broad class of bugs that is becoming increasingly common with increasing software complexity, and many of these bugs are also security vulnerabilities. Existing software and hardware approaches for finding and identifying memory bugs have a number of drawbacks including considerable performance overheads, target only a specific type of bug, implementation cost, and inefficient use of computational resources.

This article describes MemTracker, a new hardware support mechanism that can be configured to perform different kinds of memory access monitoring tasks. MemTracker associates each word of data in memory with a few bits of state, and uses a programmable state transition table to react to different events that can affect this state. The number of state bits per word, the events to which MemTracker reacts, and the transition table are all fully programmable. MemTracker's rich set of states, events, and transitions can be used to implement different monitoring and debugging checkers with minimal performance overheads, even when frequent state updates are needed. To evaluate MemTracker, we map three different checkers onto it, as well as a checker that combines all three. For the most demanding (combined) checker with 8 bits state per memory word, we observe performance overheads of only around 3%, on average, and 14.5% worst-case across different benchmark suites. Such low overheads allow continuous (always-on) use of MemTracker-enabled checkers, even in production runs.
FEATURE"At the End of the World, Plant a Tree"
Authors: Greenfield Adam , Shute Tish
Published: July 2009

Editors' Note: Adam Greenfield is Nokia's head of design direction for service and user-interface design, as well as the author of
Everyware: The Dawning Age of Ubiquitous Computing
and the upcoming
The City Is Here for You to Use.
He is also a compelling speaker and articulate blogger, and has become an authority in thinking about the impact of future ubiquitous technologies on people and society.
In a lengthy interview with Tish Shute recently published on UgoTrade.com, Greenfield covered numerous topics including augmented reality, Usman Haque's Pachube project, the networked book, the networked city, and what to do at the end of the world. The interview is dense and rich, with many of the questions raised relevant to our audience. We asked Greenfield to expand on some of his answers for
interactions.
TIMELINESUnderstanding visual thinking
Authors: Valenza Christine , Adkins Jan
Published: July 2009

Editor's Note: The Timelines column was launched in 2006 around a three-row timeline focused on the 1940s through the present, designed with an assist from a great graphic designer. This provocative column has a timeline similar in outline, designed by a great graphic artist. Would that I could use big paper as effectively as she! --Jonathan Grudin
An interview with John H. Holland
Authors: Booker Lashon B.
Published: July 2009

John Holland began his academic career as a graduate student at the University of Michigan studying with Arthur Burks, a designer of early programmable computers and colleague of John von Neumann. Under Burks' supervision, in 1959 Holland received what may have been the first Ph.D. in the world in the emerging field of computer science. He was subsequently hired as one of the first professors in the new department of Computer and Communication Science at the University of Michigan.

As the inventor of genetic algorithms, John established himself as one of the early pioneers in understanding the foundations of adaptation, learning, and modeling in both natural and artificial systems. His extensions of the genetic algorithm, first to a cognitive architecture called classifier systems and later to an ecological architecture known as Echo, have increased the reach of his ideas well beyond computer science. John Holland's imaginative, interdisciplinary approach to thinking about adaptation, emergence and complexity has made him one of the world's acknowledged leaders in the field of complex adaptive systems. In addition to his many intellectual achievements, John Holland has also been a valued mentor and friend for those of us who have had the privilege to be his students.

Holland is currently a Professor of Psychology and Professor of Electrical Engineering & Computer Science at the University of Michigan. He is also a member of the Board of Trustees and an External Professor at the Santa Fe Institute. Holland was made a MacArthur Fellow in 1992 and is a Fellow of the World Economic Forum.
It's not junk!
Authors: Congdon Clare Bates , Gaskins H. Rex , Nava Gerardo M. , Mattingly Carolyn
Published: July 2009

The human genome is approximately 3 billion basepairs long. An estimated 2--3% of DNA codes for genes; the remaining 97--98% is noncoding DNA [11]. Although the noncoding regions in DNA were once called "junk DNA" (with the assumption that these regions were not serving a purpose) it is now understood that within noncoding DNA are functional regions that affect the expression of genes [34]. However, we are still far from understanding the breadth of function in the noncoding regions, and identification of functional elements is a complex problem, difficult to study
in vitro
because of the enormous number of possibilities. In this project, we are searching
in silico
for candidate functional elements in noncoding DNA. These candidates will then be studied at the bench to assess function. Our guiding principle is that regions of noncoding DNA that have been conserved across evolutionary time are good candidates as functional elements; we use a genetic algorithms approach to search for these candidate elements, called motifs. Our system is thus called GAMI, Genetic Algorithms for Motif Inference. GAMI has been demonstrated to be a successful approach to this task, as will be described below.
Molecular Circuitry of Endocytosis at Nerve Terminals
Authors: Dittman Jeremy , Ryan Timothy A.
Published: July 2009

Presynaptic terminals are specialized compartments of neurons responsible for converting electrical signals into secreted chemicals. This self-renewing process of chemical synaptic transmission is accomplished by the calcium-triggered fusion of neurotransmitter-containing vesicles with the plasma membrane and subsequent retrieval and recycling of vesicle components. Whereas the release of neurotransmitters has been studied for over 50 years, the process of synaptic vesicle endocytosis has remained much more elusive. The advent of imaging techniques suited to monitor membrane retrieval at presynaptic terminals and the discovery of the molecules that orchestrate endocytosis have revolutionized our understanding of this critical trafficking event.
A highly energetic process couples calcium influx through L-type calcium channels to insulin secretion in pancreatic β-cells
Authors: Jung Seung-Ryoung , Reed Benjamin J. , Sweet Ian R.
Published: July 2009

Calcium (Ca2+) influx is required for the sustained secretion of insulin and is accompanied by a large rate of energy usage. We hypothesize that the energy usage reflects a process [Ca2+/metabolic coupling process (CMCP)] that couples Ca2+to insulin secretion by pancreatic islets. The aim of the study was to test this hypothesis by testing the effect of inhibiting candidate Ca2+-sensitive proteins proposed to play a critical role in the CMCP. The effects of the inhibitors on oxygen consumption rate (OCR), a reflection of ATP usage, and insulin secretion rate (ISR) were compared with those seen when L-type Ca2+channels were blocked with nimodipine. We reasoned that if a downstream Ca2+-regulated site was responsible for the OCR associated with the CMCP, then its inhibition should mimic the effect of nimodipine. Consistent with previous findings, nimodipine decreased glucose-stimulated OCR by 36% and cytosolic Ca2+by 46% and completely suppressed ISR in rat pancreatic islets. Inhibitors of three calmodulin-sensitive proteins (myosin light-chain kinase, calcineurin, and Ca2+/calmodulin-dependent protein kinase II) did not meet the criteria. In contrast, KN-62 severed the connection between Ca2+influx, OCR, and ISR without interfering with Ca2+influx. In the presence of nimodipine or KN-62, potentiators of ISR, acetylcholine, GLP-1, and arginine had little effect on insulin secretion, suggesting that the CMCP is also essential for the amplification of ISR. In conclusion, a KN-62-sensitive process directly mediates the effects of Ca2+influx via L-type Ca2+channels on OCR and ISR, supporting the essential role of the CMCP in mediating ISR.
Loss of size selectivity of the glomerular filtration barrier in rats following laparotomy and muscle trauma
Authors: Axelsson Josefin , Mahmutovic Irma , Rippe Anna , Rippe Bengt
Published: July 2009

Posttraumatic microalbuminuria may be caused by either charge- or size-selective alterations in the glomerular filtration barrier, or both, and/or to a reduction in proximal tubular protein reabsorption. This study was performed to elucidate the pathophysiology of the increases in glomerular permeability occurring in rats exposed to a laparotomy or to a laparotomy and muscle trauma. In anesthetized Wistar rats (250–280 g), the left ureter was cannulated for urine collection, while simultaneously blood access was achieved. Rats were exposed to trauma by a laparotomy (L; n = 8), or by a combination of L and muscle trauma (MT; L+MT) induced by topical blunt injury of the abdominal muscles bilaterally. After L, muscles were crushed using hemostatic forceps at either 2 × 2 sites (“small” MT; n = 9), or at 2 × 5 sites (“large” MT; n = 9). Sham groups ( n = 16), not exposed to a laparotomy, were used as controls. The glomerular sieving coefficients (θ) to polydisperse FITC-Ficoll-70/400 (molecular radius 13–80 Å) were determined at 5 or 60 min after L and L+MT, respectively, from plasma and urine samples, and analyzed by high-performance size-exclusion chromatography. A tissue-uptake technique was used to assess θ for 125I-labeled serum albumin. L, with or without MT, increased θ for Ficoll55–80Å and albumin rapidly and markedly. θ-Ficoll70Å thus increased approximately threefold, and θ for albumin significantly, for all trauma groups. According to the “two-pore model” of glomerular permeability, these changes mainly reflect an increase in the number of large pores in the glomerular filter without any primary changes in the charge-selective properties of the filter.
Impact of Synaptic Depression on Spike Timing at the Endbulb of Held
Authors: Yang Hua , Xu-Friedman Matthew A.
Published: July 2009

Many synapses show short-term depression, but it is not well understood what functional purpose depression serves and whether its effects are beneficial or detrimental to information processing. We study this issue at the synapse made by auditory-nerve (AN) fibers onto bushy cells (BCs) of the cochlear nucleus, called the “endbulb of Held.” AN fibers carry timing information about sounds and converge on BCs, which relay timing information to brain areas responsible for sound localization. Dynamic-clamp recordings of BCs in mouse brain slices indicated that nonphase-locked inputs influenced the contribution of phase-locked inputs when all inputs had equal strength. We evaluated whether this situation depended on activity-dependent synaptic plasticity. Voltage-clamp recordings indicated that the amount of depression varied over the population of endbulbs, but sibling endbulbs terminating on the same BC had similar plasticity. We tested the effects of endbulb depression on BC spiking using dynamic clamp. Under most conditions, increasing depression led to lower probability of BC spiking. However, the effects on spike timing were highly context dependent. When all inputs carried uniform timing information, depression indirectly affected BC spike precision, by determining how many inputs were required to cross threshold. Earlier work has indicated that this interacts with the temporal distribution of inputs to determine BC spike precision. When inputs carried different timing information, depression greatly improved BC precision by suppressing highly active inputs carrying little phase-locked information. These data suggest that endbulbs with different depression characteristics could produce BCs that enhance response probability or timing under different stimulus conditions.
Distinct genetic regulation of progression of diabetes and renal disease in the Goto-Kakizaki rat
Authors: Nobrega Marcelo A. , Solberg Woods Leah C. , Fleming Stewart , Jacob Howard J.
Published: July 2009

Goto-Kakizaki (GK) rats develop early-onset type 2 diabetes (T2D) symptoms, with signs of diabetic nephropathy becoming apparent with aging. To determine whether T2D and renal disease share similar genetic architecture, we ran a quantitative trait locus (QTL) analysis in the F2 progeny of a GK × Brown Norway (BN) rat cross. Further, to determine whether genetic components change over time, we ran the QTL analysis on phenotypes collected longitudinally, at 3, 6, 9 and 12 mo, from the same animals. We confirmed three chromosomal regions that are linked to early diabetes phenotypes (chromosomes 1, 5, and 10) and a single region involved in the late progression of the disorder (chromosome 4). A single region was identified for the onset of the renal phenotype proteinuria (chromosome 5). This region overlaps the diabetic QTL, although it is not certain whether similar genes are involved in both phenotypes. A second QTL linked to the progression of the renal phenotype was found on chromosome 7. Linkage for triglyceride and cholesterol levels were also identified (chromosomes 7 and 8, respectively). These results demonstrate that, in general, different genetic components control diabetic and renal phenotypes in a diabetic nephropathy model. Furthermore, these results demonstrate that, over time, different genetic components are involved in progression of disease from those that were involved in disease onset. This observation would suggest that clinical studies collecting participants over a wide age distribution may be diluting genetic effects and reducing power to detect true effects.
Analysis of the Human Cancer Glycome Identifies a Novel Group of Tumor-AssociatedN-Acetylglucosamine Glycan Antigens
Authors: Satomaa Tero , Heiskanen Annamari , Leonardsson Iréne , Ångström Jonas , Olonen Anne , Blomqvist Maria , Salovuori Noora , Haglund Caj , Teneberg Susann , Natunen Jari , Carpén Olli , Saarinen Juhani
Published: July 2009

The cell surface is covered by a dense layer of protein- and lipid-linked glycans. Although it has been known that distinct glycan structures are associated with cancer, the whole spectrum of cancer-associated glycans has remained undiscovered. In the present study, we analyzed the protein-linked cancer glycome by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric glycan profiling of cancer patient tissue samples. In lung cancer, we detected accumulation of a novel group of tumor-associated glycans. These protein-linked glycans carried abnormal nonreducing terminal β-N-acetyl-d-glucosamine (GlcNAc) residues. A similar phenomenon was also detected in structural analyses of tumor-derived glycosphingolipids. This showed that glycan biosynthesis may dramatically change in cancer and that direct glycome analysis can detect the resulting marker glycans. Based on the structural knowledge, we further devised a covalent labeling technique for the detection of GlcNAc-expressing tumors with a specific transferase enzyme. In normal tissues, terminal GlcNAc antigens are capped by galactosylation. Similarly to common cancer-associated glycan antigens T, Tn, and sialyl-Tn, the newly discovered GlcNAc antigens result from incomplete glycosylation. In conclusion, the identified terminal GlcNAc glycans should be recognized as a novel class of tumor markers. [Cancer Res 2009;69(14):5811–9]
Expression of an Exogenous Human Oct-4 Promoter Identifies Tumor-Initiating Cells in Osteosarcoma
Authors: Levings Padraic P. , McGarry Sean V. , Currie Thomas P. , Nickerson David M. , McClellan Steven , Ghivizzani Steven C. , Steindler Dennis A. , Gibbs C. Parker
Published: July 2009

We explored the nature of the tumor-initiating cell in osteosarcoma, a bone malignancy that predominately occurs in children. Previously, we observed expression of Oct-4, an embryonal transcriptional regulator, in osteosarcoma cell cultures and tissues. To examine the relationship between Oct-4 and tumorigenesis, cells from an osteosarcoma biopsy (OS521) were stably transfected with a plasmid containing the human Oct-4 promoter driving a green fluorescent protein (GFP) reporter to generate the transgenic line OS521Oct-4p. In culture, only ∼24% of the OS521Oct-4p cells were capable of activating the transgenic Oct-4 promoter; yet, xenograft tumors generated in NOD/SCID mice contained ∼67% GFP+ cells, which selectively expressed the mesenchymal stem cell–associated surface antigens CD105 and ICAM-1. Comparison of the tumor-forming capacity of GFP-enriched and GFP-depleted cell fractions revealed that the GFP-enriched fractions were at least 100-fold more tumorigenic, capable of forming tumors at doses of <300 cells, and formed metastases in the lung. Clonal populations derived from a single Oct-4/GFP+ cell were capable of forming tumors heterogeneous for Oct-4/GFP expression. These data are consistent with the cancer stem cell model of tumorigenesis in osteosarcoma and implicate a functional link between the capacity to activate an exogenous Oct-4 promoter and tumor formation. This osteosarcoma tumor-initiating cell appears highly prolific and constitutes a majority of the cell population in a primary xenograft tumor, which may provide a biological basis for the particular virulence of this type of cancer. [Cancer Res 2009;69(14):5648–55]
Human Papillomavirus E7 Oncoprotein Overrides the Tumor Suppressor Activity of p21Cip1 in Cervical Carcinogenesis
Authors: Shin Myeong-Kyun , Balsitis Scott , Brake Tiffany , Lambert Paul F.
Published: July 2009

The E7 oncoprotein of the high-risk human papillomaviruses (HPV) is thought to contribute to cervical carcinogenesis at least in part by abrogating cell cycle regulation. E7 can dysregulate the cell cycle through its interaction with several cellular proteins including the retinoblastoma suppressor protein pRb, as well as the cyclin-dependent kinase inhibitor p21Cip1. Inactivation of pRb in cervical epithelia is not sufficient to explain the ability of E7 to cause cervical cancers in transgenic mice. In the current study, we focused on the role of p21Cip1 in cervical cancer. Cervical disease was significantly increased in p21−/− mice compared with p21+/+ mice, showing that p21Cip1 can function as a tumor suppressor in this tissue. Importantly, the ability of E7 to induce cervical cancers was not significantly enhanced on the p21-null background, consistent with the hypothesis that the ability of E7 to inhibit p21Cip1 contributes to its carcinogenic properties. Further supportive of this hypothesis, cervical carcinogenesis in mice expressing a mutant form of HPV-16 E7, E7CVQ, which fails to inactivate p21Cip1, was significantly reduced compared with that in K14E7WT mice expressing wild-type HPV-16 E7. However, K14E7CVQ mice still displayed heightened levels of cervical carcinogenesis compared with that in nontransgenic mice, indicating that activities of E7 besides its capacity to inactivate p21Cip1 also contribute to cervical carcinogenesis. Taken together, we conclude that p21Cip1 functions as a tumor suppressor in cervical carcinogenesis and that p21Cip1 inactivation by HPV-16 E7 partially contributes to the contribution of E7 to cervical carcinogenesis. [Cancer Res 2009;69(14):5656–63]
Antimyeloma Activity of the Orally Bioavailable Dual Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor NVP-BEZ235
Authors: McMillin Douglas W. , Ooi Melissa , Delmore Jake , Negri Joseph , Hayden Patrick , Mitsiades Nicolas , Jakubikova Jana , Maira Sauveur-Michel , Garcia-Echeverria Carlos , Schlossman Robert , Munshi Nikhil C. , Richardson Paul G. , Anderson Kenneth C. , Mitsiades Constantine S.
Published: July 2009

The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway mediates proliferation, survival, and drug resistance in multiple myeloma (MM) cells. Here, we tested the anti-MM activity of NVP-BEZ235 (BEZ235), which inhibits PI3K/Akt/mTOR signaling at the levels of PI3K and mTOR. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric survival assays showed that MM cell lines exhibited dose- and time-dependent decreased viability after exposure to BEZ235 (IC50, 25–800 nmol/L for 48 hours). MM cells highly sensitive (IC50, <25 nmol/L) to BEZ235 (e.g., MM.1S, MM.1R, Dox40, and KMS-12-PE) included both lines sensitive and resistant to conventional (dexamethasone, cytotoxic chemotherapeutics) agents. Pharmacologically relevant BEZ235 concentrations (25–400 nmol/L) induced rapid commitment to and induction of MM.1S and OPM-2 cell death. Furthermore, normal donor peripheral blood mononuclear cells were less sensitive (IC50, >800 nmol/L) than the majority of MM cell lines tested, suggesting a favorable therapeutic index. In addition, BEZ235 was able to target MM cells in the presence of exogenous interleukin-6, insulin-like growth factor-1, stromal cells, or osteoclasts, which are known to protect against various anti-MM agents. Molecular profiling revealed that BEZ235 treatment decreased the amplitude of transcriptional signatures previously associated with myc, ribosome, and proteasome function, as well as high-risk MM and undifferentiated human embryonic stem cells. In vivo xenograft studies revealed significant reduction in tumor burden (P = 0.011) and survival (P = 0.028) in BEZ235-treated human MM tumor-bearing mice. Combinations of BEZ235 with conventional (e.g., dexamethasone and doxorubicin) or novel (e.g., bortezomib) anti-MM agents showed lack of antagonism. These results indicate that BEZ235 merits clinical testing, alone and in combination with other agents, in MM. [Cancer Res 2009;69(14):5835–42]