bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise Training in Patients With Advanced Chronic Heart Failure (NYHA IIIb) Promotes Restoration of Peripheral Vasomotor Function, Induction of Endogenous Regeneration, and Improvement of Left Ventricular Function
Authors: Erbs Sandra , Höllriegel Robert , Linke Axel , Beck Ephraim B. , Adams Volker , Gielen Stephan , Möbius-Winkler Sven , Sandri Marcus , Kränkel Nicolle , Hambrecht Rainer , Schuler Gerhard
Published: April 2010

Background—

Attenuated peripheral perfusion in patients with advanced chronic heart failure (CHF) is partially the result of endothelial dysfunction. This has been causally linked to an impaired endogenous regenerative capacity of circulating progenitor cells (CPC). The aim of this study was to elucidate whether exercise training (ET) affects exercise intolerance and left ventricular (LV) performance in patients with advanced CHF (New York Heart Association class IIIb) and whether this is associated with correction of peripheral vasomotion and induction of endogenous regeneration.

Methods and Results—

Thirty-seven patients with CHF (LV ejection fraction 24±2%) were randomly assigned to 12 weeks of ET or sedentary lifestyle (control). At the beginning of the study and after 12 weeks, maximal oxygen consumption (V
o
2
max) and LV ejection fraction were determined; the number of CD34
+
/KDR
+
CPCs was quantified by flow cytometry and CPC functional capacity was determined by migration assay. Flow-mediated dilation was assessed by ultrasound. Capillary density was measured in skeletal muscle tissue samples. In advanced CHF, ET improved V
o
2
max by +2.7±2.2 versus −0.8±3.1 mL/min/kg in control (
P
=0.009) and LV ejection fraction by +9.4±6.1 versus −0.8±5.2% in control (
P
<0.001). Flow-mediated dilation improved by +7.43±2.28 versus +0.09±2.18% in control (
P
<0.001). ET increased the number of CPC by +83±60 versus −6±109 cells/mL in control (
P
=0.014) and their migratory capacity by +224±263 versus −12±159 CPC/1000 plated CPC in control (
P
=0.03). Skeletal muscle capillary density increased by +0.22±0.10 versus −0.02±0.16 capillaries per fiber in control (
P
<0.001).

Conclusions—

Twelve weeks of ET in patients with advanced CHF is associated with augmented regenerative capacity of CPCs, enhanced flow-mediated dilation suggestive of improvement in endothelial function, skeletal muscle neovascularization, and improved LV function.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique Identifier: NCT00176384.
Endothelial Nitric Oxide Synthase Deficiency Causes Collateral Vessel Rarefaction and Impairs Activation of a Cell Cycle Gene Network During Arteriogenesis
Authors: Dai Xuming , Faber James E.
Published: April 2010

Rationale
:

The collateral circulation is tissue- and life-saving in obstructive arterial disease. Disappointing outcomes in clinical trials aimed at augmenting collateral growth highlight the need for greater understanding of collateral biology.

Objective
:

The role of endothelial nitric oxide synthase (eNOS) in forming native (preexisting) collaterals and remodeling in obstructive disease are unknown or controversial issues, respectively.

Methods and Results
:

We compared the native collateral circulation in healthy tissue and collateral remodeling after femoral artery ligation (FAL) in wild-type and eNOS-knockout (KO) mice. Perfusion after FAL fell further in adult eNOS-KOs, in association with fewer native collaterals in hindlimb (confirmed in brain). This was not attributable to impaired collateral formation in the embryo-neonate, but rather from collateral loss during growth to adulthood. Compared to wild-type, eNOS-KOs evidenced reduced collateral remodeling, angiogenesis, and flow-mediated dilation of the arterial bed supplying the collaterals, resulting in lower perfusion and greater ischemic injury at all time points over 21 days following FAL. To probe the mechanism for impaired remodeling, we performed genome-wide expression profiling of isolated, remodeling hindlimb collaterals 24 hour after FAL. Upregulation of genes encoding cytokines/chemokines, inflammatory, stress response, and cell cycle proteins was evident in wild-type mice. In contrast, expression was lower in 40 of 44 cell cycle genes in eNOS-KO mice, in association with impaired proliferation of vascular wall cells.

Conclusions
:

Our findings suggest a novel role for eNOS in maintaining native collateral density during natural growth to adulthood and in collateral remodeling in obstructive disease, the latter through regulation of cell proliferation.
Myocardial Ischemic Preconditioning Preserves Postischemic Function of the 26S Proteasome Through Diminished Oxidative Damage to 19S Regulatory Particle Subunits
Authors: Divald Andras , Kivity Shaye , Wang Ping , Hochhauser Edith , Roberts Beth , Teichberg Saul , Gomes Aldrin V. , Powell Saul R.
Published: April 2010

Rationale
:

The ubiquitin proteasome system (UPS) becomes dysfunctional as a result of ischemia/reperfusion (I/R), which may lead to dysregulation of signaling pathways. Ischemic preconditioning (IPC) may prevent dysregulation by preventing UPS dysfunction through inhibition of oxidative damage.

Objective
:

Examine the hypothesis that early IPC preserves postischemic UPS function thus facilitating prosurvival signaling events.

Methods and Results
:

I/R decreased proteasome chymotryptic activity by 50% in isolated rat heart and an in vivo murine left anterior descending coronary artery occlusion model. Following IPC, proteasome activity was decreased 25% (
P
<0.05) in isolated heart and not different from baseline in the murine model. Enriched 26S proteasome was prepared and analyzed for protein carbonyl content. Increased (
P
<0.05) carbonylation in a 53-kDa band following I/R was diminished by IPC. Immunoprecipitation studies indicated that the 53-kDa carbonylation signal was of proteasomal origin. Two-dimensional gel electrophoresis resolved the 53-kDa band into spots analyzed by liquid chromatography/tandem mass spectrometry containing Rpt3/Rpt5 both of which could be immunoprecipitated conjugated to dinitrophenylhydrazine (DNPH). Higher amounts of DNPH-tagged Rpt5 were immunoprecipitated from the I/R samples and less from the IPC samples. I/R increased Bax levels by 63% (
P
<0.05) which was decreased by IPC. Lactacystin (lac) pretreatment of preconditioned hearts increased Bax by 140% (
P
<0.05) and also increased ubiquitinated proteins. Pretreatment of hearts with a proteasome inhibitor reversed the effects of IPC on postischemic Rpt5 carbonylation, cardiac function, morphology and morphometry, and ubiquitinated and signaling proteins.

Conclusions
:

These studies suggest that IPC protects function of the UPS by diminishing oxidative damage to 19S regulatory particle subunits allowing this complex to facilitate degradation of proapoptotic proteins.
Intramyocardial VEGF-B
167
Gene Delivery Delays the Progression Towards Congestive Failure in Dogs With Pacing-Induced Dilated Cardiomyopathy
Authors: Pepe Martino , Mamdani Mohammed , Zentilin Lorena , Csiszar Anna , Qanud Khaled , Zacchigna Serena , Ungvari Zoltan , Puligadda Uday , Moimas Silvia , Xu Xiaobin , Edwards John G. , Hintze Thomas H. , Giacca Mauro , Recchia Fabio A.
Published: April 2010

Rationale
:

Vascular endothelial growth factor (VEGF)-B selectively binds VEGF receptor (VEGFR)-1, a receptor that does not mediate angiogenesis, and is emerging as a major cytoprotective factor.

Objective
:

To test the hypothesis that VEGF-B exerts non-angiogenesis-related cardioprotective effects in nonischemic dilated cardiomyopathy.

Methods and Results
:

AAV-9-carried VEGF-B
167
cDNA (10
12
genome copies) was injected into the myocardium of chronically instrumented dogs developing tachypacing-induced dilated cardiomyopathy. After 4 weeks of pacing, green fluorescent protein-transduced dogs (AAV-control, n=8) were in overt congestive heart failure, whereas the VEGF-B-transduced (AAV-VEGF-B, n=8) were still in a well-compensated state, with physiological arterial P
o
2
. Left ventricular (LV) end-diastolic pressure in AAV-VEGF-B and AAV-control was, respectively, 15.0±1.5 versus 26.7±1.8 mm Hg and LV regional fractional shortening was 9.4±1.6% versus 3.0±0.6% (all
P
<0.05). VEGF-B prevented LV wall thinning but did not induce cardiac hypertrophy and did not affect the density of α-smooth muscle actin-positive microvessels, whereas it normalized TUNEL-positive cardiomyocytes and caspase-9 and -3 activation. Consistently, activated Akt, a major negative regulator of apoptosis, was superphysiological in AAV-VEGF-B, whereas the proapoptotic intracellular mediators glycogen synthase kinase (GSK)-3β and FoxO3a (Akt targets) were activated in AAV-control, but not in AAV-VEGF-B. Cardiac VEGFR-1 expression was reduced 4-fold in all paced dogs, suggesting that exogenous VEGF-B
167
exerted a compensatory receptor stimulation. The cytoprotective effects of VEGF-B
167
were further elucidated in cultured rat neonatal cardiomyocytes exposed to 10
−8
mol/L angiotensin II: VEGF-B
167
prevented oxidative stress, loss of mitochondrial membrane potential, and, consequently, apoptosis.

Conclusions
:

We determined a novel, angiogenesis-unrelated cardioprotective effect of VEGF-B
167
in nonischemic dilated cardiomyopathy, which limits apoptotic cell loss and delays the progression toward failure.
Antithrombotic Drug Use, Cerebral Microbleeds, and Intracerebral Hemorrhage
Authors: Lovelock Caroline E. , Cordonnier Charlotte , Naka Hiromitsu , Al-Shahi Salman Rustam , Sudlow Cathie L.M. ,   The Edinburgh Stroke Study Group, Sorimachi Takatoshi , Werring David J. , Gregoire Simone M. , Imaizumi Toshio , Lee Seung-Hoon , Briley Dennis , Rothwell Peter M.
Published: April 2010

Background and Purpose—

Cerebral microbleeds (MB) are potential risk factors for intracerebral hemorrhage (ICH), but it is unclear if they are a contraindication to using antithrombotic drugs. Insights could be gained by pooling data on MB frequency stratified by antithrombotic use in cohorts with ICH and ischemic stroke (IS)/transient ischemic attack (TIA).

Methods—

We performed a systematic review of published and unpublished data from cohorts with stroke or TIA to compare the presence of MB in: (1) antithrombotic users vs nonantithrombotic users with ICH; (2) antithrombotic users vs nonusers with IS/TIA; and (3) ICH vs ischemic events stratified by antithrombotic use. We also analyzed published and unpublished follow-up data to determine the risk of ICH in antithrombotic users with MB.

Results—

In a pooled analysis of 1460 ICH and 3817 IS/TIA, MB were more frequent in ICH vs IS/TIA in all treatment groups, but the excess increased from 2.8 (odds ratio; range, 2.3–3.5) in nonantithrombotic users to 5.7 (range, 3.4–9.7) in antiplatelet users and 8.0 (range, 3.5–17.8) in warfarin users (
P
difference=0.01). There was also an excess of MB in warfarin users vs nonusers with ICH (OR, 2.7; 95% CI, 1.6–4.4;
P
<0.001) but none in warfarin users with IS/TIA (OR, 1.3; 95% CI, 0.9–1.7;
P
=0.33;
P
difference=0.01). There was a smaller excess of MB in antiplatelet users vs nonusers with ICH (OR, 1.7; 95% CI, 1.3–2.3;
P
<0.001), but findings were similar for antiplatelet users with IS/TIA (OR, 1.4; 95% CI, 1.2–1.7;
P
<0.001;
P
difference=0.25). In pooled follow-up data for 768 antithrombotic users, presence of MB at baseline was associated with a substantially increased risk of subsequent ICH (OR, 12.1; 95% CI, 3.4–42.5;
P
<0.001).

Conclusions—

The excess of MB in warfarin users with ICH compared to other groups suggests that MB increase the risk of warfarin-associated ICH. Limited prospective data corroborate these findings, but larger prospective studies are urgently required.
Comparison of Safety and Clinical and Radiographic Outcomes in Endovascular Acute Stroke Therapy for Proximal Middle Cerebral Artery Occlusion With Intubation and General Anesthesia Versus the Nonintubated State
Authors: Jumaa Mouhammad A. , Zhang Fan , Ruiz-Ares Gerardo , Gelzinis Theresa , Malik Amer M. , Aleu Aitziber , Oakley Jennifer I. , Jankowitz Brian , Lin Ridwan , Reddy Vivek , Zaidi Syed F. , Hammer Maxim D. , Wechsler Lawrence R. , Horowitz Michael , Jovin Tudor G.
Published: April 2010

Background and Purpose—

There is considerable heterogeneity in practice patterns between sedation in the intubated state vs nonintubated state during endovascular acute stroke therapy. We sought to compare clinical and radiographic outcomes between these 2 sedation modalities.

Methods—

Consecutive patients with acute stroke due to middle cerebral artery–M1 segment occlusion treated with endovascular therapy between January 2006 and July 2009 were identified in our interventional acute stroke database. Level of sedation was determined as intubated (IS) vs nonintubated (NIS) state. Final infarct volumes on follow-up imaging and clinical outcomes at 3 to 6 months were obtained.

Results—

A total of 126 patients were included (73 [58%] NIS vs 53 [42%] IS). In IS patients, intensive care unit length of stay was longer (6.5 vs 3.2 days,
P
=0.0008). Intraprocedural complications were lower in NIS patients compared with IS patients (5/73 [6%] vs 8/53 [15%], respectively), but the difference was not significant (
P
=0.13). In univariate and multivariate analyses, NIS was significantly associated with in-hospital mortality (odds ratio=0.32,
P
=0.011), good clinical outcome (odds ratio=3.06,
P
=0.042), and final infarct volume (odds ratio=0.25,
P
=0.004).

Conclusion—

In endovascular acute stroke therapy, treatment of patients in NIS appears to be as safe as treatment in IS and may result in more favorable clinical and radiographic outcomes. Our preliminary observations derived from this retrospective study await confirmation from prospective trials.
Complex Plaques in the Proximal Descending Aorta
Authors: Harloff Andreas , Simon Jan , Brendecke Stefanie , Assefa Dawit , Helbing Thomas , Frydrychowicz Alex , Weber Johannes , Olschewski Manfred , Strecker Christoph , Hennig Jürgen , Weiller Cornelius , Markl Michael
Published: April 2010

Background and Purpose—

To investigate the incidence of retrograde flow from complex plaques (≥4-mm-thick, ulcerated, or superimposed thrombi) of the descending aorta (DAo) and its potential role in embolic stroke.

Methods—

Ninety-four consecutive acute stroke patients with aortic plaques ≥3-mm-thick in transesophageal echocardiography were prospectively included. MRI was performed to localize complex plaques and to measure time-resolved 3-dimensional blood flow within the aorta. Three-dimensional visualization was used to evaluate if diastolic retrograde flow connected plaque location with the outlet of the left subclavian artery, left common carotid artery, or brachiocephalic trunk. Complex DAo plaques were considered an embolic source if retrograde flow reached a supra-aortic vessel that supplied the territory of visible acute and embolic retinal or cerebral infarction.

Results—

Only decreasing heart rate was correlated
(P
<0.02) with increasing flow reversal to the aortic arch. Retrograde flow from complex DAo plaques reached the left subclavian artery in 55 (58.5%), the left common carotid artery in 23 (24.5%), and the brachiocephalic trunk in 13 patients (13.8%). Based on routine diagnostics and MRI of the ascending aorta/aortic arch, stroke etiology was determined in 57 and cryptogenic in 37 patients. Potential embolization from DAo plaques was then identified in 19 of 57 patients (33.3%) with determined and in 9 of 37 patients (24.3%) with cryptogenic stroke.

Conclusions—

Retrograde flow from complex DAo plaques was frequent in both determined and cryptogenic stroke and could explain embolism to all brain territories. These findings suggest that complex DAo plaques should be considered a new source of stroke.
Siena Carotid Artery Stenting Score
Authors: Setacci Carlo , Chisci Emiliano , Setacci Francesco , Iacoponi Francesca , de Donato Gianmarco , Rossi Alessandro
Published: April 2010

Background and Purpose—

Carotid artery stenting (CAS) still entails a considerable peri-interventional risk of serious neurological adverse events. The aim of this study was to generate a score to grade this risk for CAS in individual patients.

Methods—

This is a 9-year prospective study. Consecutive patients with ≥70% carotid artery stenosis were treated with a standardized CAS procedure. All patients included underwent independent neurological evaluation before and after the procedure and at 30 days. The rates of transient ischemic attack and minor, major, and fatal stroke were recorded. Stroke predictors were analyzed and a score system was generated using Arabic numerals for all variables to preoperatively grade the individual patient risk of stroke.

Results—

Two thousand one-hundred twenty-four successful CAS procedures were performed. The transient ischemic attack and minor, major, and fatal stroke rates at 30 days were, respectively, 2.72% (n=60), 1.55% (n=33), 1.18% (n=25), and 0.61% (n=13). Multiple regression analysis showed that the following significantly predicted the 30-day risk of treatment-related stroke: cardiac disease, symptomatic patient, diabetes, calcification or ulceration at the level of the lesion, native and ostial lesion, lesion length >15 mm, the need for predilatation, type III arch, bovine arch, arch calcification, procedure time >30 minutes, and the operator’s experience of <50 CAS procedures. The operator’s experience of >100 CAS procedures was the only protective factor against the development of stroke at 30 days (odds ratio, 0.81; confidence interval, 0.67–0.95). The Siena CAS score was developed from these variables and predicted the risk of CAS within the 3 categories of low risk (<1%; CAS I), medium risk (1% to 3%; CAS II), and high risk (>3%; CAS III), with a sensitivity of 0.82 and specificity of 0.79.

Conclusions—

The Siena CAS risk score seems to be a useful tool to help predict stroke after CAS but needs to be validated in independent cohorts at a variety of centers before it can be recommended for application, preferably in a randomized comparison with carotid endarterectomy.
Artificial Life as a Tool for Biological Inquiry
Authors: Taylor Charles , Jefferson David
Published: April 2010

Artificial life embraces those human-made systems that possess some of the key properties of natural life. We are specifically interested in artificial systems that serve as models of living systems for the investigation of open questions in biology. First we review some of the artificial life models that have been constructed with biological problems in mind, and classify them by medium (hardware, software, or “wetware”) and by level of organization (molecular, cellular, organismal, or population). We then describe several “grand challenge” open problems in biology that seem especially good candidates to benefit from artificial life studies, including the origin of life and self-organi- zation, cultural evolution, origin and maintenance of sex, shifting balance in evolution, the relation between fitness and adaptedness, the structure of ecosystems, and the nature of mind.
Extended Molecular Evolutionary Biology: Artificial Life Bridging the Gap Between Chemistry and Biology
Authors: Schuster P.
Published: April 2010

Molecular evolution provides an ample field for the extension of Nature's principles towards novel applications. Several examples are discussed here, among them are evolution in the test tube, nucleotide chemistry with new base pairs and new backbones, enzyme-free replication of polynucleotides and template chemistry aiming at replicating structures that have nothing in common with the molecules from nature.

Molecular evolution in the test tube provides a uniquely simple system for the study of evolutionary phenomena: genotype and phenotype are two features of one and the same RNA molecule. Then fitness landscapes are nothing more than combined mappings from sequences to structures and from structures to functions, the latter being expressed in terms of rate constants. RNA landscapes are presented as examples for which an access to phenomena in reality by mathematical analysis and computer simulations is feasible. New questions concerning stability of structures in evolution can be raised and quantitative answers are given.

Evolutionary biotechnology is a spin-off from molecular evolution. Darwin's principle of variation and selection is applied to design novel biopolymers with predetermined functions. Different approaches to achieve this goal are discussed and a survey of the current state of the art is given.
Visual Models of Morphogenesis
Authors: Prusinkiewicz Przemyslaw
Published: April 2010

Rapid progress in the modeling of biological structures and simulation of their development has occurred over the last few years. It has been coupled with the visualization of simulation results, which has led to a better understanding of morphogenesis and given rise to new procedural techniques for realistic image synthesis. This paper reviews selected models of morphogenesis with a significant visual component.
The Artificial Life Roots of Artificial Intelligence
Authors: Steels Luc
Published: April 2010

Behavior-oriented Artificial Intelligence (AI) is a scientific discipline that studies how behavior of agents emerges and becomes intelligent and adaptive. Success of the field is defined in terms of success in building physical agents that are capable of maximizing their own self-preservation in interaction with a dynamically changing environment. The paper addresses this Artificial Life route toward AI and reviews some of the results obtained so far.
Genetic Algorithms and Artificial Life
Authors: Mitchell Melanie , Forrest Stephanie
Published: April 2010

Genetic algorithms are computational models of evolution that play a central role in many artificial-life models. We review the history and current scope of research on genetic algorithms in artificial life, giving illustrative examples in which the genetic algorithm is used to study how learning and evolution interact, and to model ecosystems, immune system, cognitive systems, and social systems. We also outline a number of open questions and future directions for genetic algorithms in artificial-life research.
Artificial Fishes: Autonomous Locomotion, Perception, Behavior, and Learning in a Simulated Physical World
Authors: Terzopoulos Demetri , Tu Xiaoyuan , Grzeszczuk Radek
Published: April 2010

This article develops artificial life patterned after animals as evolved as those in the superclass Pisces. It demonstrates a virtual marine world inhabited by realistic artificial fishes. Our algorithms emulate not only the appearance, movement, and behavior of individual animals, but also the complex group behaviors evident in many aquatic ecosystems. We model each animal holistically. An artificial fish is an autonomous agent situated in a simulated physical world. The agent has (a) a three-dimensional body with internal muscle actuators and functional fins that deforms and locomotes in accordance with biomechanic and hydrodynamic principles; (b) sensors, including eyes that can image the environment; and (c) a brain with motor, perception, behavior, and learning centers. Artificial fishes exhibit a repertoire of piscatorial behaviors that rely on their perceptual awareness of their dynamic habitat. Individual and emergent collective behaviors include caudal and pectoral locomotion, collision avoidance, foraging, preying, schooling, and mating. Furthermore, artificial fishes can learn how to locomote through practice and sensory reinforcement. Their motor learning algorithms discover muscle controllers that produce efficient hydrodynamic locomotion. The learning algorithms also enable artificial fishes to train themselves to accomplish higher level, perceptually guided motor tasks, such as maneuvering to reach a visible target.
Evolving 3D Morphology and Behavior by Competition
Authors: Sims Karl
Published: April 2010

This article describes a system for the evolution and coevolution of virtual creatures that compete in physically simulated three-dimensional worlds. Pairs of individuals enter one-on-one contests in which they contend to gain control of a common resource. The winners receive higher relative fitness scores allowing them to survive and reproduce. Realistic dynamics simulation including gravity, collisions, and friction, restricts the actions to physically plausible behaviors.

The morphology of these creatures and the neural systems for controlling their muscle forces are both genetically determined, and the morphology and behavior can adapt to each other as they evolve simultaneously. The genotypes are structured as directed graphs of nodes and connections, and they can efficiently but flexibly describe instructions for the development of creatures' bodies and control systems with repeating or recursive components. When simulated evolutions are performed with populations of competing creatures, interesting and diverse strategies and counterstrategies emerge.
Dynamics of Self-Assembling Systems: Analogy with Chemical Kinetics
Authors: Hosokawa Kazuo , Shimoyama Isao , Miura Hirofumi
Published: April 2010

In this article, we propose a new analyzing method for self-assembling systems. Its initial purpose was to predict the yield—the final amount of desired product—of our original self-assembling mechanical model. Moreover, the method clarifies the dynamical evolution of the system. In this method, the quantity of each intermediate product is adopted as state variables, and the dynamics that dominates the state variables is derived. The behavior of the system is reduced to a set of difference equations with a small degree of freedom. The concept is the same as in chemical kinetics or in population dynamics. However, it was never applied to self-assembling systems. The mathematical model is highly abstracted so that it is applicable to other self-assembling systems with only small modifications.
Radical Epistasis and the Genotype-Phenotype Relationship
Authors: Wilson David Sloan , Wells Alexandra
Published: April 2010

Models of evolution often assume that the offspring of two genotypes, which are genetically intermediate by definition, are also phenotypically intermediate. The continuity between genotype and phenotype interferes with the process of evolution on multipeaked adaptive landscapes because the progeny of genotypes that lie on separate adaptive peaks fall into valleys of low fitness. This problem can be solved by epistasis, which disrupts the continuity between genotype and phenotype. In a five-locus sexual haploid model with maximum epistasis, natural selection in multipeak landscapes evolves a set of genotypes that a) occupy the adaptive peaks and b) give rise to each other by recombination. The epistatic genetic system therefore “molds” the phenotypic distribution to the adaptive landscape, without assortative mating or linkage disequilibrium. If the adaptive landscape is changed, a new set of genotypes quickly evolves that satisfies conditions a and b, above, for the new peaks.

Our model may be relevant to a number of recalcitrant problems in biology and also stands in contrast to Kauffman's [3] NK model of evolution on rugged fitness surfaces, in which epistasis and recombination tend to constrain the evolutionary process.
A Simple Model of Neurogenesis and Cell Differentiation Based on Evolutionary Large-Scale Chaos
Authors: Kitano Hiroaki
Published: April 2010

This article reports on a simple neurogenesis model that is combined with evolutionary computation. Because the integration of an evolutionary process with neural networks is such an exciting field of study, with the promise of discovering new computational models and, possibly, providing novel biological insights, much research has been conducted in this area. However, only a few studies have incorporated a development stage, and none have modeled metabolism and other chemical reactions in a consistent manner. In this article, we present a simple model of neurogenesis and cell differentiation that combines evolutionary computing, metabolism, development, and neural networks. The model represents an evolutionary large-scale chaos as a mathematical foundation. An evolutionary large-scale chaos is a large-scale chaos whose map functions change through evolutionary computing. Experiments indicate that the model is capable of evolving and growing large neural networks, and exhibits phenomena analogous to cell differentiation.
Automated Optimal Design of Mechanical Conformational Switches
Authors: Saitou Kazuhiro , Jakiela Mark J.
Published: April 2010

Bacteriophage viruses spontaneously self-assemble in the presence of their component parts (certain protein molecules). It is believed that conformational switches, interacting chemical bonding sites that allow tentative incorrect bonds, facilitate this randomized assembly process. A one-dimensional conformational switch is proposed and used to study the randomized assembly of mechanical parts. A genetic algorithm is used to search the space of parameterized switch designs to maximize the rate of a desired assembly.
Semi-Algebraic Networks: An Attempt to Design Geometric Autopoietic Models
Authors: Deffuant Guillaume , Fuhs Thierry , Monneret Etienne , Bourgine Paul , Varela Francisco
Published: April 2010

This article focuses on an artificial life approach to some important problems in machine learning such as statistical discrimination, curve approximation, and pattern recognition. We describe a family of models, collectively referred to as semi-algebraic networks (SAN). These models are strongly inspired by two complementary lines of thought: the biological concept of autopoiesis and morphodynamical notions in mathematics. Mathematically defined as semi-algebraic sets, SANs involve geometric components that are submitted to two coupled processes: (a) the adjustment of the components (under the action of the learning examples), and (b) the regeneration of new components. Several examples of SANs are described, using different types of components. The geometric nature of SANs gives new possibilities for solving the bias/variance dilemma in discrimination or curve approximation problems. The question of building multilevel semi-algebraic networks is also addressed, as they are related to cognitive problems such as memory and morphological categorization. We describe an example of such multilevel models.
Evolving Compare-Exchange Networks Using Grammars
Authors: Kammeyer Thomas E. , Belew Richard K. , Williamson S. Gill
Published: April 2010

We apply a genetic algorithm whose genotypes represent simple grammars to search for families of compare-exchange networks that are merging networks. The grammars are restricted to be of a simple form based on prior knowledge about the search domain. Finding merging networks in this fashion leads to the discovery of networks that also sort if the data is cycled through them a small number of times. Random network and grammar generation results show that the problem is difficult and suggest some conjectures about how the genetic algorithm is operating for this problem. The genetic algorithm finds the best-known network of the kind for which we search, and further finds a novel, slightly suboptimal network that turns out to be an interesting combination of ideas from known, theoretically derived networks.
Evolution of Cooperation, Differentiation, Complexity, and Diversity in an Iterated Three-Person Game
Authors: Akiyama Eizo , Kaneko Kunihiko
Published: April 2010

A nonzero-sum three-person coalition game is presented to study the evolution of complexity and diversity in cooperation, where the population dynamics of players with strategies is given according to their scores in the iterated game and mutations. Two types of differentiation emerge initially: a biased one to classes and a temporal one to change their roles for coalition. Rules to change the hands are self-organized in a society through evolution. The coevolution of diversity and complexity of strategies and interactions (or communications) are found at later stages of the simulation. Relevance of our results to the biological society is briefly discussed.
Active Mutation in Self-Reproducing Networks of Machines and Tapes
Authors: Ikegami Takashi , Hashimoto Takashi
Published: April 2010

Self-reproduction via description is discussed in a network model of machines and description tapes. Tapes consist of bit strings, which encode the machines' function. A tape is replicated when it is read by adequate machines. Generally, a machine rewrites a tape without doing correct replication. The variation in a reproduced tape is taken as mutation. Because this mutation is caused by a machine's program, we call it active mutation. Which machine is translated from a given tape is dependent on what kind of a machine reads the tape. External noise is introduced in a machine's reading process to make errors. A new reaction pathway is induced by external noise via a machine's error action. We find that the induced pathways will be mimicked deterministically in an emerging core structure. This core structure will remain stable after turning off external noise. Low external noise develops a core structure of a minimal self-replicative loop. When external noise is elevated, a more complex network evolves. Machines containing a complex core network, which has been bred in high external noise, will actively rewrite tapes rather than just replicate them. Self-replication not as an individual but as a network now becomes important.
A Self-Organizing Spatial Vocabulary
Authors: Steels Luc
Published: April 2010

Language is a shared set of conventions for mapping meanings to utterances. This paper explores self-organization as the primary mechanism for the formation of a vocabulary. It reports on a computational experiment in which a group of distributed agents develop ways to identify each other using names or spatial descriptions. It is also shown that the proposed mechanism copes with the acquisition of an existing vocabulary by new agents entering the community and with an expansion of the set of meanings.
Subassembly Generation via Mechanical Conformational Switches
Authors: Saitou Kazuhiro , Jakiela Mark J.
Published: April 2010

A question is posed on how a particular subassembly sequence is generated in randomized assembly. An extended design of mechanical conformational switches [16] is proposed that can encode several subassembly sequences. A particular subassembly sequence is generated due to conformational changes of parts during one-dimensional randomized assembly. The optimal subassembly sequence that maximizes the yield of a desired assembly can be found via genetic search over a space of parameterized conformational switch designs, rather than a space of subassembly sequences. The resulting switch design encodes the optimal subassembly sequence so that the desired assemblies are put together only in the optimal sequence. The results of genetic search and rate equation analyses reveal that the optimal subassembly sequence depends on the initial concentration of parts and the defect probabilities during randomized assembly. The results indicate that abundant parts and parts with high defect probabilities should be assembled earlier rather than later.
Evolving Mobile Robots in Simulated and Real Environments
Authors: Miglino Orazio , Lund Henrik Hautop , Nolfi Stefano
Published: April 2010

The problem of the validity of simulation is particularly relevant for methodologies that use machine learning techniques to develop control systems for autonomous robots, as, for instance, the artificial life approach known as evolutionary robotics. In fact, although it has been demonstrated that training or evolving robots in real environments is possible, the number of trials needed to test the system discourages the use of physical robots during the training period. By evolving neural controllers for a Khepera robot in computer simulations and then transferring the agents obtained to the real environment we show that (a) an accurate model of a particular robot-environment dynamics can be built by sampling the real world through the sensors and the actuators of the robot; (b) the performance gap between the obtained behaviors in simulated and real environments may be significantly reduced by introducing a “conservative” form of noise; (c) if a decrease in performance is observed when the system is transferred to a real environment, successful and robust results can be obtained by continuing the evolutionary process in the real environment for a few generations.
Is Neural Darwinism Darwinism?
Authors: Van Belle Terry
Published: April 2010

Neural Darwinism is a theory of cognition developed by Gerald Edelman along with George Reeke and Olaf Sporns at Rockefeller University. As its name suggests, neural Darwinism is modeled after biological Darwinism, and its authors assert that the two processes are strongly analogous. Both operate on variation in a population, amplifying the more adaptive individuals. However, from a computational perspective, neural Darwinism is quite different from other models of natural selection, such as genetic algorithms. The individuals of neural Darwinism do not replicate, thus robbing the process of the capacity to explore new solutions over time and ultimately reducing it to a random search. Because neural Darwinism does not have the computational power of a truly Darwinian process, it is misleading to label it as such. To illustrate this disparity in adaptive power, one of Edelman's early computer experiments, Darwin I, is revisited, and it is shown that adding replication greatly improves the adaptive power of the system.
Multiple von Neumann Computers: An Evolutionary Approach to Functional Emergence
Authors: Suzuki Hideaki
Published: April 2010

A novel system composed of multiple von Neumann computers and an appropriate problem environment is proposed and simulated. Each computer has a memory to store the machine instruction program, and when a program is executed, a series of machine codes in the memory is sequentially decoded, leading to register operations in the central processing unit (CPU). By means of these operations, the computer not only can handle its generally used registers but also can read and write the environmental database. Simulation is driven by genetic algorithms (GAs) performed on the population of program memories. Mutation and crossover create program diversity in the memory, and selection facilitates the reproduction of appropriate programs. Through these evolutionary operations, advantageous combinations of machine codes are created and fixed in the population one by one, and the higher function, which enables the computer to calculate an appropriate number from the environment, finally emerges in the program memory.

In the latter half of the article, the performance of GAs on this system is studied. Under different sets of parameters, the evolutionary speed, which is determined by the time until the domination of the final program, is examined and the conditions for faster evolution are clarified. At an intermediate mutation rate and at an intermediate population size, crossover helps create novel advantageous sets of machine codes and evidently accelerates optimization by GAs.
Gecko: A Continuous 2D World for Ecological Modeling
Authors: Booth Ginger
Published: April 2010

An individual-based simulation system, named Gecko, is presented for modeling multiple species at multiple trophic levels, on a spatially explicit, continuous two-dimensional landscape. Biologically motivated rules are specified at an individual level, and resulting behaviors are observed at an ecosystem level. Individuals are represented by circles with free range on a resource-producing plane. These circles grow allometrically with biomass of fixed resources. Resource acquisition behaviors include competition by area overlap for producers, and movement based on perception and intent. Individual-level energetics are explicitly modeled with inefficient assimilation, resource transformation, and allometrically specified metabolic costs. Individual growth and reproduction requires a history of successful resource acquisition. Terrestrial producer, herbivore, and carnivore species classes are included, extensible to further classes. A grassland food chain model of “plants,” “grasshoppers,” and “spiders” is used to demonstrate ecosystem-level results of given individual-level behaviors. Ecosystem-level behaviors include a trophic cascade of indirect carnivore-producer interaction effects; stable persistence of all populations; a near-realistic biomass pyramid; and spatial competition and coexistence of multiple producer species. Initial Gecko results show promise for application in both theoretical and natural ecosystem modeling.
Modeling Malaria as a Complex Adaptive System
Authors: Janssen M. A. , Martens W. J. M.
Published: April 2010

As the resistance of the malaria parasite to antimalarial drugs continues to increase, as does that of the malarial mosquito to insecticides, the efficacy of efforts to control malaria in many tropical countries is diminishing. This trend, together with the projected consequences of climate change, may prove to exacerbate substantially the significance of malaria in the coming decades.

In this article we introduce the use of an evolutionary modeling approach to simulate the adaptation of mosquitoes and parasites to the available pesticides and drugs. By coupling genetic algorithms with a dynamic malaria-epidemiological model, we derive a complex adaptive system capable of simulating adapting and evolving processes within both the mosquito and the parasite populations.

This approach is used to analyze malaria management strategies appropriate to regions of higher and lower degrees of endemicity. The results suggest that adequate use of insecticides and drugs may reduce the occurrence of malaria in regions of low endemicity, although increased efforts would be necessary in the event of a climate change. However, our model indicates that in regions of high endemicity the use of insecticides and drugs may lead to an increase in incidence due to enhanced resistance development. Projected climate change, on the other hand, may lead to a limited reduction of the occurrence of malaria due to the presence of a higher percentage of immune persons in the older age class.
A Robot Trace Maker: Modeling the Fossil Evidence of Early Invertebrate Behavior
Authors: Prescott Tony J. , Ibbotson Carl
Published: April 2010

The study of trace fossils, the fossilized remains of animal behavior, reveals interesting parallels with recent research in behavior-based robotics. This article reports robot simulations of the meandering foraging trails left by early invertebrates that demonstrate that such trails can be generated by mechanisms similar to those used for robot wall-following. We conclude with the suggestion that the capacity for intelligent behavior shown by many behavior-based robots is similar to that of animals of the late Precambrian and early Cambrian periods approximately 530 to 565 million years ago.
Word or Word-like? Dissociating Orthographic Typicality from Lexicality in the Left Occipito-temporal Cortex
Authors: Woollams Anna M. , Silani Giorgia , Okada Kayoko , Patterson Karalyn , Price Cathy J.
Published: April 2010

Prior lesion and functional imaging studies have highlighted the importance of the left ventral occipito-temporal (LvOT) cortex for visual word recognition. Within this area, there is a posterior–anterior hierarchy of subregions that are specialized for different stages of orthographic processing. The aim of the present fMRI study was to dissociate the effects of subword orthographic typicality (e.g., cider [high] vs. cynic [low]) from the effect of lexicality (e.g., pollen [word] vs. pillen [pseudoword]). We therefore orthogonally manipulated the orthographic typicality of written words and pseudowords (nonwords and pseudohomophones) in a visual lexical decision task. Consistent with previous studies, we identified greater activation for pseudowords than words (i.e., an effect of lexicality) in posterior LvOT cortex. In addition, we revealed higher activation for atypical than typical strings, irrespective of lexicality, in a left inferior occipital region that is posterior to LvOT cortex. When lexical decisions were made more difficult in the context of pseudohomophone foils, left anterior temporal activation also increased for atypical relative to typical strings. The latter finding agrees with the behavior of patients with progressive anterior temporal lobe degeneration, who have particular difficulty recognizing words with atypical orthography. The most novel outcome of this study is that, within a distributed network of regions supporting orthographic processing, we have identified a left inferior occipital region that is particularly sensitive to the typicality of subword orthographic patterns.
Decoding Task-based Attentional Modulation during Face Categorization
Authors: Chiu Yu-Chin , Esterman Michael , Han Yuefeng , Rosen Heather , Yantis Steven
Published: April 2010

Attention is a neurocognitive mechanism that selects task-relevant sensory or mnemonic information to achieve current behavioral goals. Attentional modulation of cortical activity has been observed when attention is directed to specific locations, features, or objects. However, little is known about how high-level categorization task set modulates perceptual representations. In the current study, observers categorized faces by gender (male vs. female) or race (Asian vs. White). Each face was perceptually ambiguous in both dimensions, such that categorization of one dimension demanded selective attention to task-relevant information within the face. We used multivoxel pattern classification to show that task-specific modulations evoke reliably distinct spatial patterns of activity within three face-selective cortical regions (right fusiform face area and bilateral occipital face areas). This result suggests that patterns of activity in these regions reflect not only stimulus-specific (i.e., faces vs. houses) responses but also task-specific (i.e., race vs. gender) attentional modulation. Furthermore, exploratory whole-brain multivoxel pattern classification (using a searchlight procedure) revealed a network of dorsal fronto-parietal regions (left middle frontal gyrus and left inferior and superior parietal lobule) that also exhibit distinct patterns for the two task sets, suggesting that these regions may represent abstract goals during high-level categorization tasks.