bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison and Correlation of
Neisseria meningitidis
Serogroup B Immunologic Assay Results and Human Antibody Responses following Three Doses of the Norwegian Meningococcal Outer Membrane Vesicle Vaccine MenBvac
Authors: Findlow Jamie , Taylor Stephen , Aase Audun , Horton Rachel , Heyderman Robert , Southern Jo , Andrews Nick , Barchha Rita , Harrison Ewan , Lowe Ann , Boxer Emma , Heaton Charlotte , Balmer Paul , Kaczmarski Ed , Oster Philipp , Gorringe Andrew , Borrow Ray , Miller Elizabeth
Published: July 2006

The prediction of efficacy of
Neisseria meningitidis
serogroup B (MenB) vaccines is currently hindered due to the lack of an appropriate correlate of protection. For outer membrane vesicle (OMV) vaccines, immunogenicity has primarily been determined by the serum bactericidal antibody (SBA) assay and OMV enzyme-linked immunosorbent assay (ELISA). However, the opsonophagocytic assay (OPA), surface labeling assay, whole blood assay (WBA), and salivary antibody ELISA have been developed although correlation with protection is presently undetermined. Therefore, the aim of the study was to investigate further the usefulness of, and relationships between, MenB immunologic assays. A phase II trial of the OMV vaccine, MenBvac, with proven efficacy was initiated to compare immunologic assays incorporating the vaccine and six heterologous strains. Correlations were achieved between the SBA assay, OMV ELISA, and OPA using human polymorphonuclear leukocytes and human complement but not between an OPA using HL60 phagocytic cells and baby rabbit complement. Correlations between the surface labeling assay, the SBA assay, and the OMV ELISA were promising, although target strain dependent. Correlations between the salivary antibody ELISA and other assays were poor. Correlations to the WBA were prevented since many samples had results greater than the range of the assay. The study confirmed the immunogenicity and benefit of a third dose of MenBvac against the homologous vaccine strain using a variety of immunologic assays. These results emphasize the need for standardized methodologies that would allow a more robust comparison of assays between laboratories and promote their further evaluation as correlates of protection against MenB disease.
Interleukin-10 Inhibits Gram-Negative-Microbe-Specific Human Receptor Activator of NF-κB Ligand-Positive CD4
+
-Th1-Cell- Associated Alveolar Bone Loss In Vivo
Authors: Zhang Xiaoxia , Teng Yen-Tung A.
Published: July 2006

To study anti-inflammatory cytokine effects on RANKL
+
-T-cell-mediated osteoclastogenesis in vivo, we injected human interleukin-10 (hIL-10) into pathogen-infected HuPBL-NOD/SCID mice. The results show significantly decreased RANKL
+
Th1-associated alveolar bone loss and coexpression of human gamma interferon (hIFN-γ) and human macrophage colony-stimulating factor, but not hIL-4, in RANKL
+
Th cells compatible with those from successfully treated aggressive periodontitis subjects. Thus, there are critical cytokine interactions linking hIFN-γ
+
Th1 cells to RANKL-RANK/OPG signaling for periodontal osteoclastogenesis in vivo.
Modulation of Host Immune Responses by the Cytolethal Distending Toxin of
Helicobacter hepaticus
Authors: Pratt Jason S. , Sachen Kacey L. , Wood Heather D. , Eaton Kathryn A. , Young Vincent B.
Published: July 2006

Persistent murine infection with
Helicobacter hepaticus
leads to chronic gastrointestinal inflammation and neoplasia in susceptible strains. To determine the role of the virulence factor cytolethal distending toxin (CDT) in the pathogenesis of this organism, interleukin-10-deficient (IL-10
−/−
) mice were experimentally infected with wild-type
H. hepaticus
and a CDT-deficient isogenic mutant. Both wild-type
H. hepaticus
and the CDT-deficient mutant successfully colonized IL-10
−/−
mice, and they reached similar tissue levels by 6 weeks after infection. Only animals infected with wild-type type
H. hepaticus
developed significant typhlocolitis. However, by 4 months after infection, the CDT-deficient mutant was no longer detectable in IL-10
−/−
mice, whereas wild-type
H. hepaticus
persisted for the 8-month duration of the experiment. Animals infected with wild-type
H. hepaticus
exhibited severe typhlocolitis at 8 months after infection, while animals originally challenged with the CDT-deficient mutant had minimal cecal inflammation at this time point. In follow-up experiments, animals that cleared infection with the CDT-deficient mutant were protected from rechallenge with either mutant or wild-type
H. hepaticus
. Animals infected with wild-type
H. hepaticus
developed serum immunoglobulin G1 (IgG1) and IgG2c responses against
H. hepaticus
, while animals challenged with the CDT-deficient mutant developed significantly lower IgG2c responses and failed to mount IgG1 responses against
H. hepaticus
. These results suggest that CDT plays a key immunomodulatory role that allows persistence of
H. hepaticus
and that in IL-10
−/−
mice this alteration of the host immune response results in the development of colitis.
Identification of Antigenic Components of
Staphylococcus epidermidis
Expressed during Human Infection
Authors: Pourmand Mohammad R. , Clarke Simon R. , Schuman Richard F. , Mond James J. , Foster Simon J.
Published: July 2006

A spectrum of in vivo-expressed
Staphylococcus epidermidis
antigens was identified by probing a bacteriophage lambda library of
S. epidermidis
genomic DNA with human serum from infected and uninfected individuals. This analysis resulted in identification of 53 antigen-encoding loci. Six antigenic polypeptides were expressed from these loci and purified. These polypeptides were the propeptide, mature amidase, and repeat sequence domains of the major autolysin AtlE, GehD (lipase), and two members of a conserved family of surface proteins (ScaA [AaE] and ScaB). AtlE, ScaA, and ScaB all exhibit human ligand binding capacity. Screening a bank of human serum samples revealed that there were significant increases in the amounts of reactive immunoglobulin G in infected individuals compared to the amounts in healthy individuals for the repeat sequence and mature amidase domains of AtlE, ScaB, and GehD. Vaccination of mice with recombinant antigens stimulated an immune response which in vitro opsonized
S. epidermidis
. In this study we identified prospective candidate antigens for prophylaxis or immunotherapy to control disease.
Mutational Analysis of RetS, an Unusual Sensor Kinase-Response Regulator Hybrid Required for
Pseudomonas aeruginosa
Virulence
Authors: Laskowski Michelle A. , Kazmierczak Barbara I.
Published: July 2006

Pseudomonas aeruginosa
is an opportunistic pathogen capable of causing both acute and chronic infections in a wide range of hosts. Expression of the type III secretion system (T3SS) proteins is correlated with virulence in models of acute infection, while downregulation of the T3SS and upregulation of genes important for biofilm formation are observed during chronic infections. RetS, a hybrid sensor kinase-response regulator protein of
P. aeruginosa
, plays a key role in the reciprocal regulation of virulence factors required for acute versus chronic infection and is postulated to act in concert with two other sensor kinase-response regulator hybrids, GacS and LadS. This work examines the roles of the putative sensing and signal transduction domains of RetS in induction of the T3SS in vitro and in a murine model of acute pneumonia. We identify distinct signaling roles for the tandem receiver domains of RetS and present evidence suggesting that RetS may serve as a substrate for another sensor kinase. Phenotypes associated with RetS alleles lacking periplasmic and/or transmembrane domains further indicate that the periplasmic domain of RetS may transmit a signal that inhibits RetS activity during acute infections.
Enhanced Immunogenicity and Protective Efficacy with the Use of Interleukin-12-Encapsulated Microspheres plus AS01B in Tuberculosis Subunit Vaccination
Authors: Ha Sang-Jun , Park Su-Hyung , Kim Hye-Ju , Kim Seung-Chul , Kang Hyang-Ju , Lee Eun-Gae , Kwon Soon-Geon , Kim Byong-Moon , Lee Sung-Hee , Kim Won-Bae , Sung Young-Chul , Cho Sang-Nae
Published: July 2006

Tuberculosis subunit vaccines codelivered with interleukin-12 (IL-12)-encapsulated microspheres (IL-12EM) are designed for a sustained release of IL-12 and could induce strong Th1 immune responses specific to Ag85A and ESAT-6. The adjuvant combination of IL-12EM plus AS01B was a more efficient way to induce a sustained Th1 immunity and protection againstMycobacterium tuberculosis.
gC1qR/p33 Blockade ReducesStaphylococcus aureusColonization of Target Tissues in an Animal Model of Infective Endocarditis
Authors: Peerschke Ellinor I. B. , Bayer Arnold S. , Ghebrehiwet Berhane , Xiong Yan Q.
Published: July 2006

gC1qR/p33 (gC1qR) is a ubiquitously expressed cellular protein that is also found in plasma and the extracellular matrix. In addition to its role in modulating the activation of complement and kinin cascades, gC1qR has been identified as a putative host ligand for endovascular pathogens, includingStaphylococcus aureus. The present study provides evidence of the ability of soluble gC1qR to enhanceS. aureus-fibrinogen interactions via simultaneously binding fibrinogen andS. aureus. This interaction was inhibited in vitro by two monoclonal antibodies (MAbs 74.5.2 and 60.11) recognizing distinct structural and functional domains of gC1qR. To evaluate the in vivo role of gC1qR, MAbs 74.5.2 and 60.11 were used in an experimental rat model ofS. aureusendocarditis. Each MAb (100 mg/kg of body weight, given intraperitoneally) reached sustained (>60 h) and high (100 to 200 μg/ml) serum levels. Prophylaxis with MAb 60.11 or 74.5.2 caused substantial reductions inS. aureuscolonization of aortic valves, kidneys, and the spleen compared to untreated controls. However, only MAb 74.5.2 prophylaxis therapy reached statistical significance, and only sera from animals protected with MAb 74.5.2 inhibited gC1qR-mediatedS. aureusinteractions with fibrinogen. Although not statistically significant, the reductions in bacterial colonization achieved with MAb 60.11 alone and in combination with MAb 74.5.2 (versus MAb 74.5.2 alone) suggest that there are effects of gC1qR blockade onS. aureusinfective endocarditis in addition to blocking gC1qR-mediatedS. aureusbinding to fibrinogen. Such impacts may include direct modulation of complement (MAb 60.11) and kinin cascades (MAb 74.5.2) and/or activation of immune and inflammatory responses via localized immune complex formation.
Immunogenicity and Protective Immunity against Bubonic Plague and Pneumonic Plague by Immunization of Mice with the Recombinant V10 Antigen, a Variant of LcrV
Authors: DeBord Kristin L. , Anderson Deborah M. , Marketon Melanie M. , Overheim Katie A. , DePaolo R. William , Ciletti Nancy A. , Jabri Bana , Schneewind Olaf
Published: July 2006

In contrast to
Yersinia pestis
LcrV, the recombinant V10 (rV10) variant (lacking residues 271 to 300) does not suppress the release of proinflammatory cytokines by immune cells. Immunization with rV10 generates robust antibody responses that protect mice against bubonic plague and pneumonic plague, suggesting that rV10 may serve as an improved plague vaccine.
SdrI, a Serine-Aspartate Repeat Protein Identified in
Staphylococcus saprophyticus
Strain 7108, Is a Collagen-Binding Protein
Authors: Sakinc Türkan , Kleine Britta , Gatermann Sören G.
Published: July 2006

A gene encoding a serine-aspartate repeat protein of
Staphylococcus saprophyticus
, an important cause of
urinary tract infections in young women, has been cloned and sequenced.
In contrast to other SD repeat proteins, SdrI carries 21 additional
N-terminal repeats with a consensus sequence of
(P/A)ATKE(K/E)A(A/V)(T/I)(A/T/S)EE and has the
longest SD(AD)
(1-5)
repetitive region (854 amino acids)
described so far. This highly repetitive sequence contains only the
amino acids serine, asparagine, and a distinctly greater amount of
alanine (37%) than all other known SD repeat proteins (2.3 to 4.4%). In
addition, it is a collagen-binding protein of
S
.
saprophyticus
and the second example in this organism of a
surface protein carrying the LPXTG motif. We constructed an isogenic
sdrI
knockout mutant that showed decreased binding to
immobilized collagen compared with wild-type
S
.
saprophyticus
strain 7108. Binding could be reconstituted by
complementation. Collagen binding is specifically caused by SdrI, and
the recently described UafA protein, the only LPXTG-containing protein
in the genome sequence of the type strain, is not involved in this
trait. Our experiments suggest that, as in other staphylococci, the
presence of different LPXTG-anchored cell wall proteins is common in
S. saprophyticus
and support the notion that the
presence of matrix-binding surface proteins is common in
staphylococci.
Signal Transduction, Gene Transcription, and Cytokine Production Triggered in Macrophages by Exposure to Trypanosome DNA
Authors: Harris Tajie H. , Cooney Nicole M. , Mansfield John M. , Paulnock Donna M.
Published: July 2006

Activation of a type I cytokine response is important for early resistance to infection withTrypanosoma brucei rhodesiense, the extracellular protozoan parasite that causes African sleeping sickness. The work presented here demonstrates that trypanosome DNA activates macrophages to produce factors that may contribute to this response. Initial results demonstrated thatT. brucei rhodesienseDNA was present in the plasma of C57BL/6 and C57BL/6-scidmice following infection. Subsequently, the effect of trypanosome DNA on macrophages was investigated; parasite DNA was found to be less stimulatory thanEscherichia coliDNA but more stimulatory than murine DNA, as predicted by the CG dinucleotide content. Trypanosome DNA stimulated the induction of a signal transduction cascade associated with Toll-like receptor signaling in RAW 264.7 macrophage cells. The signaling cascade led to expression of mRNAs, including interleukin-12 (IL-12) p40, IL-6, IL-10, cyclooxygenase-2, and beta interferon. The treatment of RAW 264.7 cells and bone marrow-derived macrophages with trypanosome DNA induced the production of NO, prostaglandin E2, and the cytokines IL-6, IL-10, IL-12, and tumor necrosis factor alpha. In all cases, DNase I treatment ofT. brucei rhodesisenseDNA abolished the activation. These results suggest thatT. brucei rhodesienseDNA serves as a ligand for innate immune cells and may play an important contributory role in early stimulation of the host immune response during trypanosomiasis.
Transcribed
var
Genes Associated with Placental Malaria in MalawianWomen
Authors: Duffy Michael F. , Caragounis Aphrodite , Noviyanti Rintis , Kyriacou Helen M. , Choong Ee Ken , Boysen Katja , Healer Julie , Rowe J. Alexandra , Molyneux Malcolm E. , Brown Graham V. , Rogerson Stephen J.
Published: July 2006

Determining
the diversity of PfEMP1 sequences expressed by
Plasmodium
falciparum
-infected erythrocytes isolated from placentas is
important for attempts to develop a pregnancy-specific malaria vaccine.
The DBLγ and
var2csa
DBL3x domains of PfEMP1 molecules
are believed to mediate placental sequestration of infected
erythrocytes, so the sequences encoding these domains were amplified
from the cDNAs of placental parasites by using degenerate
oligonucleotides. The levels of specific
var
cDNAs were then
determined by quantitative reverse transcription-PCR. Homologues of
var2csa
DBL3x were the predominant sequences amplified from
the cDNAs of most placental but not most children's parasites. There
was 56% identity between all placental
var2csa
sequences. Many
different DBLγ domains were amplified from the cDNAs of
placental and children's isolates.
var2csa
transcripts were
the most abundant
var
transcripts of those tested in 11 of 12
placental isolates and 1 of 6 children's isolates. Gravidity did not
affect the levels of
var2csa
transcripts. We concluded that
placental malaria is frequently associated with transcription of
var2csa
but that other
var
genes are also expressed,
and parasites expressing high levels of
var2csa
are not
restricted to pregnant women. The diversity of
var2csa
sequences may be important for understanding immunity and for the
development of vaccines for malaria during
pregnancy.
A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction
Authors: Ogden Kevin , Thompson Janice M. , Hickner Zachary , Huang Taoying , Tang Dale D. , Watts Stephanie W.
Published: July 2006

Crk-associated substrate (CAS), a 130-kDa adaptor protein, was discovered as a tyrosine kinase substrate of Src that was important to cellular motility and actin filament formation. As the tyrosine kinase Src is utilized by the 5-hydroxytryptamine (5-HT)2Areceptor in arterial contraction, we tested the hypothesis that CAS was integral to 5-HT2Areceptor-mediated vasoconstriction. Rat thoracic aorta was used as a model of the arterial 5-HT2Areceptor. Western and immunohistochemistry analyses validated the presence of CAS in the aorta, and tissue bath experiments demonstrated reduction of contraction to 5-HT (13.5 ± 5% control maximum) and the 5-HT2receptor agonist α-methyl-5-HT (6 ± 2% maximum) by latrunculin B (10−6mol/l), an actin disruptor. In aorta contracted with 5-HT (10−5mol/l), tyrosine phosphorylation (Tyr410) of CAS was significantly increased (∼225%), and both contraction and CAS phosphorylation were reduced by the 5-HT2A/2Creceptor antagonist ketanserin (3 × 10−8mol/l). Src is one candidate for 5-HT-stimulated CAS tyrosyl-phosphorylation as 5-HT promoted interaction of Src and CAS in coimmunoprecipitation experiments, and the Src tyrosine kinase inhibitor PP1 (10−5mol/l) abolished 5-HT-induced tyrosyl-phosphorylation of CAS and reduced 5-HT- and α-methyl-5-HT-induced contraction. Antisense oligodeoxynucleotides delivered to the aorta reduced CAS expression (33% control) and arterial contraction to α-methyl-5-HT (45% of control), independent of changes in myosin light chain phosphorylation. These data are the first to implicate CAS in the signal transduction of 5-HT.
Role of diastolic properties in the transition to failure in a mouse model of the cardiac dilatation
Authors: Costandi Peter N. , Frank Lawrence R. , McCulloch Andrew D. , Omens Jeffrey H.
Published: July 2006

Although the physiological states of hypertrophic remodeling and congestive heart failure have been intensively studied, less is known about the transition from one to the other. The use of genetically engineered murine models of heart failure has proven valuable in characterizing the progression of remodeling and its ultimate decompensation to failure. Mice deficient in the cytoskeletal muscle LIM-only protein (MLP) are known to present with a clinical picture of dilated cardiomyopathy and transition to failure as adults. Longitudinal high-field magnetic resonance (MR) cardiac imaging provided a time course of remodeling where an improvement in ejection fraction and stroke volume (15- vs. 31-wk MLP−/− mice; P < 0.0001) was temporally concurrent with an abrupt phase of end-diastolic chamber dilatation. Hemodynamic analysis conducted throughout that dilatation phase showed improved ratio of maximum first derivative of pressure to end-diastolic pressure (dP/d tmax/EDP; 15- vs. 31-wk MLP−/− mice; P < 0.0005), ratio of minimum first derivative of pressure to EDP (dP/d tmin/EDP; 15- vs. 31-wk MLP−/− mice; P < 0.003), and developed pressure (15- vs. 31-wk MLP−/− mice; P < 0.0001) levels in the MLP−/− mice. Computational modeling techniques were used to estimate the EDP volume relationship, revealing that although MLP hearts possess a stiffer stress-strain relation, chamber compliance increased as a function of dilatation. This detailed physiological characterization during a phase of rapid anatomical remodeling suggests that systolic function in the MLP−/− mice may temporarily improve as a result of alterations in chamber compliance, which are mediated by dilatation. In turn, a balance may exist between exploiting the Frank-Starling mechanism and altering chamber compliance that maintains function in the absence of hypertrophic growth. Though initially compensatory, this process may exhaust itself and consequently transition to a maladaptive course.
Time course analysis of baroreflex sensitivity during postural stress
Authors: Westerhof Berend E. , Gisolf Janneke , Karemaker John M. , Wesseling Karel H. , Secher Niels H. , van Lieshout Johannes J.
Published: July 2006

Postural stress requires immediate autonomic nervous action to maintain blood pressure. We determined time-domain cardiac baroreflex sensitivity (BRS) and time delay (τ) between systolic blood pressure and interbeat interval variations during stepwise changes in the angle of vertical body axis (α). The assumption was that with increasing postural stress, BRS becomes attenuated, accompanied by a shift in τ toward higher values. In 10 healthy young volunteers, α included 20 degrees head-down tilt (−20°), supine (0°), 30 and 70 degrees head-up tilt (30°, 70°), and free standing (90°). Noninvasive blood pressures were analyzed over 6-min periods before and after each change in α. The BRS was determined by frequency-domain analysis and with xBRS, a cross-correlation time-domain method. On average, between 28 (−20°) to 45 (90°) xBRS estimates per minute became available. Following a change in α, xBRS reached a different mean level in the first minute in 78% of the cases and in 93% after 6 min. With increasing α, BRS decreased: BRS = −10.1·sin(α) + 18.7 ( r2= 0.99) with tight correlation between xBRS and cross-spectral gain ( r2∼ 0.97). Delay τ shifted toward higher values. In conclusion, in healthy subjects the sensitivity of the cardiac baroreflex obtained from time domain decreases linearly with sin(α), and the start of baroreflex adaptation to a physiological perturbation like postural stress occurs rapidly. The decreases of BRS and reduction of short τ may be the result of reduced vagal activity with increasing α.
Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury
Authors: Zhao Minqing , Fernandez Lucas G. , Doctor Allan , Sharma Ashish K. , Zarbock Alexander , Tribble Curtis G. , Kron Irving L. , Laubach Victor E.
Published: July 2006

Lung ischemia-reperfusion (I/R) injury is a biphasic inflammatory process. Previous studies indicate that the later phase is neutrophil-dependent and that alveolar macrophages (AMs) likely contribute to the acute phase of lung I/R injury. However, the mechanism is unclear. AMs become activated and produce various cytokines and chemokines in many inflammatory responses, including transplantation. We hypothesize that AMs respond to I/R by producing key cytokines and chemokines and that depletion of AMs would reduce cytokine/chemokine expression and lung injury after I/R. To test this, using a buffer-perfused, isolated mouse lung model, we studied the impact of AM depletion by liposome-clodronate on I/R-induced lung dysfunction/injury and expression of cytokines/chemokines. I/R caused a significant increase in pulmonary artery pressure, wet-to-dry weight ratio, vascular permeability, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-2 expression, as well as decreased pulmonary compliance, when compared with sham lungs. After AM depletion, the changes in each of these parameters between I/R and sham groups were significantly attenuated. Thus AM depletion protects the lungs from I/R-induced dysfunction and injury and significantly reduces cytokine/chemokine production. Protein expression of TNF-α and MCP-1 are positively correlated to I/R-induced lung injury, and AMs are a major producer/initiator of TNF-α, MCP-1, and MIP-2. We conclude that AMs are an essential player in the initiation of acute lung I/R injury.
Type II epithelial cells are critical target for hyperoxia-mediated impairment of postnatal lung development
Authors: Yee Min , Vitiello Peter F. , Roper Jason M. , Staversky Rhonda J. , Wright Terry W. , McGrath-Morrow Sharon A. , Maniscalco William M. , Finkelstein Jacob N. , O'Reilly Michael A.
Published: July 2006

Type II epithelial cells are essential for lung development and remodeling, as they are precursors for type I cells and can produce vascular mitogens. Although type II cell proliferation takes place after hyperoxia, it is unclear why alveolar remodeling occurs normally in adults whereas it is permanently disrupted in newborns. Using a line of transgenic mice whose type II cells could be identified by their expression of enhanced green fluorescent protein and endogenous expression of surfactant proteins, we investigated the age-dependent effects of hyperoxia on type II cell proliferation and alveolar repair. In adult mice, type II cell proliferation was low during room air and hyperoxia exposure but increased during recovery in room air and then declined to control levels by day 7. Eight weeks later, type II cell number and alveolar compliance were indistinguishable from those in room air controls. In newborn mice, type II cell proliferation markedly increased between birth and postnatal day 7 before declining by postnatal day 14. Exposure to hyperoxia between postnatal days 1 and 4 inhibited type II cell proliferation, which resumed during recovery and was aberrantly elevated on postnatal day 14. Eight weeks later, recovered mice had 70% fewer type II cells and 30% increased lung compliance compared with control animals. Recovered mice also had higher levels of T1α, a protein expressed by type I cells, with minimal changes detected in genes expressed by vascular cells. These data suggest that perinatal hyperoxia adversely affects alveolar development by disrupting the proper timing of type II cell proliferation and differentiation into type I cells.
Embryonics: A Path to Artificial Life?
Authors: Zhang Xuegong , Dragffy Gabriel , Pipe Anthony G.
Published: July 2006

Electronic systems, no matter how clever and intelligent they are, cannot yet demonstrate the reliability that biological systems can. Perhaps we can learn from these processes, which have developed through millions of years of evolution, in our pursuit of highly reliable systems. This article discusses how such systems, inspired by biological principles, might be built using simple embryonic cells. We illustrate how they can monitor their own functional integrity in order to protect themselves from internal failure or from hostile environmental effects and how faults caused by DNA mutation or cell death can be repaired and thus full system functionality restored.
Axiomatic Scalable Neurocontroller Analysis via the Shapley Value
Authors: Keinan Alon , Sandbank Ben , Hilgetag Claus C. , Meilijson Isaac , Ruppin Eytan
Published: July 2006

One of the major challenges in the field of neurally driven evolved autonomous agents is deciphering the neural mechanisms underlying their behavior. Aiming at this goal, we have developed the multi-perturbation Shapley value analysis (MSA)—the first axiomatic and rigorous method for deducing causal function localization from multiple-perturbation data, substantially improving on earlier approaches. Based on fundamental concepts from game theory, the MSA provides a formal way of defining and quantifying the contributions of network elements, as well as the functional interactions between them. The previously presented versions of the MSA require full knowledge (or at least an approximation) of the network's performance under all possible multiple perturbations, limiting their applicability to systems with a small number of elements. This article focuses on presenting new scalable MSA variants, allowing for the analysis of large complex networks in an efficient manner, including large-scale neurocontrollers. The successful operation of the MSA along with the new variants is demonstrated in the analysis of several neurocontrollers solving a food foraging task, consisting of up to 100 neural elements.
A Neural Learning Classifier System with Self-Adaptive Constructivism for Mobile Robot Control
Authors: Hurst Jacob , Bull Larry
Published: July 2006

For artificial entities to achieve true autonomy and display complex lifelike behavior, they will need to exploit appropriate adaptable learning algorithms. In this context adaptability implies flexibility guided by the environment at any given time and an open-ended ability to learn appropriate behaviors. This article examines the use of constructivism-inspired mechanisms within a neural learning classifier system architecture that exploits parameter self-adaptation as an approach to realize such behavior. The system uses a rule structure in which each rule is represented by an artificial neural network. It is shown that appropriate internal rule complexity emerges during learning at a rate controlled by the learner and that the structure indicates underlying features of the task. Results are presented in simulated mazes before moving to a mobile robot platform.
Evolution and Development of a Multicellular Organism: Scalability, Resilience, and Neutral Complexification
Authors: Federici Diego , Downing Keith
Published: July 2006

To increase the evolvability of larger search spaces, several indirect encoding strategies have been proposed. Among these, multicellular developmental systems are believed to offer great potential for the evolution of general, scalable, and self-repairing organisms. We reinforce this view, presenting the results achieved by such a model and comparing it against direct encoding. Extra effort has been made to make this comparison both general and meaningful. Embryonal stages, a generic method showing increased evolvability and applicable to any developmental model, are introduced. Development with embryonal stages implements what we refer to as direct neutral complexification: direct genotype complexification by neutral duplication of expressed genes. The results show that, even for high-complexity evolutionary targets, the developmental model proves more scalable. The model also shows emergent self-repair, which is used to produce highly resilient organisms.
Neurocontroller Analysis via Evolutionary Network Minimization
Authors: Ganon Zohar , Keinan Alon , Ruppin Eytan
Published: July 2006

This study presents a new evolutionary network minimization (ENM) algorithm. Neurocontroller minimization is beneficial for finding small parsimonious networks that permit a better understanding of their workings. The ENM algorithm is specifically geared to an evolutionary agents setup, as it does not require any explicit supervised training error, and is very easily incorporated in current evolutionary algorithms. ENM is based on a standard genetic algorithm with an additional step during reproduction in which synaptic connections are irreversibly eliminated. It receives as input a successfully evolved neurocontroller and aims to output a pruned neurocontroller, while maintaining the original fitness level. The small neurocontrollers produced by ENM provide upper bounds on the neurocontroller size needed to perform a given task successfully, and can provide for more effcient hardware implementations.
Biomechanical Evaluation of 2 Techniques for Ulnar Collateral Ligament Reconstruction of the Elbow
Authors: Paletta George A. , Klepps Steven J. , Difelice Gregory S. , Allen Tracy , Brodt Michael D. , Burns Meghan E. , Silva Matthew J. , Wright Rick W.
Published: July 2006

Background

Elbow medial ulnar collateral ligament tears often result in pain and instability that may be career threatening in overhead-throwing athletes. Surgical reconstruction is frequently chosen to treat this injury. Ulnar collateral ligament reconstruction as described by Jobe is the most commonly used technique. Testing of this construct has not demonstrated that the biomechanical parameters of the native ligament are restored. A more recent construct, the docking technique, may more reliably reproduce these factors.

Hypothesis

Increasing the number of strands of palmaris longus tendon graft used in ulnar collateral ligament reconstruction and tensioning them using the docking technique result in a construct with improved biomechanical parameters as compared with the Jobe technique.

Study Design

Controlled laboratory study.

Methods

Thirty-three fresh-frozen human cadaveric elbows were randomized into 3 subgroups: Jobe (11), docking (12), and native (10). The Jobe and docking groups underwent reconstruction using their described palmaris tendon graft constructs. The ulnar collateral ligament was left intact in the native group. Elbows were potted and tested using a servohydraulic materials testing machine to apply a valgus moment at 30° of elbow flexion. Maximal moments to failure, stiffness, and strain at maximal moment and with a 3 N·m force applied were determined using a 2-camera motion analysis system to track reflective markers spanning the site.

Results

The docking (14.3 N·m) and native (18.8 N·m) subgroups resulted in higher maximal moment to failure than did the Jobe (8.9 N·m) subgroup (P <. 001). There was no significant difference between native and docking groups (P >. 05). Native ligaments were stiffer (301.4 N·m) than were Jobe (74.3 N·m) or docking (80.8 N·m; P <. 001). Native ligaments demonstrated lower strain at maximal force (0.087 mm/mm) and 3 N·m forces (0.030 mm/mm) than did the Jobe (0.198/0.057 mm/mm) or docking (0.287/0.042 mm/mm) subgroups. There was no difference in stiffness or strain between the Jobe and docking subgroups (P >. 05).

Conclusion

Neither technique reproduced the biomechanical profile of the native ulnar collateral ligament; the findings of this study suggest that the docking construct may offer initial biomechanical advantage over the Jobe construct.
The Effects of Estrogen on Material and Mechanical Properties of the Intra- and Extra-articular Knee Structures
Authors: Wentorf Fred A. , Sudoh Kenji , Moses Christina , Arendt Elizabeth A. , Carlson Cathy S.
Published: July 2006

Background

Female athletes have a higher incidence of anterior cruciate ligament injuries than do male athletes in similar sports. Hormones, particularly estrogen, have been indicated by some studies to be correlated with the disproportionate number of anterior cruciate ligament injuries in female athletes.

Hypothesis

Estrogen does not affect the mechanical or material properties of primate anterior cruciate ligaments or patellar tendons.

Study Design

Controlled laboratory study.

Methods

Twenty-six cynomolgus monkeys (Macaca fascicularis) were divided into 2 groups: sham operated (estrogen maintained, n = 12) and ovariectomized (estrogen deficient, n = 14). After 2 years, the animals were sacrificed, and various properties of ligaments were tested. Two different ligaments were studied, the anterior cruciate ligament and patellar tendon.

Results

No differences were found between the sham-operated (sham) and ovariectomized group for failure load (anterior cruciate ligament: sham, 394 ± 67 N; ovariectomized, 392 ± 96 N; P >. 74), stiffness, elongation at failure, ultimate stress (anterior cruciate ligament: sham, 115 ± 30 MPa; ovariectomized, 128 ± 36 MPa; P >. 58), ultimate strain, modulus, failure sites, or energy to failure.

Conclusion

Endogenous estrogen does not directly affect the mechanical or material properties of the anterior cruciate ligament or the patellar tendon of cynomolgus macaques.

Clinical Relevance

This study supports the idea that knee ligament injury in female athletes is not a direct result of estrogen's effect on ligament properties.
Injury Rates, Risk Factors, and Mechanisms of Injury in Minor Hockey
Authors: Emery Carolyn A. , Meeuwisse Willem H.
Published: July 2006

Background

Hockey is one of the top sports for participation in youth in Canada. There are limited data on the epidemiology of injury in youth hockey.

Purpose

Through implementation and validation of an injury surveillance system, youth ice hockey injury rates, risk factors, and mechanisms of injury will be examined.

Study Design

Descriptive epidemiology study.

Methods

During the 2004-2005 season in minor hockey in Calgary, Alberta, Canada, 71 hockey teams (N = 986) were studied, including teams from each age group (Atom, 9/10 years; Pee Wee, 11/12 years; Bantam, 13/14 years; Midget, 15/16 years) and division of play (7-10 divisions per age group). A certified athletic therapist or candidate did weekly assessments of any identified hockey injury. Injury definition included any injury occurring during the regular hockey season that required medical attention, removal from a session, or missing a subsequent session.

Results

Of the 986 participating players, 216 players sustained a total of 296 injuries in the 2004-2005 season. The overall injury rate was 30.02 injuries per 100 players per season (95% confidence interval, 27.17-32.99) or 4.13 injuries per 1000 player hours (95% confidence interval, 3.67-4.62). Forty-five percent of all injuries occurred during body checking. Compared with the youngest age group, Atom, the risk of injury was greater in Pee Wee (relative risk, 2.97; 95% confidence interval, 1.63-5.8), Bantam (relative risk, 3.72; 95% confidence interval, 2.08-7.14), and Midget (relative risk, 5.43; 95% confidence interval, 3.14-10.17) leagues. The risk of injury in Pee Wee was greatest in the most elite divisions (relative risk, 2.45; 95% confidence interval, 1.15-5.81). Concussion, shoulder sprain/dislocation, and knee sprain were the most common injuries.

Conclusion

Significant differences in injury rates were found by age and division of play. The public health significance of body checking injury in minor hockey is great. Future research will include expansion of surveillance to further examine body checking injuries and prevention strategies in minor hockey.
The Effect of Tennis Racket Grip Size on Forearm Muscle Firing Patterns
Authors: Hatch George F. , Pink Marilyn M. , Mohr Karen J. , Sethi Paul M. , Jobe Frank W.
Published: July 2006

Background

Inappropriately sized tennis racket grip is often cited in the popular media as a risk factor for overuse injuries about the forearm and elbow. Currently, a hand measurement technique developed by Nirschl is commonly used by tennis racket manufacturing companies as the method for determining a player's “recommended” grip size.

Hypothesis

Quarter-inch changes from that recommended by Nirschl in tennis racket grip size will have no significant effect on forearm muscle firing patterns.

Study Design

Controlled laboratory study.

Methods

Sixteen asymptomatic Division I and II collegiate tennis players performed single-handed backhand ground strokes with rackets of 3 different grip sizes (recommended measurement, undersized 1/4 in, and oversized 1/4 in). Fine-wire electromyography was used to measure muscle activity in extensor carpi radialis longus and brevis, extensor digitorum communis, flexor carpi radialis, and pronator teres. Repeated-measure analysis of variance was used for within-group comparisons, comparing different grips in specified phases for backhand ground strokes (P [.lessequal]. 05).

Results

There were no significant differences in muscle activity between small, recommended, or big grips in any muscle tested.

Conclusion

Based on these findings, tennis racket grip size 1/4 in above or below Nirschl's recommended measurement does not significantly affect forearm muscle firing patterns.

Clinical Relevance

Alterations in tennis racket grip size within 1/4 in of Nirschl's recommended sizing do not have a significant effect on forearm muscle activity and therefore may not represent a significant risk factor for upper extremity cumulative trauma, such as lateral epicondylitis.
Prognostic significance of metallothionein in B-cell lymphomas
Authors: Poulsen Christian Bjørn , Borup Rehannah , Borregaard Niels , Nielsen Finn Cilius , Møller Michael Boe , Ralfkiaer Elisabeth
Published: July 2006

We have investigated metallothionein (MT) I and II mRNA and protein in B-cell lymphomas with particular reference to diffuse large B-cell lymphoma (DLBCL). The mRNA profiling was performed on Affymetrix arrays and showed up-regulated MT mRNA in 15 of 48 DLBCLs, including 12 of 23 activated B-cell (ABC) and 3 of 9 type-3 lesions. In contrast, MT mRNA was low to undetectable in 16 germinal center B-cell (GCB)-type DLBCLs. Only 1 of 15 patients with up-regulated MT mRNA achieved a sustained remission, suggesting that up-regulated MT mRNA constitutes a significant risk factor for treatment failure. This was confirmed in 2 independent series, which showed significantly shorter 5-year survival in DLBCL with high versus low MT-IIa levels. By immunohistology, MT was shown to be present in both macrophages and lymphoma cells. The proportion of MT-positive macrophages did not correlate with the survival. In contrast, in 115 DLBCLs, MT labeling of more than 20% lymphoma cells was associated with a significantly poorer 5-year survival, independent of the age, stage, or International Prognostic Index. Taken together, it is suggested that both increased MT mRNA and MT protein expression by more than 20% lymphoma cells constitute independent risk factors in DLBCL.
How the Group Affects the Mind: A Cognitive Model of Idea Generation in Groups
Authors: Nijstad Bernard A. , Stroebe Wolfgang
Published: July 2006

A model called search for ideas in associative memory (SIAM) is proposed to account for various research findings in the area of group idea generation. The model assumes that idea generation is a repeated search for ideas in associative memory, which proceeds in 2 stages (knowledge activation and idea production), and is controlled through negative feedback loops and cognitive failures (trials in which no idea is generated). We show that (a) turn taking (production blocking) interferes with both stages of the process; (b) ideas suggested by others aid the activation of problem-relevant knowledge; and (c) cognitive failures are important determinants of brainstorming persistence, satisfaction, and enjoyment. Implications for group decision making and group recall are discussed.
Dehumanization: An Integrative Review
Authors: Haslam Nick
Published: July 2006

The concept of dehumanization lacks a systematic theoretical basis, and research that addresses it has yet to be integrated. Manifestations and theories of dehumanization are reviewed, and a new model is developed. Two forms of dehumanization are proposed, involving the denial to others of 2 distinct senses of humanness: characteristics that are uniquely human and those that constitute human nature. Denying uniquely human attributes to others represents them as animal-like, and denying human nature to others represents them as objects or automata. Cognitive underpinnings of the “animalistic” and “mechanistic” forms of dehumanization are proposed. An expanded sense of dehumanization emerges, in which the phenomenon is not unitary, is not restricted to the intergroup context, and does not occur only under conditions of conflict or extreme negative evaluation. Instead, dehumanization becomes an everyday social phenomenon, rooted in ordinary social-cognitive processes.
Electrochemical Formation of 1,3,5-Trinaphthylbenzene Tri- and Tetraanions
Authors: Saji Tetsuo , Aoyagui Shigeru
Published: July 2006

Each of the cyclic voltammograms of tri(1-naphthyl)benzene and tri(2-naphthyl)benzene in 1,2-dimethoxyethane at −50 °C exhibits four reversible one-electron reduction steps; this may be evidence for the successive formation of the mono-, di-, tri-, and tetraanions of these hydrocarbons. The degeneracy of their π*-orbitals can account for the formation of the tri- and tetraanions.
Extraction of Bivalent Manganese, Cobalt, Copper, Zinc, and Cadmium from Hydrochloric Acid Solutions by Long-chain Alkyl Quaternary Ammonium Chloride in Various Organic Solvents
Authors: Sato Taichi , Nakamura Takato , Fujimatsu Teruo
Published: July 2006

The extraction of bivalent manganese, cobalt, copper, zinc and cadmium from hydrochloric acid solutions by tricaprylmethylammonium chloride (Aliquat-336) has been examined usmg various diluents such as benzene, chlorobenzene, o-dichlorobenzene, toluene, o-xylene, m-xylene, nitrobenzene, carbon tetrachloride, chloroform, and 1,2-dichloroethane. It was found that by assuming a regular solution, the distribution coefficient and the enthalpy change associated with metal extraction can be expressed in terms of the solubility parameters of Aliquat-336, diluent and the complex formed in the organic phase and their molar volumes. An empirical relation holds between distribution coefficient and the viscosity of diluent.
Syntheses of Derivatives of N2-Acetyl-N3-glycyl-l-2,3-diaminopropionic Acid and Their Hydrolyses by Trypsin
Authors: Minematsu Yoshihiro , Kang Shinwon , Waki Michinori , Kato Tetsuo , Izumiya Nobuo
Published: July 2006

Amide and ethyl ester of N2-acetyl-N3-glycyl-l-2,3-diaminopropionic acid replacing an ethylene group in the side chain of lysine by a peptide bond were synthesized. The susceptibility of each derivative to trypsin was compared with that of the corresponding N2-acetyl-l-lysine derivative. Each derivative was hydrolyzed by trypsin, but was less susceptible than the corresponding l-lysine derivative.
Oxidation of Unsymmetrical Disulfide and Thiosulfinic S-Esters with Peroxy Acids. Search for Formation of α-Disulfoxide as An Intermediate in the Electrophilic Oxidation of Thiosulfinic S-Ester
Authors: Oae Shigeru , Takata Toshikazu , Kim Yong Hae
Published: July 2006

Oxidation of an unsymmetrical disulfide, methyl phenyl disulfide, with peroxy acids takes place mainly at more electron-rich sulfur atom to form thiosulfinic S-ester at the first stage, while oxidation of unsymmetrical thiosulfinic S-ester with peroxy acids gives usually four thiosulfonic S-esters, together with sulfinic and sulfonic acids, further oxidation products. Oxidation of S-methyl benzenethiosulfinate 6 affords, as one of the products, S-phenyl methanethiosulfonate 11, in which the original sulfinyl oxygen is brought into methanesulfonyl group. A small amount of S-phenyl benzenethiosulfonate 9 (or benzenesulfonic acid 15) is obtained in the oxidation of S-phenyl methanethiosulfinate 7. 18O-Label of the starting thiosulfinic S-ester 6 was found to be incorporated to some extents into all four products, i.e.  8–11, while a part of 18O-label of S-phenyl methanethiosulfinate 7 was also observed in S-phenyl benzenethiosulfonate 9 and benzenesulfonic acid 15, although most of 18O-label of 7 was incorporated into S-phenyl methanethiosulfonate 11. Thiosulfinic S-esters are stable and do not undergo disproportionation and 18O-exchange under the conditions. These observations suggest the formation of α-disulfoxide as an intermediate in the oxidation of thiosulfinic S-ester to thiosulfonic S-ester, especially in the oxidation of 6, although no peak corresponding to α-disulfoxide was observed directly in the NMR spectra taken during the oxidations of a few thiosulfinic S-esters with peroxy acids. Mechanism of the oxidation is discussed.
A Reinvestigation of Small-angle Electron Scattering by CS2 and CCl4 Molecules
Authors: Nagashima Makoto , Konaka Shigehiro , Kimura Masao
Published: July 2006

A small-angle electron-diffraction unit (Jpn. J. Appl. Phys., 11, 1199 (1972)) has been improved by enlarging the scattering chamber and installing a new nozzle system and a better counting unit. The intensities of 50 keV electrons scattered by CS2 and CCl4 molecules have been measured with a ≈1% precision in the s-range from 1 to 11.5 Å−1. Theoretical intensities have been calculated for the independent-atom model by taking into account the intramolecular double-scattering effect, and those intensities have been compared with the experimental intensities. The oscillatory feature appearing in the difference function, Δσ(s)=s4(Iexptl–IIAM), of CCl4 has been ascribed mainly to the deformation of the one-electron density in chlorine atoms by chemical binding.