bluuebunny/crossref_metadata_2025 huggingface dataset:
Acetohydroxyacid Synthase, a Novel Target for Improvement of
l
-Lysine Production by
Corynebacterium glutamicum
Authors: Blombach Bastian , Hans Stephan , Bathe Brigitte , Eikmanns Bernhard J.
Published: December 2008

The influence of acetohydroxy acid synthase (AHAS) on
l
-lysine production by
Corynebacterium glutamicum
was investigated. An AHAS with a deleted C-terminal domain in the regulatory subunit IlvN was engineered by truncating the
ilvN
gene. Compared to the wild-type AHAS, the newly constructed enzyme showed altered kinetic properties, i.e., (i) an about twofold-lower
K

m

for the substrate pyruvate and an about fourfold-lower
V
max
; (ii) a slightly increased
K

m

for the substrate α-ketobutyrate with an about twofold-lower
V
max
; and (iii) insensitivity against the inhibitors
l
-valine,
l
-isoleucine, and
l
-leucine (10 mM each). Introduction of the modified AHAS into the
l
-lysine producers
C. glutamicum
DM1729 and DM1933 increased
l
-lysine formation by 43% (30 mM versus 21 mM) and 36% (51 mM versus 37 mM), respectively, suggesting that decreased AHAS activity is linked to increased
l
-lysine formation. Complete inactivation of the AHAS in
C. glutamicum
DM1729 and DM1933 by deletion of the
ilvB
gene, encoding the catalytic subunit of AHAS, led to
l
-valine,
l
-isoleucine, and
l
-leucine auxotrophy and to further-improved
l
-lysine production. In batch fermentations,
C. glutamicum
DM1729 Δ
ilvB
produced about 85% more
l
-lysine (70 mM versus 38 mM) and showed an 85%-higher substrate-specific product yield (0.180 versus 0.098 mol C/mol C) than
C. glutamicum
DM1729. Comparative transcriptome analysis of
C. glutamicum
DM1729 and
C. glutamicum
DM1729 Δ
ilvB
indicated transcriptional differences for about 50 genes, although not for those encoding enzymes involved in the
l
-lysine biosynthetic pathway.
Widespread Occurrence and Lateral Transfer of the Cyanobactin Biosynthesis Gene Cluster in Cyanobacteria
Authors: Leikoski Niina , Fewer David P. , Sivonen Kaarina
Published: December 2008

Cyanobactins are small cyclic peptides produced by cyanobacteria. Here we demonstrate the widespread but sporadic occurrence of the cyanobactin biosynthetic pathway. We detected a cyanobactin biosynthetic gene in 48 of the 132 strains included in this study. Our results suggest that cyanobactin biosynthetic genes have a complex evolutionary history in cyanobacteria punctuated by a series of ancient horizontal gene transfer events.
Uncoupling of the Patterns of Chromatin Association of Different Transcription Elongation Factors by a Histone H3 Mutant in
Saccharomyces cerevisiae
Authors: Lloyd Amanda , Pratt Katie , Siebrasse Erica , Moran Matthew D. , Duina Andrea A.
Published: December 2008

The transcription elongation complexes yFACT, Spt4/Spt5, and Spt6/Iws1 were previously shown to follow similar patterns of association across transcribed genes in
Saccharomyces cerevisiae
. Using a histone H3 mutant, we now provide evidence that the mechanism of association of yFACT across genes is separable from that adopted by Spt4/Spt5 and Spt6/Iws1.
Enhanced Immunogenicity ofPlasmodium falciparumPeptide Vaccines Using a Topical Adjuvant Containing a Potent Synthetic Toll-Like Receptor 7 Agonist, Imiquimod
Authors: Othoro Caroline , Johnston Dean , Lee Rebecca , Soverow Jonathan , Bystryn Jean-Claude , Nardin Elizabeth
Published: December 2008

Plasmodium sporozoites injected into the skin by malaria-infected mosquitoes can be effectively targeted by antibodies that block parasite invasion of host hepatocytes and thus prevent the subsequent development of blood stage infections responsible for clinical disease. Malaria subunit vaccines require potent adjuvants, as they lack known pathogen-associated molecular patterns found in attenuated viral or bacterial vaccines that function as Toll-like receptor (TLR) agonists to stimulate dendritic cells and initiate strong adaptive immune responses. A synthetic TLR7 agonist, imiquimod, which is FDA approved for topical treatment of various skin conditions, can function as a potent adjuvant for eliciting T-cell responses to intracellular pathogens and model protein antigens. In the current studies, the topical application of imiquimod at the site of subcutaneously injectedPlasmodium falciparumcircumsporozoite (CS) peptides elicited strong parasite-specific humoral immunity that protected against challenge with transgenic rodent parasites that expressP. falciparumCS repeats. In addition, injection of a simple linear peptide followed by topical imiquimod elicited strong Th1 CD4+T-cell responses, as well as high antibody titers. The correlation of high anti-repeat antibody titers with resistance to sporozoite challenge in vivo and in vitro supports use of this topical TLR7 agonist adjuvant to elicit protective humoral immunity. The safety, simplicity, and economic advantages of a topical synthetic TLR7 agonist adjuvant also apply to other vaccines requiring high antibody titers, such as malaria asexual or sexual blood stage antigens to prevent red blood cell invasion and block transmission to the mosquito vector, and to vaccines to other extracellular pathogens.
The Brucella abortus S19 Δ
vjbR
Live Vaccine Candidate Is Safer than S19 and Confers Protection against Wild-Type Challenge in BALB/c Mice When Delivered in a Sustained-Release Vehicle
Authors: Arenas-Gamboa A. M. , Ficht T. A. , Kahl-McDonagh M. M. , Gomez G. , Rice-Ficht A. C.
Published: December 2008

Brucellosis is an important zoonotic disease of nearly worldwide distribution. Despite the availability of live vaccine strains for bovine (S19, RB51) and small ruminants (Rev-1), these vaccines have several drawbacks, including residual virulence for animals and humans. Safe and efficacious immunization systems are therefore needed to overcome these disadvantages. A
vjbR
knockout was generated in the S19 vaccine and investigated for its potential use as an improved vaccine candidate. Vaccination with a sustained-release vehicle to enhance vaccination efficacy was evaluated utilizing the live S19 Δ
vjbR
::Kan in encapsulated alginate microspheres containing a nonimmunogenic eggshell precursor protein of the parasite
Fasciola hepatica
(vitelline protein B). BALB/c mice were immunized intraperitoneally with either encapsulated or nonencapsulated S19 Δ
vjbR
::Kan at a dose of 1 × 10
5
CFU per animal to evaluate immunogenicity, safety, and protective efficacy. Humoral responses postvaccination indicate that the vaccine candidate was able to elicit an anti-
Brucella
-specific immunoglobulin G response even when the vaccine was administered in an encapsulated format. The safety was revealed by the absence of splenomegaly in mice that were inoculated with the mutant. Finally, a single dose with the encapsulated mutant conferred higher levels of protection compared to the nonencapsulated vaccine. These results suggest that S19 Δ
vjbR
::Kan is safer than S19, induces protection in mice, and should be considered as a vaccine candidate when administered in a sustained-release manner.
Streptococcus pneumoniaeCapsular Serotype 19F Is More Resistant to C3 Deposition and Less Sensitive to Opsonophagocytosis than Serotype 6B
Authors: Melin Merit , Jarva Hanna , Siira Lotta , Meri Seppo , Käyhty Helena , Väkeväinen Merja
Published: December 2008

The polysaccharide capsule is a major virulence mechanism ofStreptococcus pneumoniae, shielding the bacterium from phagocytes. Capsule types may differ in their abilities to resist immune defense. Antibody-mediated complement activation and opsonophagocytosis are crucial in protection against pneumococcus. Conjugate vaccine trials suggest imperfect protection against 19F. We have previously shown that significantly more anti-19F than anti-6B antibody is needed for killing in the opsonophagocytic assay (OPA). In this study, we explored whether the amount of C3 deposited on serotype 6B and 19F pneumococcal strains reflects their sensitivity to opsonophagocytosis. We compared clinical 6B and 19F nasopharyngeal, middle ear, and blood isolates as well as reference OPA strains (n= 16) for their sensitivity to opsonophagocytosis and C3 deposition. Sixfold anticapsular antibody concentrations were required for 50% opsonophagocytic killing of 19F compared to that of 6B strains. Serotype 19F was more resistant to C3 deposition than 6B. Complement deposition and opsonophagocytosis were dependent on the concentration of anticapsular antibodies. Differences between pneumococcal serotypes in antibody-mediated protection may partly be explained by the abilities of the capsules to resist complement deposition. These findings support previous studies suggesting that higher antibody concentrations to the capsular polysaccharide are needed for protection against disease caused by serotype 19F than that caused by 6B.
Host Immune Response and Acute Disease in a Zebrafish Model ofFrancisellaPathogenesis
Authors: Vojtech Lucia N. , Sanders George E. , Conway Carla , Ostland Vaughn , Hansen John D.
Published: December 2008

Members of the bacterial genusFrancisellaare highly virulent and infectious pathogens. New models to studyFrancisellapathogenesis in evolutionarily distinct species are needed to provide comparative insight, as the mechanisms of host resistance and pathogen virulence are not well understood. We took advantage of the recent discovery of a novel species ofFrancisellato establish a zebrafish/Francisellacomparative model of pathogenesis and host immune response. Adult zebrafish were susceptible to acuteFrancisella-induced disease and suffered mortality in a dose-dependent manner. Using immunohistochemical analysis, we localized bacterial antigens primarily to lymphoid tissues and livers of zebrafish following infection by intraperitoneal injection, which corresponded to regions of local cellular necrosis.Francisellasp. bacteria replicated rapidly in these tissues beginning 12 h postinfection, and bacterial titers rose steadily, leveled off, and then decreased by 7 days postinfection. Zebrafish mounted a significant tissue-specific proinflammatory response to infection as measured by the upregulation of interleukin-1β (IL-1β), gamma interferon, and tumor necrosis factor alpha mRNA beginning by 6 h postinfection and persisting for up to 7 days postinfection. In addition, exposure of zebrafish to heat-killed bacteria demonstrated that the significant induction of IL-1β was highly specific to live bacteria. Taken together, the pathology and immune response to acuteFrancisellainfection in zebrafish share many features with those in mammals, highlighting the usefulness of this new model system for addressing both general and specific questions aboutFrancisellahost-pathogen interactions via an evolutionary approach.
Contribution of the Periplasmic Chaperone Skp to Efficient Presentation of the Autotransporter IcsA on the Surface ofShigella flexneri
Authors: Wagner Jennifer K. , Heindl Jason E. , Gray Andrew N. , Jain Sumita , Goldberg Marcia B.
Published: December 2008

IcsA is an outer membrane protein in the autotransporter family that is required forShigella flexneripathogenesis. Following its secretion through the Sec translocon, IcsA is incorporated into the outer membrane in a process that depends on YaeT, a component of an outer membrane β-barrel insertion machinery. We investigated the role of the periplasmic chaperone Skp in IcsA maturation. Skp is required for the presentation of the mature amino terminus (alpha-domain) of IcsA on the bacterial surface and contributes to cell-to-cell spread ofS. flexneriin cell culture. A mutation inskpdoes not prevent the insertion of the β-barrel into the outer membrane, suggesting that the primary role of Skp is the folding of the IcsA alpha-domain. In addition, the requirement forskpcan be partially bypassed by disruptingicsP, an ortholog ofEscherichia coli ompT, which encodes the protease that processes IcsA between the mature amino terminus and the β-barrel outer membrane anchor. These findings are consistent with a model in which Skp plays a critical role in the chaperoning of the alpha-domain of IcsA during transit through the periplasm.
The
d
-2-Hydroxyacid Dehydrogenase Incorrectly Annotated PanE Is the Sole Reduction System for Branched-Chain 2-Keto Acids in
Lactococcus lactis
Authors: Chambellon Emilie , Rijnen Liesbeth , Lorquet Frédérique , Gitton Christophe , van Hylckama Vlieg Johan E. T. , Wouters Jeroen A. , Yvon Mireille
Published: December 2008

Hydroxyacid dehydrogenases of lactic acid bacteria, which catalyze the stereospecific reduction of branched-chain 2-keto acids to 2-hydroxyacids, are of interest in a variety of fields, including cheese flavor formation via amino acid catabolism. In this study, we used both targeted and random mutagenesis to identify the genes responsible for the reduction of 2-keto acids derived from amino acids in
Lactococcus lactis
. The gene
panE
, whose inactivation suppressed hydroxyisocaproate dehydrogenase activity, was cloned and overexpressed in
Escherichia coli
, and the recombinant His-tagged fusion protein was purified and characterized. The gene annotated
panE
was the sole gene responsible for the reduction of the 2-keto acids derived from leucine, isoleucine, and valine, while
ldh
, encoding
l
-lactate dehydrogenase, was responsible for the reduction of the 2-keto acids derived from phenylalanine and methionine. The kinetic parameters of the His-tagged PanE showed the highest catalytic efficiencies with 2-ketoisocaproate, 2-ketomethylvalerate, 2-ketoisovalerate, and benzoylformate (
V
max
/

K
m

ratios of 6,640, 4,180, 3,300, and 2,050 U/mg/mM, respectively), with NADH as the exclusive coenzyme. For the reverse reaction, the enzyme accepted
d
-2-hydroxyacids but not
l
-2-hydroxyacids. Although PanE showed the highest degrees of identity to putative NADP-dependent 2-ketopantoate reductases (KPRs), it did not exhibit KPR activity. Sequence homology analysis revealed that, together with the
d
-mandelate dehydrogenase of
Enterococcus faecium
and probably other putative KPRs, PanE belongs to a new family of
d
-2-hydroxyacid dehydrogenases which is unrelated to the well-described
d
-2-hydroxyisocaproate dehydrogenase family. Its probable physiological role is to regenerate the NAD
+
necessary to catabolize branched-chain amino acids, leading to the production of ATP and aroma compounds.
Functional Analysis of the
Streptomyces coelicolor
NrdR ATP-Cone Domain: Role in Nucleotide Binding, Oligomerization, and DNA Interactions
Authors: Grinberg Inna , Shteinberg Tatyana , Hassan A. Quamrul , Aharonowitz Yair , Borovok Ilya , Cohen Gerald
Published: December 2008

Ribonucleotide reductases (RNRs) are essential enzymes in all living cells, providing the only known de novo pathway for the biosynthesis of deoxyribonucleotides (dNTPs), the immediate precursors of DNA synthesis and repair. RNRs catalyze the controlled reduction of all four ribonucleotides to maintain a balanced pool of dNTPs during the cell cycle.
Streptomyces
species contain genes,
nrdAB
and
nrdJ
, coding for oxygen-dependent class I and oxygen-independent class II RNRs, either of which is sufficient for vegetative growth. Both sets of genes are transcriptionally repressed by NrdR. NrdR contains a zinc ribbon DNA-binding domain and an ATP-cone domain similar to that present in the allosteric activity site of many class I and class III RNRs. Purified NrdR contains up to 1 mol of tightly bound ATP or dATP per mol of protein and binds to tandem 16-bp sequences, termed NrdR-boxes, present in the upstream regulatory regions of bacterial RNR operons. Previously, we showed that the ATP-cone domain alone determines nucleotide binding and that an NrdR mutant defective in nucleotide binding was unable to bind to DNA probes containing NrdR-boxes. These observations led us to propose that when NrdR binds ATP/dATP it undergoes a conformational change that affects DNA binding and hence RNR gene expression. In this study, we analyzed a collection of ATP-cone mutant proteins containing changes in residues inferred to be implicated in nucleotide binding and show that they result in pleiotrophic effects on ATP/dATP binding, on protein oligomerization, and on DNA binding. A model is proposed to integrate these observations.
Preferential Reduction of the Thermodynamically Less Favorable Electron Acceptor, Sulfate, by a Nitrate-Reducing Strain of the Sulfate-Reducing Bacterium
Desulfovibrio desulfuricans
27774
Authors: Marietou Angeliki , Griffiths Lesley , Cole Jeff
Published: December 2008

Desulfovibrio desulfuricans
strain 27774 is one of a relative small group of sulfate-reducing bacteria that can also grow with nitrate as an alternative electron acceptor, but how nitrate reduction is regulated in any sulfate-reducing bacterium is controversial. Strain 27774 grew more rapidly and to higher yields of biomass with nitrate than with sulfate or nitrite as the only electron acceptor. In the presence of both sulfate and nitrate, sulfate was used preferentially, even when cultures were continuously gassed with nitrogen and carbon dioxide to prevent sulfide inhibition of nitrate reduction. The
napC
transcription start site was identified 112 bases upstream of the first base of the translation start codon. Transcripts initiated at the
napC
promoter that were extended across the
napM-napA
boundary were detected by reverse transcription-PCR, confirming that the six
nap
genes can be cotranscribed as a single operon. Real-time PCR experiments confirmed that
nap
operon expression is regulated at the level of mRNA transcription by at least two mechanisms: nitrate induction and sulfate repression. We speculate that three almost perfect inverted-repeat sequences located upstream of the transcription start site might be binding sites for one or more proteins of the CRP/FNR family of transcription factors that mediate nitrate induction and sulfate repression of nitrate reduction by
D. desulfuricans
.
Activation of Dormant Bacterial Genes byNonomuraeasp. Strain ATCC 39727 Mutant-Type RNA Polymerase
Authors: Talà Adelfia , Wang Guojun , Zemanova Martina , Okamoto Susumu , Ochi Kozo , Alifano Pietro
Published: December 2008

There is accumulating evidence that the ability of actinomycetes to produce antibiotics and other bioactive secondary metabolites has been underestimated due to the presence of cryptic gene clusters. The activation of dormant genes is therefore one of the most important areas of experimental research for the discovery of drugs in these organisms. The recent observation that several actinomycetes possess two RNA polymerase β-chain genes (rpoB) has opened up the possibility, explored in this study, of developing a new strategy to activate dormant gene expression in bacteria. TworpoBparalogs,rpoB(S) andrpoB(R), provideNonomuraeasp. strain ATCC 39727 with two functionally distinct and developmentally regulated RNA polymerases. The product ofrpoB(R), the expression of which increases after transition to stationary phase, is characterized by five amino acid substitutions located within or close to the so-called rifampin resistance clusters that play a key role in fundamental activities of RNA polymerase. Here, we report thatrpoB(R) markedly activated antibiotic biosynthesis in the wild-typeStreptomyces lividansstrain 1326 and also in strain KO-421, a relaxed (rel) mutant unable to produce ppGpp. Site-directed mutagenesis demonstrated that therpoB(R)-specific missense H426N mutation was essential for the activation of secondary metabolism. Our observations also indicated that mutant-type or duplicated,rpoBoften exists in nature among rare actinomycetes and will thus provide a basis for further basic and applied research.
Transcription of
clpP
Is Enhanced by a Unique Tandem Repeat Sequence in
Streptococcus mutans
Authors: Zhang Jiaqin , Banerjee Anirban , Biswas Indranil
Published: December 2008

Streptococcus mutans
, the primary causative agent of human dental caries, contains a single copy of the gene encoding ClpP, the chief intracellular protease responsible for tolerance to various environmental stresses. To better understand the role of ClpP in stress response, we investigated the regulation of
clpP
expression in
S. mutans
. Using semiquantitative reverse transcription-PCR analysis, we observed that, under nonstressed conditions,
clpP
expression is somewhat constant throughout the growth phases, although it gradually decreases as cells enter the late stationary phase. The half-life of the
clpP
transcript was found to be less than 1 minute. Sequence analysis of the
clpP
locus reveals the presence of a 50-bp tandem repeat sequence located immediately upstream of the
clpP
promoter (P
clpP
). PCR and DNA sequence analyses suggest that the number of tandem repeat units can vary from as few as two to as many as nine, depending on the particular
S. mutans
isolate. Further analysis, using a transcriptional reporter fusion consisting of P
clpP
fused to a promoterless
gusA
gene, indicates that the presence of the repeat sequence region within P
clpP
results in an approximately fivefold increase in expression from P
clpP
compared to the repeat-free transcriptional reporter fusion. CtsR, a transcriptional repressor that negatively regulates
clpP
expression, has no effect on this repeat-mediated induction of
clpP
transcription. Furthermore, the repeat sequence is not necessary for the induction of
clpP
under stress conditions. Database searches indicate that the region containing the tandem repeats is absent in the
clpP
loci in other bacteria, including other closely related
Streptococcus
spp., suggesting that the repeat sequences are specific for the induction of
clpP
expression in
S. mutans
. We speculate that a host-specific transcriptional activator might be involved in the upregulation of
clpP
expression in
S. mutans
.
Extracytoplasmic Function σ Factors Regulate Expression of the
Bacillus subtilis yabE
Gene via a
cis
-Acting Antisense RNA
Authors: Eiamphungporn Warawan , Helmann John D.
Published: December 2008

Bacillus subtilis yabE
encodes a predicted resuscitation-promoting factor/stationary-phase survival (Rpf/Sps) family autolysin. Here, we demonstrate that
yabE
is negatively regulated by a
cis
-acting antisense RNA which, in turn, is regulated by two extracytoplasmic function σ factors: σ
X
and σ
M
.
Medical paternalism inHouse M.D.
Authors: Wicclair M R
Published: December 2008

The popular television seriesHouse M.D.is drawn upon to provide a critical examination of medical paternalism and how it is presented in the show. Dr Gregory House, the character named in the title of the series, is a paradigm of a paternalistic physician. He believes that he knows what is best for his patients, and he repeatedly disregards their wishes in order to diagnose and treat their illnesses. This paper examines several examples of medical paternalism and the means used to portray it favourably in the series. It is argued that the positive depiction of medical paternalism in the fictional world of the series does not apply in the real world. The paper also considers why a show that features a paternalistic physician who so blatantly flouts mainstream medical ethics might appeal to health professionals and members of the general public.
TUNNELING SPECTROSCOPY OF MANGANITES WITH NANOSCALE STRUCTURAL NON-UNIFORMITIES
Authors: SVISTUNOV V. M. , LEONOVA V. N. , BELOGOLOVSKII M. A. , MEDVEDEV Yu. V. , REVENKO Yu. F. , STRZHEMECHNY Y. M. , HUI D. , ENDO T.
Published: December 2008

We report on our recent electron-tunneling studies of bulk manganite samples that provide important information about the structure of the near-surface layers of the material and the nature of the charge transport across them. It is shown that the even part of the differential conductance of contacts formed by a metallic injector with the surface of a manganite is a power function of the voltage bias. High voltages applied to the sample are found to locally modify the conductance of the degraded native surface layer. Experiments aimed to monitor the force applied to a metal tip pressed into the surface of a manganite prove the presence of sub-surface layers with properties significantly different from those near the surface. Experimental data are analyzed and interpreted within the Glazman–Matveev theory taking into account inelastic tunneling through two metallic "drops" inside the insulating barrier.
A THEORETICAL FRAMEWORK MAPPING GRAMMAR BASED SYSTEMS AND FRACTAL DESCRIPTION
Authors: ZAMMOURI IKBAL , TOSAN ERIC , AYEB BÉCHIR
Published: December 2008

In this work, we propose a new method to describe fractal shapes using parametric L-systems. This method consists of introducing scaling factors in the production rules of the parametric L-system grammars. We present a turtle monoid on which we base our calculations to show the exact mathematical relation between L-systems and iterated function systems (IFS); we then establish the conditions for the scaling factors to produce plants' and curves' fractal shapes from parametric L-systems. We demonstrate that with specific values of the scaling factors, we find the exact relationship established by Prusinkiewicz and Hammel between L-systems and IFS. Finally, we present some examples of fractal plant forms and curves created using parametric L-systems with scaling factors.
SELF-SIMILARITY OF SATISFIABLE BOOLEAN EXPRESSIONS DECIPHERED IN TERMS OF GRAPH DIRECTED ITERATED FUNCTION SYSTEMS
Authors: NI TIAN-JIA , WEN ZHI-YING
Published: December 2008

The decision problem of satisfiability of Boolean expression in k-conjunctive normal form (kSAT) is a typical NP-complete problem. In this paper, by mapping the whole Boolean expressions in k-conjunctive normal form onto a unit hypercube, we visualize the problem space of kSAT. The pattern of kSAT is shown to have self-similarity which can be deciphered in terms of graph directed iterated function system. We provide that the Hausdorff dimension of the pattern of kSAT is equal to the box-counting dimension and increases with k. This suggests that the time complexity of kSAT increases with k.
FRACTAL, A MICROSCOPIC CROWD MODEL
Authors: WIDYARTO SETYAWAN , LATIFF M. S. ABD.
Published: December 2008

The core of this research is related to the human crowd problem. Some major problems are congestion, emergency evacuation, and fatal catastrophe. In fact, it has been realized that many crowd related problems can be resolved by influencing (controlling) human flow with providing various control measures. Thus, the problem itself becomes the motivation for this research and the solution is approached through model and simulation within the virtual environment.

The relationship between fractal pattern and crowd behavior is produced with respect to the crowd behavior model. It exposes a comparison between the crowd paths resulting from the model developed and the fractal formation created to imitate the crowd paths. A new approach for crowd behavior modeling is proposed based on fractal features and, thus, gives new understanding about a relationship between fractal pattern and crowd behavior. Several innovations of fractal patterns that can be used in crowd behavior model applications adds to the novelty of the research contribution. Ultimately, the new method of modeling the crowd can be obtained and at the same time the new direction of crowd modeling research can be directed.
RENDERING OF THE INSIDE STRUCTURE OF THE GENERALIZED M SET PERIOD BULBS BASED ON THE PRE-PERIOD
Authors: WANG XINGYUAN , JIA RUIHONG
Published: December 2008

This paper modifies the escape-time method, analyzes the process that the points inside a period bulb of the generalized Mandelbrot set (the generalized M set) after iterating a certain pre-period process finally enter into the periodic orbit. All the points with same pre-period form a circularity structure which shapes similar as the period bulb; as pre-period grows the circularity structure diffuses towards the period bulb boundary until crams the whole period bulb. Besides, we present a particular experimental observation of the rule of the pre-period bulb graphic of the generalized M set and its growing process and offer the theory proof.
Contribution of upper airway geometry to convective mixing
Authors: Jayaraju Santhosh T. , Paiva Manuel , Brouns Mark , Lacor Chris , Verbanck Sylvia
Published: December 2008

We investigated the axial dispersive effect of the upper airway structure (comprising mouth cavity, oropharynx, and trachea) on a traversing aerosol bolus. This was done by means of aerosol bolus experiments on a hollow cast of a realistic upper airway model (UAM) and three-dimensional computational fluid dynamics (CFD) simulations in the same UAM geometry. The experiments showed that 50-ml boluses injected into the UAM dispersed to boluses with a half-width ranging from 80 to 90 ml at the UAM exit, across both flow rates (250, 500 ml/s) and both flow directions (inspiration, expiration). These experimental results imply that the net half-width induced by the UAM typically was 69 ml. Comparison of experimental bolus traces with a one-dimensional Gaussian-derived analytical solution resulted in an axial dispersion coefficient of 200–250 cm2/s, depending on whether the bolus peak and its half-width or the bolus tail needed to be fully accounted for. CFD simulations agreed well with experimental results for inspiratory boluses and were compatible with an axial dispersion of 200 cm2/s. However, for expiratory boluses the CFD simulations showed a very tight bolus peak followed by an elongated tail, in sharp contrast to the expiratory bolus experiments. This indicates that CFD methods that are widely used to predict the fate of aerosols in the human upper airway, where flow is transitional, need to be critically assessed, possibly via aerosol bolus simulations. We conclude that, with all its geometric complexity, the upper airway introduces a relatively mild dispersion on a traversing aerosol bolus for normal breathing flow rates in inspiratory and expiratory flow directions.
Crystal structure and thermal properties of compound K2Zn3(P2O7)2
Authors: Ji L. N. , Cai G. M. , Li J. B. , Luo J. , Liang J. K. , Zhang J. Y. , Liu Y. H. , Rao G. H. , Chen X. L.
Published: December 2008

K2Zn3(P2O7)2was synthesized by solid state reaction and its crystal structure was determined byab initiomethod from powder X-ray diffraction (XRD) data. The title compound was determined to be orthorhombic with space groupP212121,Z=4, and lattice parametersa=12.901(8) Å,b=10.102(6) Å, andc=9.958(1) Å. Values of lattice parameters from 303 to 573 K were measured by temperature-dependent XRD. Thermal expansion coefficientsα0, lattice parameters, and cell volume at 0 K were determined to beα0(a)=1.62327×10−4/K,a0=12.855(4) Å,α0(b)=1.17921×10−4/K,b0=10.070(8) Å,α0(c)=2.62364×10−4/K,c0=9.880(4) Å, andα0(V)=6.599×10−2/K,V0=1278.967(0) Å3. The specific heat equation as a function of temperature was determined to beCp=0.77115+0.00231T−1241.60027T−2−1.4133×10−6T2(J/K g), for temperatures from 198 to 710 K. The melting point estimated from theμ-DTA heating curve is 795 °C.
Ab initio structure determination of the low-temperature phase of succinonitrile from laboratory X-ray powder diffraction data—Coping with potential poor powder quality using DFT ab initio methods
Authors: Whitfield P. S. , Le Page Y. , Abouimrane A. , Davidson I. J.
Published: December 2008

Without experimental or predicted literature crystal structures for succinonitrile at low temperature, structure solution was attempted from powder diffraction data taken at 173 and 90 K from a solid sample. Its room-temperature plastic-crystal state makes production of a sample with good particle statistics and random orientation almost impossible. Combining constrained models, simulated annealing, and careful application of second-order spherical harmonic corrections nevertheless produced viable-looking structures at 90 and 173 K, yielding two distinct structure models with the same projection down c. VASP optimization of atom coordinates in the experimental cell agreed well with the 90 K model but poorly with the model derived from the 173 K data. The refined 90 K structure changed little on optimization and fitted all datasets from 85 to 225 K. Plots of cell data, torsion angles, and isotropic displacement parameters against temperature suggest possible phase transitions around 100, 120, and 180 K. Cell data at 90 K: monoclinic P21/a, a=9.0851(5) Å, b=8.5617(5) Å, c=5.8343(3) Å, β=79.295(2)°, and Z=4. Succinonitrile has gauche conformation, in agreement with literature spectroscopy data.
Time‐Frequency Characterization of Rotating Instabilities in a Centrifugal Pump with a Vaned Diffuser
Authors: Pavesi G. , Cavazzini G. , Ardizzon G.
Published: December 2008

This paper presents acoustic and flowdynamic investigations of large‐scale instabilities in a radial pump with a vaned diffuser. Pressure fluctuations were measured with transducers placed flush at the inlet duct, at the impeller discharge, and in the vane diffuser walls. Two impeller rotation speeds were analyzed in the study, at design, and at off‐design flow rates. A spectral analysis was carried out on the pressure signals in frequency and in time‐frequency domains to identified precursors, inception, and evolution of the pressure instabilities. The results highlighted the existence of a rotating pressure structure at the impeller discharge, having a fluid‐dynamical origin and propagating both in the radial direction and inside the impeller. The experimental data were then compared with the results obtained with help of ANSYS CFX computer code; focusing on the changing flow field at part load. Turbulence was reproduced by DES model.
Gratings in Structured Optical Fibres
Authors: Canning John , Groothoff Nathaniel , Cook Kevin , Martelli Cicero , Pohl Alexandre , Holdsworth John , Bandyopadhyay Somnath , Stevenson Michael
Published: December 2008

Grating writing in structured optical fibres and their properties and applications are reviewed. To date, most gratings have been written in a straightforward
manner into structured fibres containing a photosensitive germanosilicate step-index core. However, gratings have also been written directly into single material, structured silica fibres and into air-clad cores using two and higher-photon processes with both UV and near IR pulsed (nanosecond-femtosecond) light. Given the intrinsic-added functionality possible within a structured optical fibre, structured fibre gratings offer further capabilities for sensors, diagnostics, lasers, and devices.
Different Effects of Angiotensin Converting Enzyme Inhibitors on Endothelin‐1 and Nitric Oxide Balance in Human Vascular Endothelial Cells: Evidence of an Oxidant‐Sensitive Pathway
Authors: Desideri Giovambattista , Grassi Davide , Croce Giuseppe , Bocale Raffaella , Tiberi Sergio , Evangelista Stefano , Necozione Stefano , Di Orio Ferdinando , Ferri Claudio
Published: December 2008

Angiotensin converting enzyme inhibitors (ACE‐I) are known to affect the endothelial function decreasing the formation of the potent vasoconstrictor angiotensin II and increasing the bioavailability of the vasodilators bradykinin and nitric oxide. In order to test the potential differences among the class of ACE‐I, we have evaluated their effects on endothelin‐1 and nitric oxide availability, and on reactive oxygen species generation in human vascular endothelial cells (HUVECs) obtained from umbilical cord veins. HUVECs were cultured in the presence of either sulfhydryl‐containing ACE‐I (zofenoprilat or captopril) or nonsulfhydryl‐containing ACE‐I (enalaprilat or lisinopril). After 24 hours, all ACE‐I reduced endothelin‐1 secretion and increased nitric oxide production. However, zofenoprilat
(−42% after 8 hours of incubation) was more effective (P < .05) than enalaprilat
(−25%), lisinopril (−21%), and captopril (−30%) in reducing endothelin‐1 secretion. Similarly, zofenoprilat (+110% after 8 hours of incubation) was more effective (P < .05) than enalaprilat (+64%), lisinopril (+63%), and captopril (+65%) in increasing nitrite plus nitrate production. The effect of ACE‐I on the nitric oxide availability and on endothelin‐1 secretion is mediated by the activation of bradykinin
B2 receptor being reverted, at least in part, by a specific antagonist. Zofenoprilat and, to a lesser extent, captopril also blunted tumour necrosis factor (TNF)α‐stimulated production of reactive oxygen species and decreased TNFα‐stimulated glutathione consumption in endothelial cells. In conclusion, structural differences among the class of ACE‐I play a role in their interaction with mediators that influence the homeostasis of the endothelium. The marked antioxidant effects exerted by zofenoprilat due to its sulphydryl group and lipophilia seem to be responsible for its greater endothelium protective activity.
BlogWall: Social and Cultural Interaction for Children
Authors: Cheok Adrian David , Fernando Owen Noel Newton , Wijesena Janaka Prasad , Mustafa Abd-ur-Rehman , Shankar Ramkumar , Barthoff Anne-Katrin , Tosa Naoko , Choi Yongsoon , Agarwal Mayank
Published: December 2008

Short message service (SMS) is extremely popular today. Currently, it is being mainly used for peer-to-peer communication. However, SMS could be used as public media platform to enhance social and public interactions in an intuitive way. We have developed BlogWall to extend the SMS to a new level of self-expression and public communication by combining art and poetry. Furthermore, it will provide a means of expression in the language that children can understand, and the forms of social communication. BlogWall can also be used to educate the children while they interact and play with the system. The most notable feature of the system is its ability to mix up and generate poetry in multiple languages such as English, Korean, Chinese poems, or Japanese “Haiku” all based on the SMS. This system facilitates a cultural experience to children unknowingly, thus it is a step into new forms of cultural computing.
Thermal Arrest Memory Effect in Ni-Mn-Ga Alloys
Authors: Rudajevova A.
Published: December 2008

Dilatation characteristics were measured to investigate the thermal arrest memory effect inNi53.6Mn27.1Ga19.3andNi54.2Mn29.4Ga16.4alloys. Interruption of the martensite-austenite phase transformation is connected with the reduction of the sample length after thermal cycle. If a total phase transformation took place in the complete thermal cycle following the interruption, then the sample length would return to its original length. Analysis of these results has shown that the thermal arrest memory effect is a consequence of a stress-focusing effect and shape memory effect. The stress-focusing effect occurs when the phase transformation propagates radially in a cylindrical sample from the surface, inward to the center. Evolution and release of the thermoelastic deformations in both alloys during heating and cooling are analyzed.
On the Use of Magnetic RAMs in Field-Programmable Gate Arrays
Authors: Guillemenet Y. , Torres L. , Sassatelli G. , Bruchon N.
Published: December 2008

This paper describes the integration of field-induced magnetic switching (FIMS) and thermally assisted switching (TAS) magnetic random access memories in FPGA design. The nonvolatility of the latter is achieved through the use of magnetic tunneling junctions (MTJs) in the MRAM cell. A thermally assisted switching scheme helps to reduce power consumption during write operation in comparison to the writing scheme in the FIMS-MTJ device. Moreover, the nonvolatility of such a design based on either an FIMS or a TAS writing scheme should reduce both power consumption and configuration time required at each power up of the circuit in comparison to classical SRAM-based FPGAs. A real-time reconfigurable (RTR) micro-FPGA using FIMS-MRAM or TAS-MRAM allows dynamic reconfiguration mechanisms, while featuring simple design architecture.
Size Dependence of Dislocation‐Mediated Plasticity in Ni Single Crystals: Molecular Dynamics Simulations
Authors: Li Xiaoyan , Yang Wei
Published: December 2008

We investigate the compressive yielding of Ni single crystals by performing atomistic simulations with the sample diameters in the range of 5 nm ∼ 40 nm. Remarkable effects of sample sizes on the yield strength are observed in the nanopillars with two different orientations. The deformation mechanisms are characterized by massive dislocation activities within a single slip system and a nanoscale deformation twining in an octal slip system. A dislocation dynamics‐based model is proposed to interpret the size and temperature effects in single slip‐oriented nanopillars by considering the nucleation of incipient dislocations.
Enhancing E-Health Information Systems with Agent Technology
Authors: Nguyen Minh Tuan , Fuhrer Patrik , Pasquier-Rocha Jacques
Published: December 2008

Agent Technology is an emerging and promising research area in software technology, which increasingly contributes to the development of value-added information systems for large healthcare organizations. Through the MediMAS prototype, resulting from a case study conducted at a local Swiss hospital, this paper aims at presenting the advantages of reinforcing such a complex E-health man-machine information organization with software agents. The latter will work on behalf of human agents, taking care of routine tasks, and thus increasing the speed, the systematic, and ultimately the reliability of the information exchanges. We further claim that the modeling of the software agent layer can be methodically derived from the actual “classical” laboratory organization and practices, as well as seamlessly integrated with the existing information system.
The Effects of Thiazolidinediones on Metabolic Complications and Lipodystrophy in HIV‐Infected Patients
Authors: Sutinen Jussi
Published: December 2008

Highly active antiretroviral therapy (HAART)‐associated metabolic complications include lipoatrophy (loss of subcutaneous adipose tissue (SAT)) and insulin resistance. Thiazolidinediones are insulin‐sensitizing antidiabetic agents which—as an untoward side effect in obese diabetic patients—increase SAT. Furthermore, troglitazone has improved lipoatrophy and glycemic control in non‐HIV patients with various forms of lipodystrophy. These data have led to 14 clinical trials to examine whether thiazolidinediones could be useful in the treatment of HAART‐associated metabolic complications. The results of these studies indicate very modest, if any, effect on lipoatrophic SAT, probably due to ongoing HAART negating the beneficial effect. The benefit might be more prominent in patients not taking thymidine analoges. Despite the poor effect on lipoatrophy, thiazolidin‐ediones improved insulin sensitivity. However, especially rosiglitazone induced harmful effects on blood lipids. Current data do not provide evidence for the use of thiazolidinediones in the treatment of HAART‐associated lipoatrophy, but treatment of lipoatrophy‐associated diabetes may be warranted. The role of thiazolidinediones for novel indications, such as hepatosteatosis, should be studied in these patients.
HIV‐1 Infection and the PPARγ‐Dependent Control of Adipose Tissue Physiology
Authors: Giralt Marta , Domingo Pere , Villarroya Francesc
Published: December 2008

PPARγis a ligand‐dependent master transcription factor controlling adipocyte differentiation as well as multiple biological processes taking place in other cells present in adipose tissue depots such as macrophages. Recent research indicates that HIV‐1 infection‐related events may alter adipose tissue biology through several mechanisms involving PPARγ, ranging from direct effects of HIV‐1‐encoded proteins on adipocytes to the promotion of a proinflammatory environment that interferes with PPARγactions. This effect of HIV‐1 on adipose tissue cells can occur even in the absence of direct infection of adipocytes, as soluble HIV‐1‐encoded proteins such as Vpr may enter cells and inhibit PPARγaction. Moreover, repression of PPARγactions may relieve inhibitory pathways of HIV‐1 gene transcription, thus enhancing HIV‐1 effects in infected cells. HIV‐1 infection‐mediated interference of PPARγ‐dependent pathways in adipocytes and other cells inside adipose depots such as macrophages is likely to create an altered local environment that, after antiretroviral treatment, leads to lipodystrophy in HIV‐1‐infected and HAART‐treated patients.
Antiaversive Effects of Cannabinoids: Is the Periaqueductal Gray Involved?
Authors: Moreira F. A. , Aguiar D. C. , Campos A. C. , Lisboa S. F. , Terzian A. L. , Resstel L. B. , Guimarães F. S.
Published: December 2008

Cannabinoids play an important role in activity-dependent changes in synaptic activity and can interfere in several brain functions, including responses to aversive stimuli. The regions responsible for their effects, however, are still unclear. Cannabinoid type 1 (CB1) receptors are widely distributed in the central nervous system and are present in the periaqueductal gray (PAG), a midbrain structure closely involved in responses related to aversive states. Accordingly, exposure to stressful stimuli increases endocannabinoid (eCB) levels in the PAG, and local administration of CB1 agonists or drugs that facilitate eCB-mediated neurotransmission produces antinociceptive and antiaversive effects. To investigate if these drugs would also interfere in animal models that are sensitive to anxiolytic drugs, we verified the responses to intra-PAG injection of CB1 agonists in rats submitted to the elevated plus-maze, the Vogel punished licking test, or contextual aversive conditioning model. The drugs induced anxiolytic-like effects in all tests. The same was observed with the transient receptor potential vanilloid type 1 (TRPV1) antagonist capsazepine and with cannabidiol, a nonpsychotomimetic phytocannabinoid that produces anxiolytic-like effects after systemic administration in humans and laboratory animals. These results, therefore, suggest that the PAG could be an important site for the antiaversive effects of cannabinoids.
Alterations in Circulatory and Renal Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 in Fetal Programmed Hypertension
Authors: Shaltout Hossam A. , Figueroa Jorge P. , Rose James C. , Diz Debra I. , Chappell Mark C.
Published: December 2008

Antenatal betamethasone treatment is a widely accepted therapy to accelerate lung development and improve survival in preterm infants. However, there are reports that infants who receive antenatal glucocorticoids exhibit higher systolic blood pressure in their early adolescent years. We have developed an experimental model of programming whereby the offspring of pregnant sheep administered clinically relevant doses of betamethasone exhibit elevated blood pressure. We tested the hypothesis as to whether alterations in angiotensin-converting enzyme (ACE), ACE2, and neprilysin in serum, urine, and proximal tubules are associated with this increase in mean arterial pressure. Male sheep were administered betamethasone (2 doses of 0.17 mg/kg, 24 hours apart) or vehicle at the 80th day of gestation and delivered at term. Sheep were instrumented at adulthood (1.8 years) for direct conscious recording of mean arterial pressure. Serum and urine were collected and proximal tubules isolated from the renal cortex. Betamethasone-treated animals had elevated mean arterial pressure (97±3 versus 83±2 mm Hg;
P
<0.05) and a 25% increase in serum ACE activity (48.4±7.0 versus 36.0±2.7 fmol/mL per minute) but a 40% reduction in serum ACE2 activity (18.8±1.2 versus 31.4±4.4 fmol/mL per minute). In isolated proximal tubules, ACE2 activity and expression were 50% lower in the treated sheep with no significant change in ACE or neprilysin activities. We conclude that antenatal steroid treatment results in the chronic alteration of ACE and ACE2 in the circulatory and tubular compartments, which may contribute to the higher blood pressure in this model of fetal programming–induced hypertension.