bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the relationship between true and measured resist feature critical dimension and line edge roughness using a detailed scanning electron microscopy simulator
Authors: Lawson Richard A. , Henderson Clifford L.
Published: November 2010

Top-down critical dimension scanning electron microscopy (SEM) is still the workhorse metrology tool used for nanoscale structure analysis, such as measurement of photoresist features, during integrated circuit manufacturing. However, the degree to which top-down SEM imaging can accurately be used to quantitatively determine the size, shape, and roughness characteristics of three-dimensional structures such as photoresist features has not been carefully characterized. A rigorous Monte Carlo simulation of scanning electron microscopy has been developed to probe the relationship between the roughness of a three-dimensional feature and the line edge roughness (LER) as measured by SEM. The model uses the differential Mott cross section to compute elastic scattering, while inelastic scattering and secondary electron generation are handled using dielectric function theory. The model can calculate the electron scattering for any arbitrary three-dimensional geometry. Experimental SEM measurements of photoresist nanostructures show good agreement with the simulation output. The critical dimension of the resist determined from SEM best matches the true resist feature width when the line edge is defined using a high image threshold because the roughness on the outer edge of the resist tends to cause an increase in SEM signal that is nonproportional to the amount of material on the outer edge of the feature. LER determined from SEM was found to be significantly smaller than the true resist feature sidewall roughness. The measured LER is typically greater than 50% smaller than the actual sidewall roughness.
Revisiting perceptual compensation for effects of reverberation in speech identification
Authors: Nielsen Jens Bo , Dau Torsten
Published: November 2010

Listeners were given the task to identify the stop-consonant [t] in the test-word “stir” when the word was embedded in a carrier sentence. Reverberation was added to the test-word, but not to the carrier, and the ability to identify the [t] decreased because the amplitude modulations associated with the [t] were smeared. When a similar amount of reverberation was also added to the carrier sentence, the listeners’ ability to identify the stop-consonant was restored. This phenomenon has in previous research been considered as evidence for an extrinsic compensation mechanism for reverberation in the human auditory system [Watkins (2005). J. Acoust. Soc. Am. 118, 249–262]. In the present study, the reverberant test-word was embedded in additional non-reverberant carriers, such as white noise, speech-shaped noise and amplitude modulated noise. In addition, a reference condition was included where the test-word was presented in isolation, i.e., without any carrier stimulus. In all of these conditions, the ability to identify the stop-consonant [t] was enhanced relative to the condition using the non-reverberant speech carrier. The results suggest that the non-reverberant speech carrier produces an interference effect that impedes the identification of the stop-consonant. These findings raise doubts about the existence of the compensation mechanism.
In Silico
Screening, Structure-Activity Relationship, and Biologic Evaluation of Selective Pteridine Reductase Inhibitors Targeting Visceral Leishmaniasis
Authors: Kaur Jaspreet , Kumar Pranav , Tyagi Sargam , Pathak Richa , Batra Sanjay , Singh Prashant , Singh Neeloo
Published: November 2010

In this study we utilized the concept of rational drug design to identify novel compounds with optimal selectivity, efficacy and safety, which would bind to the target enzyme pteridine reductase 1 (PTR1) in
Leishmania
parasites. Twelve compounds afforded from Baylis-Hillman chemistry were docked by using the QUANTUM program into the active site of
Leishmania donovani
PTR1 homology model. The biological activity for these compounds was estimated in green fluorescent protein-transfected
L. donovani
promastigotes, and the most potential analogue was further investigated in intracellular amastigotes. Structure-activity relationship based on homology model drawn on our recombinant enzyme was substantiated by recombinant enzyme inhibition assay and growth of the cell culture. Flow cytometry results indicated that 7-(4-chlorobenzyl)-3-methyl-4-(4-trifluoromethyl-phenyl)-3,4,6,7,8,9-hexahydro-pyrimido[1,2-a]pyrimidin-2-one (compound 7) was 10 times more active on
L. donovani
amastigotes (50% inhibitory concentration [IC
50
] = 3 μM) than on promastigotes (IC
50
= 29 μM). Compound 7 exhibited a

K
i

value of 0.72 μM in a recombinant enzyme inhibition assay. We discovered that novel pyrimido[1,2-a]pyrimidin-2-one systems generated from the allyl amines afforded from the Baylis-Hillman acetates could have potential as a valuable pharmacological tool against the neglected disease visceral leishmaniasis.
In Vitro
Activity and
In Vivo
Efficacy of Posaconazole in Treatment of Murine Infections by Different Isolates of the
Aspergillus terreus
Complex
Authors: Salas Valentina , Pastor F. Javier , Rodríguez M. M. , Calvo Enrique , Mayayo Emilio , Guarro Josep
Published: November 2010

Posaconazole (PSC) is an antifungal drug recommended as an alternative for the treatment of invasive aspergillosis in patients who are refractory or intolerant to primary antifungal therapy. We have evaluated the
in vitro
activity of PSC against 21 strains of the
Aspergillus terreus
complex using both broth microdilution and disk diffusion (Neo Sensitabs) methods. PSC showed the same high level of activity against all the strains with the two
in vitro
methods used. We developed a murine model of disseminated infection to evaluate the efficacy of PSC at 5, 10, or 20 mg/kg of body weight twice a day by using 6 different strains chosen randomly. PSC showed good efficacy, especially at 20 mg/kg, as measured by prolonged survival, tissue burden reduction, histopathology, and lowered galactomannan levels. The PSC levels in serum on the fourth day of treatment were higher than the MICs for the strains tested.
In Vitro
Antimicrobial Susceptibility of Bacterial Enteropathogens Isolated from International Travelers to Mexico, Guatemala, and India from 2006 to 2008
Authors: Ouyang-Latimer Jeannette , Jafri Syed , VanTassel Audrey , Jiang Zhi-Dong , Gurleen Kaur , Rodriguez Savio , Nandy Ranjan K. , Ramamurthy Thandavaryan , Chatterjee Santanu , McKenzie Robin , Steffen Robert , DuPont Herbert L.
Published: November 2010

The incidence rates of travelers' diarrhea (TD) have remained high for the last 50 years. More recently, there have been increasing recommendations for self-initiated therapy and use of prophylactic drugs for TD. We last examined the
in vitro
susceptibilities of commonly used antibiotics against TD pathogens in 1997. We now examine 456 enteropathogens isolated from adult travelers to Mexico, India, and Guatemala with diarrhea acquired between 2006 and 2008 to determine changes in susceptibility against 10 different antimicrobials by the agar dilution method. Traditional antibiotics, such as ampicillin, trimethoprim-sulfamethoxazole, and doxycycline, continue to show high levels of resistance. Current first-line antibiotic agents, including fluoroquinolones and azithromycin, showed significantly higher MICs than in our earlier study, and MIC
90
levels were above the Clinical and Laboratory Standards Institute cutoffs for resistance. There were significant geographical differences in resistance patterns when Central America was compared with India. Entertoxigenic
Escherichia coli
(ETEC) isolates showed increased resistance to ciprofloxacin (
P
= 0.023) and levofloxacin (
P
= 0.0078) in India compared with Central America. Enteroaggregative
E. coli
(EAEC) isolates from Central America showed increased resistance to nearly all of the antibiotics tested. Compared to MICs of isolates 10 years prior, there were 4- to 10-fold increases in MIC
90
values for ceftriaxone, ciprofloxacin, levofloxacin, and azithromycin for both ETEC and EAEC. There were no significant changes in rifaximin MICs. Rising MICs over time imply the need for continuous surveillance of susceptibility patterns worldwide and geographically specific recommendations in TD therapy.
T-705 (Favipiravir) Inhibition of Arenavirus Replication in Cell Culture
Authors: Mendenhall Michelle , Russell Andrew , Juelich Terry , Messina Emily L. , Smee Donald F. , Freiberg Alexander N. , Holbrook Michael R. , Furuta Yousuke , de la Torre Juan-Carlos , Nunberg Jack H. , Gowen Brian B.
Published: November 2010

A number of New World arenaviruses (Junín [JUNV], Machupo [MACV], and Guanarito [GTOV] viruses) can cause human disease ranging from mild febrile illness to a severe and often fatal hemorrhagic fever syndrome. These highly pathogenic viruses and the Old World Lassa fever virus pose a significant threat to public health and national security. The only licensed antiviral agent with activity against these viruses, ribavirin, has had mixed success in treating severe arenaviral disease and is associated with significant toxicities. A novel pyrazine derivative currently in clinical trials for the treatment of influenza virus infections, T-705 (favipiravir), has demonstrated broad-spectrum activity against a number of RNA viruses, including arenaviruses. T-705 has also been shown to be effective against Pichinde arenavirus infection in a hamster model. Here, we demonstrate the robust antiviral activity of T-705 against authentic highly pathogenic arenaviruses in cell culture. We show that T-705 disrupts an early or intermediate stage in viral replication, distinct from absorption or release, and that its antiviral activity in cell culture is reversed by the addition of purine bases and nucleosides, but not with pyrimidines. Specific inhibition of viral replication/transcription by T-705 was demonstrated using a lymphocytic choriomeningitis arenavirus replicon system. Our findings indicate that T-705 acts to inhibit arenavirus replication/transcription and may directly target the viral RNA-dependent RNA polymerase.
Impact of Outpatient Antibiotic Use on Carriage of Ampicillin-Resistant
Escherichia coli
Authors: Samore Matthew H. , Tonnerre Claude , Hannah Elizabeth Lyon , Stoddard Gregory J. , Borotkanics Robert J. , Haddadin Bassam , Harbarth Stephan
Published: November 2010

Studies about the relationship between antibiotic consumption and carriage of antibiotic-resistant
Escherichia coli
in individual patients have yielded conflicting results. The goal of this study was to identify individual- and household-level factors associated with carriage of ampicillin (AMP)-resistant
E. coli
during consumption of a course of oral antibiotics. We enrolled outpatients and their families in a prospective household study of AMP-resistant or AMP-susceptible
E. coli
carriage. Two kinds of index patients were identified. Group 1 consisted of outpatients who were being initiated on a new antibiotic course at the time of a clinic visit, and group 2 consisted of outpatients not starting antibiotics. Each participant was asked to submit three stool swab samples (at baseline, week 1, and week 4) and to complete a questionnaire. Antimicrobial susceptibility testing was performed on each phenotypically distinct
E. coli
colony. The study included 149 group 1 households (total, 570 participants) and 38 group 2 households (total, 131 participants). AMP-resistant
E. coli
was recovered from 29% of stool samples. Observed associations with antibiotic exposure varied by drug class. Penicillins, which were the most frequently prescribed drug class, were associated with a modest increase in AMP-resistant
E. coli
carriage and a modest decrease in AMP-susceptible
E. coli
carriage. Neither change by itself was statistically significant. Macrolides were associated with reduced carriage of both AMP-resistant
E. coli
and AMP-susceptible
E. coli
(
P
< 0.05). Both AMP-resistant and AMP-susceptible
E. coli
demonstrated household clustering (
P
< 0.001). In summary, the overall effect of antibiotics on individual risk of carriage of AMP-resistant
E. coli
was small. However, even a modest alteration of the competitive balance between AMP-resistant and AMP-susceptible
E. coli
may promote population spread of resistant
E. coli
. Examining changes in both resistant and susceptible organisms in antibiotic-treated individuals and their close contacts improves understanding of antibiotic selection pressure.
Quantification of the Relationship between Bacterial Kinetics and Host Response for Monkeys Exposed to Aerosolized
Francisella tularensis
Authors: Huang Yin , Haas Charles N.
Published: November 2010

Francisella tularensis
can be disseminated via aerosols, and once inhaled, only a few microorganisms may result in tularemia pneumonia. Effective responses to this threat depend on a thorough understanding of the disease development and pathogenesis. In this study, a class of time-dose-response models was expanded to describe quantitatively the relationship between the temporal probability distribution of the host response and the
in vivo
bacterial kinetics. An extensive literature search was conducted to locate both the dose-dependent survival data and the
in vivo
bacterial count data of monkeys exposed to aerosolized
F. tularensis
. One study reporting responses of monkeys to four different sizes of aerosol particles (2.1, 7.5, 12.5, and 24.0 μm) of the SCHU S4 strain and three studies involving five
in vivo
growth curves of various strains (SCHU S4, 425, and live vaccine strains) initially delivered to hosts in aerosol form (1 to 5 μm) were found. The candidate models exhibited statistically acceptable fits to the time- and dose-dependent host response and provided estimates for the bacterial growth distribution. The variation pattern of such estimates with aerosol size was found to be consistent with the reported pathophysiological and clinical observations. The predicted growth curve for 2.1-μm aerosolized bacteria was highly consistent with the available bacterial count data. This is the first instance in which the relationship between the
in vivo
growth of
F
.
tularensis
and the host response can be quantified by mechanistic mathematical models.
Ecological Basis of the Interaction between
Pseudozyma flocculosa
and Powdery Mildew Fungi
Authors: Hammami Walid , Castro Candy Quiroga , Rémus-Borel Wilfried , Labbé Caroline , Bélanger Richard R.
Published: November 2010

In this work, we sought to understand how glycolipid production and the availability of nutrients could explain the ecology of
Pseudozyma flocculosa
and its biocontrol activity. For this purpose, we compared the development of
P. flocculosa
to that of a close relative, the plant pathogen
Ustilago maydis
, under different environmental conditions. This approach was further supported by measuring the expression of
cyp1
, a pivotal gene in the synthesis of unique antifungal cellobiose lipids of both fungi. On healthy cucumber and tomato plants, the expression of
cyp1
remained unchanged over time in
P. flocculosa
and was undetected in
U. maydis
. At the same time, green fluorescent protein (GFP) strains of both fungi showed only limited green fluorescence on control leaves. On powdery mildew-infected cucumber leaves,
P. flocculosa
induced a complete collapse of the pathogen colonies, but glycolipid production, as studied by
cyp1
expression, was still comparable to that of controls. In complete contrast,
cyp1
was upregulated nine times when
P. flocculosa
was applied to
Botrytis cinerea
-infected leaves, but the biocontrol fungus did not develop very well on the pathogen. Analysis of the possible nutrients that could stimulate the growth of
P. flocculosa
on powdery mildew structures revealed that the complex Zn/Mn played a key role in the interaction. Other related fungi such as
U. maydis
do not appear to have the same nutritional requirements and hence lack the ability to colonize powdery mildews. Whether production of antifungal glycolipids contributes to the release of nutrients from powdery mildew colonies is unclear, but the specificity of the biocontrol activity of
P. flocculosa
toward Erysiphales does appear to be more complex than simple antibiosis.
Peptide Biomarkers as Evidence of Perchlorate Biodegradation
Authors: Bansal Reema , Crawford Ronald L. , Paszczynski Andrzej J.
Published: November 2010

Perchlorate is a known health hazard for humans, fish, and other species. Therefore, it is important to assess the response of an ecosystem exposed to perchlorate contamination. The data reported here show that a liquid chromatography-mass spectrometry-based proteomics approach for the detection of perchlorate-reducing enzymes can be used to measure the ability of microorganisms to degrade perchlorate, including determining the current perchlorate degradation status. Signature peptides derived from chlorite dismutase (CD) and perchlorate reductase can be used as biomarkers of perchlorate presence and biodegradation. Four peptides each derived from CD and perchlorate reductase subunit A (PcrA) and seven peptides derived from perchlorate reductase subunit B (PcrB) were identified as signature biomarkers for perchlorate degradation, as these sequences are conserved in the majority of the pure and mixed perchlorate-degrading microbial cultures examined. However, chlorite dismutase signature biomarker peptides fromDechloromonas agitataCKB were found to be different from those in other cultures used and should also be included with selected CD biomarkers. The combination of these peptides derived from the two enzymes represents a promising perchlorate presence/biodegradation biomarker system. The biomarker peptides were detected at perchlorate concentrations as low as 0.1 mM and at different time points both in pure cultures and within perchlorate-reducing environmental enrichment consortia. The peptide biomarkers were also detected in the simultaneous presence of perchlorate and an alternate electron acceptor, nitrate. We believe that this technique can be useful for monitoring bioremediation processes for other anthropogenic environmental contaminants with known metabolic pathways.
Determination of Serotypes of Shiga Toxin-ProducingEscherichia coliIsolates by Intact Cell Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry
Authors: Karger Axel , Ziller Mario , Bettin Barbara , Mintel Birgit , Schares Susann , Geue Lutz
Published: November 2010

Shiga toxin-producingEscherichia coli(STEC) isolates representing the serotypes O165:H25, O26:H11/H32, and O156:H25 were analyzed by matrix-assisted laser desorption/ionization (MALDI) mass spectra of whole cells, a procedure also known as intact cell mass spectrometry (ICMS or IC-MALDI MS) or MALDI-typing. We demonstrate that within the given species the three serotypes can be well discriminated by ICMS. Conditions for the construction of serotype-specific prototypic mass spectra were systematically optimized by filtering out masses that do not contribute to the discrimination of the serotypes. Binary distances between prototypic spectra and sample spectra were used to determine serotypes of unknown samples. With parameters optimized, only 0.7% of the assignments were incorrect compared to 31% when distances were calculated from alignments of unfiltered mass spectra. Within the different serotypes, clusters of genetically relatedE. colimost probably originating from single clones could be distinguished by restriction fragment length polymorphism analysis. Since ICMS did not reproduce these clusters, we conclude that the power of ICMS is just sufficient to discriminateE. coliserotypes under certain conditions but fails for the differentiation ofE. colibelow this level.
Characterization of a Mannose-6-Phosphate Isomerase from
Thermus thermophilus
and Increased
l
-Ribose Production by Its R142N Mutant
Authors: Yeom Soo-Jin , Seo Eun-Sun , Kim Bi-Na , Kim Yeong-Su , Oh Deok-Kun
Published: November 2010

An uncharacterized gene from
Thermus thermophilus
, thought to encode a mannose-6-phosphate isomerase, was cloned and expressed in
Escherichia coli
. The maximal activity of the recombinant enzyme for
l
-ribulose isomerization was observed at pH 7.0 and 75°C in the presence of 0.5 mM Cu
2+
. Among all of the pentoses and hexoses evaluated, the enzyme exhibited the highest activity for the conversion of
l
-ribulose to
l
-ribose, a potential starting material for many
l
-nucleoside-based pharmaceutical compounds. The active-site residues, predicted according to a homology-based model, were separately replaced with Ala. The residue at position 142 was correlated with an increase in
l
-ribulose isomerization activity. The R142N mutant showed the highest activity among mutants modified with Ala, Glu, Tyr, Lys, Asn, or Gln. The specific activity and catalytic efficiency (
k
cat
/

K
m

) for
l
-ribulose using the R142N mutant were 1.4- and 1.6-fold higher than those of the wild-type enzyme, respectively. The
k
cat
/

K
m

of the R142N mutant was 3.8-fold higher than that of
Geobacillus thermodenitrificans
mannose-6-phosphate isomerase, which exhibited the highest activity to date for the previously reported
k
cat
/

K
m

. The R142N mutant enzyme produced 213 g/liter
l
-ribose from 300 g/liter
l
-ribulose for 2 h, with a volumetric productivity of 107 g liter
−1
h
−1
, which was 1.5-fold higher than that of the wild-type enzyme.
Volatile-Mediated Killing of
Arabidopsis thaliana
by Bacteria Is Mainly Due to Hydrogen Cyanide
Authors: Blom Dirk , Fabbri Carlotta , Eberl Leo , Weisskopf Laure
Published: November 2010

The volatile-mediated impact of bacteria on plant growth is well documented, and contrasting effects have been reported ranging from 6-fold plant promotion to plant killing. However, very little is known about the identity of the compounds responsible for these effects or the mechanisms involved in plant growth alteration. We hypothesized that hydrogen cyanide (HCN) is a major factor accounting for the observed volatile-mediated toxicity of some strains. Using a collection of environmental and clinical strains differing in cyanogenesis, as well as a defined HCN-negative mutant, we demonstrate that bacterial HCN accounts to a significant extent for the deleterious effects observed when growing
Arabidopsis thaliana
in the presence of certain bacterial volatiles. The environmental strain
Pseudomonas aeruginosa
PUPa3 was less cyanogenic and less plant growth inhibiting than the clinical strain
P. aeruginosa
PAO1. Quorum-sensing deficient mutants of
C. violaceum
CV0,
P. aeruginosa
PAO1, and
P. aeruginosa
PUPa3 showed not only diminished HCN production but also strongly reduced volatile-mediated phytotoxicity. The double treatment of providing plants with reactive oxygen species scavenging compounds and overexpressing the alternative oxidase AOX1a led to a significant reduction of volatile-mediated toxicity. This indicates that oxidative stress is a key process in the physiological changes leading to plant death upon exposure to toxic bacterial volatiles.
Modeling the Effects of Sodium Chloride, Acetic Acid, and Intracellular pH on Survival of
Escherichia coli
O157:H7
Authors: Hosein Althea M. , Breidt Frederick , Smith Charles E.
Published: November 2010

Microbiological safety has been a critical issue for acid and acidified foods since it became clear that acid-tolerant pathogens such as
Escherichia coli
O157:H7 can survive (even though they are unable to grow) in a pH range of 3 to 4, which is typical for these classes of food products. The primary antimicrobial compounds in these products are acetic acid and NaCl, which can alter the intracellular physiology of
E. coli
O157:H7, leading to cell death. For combinations of acetic acid and NaCl at pH 3.2 (a pH value typical for non-heat-processed acidified vegetables), survival curves were described by using a Weibull model. The data revealed a protective effect of NaCl concentration on cell survival for selected acetic acid concentrations. The intracellular pH of an
E. coli
O157:H7 strain exposed to acetic acid concentrations of up to 40 mM and NaCl concentrations between 2 and 4% was determined. A reduction in the intracellular pH was observed for increasing acetic acid concentrations with an external pH of 3.2. Comparing intracellular pH with Weibull model predictions showed that decreases in intracellular pH were significantly correlated with the corresponding times required to achieve a 5-log reduction in the number of bacteria.
The Dependence of the
Yersinia
pestis
Capsule on Pathogenesis Is Influenced by the Mouse Background
Authors: Weening Eric H. , Cathelyn Jason S. , Kaufman Greer , Lawrenz Matthew B. , Price Paul , Goldman William E. , Miller Virginia L.
Published: November 2010

Yersinia
pestis
is a highly pathogenic Gram-negative organism and the causative agent of bubonic and pneumonic plague.
Y
.
pestis
is capable of causing major epidemics; thus, there is a need for vaccine targets and a greater understanding of the role of these targets in pathogenesis. Two prime
Y
.
pestis
vaccine candidates are the usher-chaperone fimbriae Psa and Caf. Herein we report that
Y
.
pestis
requires, in a nonredundant manner, both PsaA and Caf1 to achieve its full pathogenic ability in both pneumonic and bubonic plague in C57BL/6J mice. Deletion of
psaA
leads to a decrease in the organ bacterial burden and to a significant increase in the 50% lethal dose (LD
50
) after subcutaneous infection. Deletion of
caf1
also leads to a significant decrease in the organ bacterial burden but more importantly leads to a significantly greater increase in the LD
50
than was observed for the Δ
psaA
mutant strain after subcutaneous infection of C57BL/6J mice. Furthermore, the degree of attenuation of the Δ
caf1
mutant strain is mouse background dependent, as the Δ
caf1
mutant strain was attenuated to a lesser degree in BALB/cJ mice by the subcutaneous route than in C57BL/6J mice. This observation that the degree of requirement for Caf1 is dependent on the mouse background indicates that the virulence of
Y
.
pestis
is dependent on the genetic makeup of its host and provides further support for the hypothesis that PsaA and Caf1 have different targets.
Comparative Kinetics ofEscherichia coli- andStaphylococcus aureus-Specific Activation of Key Immune Pathways in Mammary Epithelial Cells Demonstrates ThatS. aureusElicits a Delayed Response Dominated by Interleukin-6 (IL-6) but Not by IL-1A or Tumor Necrosis Factor Alpha
Authors: Günther Juliane , Esch Kathrin , Poschadel Norbert , Petzl Wolfram , Zerbe Holm , Mitterhuemer Simone , Blum Helmut , Seyfert Hans-Martin
Published: November 2010

Infections of the udder byEscherichia colivery often elicit acute inflammation, whileStaphylococcus aureusinfections tend to cause mild, subclinical inflammation and persistent infections. The molecular causes underlying the different disease patterns are poorly understood. We therefore profiled the kinetics and extents of global changes in the transcriptome of primary bovine mammary epithelial cells (MEC) after challenging them with heat-inactivated preparations ofE. coliorS. aureuspathogens.E. coliswiftly and strongly induced an expression of cytokines and bactericidal factors.S. aureuselicited a retarded response and failed to quickly induce an expression of bactericidal factors. Both pathogens induced similar patterns of chemokines for cell recruitment into the udder, butE. colistimulated their synthesis much faster and stronger. The genes that are exclusively and most strongly upregulated byE. colimay be clustered into a regulatory network with tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1) in a central position. In contrast, the expression of these master cytokines is barely regulated byS. aureus. Both pathogens quickly trigger an enhanced expression of IL-6. This is still possible after completely abrogating MyD88-dependent Toll-like receptor (TLR) signaling in MEC. TheE. coli-specific strong induction of TNF-α and IL-1 expression may be causative for the severe inflammatory symptoms of animals suffering fromE. colimastitis, while the avoidance to quickly induce the synthesis of bactericidal factors may support the persistent survival ofS. aureuswithin the udder. We suggest thatS. aureussubverts the MyD88-dependent activation of immune gene expression in MEC.
Adenosine Deaminase Inhibition PreventsClostridium difficileToxin A-Induced Enteritis in Mice
Authors: de Araújo Junqueira Ana Flávia Torquato , Dias Adriana Abalen Martins , Vale Mariana Lima , Spilborghs Graziela Machado Gruner Turco , Bossa Aline Siqueira , Lima Bruno Bezerra , Carvalho Alex Fiorini , Guerrant Richard Littleton , Ribeiro Ronaldo Albuquerque , Brito Gerly Anne
Published: November 2010

Toxin A (TxA) is able to induce most of the classical features ofClostridium difficile-associated disease in animal models. The objective of this study was to determine the effect of an inhibitor of adenosine deaminase, EHNA [erythro-9-(2-hydroxy-3-nonyl)-adenine], on TxA-induced enteritis in C57BL6 mice and on the gene expression of adenosine receptors. EHNA (90 μmol/kg) or phosphate-buffered saline (PBS) was injected intraperitoneally (i.p.) 30 min prior to TxA (50 μg) or PBS injection into the ileal loop. A2Aadenosine receptor agonist (ATL313; 5 nM) was injected in the ileal loop immediately before TxA (50 μg) in mice pretreated with EHNA. The animals were euthanized 3 h later. The changes in the tissue were assessed by the evaluation of ileal loop weight/length and secretion volume/length ratios, histological analysis, myeloperoxidase assay (MPO), the local expression of inducible nitric oxide synthase (NOS2), pentraxin 3 (PTX3), NF-κB, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) by immunohistochemistry and/or quantitative reverse transcription-PCR (qRT-PCR). The gene expression profiles of A1, A2A, A2B, and A3adenosine receptors also were evaluated by qRT-PCR. Adenosine deaminase inhibition, by EHNA, reduced tissue injury, neutrophil infiltration, and the levels of proinflammatory cytokines (TNF-α and IL-1β) as well as the expression of NOS2, NF-κB, and PTX3 in the ileum of mice injected with TxA. ATL313 had no additional effect on EHNA action. TxA increased the gene expression of A1and A2Aadenosine receptors. Our findings show that the inhibition of adenosine deaminase by EHNA can preventClostridium difficileTxA-induced damage and inflammation possibly through the A2Aadenosine receptor, suggesting that the modulation of adenosine/adenosine deaminase represents an important tool in the management ofC. difficile-induced disease.
The ThreeVibrio choleraeChromosome II-Encoded ParE Toxins Degrade Chromosome I following Loss of Chromosome II
Authors: Yuan Jie , Yamaichi Yoshiharu , Waldor Matthew K.
Published: November 2010

Three homologues of the plasmid RK2 ParDE toxin-antitoxin system are present in theVibrio choleraegenome within the superintegron on chromosome II. Here we found that these three loci—two of which have identical open reading frames and regulatory sequences—encode functional toxin-antitoxin systems. The ParE toxins inhibit bacterial division and reduce viability, presumably due to their capacity to damage DNA. Thein vivoeffects of ParE1/3 mimic those of ParE2, which we have previously demonstrated to be a DNA gyrase inhibitorin vitro, suggesting that ParE1/3 is likewise a gyrase inhibitor, despite its relatively low degree of sequence identity. ParE-mediated DNA damage activates theV. choleraeSOS response, which in turn likely accounts for ParE's inhibition of cell division. Each toxin's effects can be prevented by the expression of its cognate ParD antitoxin, which acts in a toxin-specific fashion both to block toxicity and to repress the expression of itsparDEoperon. Derepression of ParE activity in ΔparAB2mutantV. choleraecells that have lost chromosome II contributes to the prominent DNA degradation that accompanies the death of these cells. Overall, our findings suggest that the ParE toxins lead to the postsegregational killing of cells missing chromosome II in a manner that closely mimics postsegregational killing mediated by plasmid-encoded homologs. Thus, theparDEloci aid in the maintenance of the integrity of theV. choleraesuperintegron and in ensuring the inheritance of chromosome II.
Unifying Themes in Microbial Associations with Animal and Plant Hosts Described Using the Gene Ontology
Authors: Torto-Alalibo Trudy , Collmer Candace W. , Gwinn-Giglio Michelle , Lindeberg Magdalen , Meng Shaowu , Chibucos Marcus C. , Tseng Tsai-Tien , Lomax Jane , Biehl Bryan , Ireland Amelia , Bird David , Dean Ralph A. , Glasner Jeremy D. , Perna Nicole , Setubal Joao C. , Collmer Alan , Tyler Brett M.
Published: November 2010

Microbes form intimate relationships with hosts (symbioses) that range from mutualism to parasitism. Common microbial mechanisms involved in a successful host association include adhesion, entry of the microbe or its effector proteins into the host cell, mitigation of host defenses, and nutrient acquisition. Genes associated with these microbial mechanisms are known for a broad range of symbioses, revealing both divergent and convergent strategies. Effective comparisons among these symbioses, however, are hampered by inconsistent descriptive terms in the literature for functionally similar genes. Bioinformatic approaches that use homology-based tools are limited to identifying functionally similar genes based on similarities in their sequences. An effective solution to these limitations is provided by the Gene Ontology (GO), which provides a standardized language to describe gene products from all organisms. The GO comprises three ontologies that enable one to describe the molecular function(s) of gene products, the biological processes to which they contribute, and their cellular locations. Beginning in 2004, the Plant-Associated Microbe Gene Ontology (PAMGO) interest group collaborated with the GO consortium to extend the GO to accommodate terms for describing gene products associated with microbe-host interactions. Currently, over 900 terms that describe biological processes common to diverse plant- and animal-associated microbes are incorporated into the GO database. Here we review some unifying themes common to diverse host-microbe associations and illustrate how the new GO terms facilitate a standardized description of the gene products involved. We also highlight areas where new terms need to be developed, an ongoing process that should involve the whole community.
Speaking to the yet unknowing world:Hamlet, Horatio and the problem of imperfect witness
Authors: Phillips Christine
Published: November 2010

Every day doctors bear witness to others about the experiences, needs and feelings of their patients, drawing on what they have learnt from clinical consultations. This paper considers the medical task of bearing honourable and truthful witness through an examination of the role and actions of Horatio inHamlet. Horatio is simultaneously located among the background machinery of the play, separate from the lives of the protagonists, and in the foreground, where his authoritative witness is repeatedly called upon by the play's characters. Horatio is invited to watch an unfolding disaster, his warnings are not heard, and at its conclusion he stands apart from the drama to give its account. The tensions between engagement and observation, and between partial and impartial accounting echo those faced by doctors in everyday clinical practice. The act of bearing witness, Shakespeare suggests, even for those who are tasked with being objective, is necessarily imperfect, and not dispassionate. Those people, including doctors, who are expected to construct authoritative accounts of the motives and actions of others may find inHamleta small lesson on the need to approach their summary narratives about others more humbly, aware of the narrowness and partiality of their perspective.
Breast cancer between faith and medicine: the Peres Maldonado ex-voto: Figure 1
Authors: Pon Lisa , Amatruda James F
Published: November 2010

An ex-voto (from the Latin for ‘from the vow’) is an image made to express the patron's gratitude for divine assistance in the face of personal difficulty. Here, we describe a late 18th century Mexican painting that shows Doña Josefa Peres Maldonado undergoing a mastectomy, and, as an ex-voto, expresses her thanks for divine aid in having survived the operation. As such, the painting manifests Doña Josefa's response to her disease, drawing on both medical and religious sources of support. This brief report analyses the unusual double dedication of the ex-voto, the elaborate home altar it depicts and the surgical technique it demonstrates.
Joseph Beuys: trauma and catharsis: Figure 1
Authors: Ottomann C , Stollwerck P L , Maier H , Gatty I , Muehlberger T
Published: November 2010

Joseph Beuys was one of the most significant artists of the 20th century. He was a gunner and radio operator in the German Air Force during World War II, and was severely injured several times. In March 1943 he had a life-changing experience after the dive bomber he was assigned to crashed in the Crimean peninsula. This trauma influenced Beuys' entire artistic career, and is known in art history as the ’Tartar Legend’ or ’Tartar Myth’. Profoundly affected by the crash, the severe trauma, the near-death experience and his rescue, which he perceived as a “rebirth”, Beuys no longer saw himself, other people or society as a whole in the same way as previously. With his new consciousness, he ignored boundaries and created visions whereby all mankind could experience the healing he had undergone. Beuys did not bring society far enough for the turning point towards “the healing of the world” to be visible, yet today it is important to keep his work alive as a record of his extraordinary strength, which arose from trauma and severe injury, and was carried by a passionate commitment to mankind and to life itself.
Humane images: visual rhetoric in depictions of atypical genital anatomy and sex differentiation
Authors: Wall Shelley
Published: November 2010

Visual images are widely used in medical and patient education to enhance spoken or written explanations. This paper considers the role of such illustrations in shaping conceptions of the body; specifically, it addresses depictions of variant sexual anatomy and their part in the discursive production of intersex bodies. Visual language—even didactic, ‘factual’ visual language—carries latent as well as manifest content, and influences self-perceptions and social attitudes. In the case of illustrations about atypical sex development, where the need for non-stigmatising communication is crucial, it is especially important to consider the implicit messages conveyed by imagery and compositional strategies.
The effect of HIV infection on time off work in a large cohort of gold miners with known dates of seroconversion
Authors: Sonnenberg Pam , Copas Andrew , Glynn Judith R , Bester Andre , Nelson Gill , Shearer Stuart , Murray Jill
Published: November 2010

Objectives

To estimate the effect of HIV infection on time off work. To provide baseline estimates for economic and actuarial models, and for evaluations of ART and other workplace interventions.

Methods

A retrospective cohort study of gold miners with known dates of seroconversion to HIV, and an HIV-negative comparison group, used routinely collected data to estimate the proportion of time off work by calendar period (1992–2002, prior to the introduction of ART), age, time since seroconversion and period before death. The authors calculated ORs for overall time off work and RR ratios (RRR, using multinomial logistic regression) for reasons off work relative to being at work.

Results

1703 HIV-positive and 4859 HIV-negative men were followed for 34 424 person-years. HIV-positive miners spent a higher proportion of time off work than negative miners (20.7% vs 16.1%) due to greater medical and unauthorised absence. Compared with HIV-negative miners, overall time off work increased in the first 2 years after seroconversion (adjusted OR 1.40 (95% CI 1.36 to 1.45)) and then remained broadly stable for a number years, reaching 38.8% in the final year before death (adjusted OR 3.27, 95% CI 2.95 to 3.63). Absence for medical reasons showed the strongest link to HIV infection, increasing from an adjusted RRR of 2.66 (95% CI 2.45 to 2.90) for the first 2 years since seroconversion to 13.6 (95% CI 11.8 to 15.6) in the year prior to death.

Conclusions

Time off work provides a quantifiable measure of the effect of HIV on overall morbidity. HIV/AIDS affects both labour supply (increased time off work) and demand for health services (increased medical absence). The effects occur soon after seroconversion and stabilise before reaching very high levels in the period prior to death. Occupational health services are an important setting to identify HIV-infected men early.
THE EFFECT OF THE HETEROGENEITY ON THE TRAFFIC FLOW BEHAVIOR
Authors: JETTO K. , EZ-ZAHRAOUY H. , BENYOUSSEF A.
Published: November 2010

We propose a traffic flow model which takes into account the disorder in the length and the maximal speed of cars. Using cellular automaton model in parallel dynamics we have studied the behavior of traffic flow, especially the condition of formation (active phase) and the dissociation (absorbing phase) of platoons. It is found that the transition from active to absorbing phase depend on the length of the slow vehicles L2. Indeed, the transition is discontinuous for L2 = 1 and continuous when L2 > 1. In the later case, the critical exponent is calculated near the transition density, and the space-time diagram shows the presence of the two phases. Furthermore, we have found that the fundamental diagram exhibit a plateau which depend on the size of the system.
BOUND OF NONCOMMUTATIVITY PARAMETER BASED ON BLACK HOLE ENTROPY
Authors: KIM WONTAE , LEE DAEHO
Published: November 2010

We study the bound of the noncommutativity parameter in the noncommutative Schwarzschild black hole which is a solution of the noncommutative ISO(3, 1) Poincaré gauge group. The statistical entropy satisfying the area law in the brick wall method yields a cutoff relation which depends on the noncommutativity parameter. Requiring both the cutoff parameter and the noncommutativity parameter to be real, the noncommutativity parameter can be shown to be bounded as Θ > 8.4 × 10-2lp.
D = 11 SUPERGRAVITY WITH MANIFEST SUPERSYMMETRY
Authors: CEDERWALL MARTIN
Published: November 2010

The complete supersymmetric classical Batalin–Vilkovisky action for 11-dimensional supergravity is presented. The action is polynomial in the scalar fermionic pure spinor superfield, and contains only a minor modification to the recently proposed three-point coupling.
THE QUANTUM H3 INTEGRABLE SYSTEM
Authors: GARCÍA MARCOS A. G. , TURBINER ALEXANDER V.
Published: November 2010

The quantum H3 integrable system is a three-dimensional system with rational potential related to the noncrystallographic root system H3. It is shown that the gauge-rotated H3 Hamiltonian as well as one of the integrals, when written in terms of the invariants of the Coxeter group H3, is in algebraic form: it has polynomial coefficients in front of derivatives. The Hamiltonian has infinitely-many finite-dimensional invariant subspaces in polynomials, they form the infinite flag with the characteristic vector [Formula: see text]. One among possible integrals is found (of the second order) as well as its algebraic form. A hidden algebra of the H3 Hamiltonian is determined. It is an infinite-dimensional, finitely-generated algebra of differential operators possessing finite-dimensional representations characterized by a generalized Gauss decomposition property. A quasi-exactly-solvable integrable generalization of the model is obtained. A discrete integrable model on the uniform lattice in a space of H3-invariants "polynomially"-isospectral to the quantum H3 model is defined.
A NEAR-NHEK/CFT CORRESPONDENCE
Authors: RASMUSSEN JØRGEN
Published: November 2010

We consider excitations around the recently introduced near-NHEK metric describing the near-horizon geometry of the near-extremal four-dimensional Kerr black hole. This geometry has a U (1)L × U (1)R isometry group which can be enhanced to a pair of commuting Virasoro algebras. We present boundary conditions for which the conserved charges of the corresponding asymptotic symmetries are well defined and nonvanishing and find the central charges cL = 12J/ℏ and cR = 0 where J is the angular momentum of the black hole. Applying the Cardy formula reproduces the Bekenstein–Hawking entropy of the black hole. This suggests that the near-extremal Kerr black hole is holographically dual to a nonchiral two-dimensional conformal field theory.
LARGE DEVIATION PRINCIPLES FOR ISOTROPIC STOCHASTIC FLOW OF HOMEOMORPHISMS ON Sd
Authors: XU TIANGE , ZHANG TUSHENG
Published: November 2010

In this paper, we obtain a large deviation principle for the flow of homeomorphisms of the stochastic differential equations on the sphere Sd associated with the critical Sobolev Brownian vector fields.
PARAMETER ESTIMATION FOR SPDEs WITH MULTIPLICATIVE FRACTIONAL NOISE
Authors: CIALENCO IGOR
Published: November 2010

We study parameter estimation problem for diagonalizable stochastic partial differential equations driven by a multiplicative fractional noise with any Hurst parameter H ∈ (0, 1). Two classes of estimators are investigated: traditional maximum likelihood type estimators, and a new class called closed-form exact estimators. Finally the general results are applied to stochastic heat equation driven by a fractional Brownian motion.
ROBOT-ASSISTED STROKE REHABILITATION: JOINT TORQUE/FORCE CONVERSION FROM EMG USING GA PROCESS
Authors: PARASURAMAN S. , OYONG ARIF WICAKSONO
Published: November 2010

This project focuses on the development of robot-assisted stroke rehabilitation by implementing electromyography (EMG) as the interface between robot and user communication. The key issue in the implementation of EMG in this application is the conversion of EMG signal into torque data. This article presents a methodology of EMG signal to estimated joint torque conversion by using genetic algorithm (GA). The basic principle of GA, formulation, and implementation to the problem are discussed in this article. Experimentation with real-life EMG data has been carried out to assess the feasibility of the methodology in robot-assisted stroke rehabilitation problem. Preliminary investigations show that the methodology can be used in EMG to joint torque conversion algorithm.
Fold–thrust belts at Peak Oil
Authors: Roeder Dietrich
Published: November 2010

Outside the Middle East, onshore fold–thrust belts (FTB) of Tertiary to Recent age contain a significant part of the globally developed petroleum, but far less of the oil and gas remaining undiscovered. Depending on high quality data and on deep drilling, renewed exploration of former failures is commercially attractive, and it will help in exploring the deepwater belts of compression. In FTB with a defined petroleum system, an under-explored trend may be the informally named ‘deep-updip’ or DUD trend. Shale-gas-prone formations in FTB require new exploration strategies, but in the public domain, this type of prospect has not yet been discussed. FTB discoveries require geological insight, persistence and exponentially rising investment. The paper includes examples from the Northern Alps, from the Llanos foothills of Colombia, from Eastern Venezuela and from the Po Valley basin of Italy.