bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the thermal stability of nickel monosilicide thin films by combining annealing with the use of an interlayer and a capping layer
Authors: Park Bong-Jun , Jeong Sang-Yong , Kim Jun-Ho , Seong Tae-Yeon , Choi Chel-Jong
Published: March 2011

The authors investigated the effects of preannealing a 2-nm-thick Pd interlayer and a 20-nm-thick TiN capping layer on the electrical and thermal stability of nickel silicides as a function of the annealing temperature. The preannealed samples (prepoly-Si) produce lower sheet resistances compared to the samples without preannealing. For the preannealed samples, NiSi remains stable up to 600 °C. Transmission electron microscopy results show that the preannealed samples have a higher resistance against layer inversion. The addition of a Pd interlayer at the Ni film/prepoly-Si interface increases the formation temperature of NiSi2 to 900 °C. The use of the capping layer on the Pd-interlayered prepoly-Si samples improves the electrical and morphological stabilities of NiSi. The possible mechanisms for the preannealing and interlayer-induced improvement of the thermal stabilities of the Ni-silicide samples are discussed in terms of grain growth and simple thermodynamic relations.
Strong enhancement of ultraviolet emission from ZnO films by V implantation
Authors: Kim Chang Oh , Shin Dong Hee , Choi Suk-Ho , Belay K. , Elliman R. G.
Published: March 2011

ZnO films were prepared on Si(100) wafers by rf sputtering and subsequently implanted with V ions to fluences of (1,2.5,5,10)×1015 cm−2. The room-temperature ultraviolet photoluminescence (PL) intensity of the implanted films is shown to increase with increasing fluence up to 2.5×1015 cm−2, becoming ∼37 times more intense than the emission from the unimplanted ZnO film, before decreasing at higher fluences. The increase in PL intensity is correlated with improved crystallinity of ZnO, accompanied by a reduction in the concentration of deep-level native defects by V incorporation into the ZnO lattice, as verified by x-ray diffraction, x-ray photoelectron spectroscopy, and low-temperature PL. The subsequent reduction in PL intensity at fluences higher than 2.5×1015 cm−2 is shown to result from the deterioration of the crystal quality and the precipitation of V secondary phase possibly introducing defects in the films.
Stretching and folding versus cutting and shuffling: An illustrated perspective on mixing and deformations of continua
Authors: Christov Ivan C. , Lueptow Richard M. , Ottino Julio M.
Published: March 2011

We compare and contrast two types of deformations inspired by mixing applications—one from the mixing of fluids (stretching and folding) and the other from the mixing of granular matter (cutting and shuffling). The connection between mechanics and dynamical systems is discussed in the context of the kinematics of deformation, emphasizing the equivalence between stretches and Lyapunov exponents. The stretching and folding motion exemplified by the baker’s map is shown to give rise to a dynamical system with a positive Lyapunov exponent, the hallmark of chaotic mixing. In contrast, cutting and shuffling does not stretch. When an interval exchange transformation is used as the basis for cutting and shuffling, we establish that all of the map’s Lyapunov exponents are zero. Mixing, as quantified by the interfacial area per unit volume, is shown to be exponential when there is stretching and folding but linear when there is only cutting and shuffling. We also discuss how a simple computational approach can discern stretching in discrete data.
Vernier scales and other early devices for precise measurement
Authors: Kwan Alistair
Published: March 2011

Vernier scales have been extensively used since the 17th century. They replaced the Nonius scale, a unpopular device due to difficulty in its fabrication and use, and they coexisted alongside other types of scales that increased measurement precision and accuracy in complementary ways. I suggest that the success of Vernier and diagonal scales is due not only to simplicity of fabrication, but also to their exploitation of visual hyperacuities.
How physicists disagree on the meaning of entropy
Authors: Swendsen Robert H.
Published: March 2011

Discussions of the foundations of statistical mechanics, how they lead to thermodynamics, and the appropriate definition of entropy have occasioned many disagreements. I believe that some or all of these disagreements arise from differing, but unstated assumptions, which can make opposing opinions difficult to reconcile. To make these assumptions explicit, I discuss the principles that have guided my own thinking about the foundations of statistical mechanics, the microscopic origins of thermodynamics, and the definition of entropy. The purpose of this paper will be fulfilled if it paves the way to a final consensus, whether or not that consensus agrees with my point of view.
Inducible Gene Expression in Mammals: Plants Add to the Menu
Authors: Cutler Sean R.
Published: March 2011

The plant abscisic acid signaling components can be leveraged to inducibly control protein interactions in mammals.
Healed into Cancer
Authors: Gough Nancy R.
Published: March 2011

Recruitment of hair stem cells with activating mutations in the Hedgehog pathway to sites of skin injury leads to tumor formation.
Messing with the Brakes
Authors: Foley John F.
Published: March 2011

An additional point of contact with its regulatory subunit distinguishes p110β from other class IA PI3K isoforms.
Evaluation of the Mean Corpuscular Volume of Peripheral Blood Mononuclear Cells of HIV Patients by a Coulter Counter To Determine Intracellular Drug Concentrations
Authors: Simiele Marco , D'Avolio Antonio , Baietto Lorena , Siccardi Marco , Sciandra Mauro , Agati Silvia , Cusato Jessica , Bonora Stefano , Di Perri Giovanni
Published: March 2011

The mean corpuscular volume (MCV) of peripheral blood mononuclear cells (PBMCs) was determined by Coulter Counter, and data were used to calculate the intracellular drug concentrations. A total of 574 PBMC samples were collected from 190 patients. The MCV was 282.9 fl (minimum, 207.0; maximum, 354.6), with a standard deviation of 8.8%. Previous reports have often used a fixed value of 400 fl for the MCV, which may result in artificially low estimates of the intracellular concentrations of antivirals.
Optimization of Aminoglycoside Therapy
Authors: Drusano G. L. , Louie Arnold
Published: March 2011

Aminoglycosides are experiencing a resurgence in use because of the spread of multiresistant Gram-negative pathogens. Use of these agents is attended by the occurrence of nephrotoxicity. Aminoglycoside optimization of dose can be defined as the dose having the highest likelihood of a good outcome and the lowest likelihood of toxicity. We have defined the metric Δ as the difference between the likelihoods of good outcome and toxicity, with higher values being better. We developed a method for explicitly evaluating Δ for different daily doses of drug and different schedules of administration. In the empirical therapy setting, when aminoglycosides are administered every 12 h, treatment of infections caused by microbes with MIC values greater than 1 mg/liter cannot attain a high enough likelihood of a good outcome without engendering an unacceptable toxicity likelihood. Daily administration, by decrementing the likelihood of toxicity, allows higher doses to be employed with more acceptable probabilities of toxicity. Obtaining patient-specific information (concentration-time data) allows better identification of the patient's specific pharmacokinetic parameters and dispersion. As these become better identified, optimal doses become rapidly identified so that optimal outcomes are attained. Optimization of therapy for aminoglycosides requires understanding the relationship between exposure and response as well as that between exposure and toxicity. Furthermore, daily administration is much preferred, and stopping therapy as quickly as possible (a week or less may be optimal) will contribute to the ability to optimize therapy.
Microtiter Plate-Based Assay for Inhibitors of Penicillin-Binding Protein 2a from Methicillin-Resistant Staphylococcus aureus
Authors: Bobba Sudheer , Ponnaluri V. K. Chaithanya , Mukherji Mridul , Gutheil William G.
Published: March 2011

Penicillin-binding protein 2a (PBP2a), the molecular determinant for high-level β-lactam resistance in methicillin-resistant
Staphylococcus aureus
(MRSA), is intrinsically resistant to most β-lactam antibiotics. The development and characterization of new inhibitors targeting PBP2a would benefit from an effective and convenient assay for inhibitor binding. This study was directed toward the development of a fluorescently detected β-lactam binding assay for PBP2a from MRSA. Biotinylated ampicillin and biotinylated cephalexin were tested as tagging reagents for fluorescence detection by using a streptavidin-horseradish peroxidase conjugate. Both bound surprisingly well to PBP2a, with binding constants of 1.6 ± 0.4 μM and 13.6 ± 0.8 μM, respectively. Two forms of the assay were developed, a one-step direct competition form of the assay and a two-step indirect competition form of the assay, and both forms of the assay gave comparable results. This assay was then used to characterize PBP2a binding to ceftobiprole, which gave results consistent with previous studies of ceftobiprole-PBP2a binding. This assay was also demonstrated for screening for PBP2a inhibitors by screening a set of 13 randomly selected β-lactams for PBP2a inhibition at 750 μM. Meropenem was observed to give substantial inhibition in this screen, and a follow-up titration experiment determined its apparent

K
i

to be 480 ± 70 μM. The availability of convenient and sensitive microtiter-plate based assays for the screening and characterization of PBP2a inhibitors is expected to facilitate the discovery and development of new PBP2a inhibitors for use in combating the serious public health problem posed by MRSA.
Regulation of Efflux Pump Expression and Drug Resistance by the Transcription Factors Mrr1, Upc2, and Cap1 in Candida albicans
Authors: Schubert Sabrina , Barker Katherine S. , Znaidi Sadri , Schneider Sabrina , Dierolf Franziska , Dunkel Nico , Aïd Malika , Boucher Geneviève , Rogers P. David , Raymond Martine , Morschhäuser Joachim
Published: March 2011

Constitutive overexpression of the Mdr1 efflux pump is an important mechanism of acquired drug resistance in the yeast
Candida albicans
. The zinc cluster transcription factor Mrr1 is a central regulator of
MDR1
expression, but other transcription factors have also been implicated in
MDR1
regulation. To better understand how
MDR1
-mediated drug resistance is achieved in this fungal pathogen, we studied the interdependence of Mrr1 and two other
MDR1
regulators, Upc2 and Cap1, in the control of
MDR1
expression. A mutated, constitutively active Mrr1 could upregulate
MDR1
and confer drug resistance in the absence of Upc2 or Cap1. On the other hand, Upc2 containing a gain-of-function mutation only slightly activated the
MDR1
promoter, and this activation depended on the presence of a functional
MRR1
gene. In contrast, a C-terminally truncated, activated form of Cap1 could upregulate
MDR1
in a partially Mrr1-independent fashion. The induction of
MDR1
expression by toxic chemicals occurred independently of Upc2 but required the presence of Mrr1 and also partially depended on Cap1. Transcriptional profiling and
in vivo
DNA binding studies showed that a constitutively active Mrr1 binds to and upregulates most of its direct target genes in the presence or absence of Cap1. Therefore, Mrr1 and Cap1 cooperate in the environmental induction of
MDR1
expression in wild-type
C. albicans
, but gain-of-function mutations in either of the two transcription factors can independently mediate efflux pump overexpression and drug resistance.
A New Small Molecule Specifically Inhibits the Cariogenic Bacterium Streptococcus mutans in Multispecies Biofilms
Authors: Liu Chang , Worthington Roberta J. , Melander Christian , Wu Hui
Published: March 2011

Streptococcus mutans
is a major cariogenic bacterium. It has adapted to the biofilm lifestyle, which is essential for pathogenesis of dental caries. We aimed to identify small molecules that can inhibit cariogenic
S. mutans
and to discover lead structures that could give rise to therapeutics for dental caries. In this study, we screened a focused small-molecule library of 506 compounds. Eight small molecules which inhibited
S. mutans
at a concentration of 4 μM or less but did not affect cell growth or biofilm formation of commensal bacteria, represented by
Streptococcus sanguinis
and
Streptococcus gordonii
, in monospecies biofilms were identified. The active compounds share similar structural properties, which are characterized by a 2-aminoimidazole (2-AI) or 2-aminobenzimidazole (2-ABI) subunit. In multispecies biofilm models, the most active compound also inhibited cell survival and biofilm formation of
S. mutans
but did not affect commensal streptococci. This inhibitor downregulated the expression of six biofilm-associated genes,
ftf
,
pac
,
relA
,
comDE
,
gbpB
, and
gtfB
, in planktonic
S. mutans
cells, while it downregulated the expression of only
ftf
,
pac
, and
relA
in the biofilm cells of
S. mutans
. The most potent compound also inhibited production of two key adhesins of
S. mutans
, antigen I/II and glucosyltransferase (GTF). However, the compound did not alter the expression of the corresponding genes in both
S. sanguinis
and
S. gordonii
, indicating that it possesses a selective inhibitory activity against
S. mutans
.
Structure-Activity Studies and Therapeutic Potential of Host Defense Peptides of Human Thrombin
Authors: Kasetty Gopinath , Papareddy Praveen , Kalle Martina , Rydengård Victoria , Mörgelin Matthias , Albiger Barbara , Malmsten Martin , Schmidtchen Artur
Published: March 2011

Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria
Escherichia coli
and
Pseudomonas aeruginosa
, the Gram-positive bacterium
Staphylococcus aureus
, and the fungus
Candida albicans
. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and
P. aeruginosa
sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.
Evolution and Spread of a Multidrug-Resistant Proteus mirabilis Clone with Chromosomal AmpC-Type Cephalosporinases in Europe
Authors: D'Andrea M. M. , Literacka E. , Zioga A. , Giani T. , Baraniak A. , Fiett J. , Sadowy E. , Tassios P. T. , Rossolini G. M. , Gniadkowski M. , Miriagou V.
Published: March 2011

Proteus mirabilis
isolates obtained in 1999 to 2008 from three European countries were analyzed; all carried chromosomal AmpC-type cephalosporinase
bla
CMY
genes from a
Citrobacter freundii
origin (
bla
CMY-2
-like genes). Isolates from Poland harbored several
bla
CMY
genes (
bla
CMY-4
,
bla
CMY-12
,
bla
CMY-14
,
bla
CMY-15
, and
bla
CMY-38
and the new gene
bla
CMY-45
), while isolates from Italy and Greece harbored
bla
CMY-16
only. Earlier isolates with
bla
CMY-4
or
bla
CMY-12
, recovered in France from Greek and Algerian patients, were also studied. All isolates showed striking similarities. Their
bla
CMY
genes resided within IS
Ecp1
transposition modules, named Tn
6093
, characterized by a 110-bp distance between IS
Ecp1
and
bla
CMY
, and identical fragments of both
C. freundii
DNA and a ColE1-type plasmid backbone. Moreover, these modules were inserted into the same chromosomal site, within the
pepQ
gene. Since ColE1 plasmids carrying IS
Ecp1
with similar
C. freundii
DNA fragments (Tn
6114
) had been identified earlier, it is likely that a similar molecule had mediated at some stage this DNA transfer between
C. freundii
and
P. mirabilis
. In addition, isolates with
bla
CMY-12
,
bla
CMY-15
, and
bla
CMY-38
genes harbored a second
bla
CMY
copy within a shorter IS
Ecp1
module (Tn
6113
), always inserted downstream of the
ppiD
gene. Sequence analysis of all mobile
bla
CMY-2
-like genes indicated that those integrated in the
P. mirabilis
chromosome form a distinct cluster that may have evolved by the stepwise accumulation of mutations. All of these observations, coupled to strain typing data, suggest that the
bla
CMY
genes studied here may have originated from a single IS
Ecp1
-mediated mobilization-transfer-integration process, followed by the spread and evolution of a
P. mirabilis
clone over time and a large geographic area.
Staphylococcus aureus Transporters Hts, Sir, and Sst Capture Iron Liberated from Human Transferrin by Staphyloferrin A, Staphyloferrin B, and Catecholamine Stress Hormones, Respectively, and Contribute to Virulence
Authors: Beasley Federico C. , Marolda Cristina L. , Cheung Johnson , Buac Suzana , Heinrichs David E.
Published: March 2011

Staphylococcus aureus
is a frequent cause of bloodstream, respiratory tract, and skin and soft tissue infections. In the bloodstream, the iron-binding glycoprotein transferrin circulates to provide iron to cells throughout the body, but its iron-binding properties make it an important component of innate immunity. It is well established that siderophores, with their high affinity for iron, in many instances can remove iron from transferrin as a means to promote proliferation of bacterial pathogens. It is also established that catecholamine hormones can interfere with the iron-binding properties of transferrin, thus allowing infectious bacteria access to this iron pool. The present study demonstrates that
S. aureus
can use either of two carboxylate-type siderophores, staphyloferrin A and staphyloferrin B, via the transporters Hts and Sir, respectively, to access the transferrin iron pool. Growth of staphyloferrin-producing
S. aureus
in serum or in the presence of holotransferrin was not enhanced in the presence of catecholamines. However, catecholamines significantly enhanced the growth of staphyloferrin-deficient
S. aureus
in human serum or in the presence of human holotransferrin. It was further demonstrated that the Sst transporter was essential for this activity as well as for the utilization of bacterial catechol siderophores. The substrate binding protein SstD was shown to interact with ferrated catecholamines and catechol siderophores, with low to submicromolar affinities. Experiments involving mice challenged intravenously with wild-type
S. aureus
and isogenic mutants demonstrated that the combination of Hts, Sir, and Sst transport systems was required for full virulence of
S. aureus
.
Joint Effects of Host Genetic Background and Mycobacterial Pathogen on Susceptibility to Infection
Authors: Di Pietrantonio Tania , Correa José A. , Orlova Marianna , Behr Marcel A. , Schurr Erwin
Published: March 2011

The present study examined the differential contribution of host genetic background and mycobacterial pathogen variability to biological and mechanistic phenotypes of infection. For this purpose, A/J and C57BL/6J mice were infected intravenously with a low dose ofMycobacterium tuberculosisH37Rv or the Russia, Japan, and Pasteur substrains ofMycobacterium bovisbacille Calmette-Guérin (BCG). The pulmonary bacterial counts (number of CFU) and transcript levels of select cytokines (e.g.,Ifng,Il12b, andIl4) at 1, 3, and 6 weeks postinfection were measured as biological and mechanistic phenotypes, respectively. The individual and combined impact of the host and mycobacteria on these phenotypes was assessed using three-way analysis of variance (ANOVA), which partitions phenotypic variation into host, pathogen, time, and interaction effects. All phenotypes, except pulmonaryIl4transcript levels, displayed evidence for host-mycobacterium specificity by means of significant interaction terms. Pulmonary expression profiles of 34 chemokines and chemokine-related genes were compared across the hosts and mycobacteria. The differences in induction of these immune messenger genes between A/J and C57BL/6J mice were modest and generally failed to reach significance. In contrast, the mycobacteria induced significant variance in a subset of the immune messenger genes, which was more evident in A/J mice relative to that in C57BL/6J mice. Overall, the results demonstrated the importance of considering the joint effects of the mycobacterial and host genetic backgrounds on susceptibility to mycobacterial infections.
Cross-Reactive Protection against Enterohemorrhagic Escherichia coli Infection by Enteropathogenic E. coli in a Mouse Model
Authors: Calderon Toledo Carla , Arvidsson Ida , Karpman Diana
Published: March 2011

Enteropathogenic
Escherichia coli
(EPEC) and enterohemorrhagic
E. coli
(EHEC) are related attaching and effacing (A/E) pathogens. The genes responsible for the A/E pathology are carried on a chromosomal pathogenicity island termed the locus of enterocyte effacement (LEE). Both pathogens share a high degree of homology in the LEE and additional O islands. EHEC prevalence is much lower in areas where EPEC is endemic. This may be due to the development of antibodies against common EPEC and EHEC antigens. This study investigated the hypothesis that EPEC infections may protect against EHEC infections. We used a mouse model to inoculate BALB/c mice intragastrically, first with EPEC and then with EHEC (
E. coli
O157:H7). Four control groups received either a nonpathogenic
E. coli
(NPEC) strain followed by EHEC (NPEC/EHEC), phosphate-buffered saline (PBS) followed by EHEC (PBS/EHEC), EPEC/PBS, or PBS/PBS. Mice were monitored for weight loss and symptoms. EPEC colonized the intestine after challenge, and mice developed serum antibodies to intimin and
E. coli
secreted protein B (encoded in the LEE). Prechallenge with an EPEC strain had a protective effect after EHEC infection, as only a few mice developed mild symptoms, from which they recovered. These mice had an increase in body weight similar to that in control animals, and tissue morphology exhibited mild intestinal changes and normal renal histology. All mice that were not prechallenged with the EPEC strain developed mild to severe symptoms after EHEC infection, with weight loss as well as intestinal and renal histopathological changes. These data suggest that EPEC may protect against EHEC infection in this mouse model.
Type I Interferons Increase Host Susceptibility to Trypanosoma cruzi Infection
Authors: Chessler Anne-Danielle C. , Caradonna Kacey L. , Da'dara Akram , Burleigh Barbara A.
Published: March 2011

Trypanosoma cruzi, the protozoan parasite that causes human Chagas' disease, induces a type I interferon (IFN) (IFN-α/β) response during acute experimental infection in mice and in isolated primary cell types. To examine the potential impact of the type I IFN response in shaping outcomes in experimentalT. cruziinfection, groups of wild-type (WT) and type I IFN receptor-deficient (IFNAR−/−) 129sv/ev mice were infected with two differentT. cruzistrains under lethal and sublethal conditions and several parameters were measured during the acute stage of infection. The results demonstrate that type I IFNs are not required for early host protection againstT. cruzi. In contrast, under conditions of lethalT. cruzichallenge, WT mice succumbed to infection whereas IFNAR−/−mice were ultimately able to control parasite growth and survive.T. cruziclearance in and survival of IFNAR−/−mice were accompanied by higher levels of IFN-γ production by isolated splenocytes in response to parasite antigen. The suppression of IFN-γ in splenocytes from WT mice was independent of IL-10 levels. While the impact of type I IFNs on the production of IFN-γ and other cytokines/chemokines remains to be fully determined in the context ofT. cruziinfection, our data suggest that, under conditions of high parasite burden, type I IFNs negatively impact IFN-γ production, initiating a detrimental cycle that contributes to the ultimate failure to control infection. These findings are consistent with a growing theme in the microbial pathogenesis field in which type I IFNs can be detrimental to the host in a variety of nonviral pathogen infection models.
Dictyostelium discoideum as a Model System for Identification of Burkholderia pseudomallei Virulence Factors
Authors: Hasselbring Benjamin M. , Patel Maharsh K. , Schell Mark A.
Published: March 2011

Burkholderia pseudomallei
is an emerging bacterial pathogen and category B biothreat. Human infections with
B. pseudomallei
(called melioidosis) present as a range of manifestations, including acute septicemia and pneumonia. Although melioidosis can be fatal, little is known about the molecular basis of
B. pseudomallei
pathogenicity, in part because of the lack of simple, genetically tractable eukaryotic models to facilitate
en masse
identification of virulence determinants or explore host-pathogen interactions. Two assays, one high-throughput and one quantitative, were developed to monitor levels of resistance of
B. pseudomallei
and the closely related nearly avirulent species
Burkholderia thailandensis
to predation by the phagocytic amoeba
Dictyostelium discoideum
. The quantitative assay showed that levels of resistance to, and survival within, amoeba by these bacteria and their known virulence mutants correlate well with their published levels of virulence in animals. Using the high-throughput assay, we screened a 1,500-member
B. thailandensis
transposon mutant library and identified 13 genes involved in resistance to predation by
D. discoideum
. Orthologs of these genes were disrupted in
B. pseudomallei
, and nearly all mutants had similarly decreased resistance to predation by
D. discoideum
. For some mutants, decreased resistance also correlated with reduced survival in and cytotoxicity toward macrophages, as well as attenuated virulence in mice. These observations suggest that some factors required by
B. pseudomallei
for resistance to environmental phagocytes also aid in resistance to phagocytic immune cells and contribute to disease in animals. Thus,
D. discoideum
provides a novel, high-throughput model system for facilitating inquiry into
B. pseudomallei
virulence.
Longitudinal Analysis of the Prevalence, Maintenance, and IgA Response to Species of the Order Bacteroidales in the Human Gut
Authors: Zitomersky Naamah Levy , Coyne Michael J. , Comstock Laurie E.
Published: March 2011

Bacteroidales
species are the most abundant Gram-negative bacteria of the human intestinal microbiota. These bacteria evolved to synthesize numerous capsular polysaccharides (PS) that are subject to phase variation. In
Bacteroides fragilis
, PS synthesis is regulated so that only one of the eight PS biosynthesis loci is transcribed at a time in each bacterium. To determine if the bacteria evolved this unusual property to evade a host IgA response, we directly studied the human fecal ecosystem. We performed a longitudinal analysis of the abundant
Bacteroidales
species from 15 healthy adults at four intervals over a year. For this study, we used bacterial culture to perform analyses not accurate with DNA-based methods, including quantification of total viable
Bacteroidales
bacteria, strain maintenance, and IgA responses. Abundant
Bacteroidales
isolates were identified to the species level using multiplex PCR and 16S rRNA gene sequencing. Arbitrarily primed PCR was used for strain typing. IgA responses to endogenous strains carried over the year were analyzed, and the orientations of the invertible PS locus promoters from the ecosystem were quantified. Subjects consistently harbored from 5 × 10
8
to 8 × 10
10
Bacteroidales
bacteria/g of feces. Within the cohort, 20 different
Bacteroidales
species were detected at high concentrations.
Bacteroides uniformis
was the most prevalent; however, abundant
Bacteroidales
species varied between subjects. Strains could be maintained over the year within the ecosystem at high density. IgA responses were often not induced and did not correlate with the elimination of a strain or major changes in the orientations of the capsular PS locus promoters.
Complex Cellular Responses of Helicobacter pylori-Colonized Gastric Adenocarcinoma Cells
Authors: Schneider Sabine , Carra Gert , Sahin Ugur , Hoy Benjamin , Rieder Gabriele , Wessler Silja
Published: March 2011

Helicobacter pylori
is an important class I carcinogen that persistently infects the human gastric mucosa to induce gastritis, gastric ulceration, and gastric cancer.
H. pylori
pathogenesis strongly depends on pathogenic factors, such as VacA (vacuolating cytotoxin A) or a specialized type IV secretion system (T4SS), which injects the oncoprotein CagA (cytotoxin-associated gene A product) into the host cell. Since access to primary gastric epithelial cells is limited, many studies on the complex cellular and molecular mechanisms of
H. pylori
were performed in immortalized epithelial cells originating from individual human adenocarcinomas. The aim of our study was a comparative analysis of 14 different human gastric epithelial cell lines after colonization with
H. pylori
. We found remarkable differences in host cell morphology, extent of CagA tyrosine phosphorylation, adhesion to host cells, vacuolization, and interleukin-8 (IL-8) secretion. These data might help in the selection of suitable cell lines to study host cell responses to
H. pylori
in vitro
, and they imply that different host cell factors are involved in the determination of
H. pylori
pathogenesis. A better understanding of
H. pylori
-directed cellular responses can provide novel and more balanced insights into the molecular mechanisms of
H. pylori
-dependent pathogenesis
in vivo
and may lead to new therapeutic approaches.
Double Blinding with a New Placebo Needle: A Validation Study on Participant Blinding
Authors: Takakura Nobuari , Takayama Miho , Kawase Akiko , Yajima Hiroyoshi
Published: March 2011

Background

A no-touch control needle in which the needle tip cannot reach the skin has been designed, and has been validated for practitioner blinding in a previous study but not for participant blinding.

Objective

To test whether the no-touch control needle can effectively blind subjects.

Methods

An acupuncturist applied, in turn, a no-touch control, skin-touch placebo and penetrating needle in one forearm of 80 healthy subjects. After removing each needle, the subjects were asked to judge the type of needle and rate the sensation of skin penetration/penetration-like or skin pressure/pressure-like pain on a 100 mm visual analogue scale.

Results

The subjects correctly identified 67% of needles overall. 17 of the 80 no-touch control needles were judged as skin-touch, and one as penetrating. In addition, six skin-touch placebo needles, and no penetrating needles, were judged as no-touch. Half of the 80 skin-touch placebo needles and 65 of the 80 penetrating needles and two no-touch control needles elicited pain. Of 240 needles, the practitioner identified 120 correctly that did not fit the probability of 1/3 (χ2=30.00, p<0.01).

Conclusions

The no-touch control needles may be used as a blind control for the acupuncture procedure, or to test the physiological effect of the skin-touch needles, but are not suitable for double-blind testing of the needle effect.
The additional effect of orthotic devices on exercise therapy for patients with patellofemoral pain syndrome: a systematic review
Authors: Swart Nynke M , van Linschoten Robbart , Bierma-Zeinstra Sita M A , van Middelkoop Marienke
Published: March 2011

The aim of the study is to determine “the additional effect of... function” for patellofemoral pain syndrom (PFPS). The additional effect of orthotic devices over exercise therapy on pain and function. A systematic literature search was conducted in MEDLINE, CINAHL, EMBASE, Cochrane and PEDro. Randomised controlled trials and controlled clinical trials of patients diagnosed with PFPS evaluating a clinically relevant outcome were included. Treatment had to include exercise therapy combined with orthotics, compared with an identical exercise programme with or without sham orthotics. Data were summarised using a best evidence synthesis. Eight trials fulfilled the inclusion criteria, of which three had a low risk of bias. There is moderate evidence for no additive effectiveness of knee braces to exercise therapy on pain (effect sizes (ES) varied from −0.14 to 0.04) and conflicting evidence on function (ES −0.33). There is moderate evidence for no difference between knee braces and exercise therapy versus placebo knee braces and exercise therapy on pain and function (ES −0.1–0.10). More studies of high methodological quality are needed to draw definitive conclusions.
Increased running speed and pre-race muscle damage as risk factors for exercise-associated muscle cramps in a 56 km ultra-marathon: a prospective cohort study
Authors: Schwellnus Martin P , Allie Siddieq , Derman Wayne , Collins Malcolm
Published: March 2011

Background

Despite the high prevalence of exercise-associated muscle cramping (EAMC) in endurance runners, the aetiology and risk factors for this condition are not fully understood.

Purpose

The purpose of this prospective cohort study was to identify risk factors associated with the development of EAMC in ultra-distance runners.

Methods

49 runners participating in a 56 km race completed a validated pre-race questionnaire. Pre-race muscle pain in the calves, hamstrings and quadriceps muscles was recorded (visual analogue scale) and pre-race serum creatine kinase (CK) activity was measured. 20 runners reported EAMC (EAMC group) during or within 6 h after the event, while 29 runners reported no cramping (CON group).

Results

EAMC was not associated with age, body mass index, sex, recent and past personal best running times, pre-race muscle pain and pre-race training (duration and frequency). Runners in the EAMC group tended to report on average longer training sessions during the 3 days before the race (EAMC 1.2 (1.1), CON 0.6 (1.0); p=0.077). Significant risk factors for EAMC were a past history of EAMC (EAMC 100%, CON 48%; p<0.001) and a faster running time (min) for the first 28 km split time of the race (EAMC 144 (20), CON 157 (14); p=0.029) despite being matched for recent (<15 weeks before race) personal best times in the 42.2 km race. Pre-race CK activity tended to be higher in the EAMC group (EAMC 89 (80), CON 58 (35); p=0.066).

Conclusions

Novel risk factors for EAMC in distance runners are a past history of EAMC, faster running pace at the early stage of a race and possibly pre-race muscle damage.
A PARTIAL ORDER ON THE SET OF PRIME KNOTS WITH UP TO 11 CROSSINGS
Authors: HORIE KEIICHI , KITANO TERUAKI , MATSUMOTO MINEKO , SUZUKI MASAAKI
Published: March 2011

Let K be a prime knot in S3 and G(K) = π1(S3 - K) the knot group. We write K1 ≥ K2 if there exists a surjective homomorphism from G(K1) onto G(K2). In this paper, we determine this partial order on the set of prime knots with up to 11 crossings. There exist such 801 prime knots and then 640, 800 should be considered. The existence of a surjective homomorphism can be proved by constructing it explicitly. On the other hand, the non-existence of a surjective homomorphism can be proved by the Alexander polynomial and the twisted Alexander polynomial.
ALGEBRAIC APPROACH TO THE KLEIN–GORDON EQUATION WITH HYPERBOLIC SCARF POTENTIAL
Authors: DONG SHISHAN , DONG SHI-HAI , BAHLOULI H. , BEZERRA V. B.
Published: March 2011

Using the shape invariance approach we obtain exact solutions of one-dimensional Klein–Gordon equation with equal types of scalar and vector hyperbolic Scarf potentials. This is considered in the framework of supersymmetric quantum mechanics method.
VIOLATION OF THE WEAK EQUIVALENCE PRINCIPLE IN BEKENSTEIN'S THEORY
Authors: KRAISELBURD L. , VUCETICH H.
Published: March 2011

Bekenstein has shown that violation of Weak Equivalence Principle is strongly suppressed in his model of charge variation. In this paper, it is shown that nuclear magnetic energy is large enough to produce observable effects in Eötvös experiments.
ALPHA DECAY HALF-LIVES OF EXOTIC NUCLEI AROUND SHELL CLOSURES
Authors: WANG Y. Z. , GU Q. F. , DONG J. M. , PENG B. B.
Published: March 2011

In the framework of the generalized liquid drop model (GLDM) and improved Royer's formula with a set of new coefficients derived by N. D. Schubert et al. [Eur. Phys. J. A42 (2009) 121], the favored and unfavored α-decay half-lives of exotic nuclei around closed shells Z = 82 and N = 126 are investigated. The calculated results are in good agreement with the experimental data. It is shown that our method can be used to study the α-decay half-lives of exotic nuclei around shell closures successfully and is helpful for future research on superheavy nuclei around the next proton and neutron shell closures. In addition, some α-decay half-lives for the cases where the experimental values are unavailable are predicted. We hope our predicted results are useful for future experiments.
DEFINITION AND VALIDATION OF REQUIREMENTS FOR COLLABORATIVE DECISION-MAKING IN ENTERPRISE ARCHITECTURE CREATION
Authors: NAKAKAWA AGNES , VAN BOMMEL PATRICK , PROPER H. A.
Published: March 2011

Gartner advises that for enterprise architecture development to be successful, it is vital that enterprise architects ensure effective communication and also form virtual teams that create and agree on enterprise architecture content. One of the ways to achieve this is to enforce Collaborative Decision Making (CDM) during enterprise architecture creation. Guided by Design Science, we are developing a method referred to as Collaborative Evaluation of (Enterprise) Architecture Design Alternatives (CEADA) to enable CDM during enterprise architecture creation. The method attempts to resolve challenges in enterprise architecting that are caused by ineffective collaboration between enterprise architects and organizational stakeholders. Requirements for CEADA have been defined based on the causality analysis theory, the generic decision-making process, enterprise architecture frameworks (and literature), and the CDM theory. In addition, Collaboration Engineering has been used to design a collaboration process to address these requirements. Models describing the requirements and the design of the collaboration process, have been evaluated using the analytical, experimental, and observational methods. This paper discusses the implications of findings from these evaluations and presents the validated requirements for realizing CDM in enterprise architecture creation. Thus, this research generally attempts to strengthen enterprise architecting guidelines with collaborative activities, so as to enable effective execution of collaboration-dependent tasks.
TECHNOLOGY DIFFUSION AND FORECASTING: THE CASE OF COMPUTATIONAL FLUID DYNAMICS (CFD) FOR SIMULATION OF GREENHOUSE INTERNAL ENVIRONMENTS
Authors: PRETORIUS LEON , BENADE SIEBERT , KRUGER SUNITA
Published: March 2011

Forecasting emerging technologies as well the rate of diffusion of resultant products are complex in the context of management of technology usually because of a lack of relevant data. Techniques such as bibliometric analysis and the Bass diffusion model are utilized in this paper to assess the growth rate and market penetration of computational fluid dynamics (CFD) as a technology. The penetration and growth rate of user acceptance of two CFD codes (not identified) are simulated. Furthermore, a technology forecasting model of research and innovation in the field of application of CFD in the assessment of greenhouses is presented. Some CFD results of simulations for internal and external flow in an eight-span greenhouse are presented as an illustration of the power of CFD as technology.
THE EMBEDDING OF THE SPACETIME IN HIGHER-DIMENSIONAL RIEMANN–CARTAN MANIFOLDS AND CLASSICAL CONFINEMENT OF TEST PARTICLES
Authors: ROMERO C. , FORMIGA J. B. , DA SILVA L. F. P. , DAHIA F.
Published: March 2011

We revisit the Riemann–Cartan geometry in the context of recent higher-dimensional theories of spacetime. After introducing the concept of torsion in a modern geometrical language we present some results that represent extensions of Riemannian theorems. We consider the theory of local embeddings and submanifolds in the context of Riemann–Cartan geometries and show how a Riemannian spacetime may be locally and isometrically embedded in a bulk with torsion. As an application of this result, we discuss the problem of classical confinement and the stability of motion of particles and photons in the neighborhood of branes for the case when the bulk has torsion. We illustrate our ideas considering the particular case when the embedding space has the geometry of a warped product space. We show how the confinement and stability properties of geodesics near the brane may be affected by the torsion of the embedding manifold. In this way we construct a classical analogue of quantum confinement inspired in theoretical-field models by replacing a scalar field with a torsion field.
Security of multithreaded programs by compilation
Authors: Barthe Gilles , Rezk Tamara , Russo Alejandro , Sabelfeld Andrei
Published: March 2011

End-to-End security of mobile code requires that the code neither intentionally nor accidentally propagates sensitive information to an adversary. Although mobile code is commonly multithreaded low-level code, there lack enforcement mechanisms that ensure information security for such programs. The modularity is three-fold: we give modular extensions of sequential semantics, sequential security typing, and sequential security-type preserving compilation that allow us enforcing security for multithreaded programs. Thanks to the modularity, there are no more restrictions on multithreaded source programs than on sequential ones, and yet we guarantee that their compilations are provably secure for a wide class of schedulers.
The role mining problem
Authors: Vaidya Jaideep , Atluri Vijayalakshmi , Guo Qi
Published: March 2011

Devising a complete and correct set of roles has been recognized as one of the most important and challenging tasks in implementing role-based access control. A key problem related to this is the notion of goodness/interestingness—when is a role good/interesting? In this article, we define the
Role Mining Problem
(RMP) as the problem of discovering an optimal set of roles from existing user permissions. The main contribution of this article is to formally define RMP and analyze its theoretical bounds. In addition to the above basic RMP, we introduce two different variations of the RMP, called the
δ-Approx RMP
and the
minimal-noise RMP
that have pragmatic implications. We reduce the known “Set Basis Problem” to RMP to show that RMP is an NP-complete problem. An important contribution of this article is also to show the relation of the RMP to several problems already identified in the data mining and data analysis literature. By showing that the RMP is in essence reducible to these known problems, we can directly borrow the existing implementation solutions and guide further research in this direction. We also develop a heuristic solution based on the previously proposed FastMiner algorithm, which is very accurate and efficient.
Determination of Maintainability Index for Object Oriented Systems
Authors: Kaur Kulwant , Singh Hardeep
Published: March 2011

In Object Oriented System, the quality of software depends significantly on the decision taken at early phases of the development. As per available artefact, quality of the class description is very crucial for system development. Maintenance is to repair defects in software, to adapt the software to different operational environments and to add or modify the functionality of the system. In Object Oriented Systems, maintainability factor needs more aspects to explore. We have proposed Maintainability Index using Package Metrics. We performed empirical evaluation using three case studies.
Agile Testing: Introducing PRAT as a Metric of Testing Quality in Scrum
Authors: Kayes Imrul
Published: March 2011

Scrum methodology has originated from agile software develop-ment as an elixir to software projects which are behind the sche-dule or which are highly likely to have a problematic development phase. Also unlike any other agile methodology, scrum is adaptive in nature. This paper presents a metric that focuses on measuring test quality in scrum. As product quality and process quality is closely correlated, improved test quality can ensure high quality deliverable product. Proposed metric measures test quality of each sprint/ iteration of scrum based upon some factor ratings which can be used to get a comprehensive test quality overview of testing process over longer periods.
Agile software architecture
Authors: Miyachi Christine
Published: March 2011

When the Agile software development became popular in software development communities, some engineers thought that software architecture would die out. But no matter what, a software project will have an architecture, whether documented intentionally or created on the fly. Software Architecture should enable Agile development methods by itself being Agile. But how? In this paper, I will discuss my experience of doing architecture in an Agile way and in a non-Agile way. Have an architecture that follows the Agile principles is key to obtaining success in an Agile development environment.
Aggregation of experiences in experience factories into software patterns
Authors: Rech Jörg , Ras Eric
Published: March 2011

In software engineering Experience Factories have been in use for a long time to store and manage experiences from software projects, typically in large organizations. Beside the preservation of quantitative or numerical experiences, e.g., in form of project effort data or data from empirical studies, many experience facto-ries also preserve subjective or qualitative experiences, e.g., in form of observations or lessons learned from the projects. A key issue of experience management is to aggregate these documented experiences into more valuable software patterns. In this article we report about the aggregation (i.e., formalization and generalization) of documented experiences in an experience factory to software patterns. Observations from real-world projects are formalized (i.e., structurally contextualized) into semi-formal experiences and, over time, several similar of these experiences are generalized (i.e., systematically de-contextualized) into software patterns.
LR(1) parser generation system
Authors: Sorkin Arthur , Donovan Peter
Published: March 2011

The LR(1) Parser Generation System generates full LR(1) parsers that are comparable in speed and size to those generated by LALR(1) parser generators, such as yacc [5]. In addition to the inherent advantages of full LR(1) parsing, it contains a number of novel features. This paper discusses three of them in detail: an LR(1) grammar specified automatic error recovery algorithm, oracles, and generic tokens.

The error recovery algorithm depends on the fact that full LR(1) parse tables preserve context. Oracles are pieces of code that are defined in a grammar and that are executed between the scanner and parser. They are used to resolve token ambiguities, including semantic ones. Generic tokens are used to replace syntactically identical tokens with a single token, which is, in effect, a variable representing a set of tokens.