bluuebunny/crossref_metadata_2025 huggingface dataset:
Interlaminar Crack Growth in Fiber Reinforced Composites During Fatigue
Authors: Wang S. S. , Wang H. T.
Published: August 2010

This paper presents an investigation of interlaminar crack growth behavior in fiber-reinforced composites subjected to fatigue loading. In the experimental phase of the study, interlaminar crack propagation rates and mechanisms were determined for the cases of various geometries, laminate parameters and cyclic stress levels. An advanced singular hybrid-stress finite element method was used in conjunction with the experimental results to examine the local crack-tip behavior and to characterize the crack propagation during fatigue. Results elucidate the basic nature of the cyclic delamination damage and relate the interlaminar crack growth rate to the range of mixed-mode crack-tip stress intensity factors. The study provides fundamental insight into the problem, reveals several important features of the interlaminar fatigue failure, and should be of practical importance in selection, testing and design of composite materials.
Fatigue Crack Propagation of Short Cracks
Authors: El Haddad M. H. , Smith K. N. , Topper T. H.
Published: August 2010

Previous studies have shown that both threshold stress intensity factors and fatigue crack growth rates are dependent on crack size. The average growth rates for very short cracks considerably exceed those given by conventional stress intensity-crack growth laws fitted to long crack data. Elastic and elastic plastic fracture mechanics solutions are modified to predict this behavior of short cracks by introducing an effective crack length l0 into the solutions for intensity factors and the J integral method of analysis. The threshold stress at a very short crack length approaches the fatigue limit of the material, and therefore the value of l0 can be obtained once the threshold stress intensity factor and the fatigue limit are known. The accuracy of the term l0 in predicting crack growth rates for short cracks is found to be independent of the applied strain level. It varies linearly with the grain size of the material and can be considered at the surface as a measure of the reduced flow resistance of surface grains due to their lack of constraint.
50-Fold Difference in Region-II Fatigue Crack Propagation Resistance of Titanium Alloys: A Grain-Size Effect
Authors: Yoder G. R. , Cooley L. A. , Crooker T. W.
Published: August 2010

Fatigue crack growth rates (da/dN) in ambient laboratory air have been determined for a wide variety of materials from four basic α + β titanium alloy systems. Each material was cyclically loaded with a haversine waveform and a load ratio, R = 0.10. The results indicate that, at a constant value of stress-intensity range (ΔK), the width of the da/dN data band exceeds an order of magnitude. For example, at ΔK = 21 MPa·m1/2, a 50-fold difference in fatigue crack propagation rates is observed. Analysis of the crack growth rate data at this point indicates a systematic dependence on grain size (l), viz. that da/dN decreases with increasing l. An interpretation of this effect is offered in terms of reversed (cyclic) plastic zone size considerations.
The Influence of Impurity-Defect Interactions on Radiation Hardening and Embrittlement
Authors: Wechsler M. S.
Published: August 2010

It has been established that copper and other trace elements have a detrimental effect on the notch-impact properties of ferritic pressure vessel steels irradiated at reactor operating temperatures of about 288°C (550°F). The underlying cause, however, of this trace element effect has not been established. But based on radiation damage work on vanadium containing oxygen and iron containing nitrogen, a possible mechanism appears to involve stabilization of radiation-produced defects as a result of migration of impurity atoms to the defects where they become trapped. The evidence for this impurity-defect interaction in vanadium and iron is described, and its effect on radiation hardening and embrittlement is discussed. The influence of dislocation channeling in promoting the early onset of plastic instability is also discussed, and the possible relevance of dislocation channeling is indicated with regard to the radiation-produced increase in ductile-brittle transition temperature and decrease in ductile shelf energy.
Application of J-Integral to High-Temperature Crack Propagation: Part I—Creep Crack Propagation
Authors: Taira Shuji , Ohtani Ryuichi , Kitamura Takayuki
Published: August 2010

Crack propagation tests in creep were carried out on 0.16 percent carbon steel at 400 and 500°C in air and at 400°C in vacuum, on Type 316 stainless steel at 600 and 650°C in air, and on Type 304 stainless steel at 650°C in air and vacuum. As a nonlinear fracture mechanics approach, the applicability of the creep J-integral for a controlling parameter of the crack propagation rate was investigated using a few types of specimens subjected to constant tensile loads. A good correlation was obtained between crack propagation rate and creep J-integral. Crack propagation rate was nearly proportional to the creep J-integral, and the relationship was almost independent on the width of plate specimens, the test temperatures, the testing environments, and the fracture mode. The creep crack propagation rate in round notched bar specimens was a little smaller than that in the center notched plate specimens at the same magnitude of the creep J-integral.
Effect of Metal Composition on Carburizing of Steels
Authors: Johnson E. O. , Scott V. D. , Thornton P. C.
Published: August 2010

The effect of metal composition on the diffusivity of carbon during carburizing several commercial steels has been investigated using electron probe microanalysis as well as hardness measurements and microscopy. Additions (up to several wt. percent) of nickel and chromium have little effect on thickness of carburized case but increase the total carbon level in immediate surface regions by forming iron carbide; the amount actually dissolved in the alloy is lower than in a plain carbon steel.
Application of Corrosion Fatigue Crack Growth Rate Data to Integrity Analyses of Nuclear Reactor Vessels
Authors: Bamford W. H.
Published: August 2010

The methodology of fatigue crack growth analysis in evaluating structural integrity of nuclear components has been well established over the years, even to the point where a recommended practice has been incorporated in Appendix A to Section XI of the ASME Code. The present reference curve for crack growth rates of pressure vessel steels in reactor water environment was developed in 1973, and since that time a great deal of data have become available. The original curve was meant to be a bounding curve, and some recent data have exceeded it, so an important question to address is which reference curve to use for these calculations. The important features of fatigue crack growth behavior in a reactor water environment are reviewed, along with some suggested explanation for the observed environmental enhancement and overall trends. The variables which must be accounted for in any reference crack growth rate curve are delineated and various methods for accomplishing this task are discussed. Improvements to the present reference curve are suggested, and evaluated as to their accuracy relative to the present curve. The impact of the alternative curves is also evaluated through solution of an example problem. A discussion of the conservatisms included in the alternative reference curves as compared with the present reference curve is included. Also research work is identified which could lead to further improvement in the reference curves.
Effects of Stress Ratio and Hold-Time on Fatigue Crack Growth in Alloy 718
Authors: Shahinian P. , Sadananda K.
Published: August 2010

Crack growth rate da/dN in Alloy 718 at 650°C, compared on the conventional ΔK basis, increased with increase in R (Kmin/Kmax) and also generally with inclusion of hold time at Kmax and Kmin. An exception, however, was that a 1-min hold at a Kmin just below the threshold K for creep crack growth caused retardation of crack growth. Correlation of da/dN for various R levels was better with Kmax than with other parameters such as Kmin, ΔK, and Δ J-integral. Fatigue crack growth in the alloy was found to be time dependent and Kmax controlled under these test conditions and consequently the best overall correlation was given by da/dt with Kmax. An unusual observation was that the addition of hold time to the loading cycle at near zero Kmin (R = 0.05) caused an increase in da/dN, as the result of an environmental interaction.
Analytical Formulation of a Rate and Temperature Dependent Stress-Strain Relation
Authors: Merzer A. , Bodner S. R.
Published: August 2010

The equation for plastic strain rate in the Bodner-Partom viscoplastic formulation is integrated under conditions of uniaxial stress, constant plastic strain rate, and isotropic hardening to give an analytical expression for the stress as a function of plastic strain and strain rate. Temperature dependence is introduced which leads to a general relationship between stress, strain, strain rate, and temperature. The resulting equation indicates an asymptotic saturation stress whose dependence on strain rate and temperature appears to agree with experimental results. Strain hardening given by the analytical equation also seems to be consistent with experiments. A possible new definition of yield stress is a consequence of the rate dependent stress-strain relation.
An Analysis of the Rupture Behavior of Pressurized Fast Reactor Cladding Tubes Subjected to Thermal Transients
Authors: Kramer J. M. , DiMelfi R. J.
Published: August 2010

The rupture behavior of 20 percent cold-worked type 316 stainless steel fast reactor fuel cladding, subjected to thermal transients typical of hypothetical accident conditions, is studied by considering the response of a thin-walled cylinder loaded by constant internal pressure. The high-stress low-temperature failure behavior is analyzed using a correlation from low temperature tensile properties. The low-stress high-temperature regime is shown to be described by a combined creep-deformation crack-growth-law formulation including annealing effects via grain growth. Failure temperatures and failure ductilities calculated using these models, compare favorably with experiment. It is also shown how the models can be extended to explain the observed reduction in failure temperature and failure ductility of cladding tubes that have been exposed to irradiation and/or corrosive environments.
Isotropic Properties of Platelet-Reinforced Media
Authors: Christensen R. M.
Published: August 2010

The effective moduli are derived for a composite material containing platelet-type inclusions. The platelets are taken to be randomly oriented in three-dimensional space and to have so large a diameter-to-thickness ratio that edge effects can be neglected. The effective moduli that are derived reduce to known results in the special case of a dilute suspension. Comparisons are made with the corresponding type of composite medium that involves randomly oriented fibers. For the same volume fraction of reinforcing phase, the platelet case provides a stiffening effect about three times greater than the fiber case.
Student Blogging about Physics
Authors: Daniels Karen E.
Published: August 2010

In traditional introductory physics classes, there is often limited opportunity for students to contribute their own ideas, interests, and experiences as they engage with the subject matter. This situation is exacerbated in university lecture-format classes, where students may not feel comfortable speaking during class. In the last few years, Internet blogs have become a decentralized format for diarists, independent journalists, and opinion makers to both post entries and allow commentary from their readers. Below, I will describe some techniques for using student blogging about physics to engage students from two different classroom environments: a calculus-based introductory mechanics class for scientists and engineers, and an honors seminar for first-year students. These assignments required them to make their own connections between classroom knowledge and situations where it might find applications. A second goal of including blogging in the introductory physics course was to induce students to write about the physics content of the class in a more substantive way than was previously part of the class.
Using a Force Probe to Study Transverse Pulses and Reflections on a Plucked Elastic Cord
Authors: Hämäläinen Ari , Abbott David
Published: August 2010

Before the advent of microcomputer-based labware (MBL), “time-of-flight” measurements1,2 for the speed of a transverse pulse on a string required elegant apparatus. This paper describes how to use an off-the-shelf MBL force sensor and a computer to perform the measurement. The data shown in this paper were collected using Vernier Software's wireless dynamics sensor system and Logger Pro software,3 but almost any common force sensor coupled with a computer or graphing calculator should work. You will also need about 2 m of string or elastic cord4 and a meterstick or tape measure.
Hydromonochord: Visualizing String Vibration by Water Swirls
Authors: Sommer Wilfried , Meier-Böke Ralf , Meinzer Nicholas
Published: August 2010

The hydromonochord is a horizontal vibrating string that just makes contact with the surface of a water bath. The motion of the string sets up a pattern of swirls on the surface of the water, thus complementing the usual pattern of nodes and antinodes. The device is based on the traditional monochord.1 A water basin (Fig. 1) has two slits in the opposite walls on the left-hand side, with the width of the slits equal to the diameter of the string. Consequently, the slits function as fixed bridges and form the nodes of a standing wave. The string is bowed or plucked on the part outside the basin, and the frequency is controlled by the position of the variable bridge on the right-hand end of the string. If the position of this bridge is related in a simple way with the length of the basin, patterns of swirls will occur on the surface of the water, visualizing the vibration of the string. We will present a series of experiments and show how to integrate them into the very first stage of teaching acoustics.
Why Are So Many Things in the Solar System Round?
Authors: Heilig Steven J.
Published: August 2010

Several years ago a student asked why so many things in the solar system were round. He noted that many objects in the solar system, although not all, are round. The standard answer, which he knew, is that the mutual gravitational attraction of the molecules pulls them into the shape that gets them as close to each other as possible: a sphere. This argument works fine for fluid bodies such as the Sun or Jupiter, but it isn't so simple for a solid object—we have all seen rocks that are not round. There is still a gravitational attraction acting between the rock's molecules, butfor small rocks that force does not overcome the strength of the bonds holding those molecules in their relative positions. Since the strength of the gravitational force grows with the size of the object, a large enough rock will have a strong enough gravitational attraction to force a deformation into a round shape. But how large is that? A simple model gives an answer to this question. There is also renewed interest in this topic as a result of the new definition of a planet approved by the International Astronomical Union, which says in part, “A ‘planet’ is a celestial body that… has sufficient mass for its self-gravity to overcome rigid body forces so that it assumes a hydrostatic equilibrium (nearly round) shape.”1 What size object is large enough to satisfy this criterion? Where does Pluto fall regarding this question?
A Simple Demonstration for Estimating the Persistence of Vision
Authors: MacInnes Iain , Smith Stuart
Published: August 2010

In the “The Science Study Series” book The Physics of Television,1 it is stated that persistence of vision lasts for about a tenth of a second. This will be a notional figure just as 25 cm is taken to be the least distance of distinct vision. Estimates range from 1/8 to 1/16 s.
Innovative Physics Teaching Conferences in the Czech Republic
Authors: Milbrandt Rod
Published: August 2010

Even today, with all of the instant communication technologies available, we are still often unaware of all that happens in other parts of the world. In the middle of Europe, in the Czech Republic, physics teachers have created a couple of innovative conferences—or workshops might be a better term. Having attended two of each, I think they're worth publicizing more broadly.
A Trick of Gravity
Authors: Newburgh Ronald
Published: August 2010

It's both surprising and rewarding when an old, standard problem reveals a subtlety that expands its pedagogic value. I realized recently that the role of gravity in the range equation for a projectile is not so simple as first appears. This realization may be completely obvious to others but was quite new to me.
Thermodynamics and Human Population
Authors: Cordry Sean M.
Published: August 2010

This paper discusses a Fermi-problem exercise through which I take students in several of my college courses. Students work in teams, determining the average daily Caloric needs per person. Then they use insolation values to determine the size of a collection area needed to absorb the previously determined daily energy requirements. Adjustments to the size of the collection area are made based on energy absorption per biological trophic level, as well as the consideration that most diets are a mixture of plant- and animal-derived elements. Finally, using the total amount of farmland available on the planet, students calculate a maximum population value. Although the maximum population values derived herewith should not be considered authoritative, the exercise has three beneficial purposes: 1) a chance to talk about the modeling process and extrapolations, 2) an unexpected application of physics to social contexts, and 3) raising student awareness of population and energy issues.
From Collaboration to Publication
Authors: O'Connor Jerry , Marshall Jill
Published: August 2010

As co-authors of a recent publication in Physical Review Special Topics- Physics Education Research,1 we have received inquiries about the publication process.2 We will describe the process of creating an article based on team work, in our case the work of the Texas Physics Assessment Team. Many physics teachers have opportunities to participate in collaborations for organizations like the AAPT and state education agencies. We may think of this work as service or professional development rather than research, but it can provide valuable information to the community as a whole and merits publication when presented in an appropriate format. Collaboration can provide a particularly important avenue toward publication for those of us at institutions dedicated primarily to teaching rather than research. Many data-gathering efforts require the collaboration of individuals and institutions at all degree levels. Community colleges have more diverse student populations than large research institutions, and may be able to provide different perspectives on common problems in teaching and learning physics. We will present suggestions for future team work publications, including prospective publications reporting the work of AAPT area committees.
Teaching Introductory Physics with an Environmental Focus
Authors: Martinuk Mathew “Sandy” , Moll Rachel F. , Kotlicki Andrzej
Published: August 2010

Throughout North America the curriculum of introductory physics courses is nearly standardized. In 1992, Tobias wrote that four texts dominate 90% of the introductory physics market1 and current physics education research is focusing on how to sustain educational reforms.2 The instructional team at the University of British Columbia (UBC) recently implemented some key curriculum and pedagogical changes in Physics 100, their algebra-based introductory course for non-physics majors. These changes were aimed at improving their students' attitudes toward physics and their ability to apply physics concepts to useful real-life situations. In order to demonstrate that physics is relevant to real life, a theme of energy and environment was incorporated into the course.
Wheel Diameter and Speedometer Reading
Authors: Murray Clifton
Published: August 2010

Most introductory physics students have seen vehicles with nonstandard wheel diameters; some may themselves drive “low-rider” cars or “big-wheel” pickup trucks. But how does changing wheel diameter affect speedometer readout for a given speed? Deriving the answer can be followed readily by students who have been introduced to rotation, and it makes a good illustration of how reasoning in physics can lead to a result that is useful outside the classroom.
Synapse Specification Goes Retro
Authors: Wong Wei
Published: August 2010

Endosomes containing NGF and its receptor TrkA are transported in a retrograde fashion to induce synapse formation.
Promoting Processing
Authors: Foley John F.
Published: August 2010

Smad proteins regulate the generation of microRNAs by binding to precursor molecules and promoting their processing.
A Gut Feeling
Authors: Mueller Kristen L.
Published: August 2010

Gut-specific signaling pathways regulate immune cell–mediated tolerance in the intestine.
Peripheral Quality Control
Authors: Hurtley Stella M.
Published: August 2010

Cells clear misfolded and damaged proteins from the cell surface, sometimes frustrating attempts to treat protein-folding diseases.
ampG
Gene of
Pseudomonas aeruginosa
and Its Role in β-Lactamase Expression
Authors: Zhang Ying , Bao Qiyu , Gagnon Luc A. , Huletsky Ann , Oliver Antonio , Jin Shouguang , Langaee Taimour
Published: August 2010

In enterobacteria, the
ampG
gene encodes a transmembrane protein (permease) that transports 1,6-GlcNAc-anhydro-MurNAc and the 1,6-GlcNAc-anhydro-MurNAc peptide from the periplasm to the cytoplasm, which serve as signal molecules for the induction of
ampC
β-lactamase. The role of AmpG as a transporter is also essential for cell wall recycling.
Pseudomonas aeruginosa
carries two AmpG homologues, AmpG (PA4393) and AmpGh1 (PA4218), with 45 and 41% amino acid sequence identity, respectively, to
Escherichia coli
AmpG, while the two homologues share only 19% amino acid identity. In
P. aeruginosa
strains PAO1 and PAK, inactivation of
ampG
drastically repressed the intrinsic β-lactam resistance while
ampGh1
deletion had little effect on the resistance. Further, deletion of
ampG
in an
ampD
-null mutant abolished the high-level β-lactam resistance that is associated with the loss of AmpD activity. The cloned
ampG
gene is able to complement both the
P. aeruginosa
and the
E. coli ampG
mutants, while that of
ampGh1
failed to do so, suggesting that PA4393 encodes the only functional AmpG protein in
P. aeruginosa
. We also demonstrate that the function of AmpG in laboratory strains of
P. aeruginosa
can effectively be inhibited by carbonyl cyanide
m
-chlorophenylhydrazone (CCCP), causing an increased sensitivity to β-lactams among laboratory as well as clinical isolates of
P. aeruginosa
. Our results suggest that inhibition of the AmpG activity is a potential strategy for enhancing the efficacy of β-lactams against
P. aeruginosa
, which carries inducible chromosomal
ampC
, especially in AmpC-hyperproducing clinical isolates.
bla
ROB-1
Presence on pB1000 in
Haemophilus influenzae
Is Widespread, and Variable Cefaclor Resistance Is Associated with Altered Penicillin-Binding Proteins
Authors: Tristram Stephen G. , Littlejohn Rachael , Bradbury Richard S.
Published: August 2010

Plasmid pB1000 is a small replicon recently identified as bearing
bla
ROB-1
in animal and human
Pasteurellaceae
in Spain. We identified pB1000 in 11
bla
ROB-1
-positive Australian and North American
Haemophilus influenzae
isolates, suggesting a wider role for pB1000 in disseminating
bla
ROB-1
. Native
H. influenzae
conjugative elements can mobilize plasmids similar to pB1000 at a low frequency of 10
−8
, and this might account for the infrequency of
bla
ROB-1
compared to the rate of occurrence of
bla
TEM-1
. Altered penicillin-binding protein 3 was associated with an increased cefaclor MIC in 3 isolates.
Diversity of Staphylococcal Cassette Chromosome
mec
Elements in Predominant Methicillin-Resistant
Staphylococcus aureus
Clones in a Small Geographic Area
Authors: Basset Patrick , Senn Laurence , Vogel Valérie , Zanetti Giorgio , Blanc Dominique S.
Published: August 2010

Recent population genetic studies suggest that staphylococcal cassette chromosome
mec
(SCC
mec
) was acquired much more frequently than previously thought. In the present study, we aimed to investigate the diversity of SCC
mec
elements in a local methicillin-resistant
Staphylococcus aureus
(MRSA) population. Each MRSA isolate (one per patient) recovered in the Vaud canton of Switzerland from January 2005 to December 2008 was analyzed by the double-locus sequence typing (DLST) method and SCC
mec
typing. DLST analysis indicated that 1,884/2,036 isolates (92.5%) belong to four predominant clones. As expected from the local spread of a clone, most isolates within clones harbored an identical SCC
mec
type. However, three to seven SCC
mec
types have been recovered in every predominant DLST clone, suggesting that some of these elements might have been acquired locally. This pattern could also be explained by distinct importations of related isolates into the study region. The addition of a third highly variable locus to further increase the discriminatory power of typing as well as epidemiological data suggested that most ambiguous situations were explained by the second hypothesis. In conclusion, our study showed that even if the acquisition of new SCC
mec
elements at a local level likely occurs, it does not explain all the diversity observed in the study region.
Demonstration of Conjugative Transposon (Tn
5397
)-Mediated Horizontal Gene Transfer between
Clostridium difficile
and
Enterococcus faecalis
Authors: Jasni Azmiza S. , Mullany Peter , Hussain Haitham , Roberts Adam P.
Published: August 2010

Antibiotic-resistant
Enterococcus faecalis
and
Clostridium difficile
are responsible for nosocomial infections in humans, in which they inhabit the same niche. Here, we demonstrate transfer of the conjugative transposon Tn
5397
from
C. difficile
630 to
E. faecalis
JH2-2, the first reported gene transfer between these two bacteria. Furthermore, transfer from the
E. faecalis
EF20A transconjugant to the epidemic ribotype 027
C. difficile
strain R20291 was also demonstrated. Tn
5397
was shown to use a single specific target site in
E. faecalis
; it also has specific target sites in
C. difficile
. These experiments highlight the importance of continual monitoring for emerging resistances in these bacteria.
Efficacy of Calcium-EDTA as an Inhibitor for Metallo-β-Lactamase in a Mouse Model of
Pseudomonas aeruginosa
Pneumonia
Authors: Aoki Nobumasa , Ishii Yoshikazu , Tateda Kazuhiro , Saga Tomoo , Kimura Soichiro , Kikuchi Yoshiaki , Kobayashi Tetsuo , Tanabe Yoshinari , Tsukada Hiroki , Gejyo Fumitake , Yamaguchi Keizo
Published: August 2010

In this study, we have evaluated the efficacy of calcium-EDTA (Ca-EDTA) as an inhibitor of bacterial metalloenzymes, such as metallo-β-lactamase (MBL) and other proteases, in a mouse model of
Pseudomonas aeruginosa
pneumonia. The simultaneous presence of Ca-EDTA (32 μg/ml) reduced the MICs of imipenem (IPM) in all MBL-producing
P. aeruginosa
isolates (IMP-1, -2, -7, and -10 and VIM-2) but not non-MBL-producing strains. In the pneumonia model, mice were intranasally infected with MBL-producing
P. aeruginosa
and then kept under conditions of hyperoxia to mimic ventilator-associated pneumonia. With both intranasal and subcutaneous administrations, Ca-EDTA significantly potentiated survival benefits of IPM compared to those of IPM alone. Ca-EDTA combination therapy induced a significant reduction of the bacterial burden in the lungs (
P
< 0.05). Furthermore, the inhibition activity of Ca-EDTA against MBL activity was confirmed by using the purified IMP-1 enzyme, which was characterized by a 50% inhibitory concentration (IC
50
) of 55 ± 8.2 μM. Finally, the protective effects of Ca-EDTA were demonstrated by culture supernatant-induced epithelial cell damage and acute lung injury in mice. These data suggest the therapeutic potential of Ca-EDTA not only by the blocking of MBLs but also by neutralizing tissue-damaging metalloproteases in
P. aeruginosa
infections.
A Novel Galacto-Glycerolipid from
Oxalis corniculata
Kills
Entamoeba histolytica
and
Giardia lamblia
Authors: Manna Dipak , Dutta Pradeep K. , Achari Basudeb , Lohia Anuradha
Published: August 2010

Oxalis corniculata
is a naturally occurring weed that has been used in traditional medicine for the cure of dysentery and diarrhea in India. One of the common causes of dysentery is due to infection by the protist pathogen
Entamoeba histolytica.
Bioactivity profiling of extracts from
O. corniculata
identified several compounds that showed antiamoebic activity in axenic cultures of
E. histolytica
. These were characterized by nuclear magnetic resonance, infrared, and mass spectrometry as (i) Oc-1, a mixture of saturated fatty acids C
24
to C
28
; (ii) Oc-2, a mixture of long-chain alcohols C
18
to C
28
; and (iii) Oc-3, a single compound that was a galacto-glycerolipid (GGL). Of the different compounds that were obtained, the strongest antiamoebic activity was found in GGL. The addition of GGL to
E. histolytica
xenic cultures containing other microbial flora from the large intestine did not affect its antiamoebic activity. Amoebicidal concentrations of GGL had no effect on intestinal microbial flora or on the mammalian cell line HEK-293. GGL was also found to be equally effective in killing another protist pathogen,
Giardia lamblia
, that causes diarrhea in humans. The importance of this study is based on the identification of novel natural products and the possibility of developing these compounds as active agents to treat at least two pathogenic parasitic intestinal infections endemic to tropical regions.
Sulfated Derivatives of
Escherichia coli
K5 Capsular Polysaccharide Are Potent Inhibitors of Human Cytomegalovirus
Authors: Mercorelli Beatrice , Oreste Pasqua , Sinigalia Elisa , Muratore Giulia , Lembo David , Palù Giorgio , Loregian Arianna
Published: August 2010

To date, there are few drugs licensed for the treatment of human cytomegalovirus (HCMV) infections, most of which target the viral DNA polymerase and suffer from many drawbacks. Thus, there is still a strong need for new anti-HCMV compounds with novel mechanisms of action. In this study, we investigated the anti-HCMV activity of chemically sulfated derivatives of
Escherichia coli
K5 capsular polysaccharide. These compounds are structurally related to cellular heparan sulfate and have been previously shown to be effective against some enveloped and nonenveloped viruses. We demonstrated that two derivatives, i.e., K5-N,OS(H) and K5-N,OS(L), are able to prevent cell infection by different strains of HCMV at concentrations in the nanomolar range while having no significant cytotoxicity. Studies performed to elucidate the mechanism of action of their anti-HCMV activity revealed that these compounds do not interact with either the host cell or the viral particle but need a virus-cell interaction to exert antiviral effects. Furthermore, these K5 derivatives were able to inhibit the attachment step of HCMV infection, as well as the viral cell-to-cell spread. Since the mode of inhibition of these compounds appears to differ from that of the available anti-HCMV drugs, sulfated K5 derivatives could represent the basis for the development of a novel class of potent anti-HCMV compounds. Interestingly, our studies highlight that small variations of the K5 derivatives structure can modulate the selectivity and potency of their activities against different viruses, including viruses belonging to the same family.
Emergence and Distribution of Plasmids Bearing the
bla
OXA-51
-Like Gene with an Upstream IS
Aba1
in Carbapenem-Resistant
Acinetobacter baumannii
Isolates in Taiwan
Authors: Chen Te-Li , Lee Yi-Tzu , Kuo Shu-Chen , Hsueh Po-Ren , Chang Feng-Yee , Siu Leung-Kei , Ko Wen-Chien , Fung Chang-Phone
Published: August 2010

The
bla
OXA-51
-like gene with an upstream IS
Aba1
(IS
Aba1
-
bla
OXA-51
-like gene) was originally found on the chromosomes of carbapenem-resistant or -susceptible
Acinetobacter baumannii
isolates. However, a plasmid-borne IS
Aba1
-
bla
OXA-51
-like gene has recently been identified in
Acinetobacter
genomic species 13TU and several
A. baumannii
isolates in Taiwan, and all of the isolates are carbapenem resistant. This study aimed to characterize the plasmids bearing the IS
Aba1
-
bla
OXA-51
-like gene and their significance in
A. baumannii
. Among the 117 IS
Aba1
-
bla
OXA-51
-like-harboring isolates collected from 10 hospitals in Taiwan, 58 isolates (49.6%) from 24 clones had the genes located on plasmids that likely originated from a common progenitor. Among the 58 isolates, four had additional copy of the IS
Aba1
-
bla
OXA-51
-like gene on their chromosomes. Based on the analysis of these four isolates, the plasmid-located IS
Aba1
-
bla
OXA-51
-like gene appeared to be acquired via one-ended transposition (Tn
6080
). The isolates with a plasmid bearing the IS
Aba1
-
bla
OXA-51
-like gene had higher rates of resistance to imipenem (98% versus 46.6%;
P
< 0.001) and meropenem (98% versus 69%;
P
= 0.019) than those with the genes chromosomally encoded, which is most likely due to increased gene dosage provided by the higher copy number of associated plasmids. Transformation with a recombinant plasmid harboring only the IS
Aba1
-
bla
OXA-51
-like gene was enough to confer a high level of carbapenem resistance to
A. baumannii
, eliminating the possible contribution of other factors on the original plasmids. This study demonstrated that the carbapenem resistance-associated plasmids carrying the IS
Aba1
-
bla
OXA-51
-like gene are widespread in
A. baumannii
strains in Taiwan.
Reductions in Skin and Systemic Parasite Burdens as a Combined Effect of Topical Paromomycin and Oral Miltefosine Treatment of Mice Experimentally Infected with
Leishmania
(
Leishmania
)
amazonensis
Authors: Aguiar Marta Gontijo , Pereira Aline Márcia Machado , Fernandes Ana Paula , Ferreira Lucas Antonio Miranda
Published: August 2010

This study aimed to investigate the activity of a combination of topical paromomycin gel and oral miltefosine for the treatment of experimental cutaneous leishmaniasis caused by
Leishmania
(
Leishmania
)
amazonensis
. The efficacy of the combination, evaluated by measuring lesion size and parasite burden in the skin and spleen, was assessed in BALB/c mice infected by
L
. (
L.
)
amazonensis
. The miltefosine was administered orally at 10 mg/kg of body weight/day for 10 days, while 10% paromomycin gel was applied topically twice a day for 20 days. Treatment of the experimentally infected animals with a topical paromomycin-oral miltefosine combination induced a statistically significant reduction in lesion size and parasite burden in the skin and spleen, with complete healing of ulcers, compared with those treated with a placebo group. A combination of topical paromomycin gel and oral miltefosine provided enhanced efficacy in the treatment of
L.
(
L.
)
amazonensis
-infected mice, showing activity higher than that observed for the monotherapeutic regimens.
Bactericidal Potencies of New Regimens Are Not Predictive of Their Sterilizing Potencies in a Murine Model of Tuberculosis
Authors: Andries Koen , Gevers Tom , Lounis Nacer
Published: August 2010

TMC207, rifapentine, and moxifloxacin are in clinical testing for the treatment of tuberculosis. Five experimental regimens with various combinations of TMC207, rifapentine, moxifloxacin, and pyrazinamide were tested for their bactericidal and sterilizing potencies in Swiss mice intravenously inoculated with
Mycobacterium tuberculosis
bacilli. TMC207 had the strongest bactericidal efficacy, while rifapentine was the strongest contributor to sterilizing efficacy. The rank order of sterilizing potencies was different from the rank order of bactericidal potencies, underlining the importance of prioritizing new regimens designed to shorten the treatment duration by their sterilizing potencies rather than by their bactericidal potencies. Both 3 months of treatment with a regimen combining TMC207, pyrazinamide, and rifapentine and 5 months of treatment with a regimen combining TMC207, pyrazinamide, and moxifloxacin resulted in relapse rates similar to the rate obtained by 6 months of treatment with rifampin-isoniazid-pyrazinamide.
New Candidate Vaccines against Blood-StagePlasmodium falciparumMalaria: Prime-Boost Immunization Regimens Incorporating Human and Simian Adenoviral Vectors and Poxviral Vectors Expressing an Optimized Antigen Based on Merozoite Surface Protein 1
Authors: Goodman Anna L. , Epp C. , Moss D. , Holder A. A. , Wilson J. M. , Gao G. P. , Long C. A. , Remarque E. J. , Thomas A. W. , Ammendola V. , Colloca S. , Dicks M. D. J. , Biswas S. , Seibel D. , van Duivenvoorde L. M. , Gilbert S. C. , Hill A. V. S. , Draper S. J.
Published: August 2010

Although merozoite surface protein 1 (MSP-1) is a leading candidate vaccine antigen for blood-stage malaria, its efficacy in clinical trials has been limited in part by antigenic polymorphism and potentially by the inability of protein-in-adjuvant vaccines to induce strong cellular immunity. Here we report the design of novel vectoredPlasmodium falciparumvaccines capable of overcoming such limitations. We optimized an antigenic insert comprising the four conserved blocks of MSP-1 fused to tandemly arranged sequences that represent both allelic forms of the dimorphic 42-kDa C-terminal region. Inserts were expressed by adenoviral and poxviral vectors and employed in heterologous prime-boost regimens. Simian adenoviral vectors were used in an effort to circumvent preexisting immunity to human adenoviruses. In preclinical studies these vaccines induced potent cellular immune responses and high-titer antibodies directed against MSP-1. The antibodies induced were found to have growth-inhibitory activity against dimorphic allelic families ofP. falciparum. These vectored vaccines should allow assessment in humans of the safety and efficacy of inducing strong cellular as well as cross-strain humoral immunity toP. falciparumMSP-1.
CD4+CD25+Foxp3+Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?
Authors: Gonçalves Raquel M. , Salmazi Karina C. , Santos Bianca A. N. , Bastos Melissa S. , Rocha Sandra C. , Boscardin Sílvia B. , Silber Ariel M. , Kallás Esper G. , Ferreira Marcelo U. , Scopel Kézia K. G.
Published: August 2010

Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections withPlasmodium falciparumandP. vivaxin the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4+CD25+Foxp3+Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123+), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third ofP. vivax-infected patients, but noP. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-α) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and long-lasting protective immunity to malaria.
Invasion of Bovine Peripheral Blood Mononuclear Cells and Erythrocytes byMycoplasma bovis
Authors: van der Merwe Jacques , Prysliak Tracy , Perez-Casal Jose
Published: August 2010

Mycoplasma bovisis a small, cell wall-less bacterium that contributes to a number of chronic inflammatory diseases in both dairy and feedlot cattle, including mastitis and bronchopneumonia. Numerous reports have implicatedM. bovisin the activation of the immune system, while at the same time inhibiting immune cell proliferation. However, it is unknown whether the specific immune-cell populationM. bovisis capable of attaching to and potentially invading. Here, we demonstrate that incubation ofM. bovisMb1 with bovine peripheral blood mononuclear cells (PBMC) resulted in a significant reduction in their proliferative responses while still remaining viable and capable of gamma interferon secretion. Furthermore, we show thatM. bovisMb1 can be found intracellularly (suggesting a role for either phagocytosis or attachment/invasion) in a number of select bovine PBMC populations (T cells, B cells, monocytes, γδ T cells, dendritic cells, NK cells, cytotoxic T cells, and T-helper cells), as well as red blood cells, albeit it at a significantly lower proportion.M. bovisMb1 appeared to display three main patterns of intracellular staining: diffuse staining, an association with the intracellular side of the cell membrane, and punctate/vacuole-like staining. The invasion of circulating immune cells and erythrocytes could play an important role in disease pathogenesis by aiding the transport ofM. bovisfrom the lungs to other sites.
LT-IIc, a New Member of the Type II Heat-Labile Enterotoxin Family Encoded by an
Escherichia coli
Strain Obtained from a Nonmammalian Host
Authors: Nawar Hesham F. , King-Lyons Natalie D. , Hu John C. , Pasek Raymond C. , Connell Terry D.
Published: August 2010

Two families of bacterial heat-labile enterotoxins (HLTs) have been described: the type I HLTs are comprised of cholera toxin (CT) of
Vibrio cholerae
, LT-I of
Escherichia coli
, and several related HLTs; the type II HLTs are comprised of LT-IIa and LT-IIb. Herein, we report LT-IIc, a new type II HLT encoded from an enterotoxigenic
E. coli
(ETEC) strain isolated from an avian host. Using a mouse Y1 adrenal cell bioassay, LT-IIc was shown to be less cytotoxic than CT, LT-IIa, or LT-IIb. Cytotoxicity of LT-IIc was partially neutralized by antisera recognizing LT-IIa or LT-IIb but not by anti-CT antiserum. Genes encoding putative A polypeptide and B polypeptides of LT-IIc were arranged in an operon which was flanked by potential prophage sequences. Analysis of the nucleotide and predicted amino acid sequences demonstrated that the A polypeptide of LT-IIc has moderate homology to the A polypeptides of CT and LT-I and high homology to the A polypeptides of LT-IIa and LT-IIb. The B polypeptide of LT-IIc exhibited no significant homology to the B polypeptides of CT and LT-I and only moderate homology to the B polypeptides of LT-IIa and LT-IIb. The binding pattern of LT-IIc for gangliosides was distinctive from that of either LT-IIa or LT-IIb. The data suggest that other types of the type II HLT subfamily are circulating in the environment and that host specificity of type II HLT is likely governed by changes in the B polypeptide which mediate binding to receptors.
The Inflammatory Response Induced by Aspartic Proteases of
Candida albicans
Is Independent of Proteolytic Activity
Authors: Pietrella Donatella , Rachini Anna , Pandey Neelam , Schild Lydia , Netea Mihai , Bistoni Francesco , Hube Bernhard , Vecchiarelli Anna
Published: August 2010

The secretion of aspartic proteases (Saps) has long been recognized as a virulence-associated trait of the pathogenic yeast
Candida albicans
. In this study, we report that different recombinant Saps, including Sap1, Sap2, Sap3, and Sap6, have differing abilities to induce secretion of proinflammatory cytokines by human monocytes. In particular Sap1, Sap2, and Sap6 significantly induced interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 production. Sap3 was able to stimulate the secretion of IL-1β and TNF-α. All Saps tested were able to induce Ca
2+
influx in monocytes. Treatment of these Saps with pepstatin A did not have any effect on cytokine secretion, indicating that their stimulatory potential was independent from their proteolytic activity. The capacity of Saps to induce inflammatory cytokine production was also independent from protease-activated receptor (PAR) activation and from the optimal pH for individual Sap activity. The interaction of Saps with monocytes induced Akt activation and phosphorylation of IκBα, which mediates translocation of NF-κB into the nucleus. Overall, these results suggest that individual Sap proteins can induce an inflammatory response and that this phenomenon is independent from the pH of a specific host niche and from Sap enzymatic activity. The inflammatory response is partially dependent on Sap denaturation and is triggered by the Akt/NF-κB activation pathway. Our data suggest a novel, activity-independent aspect of Saps during interactions of
C. albicans
with the host.
Gelatinase Contributes to the Pathogenesis of Endocarditis Caused byEnterococcus faecalis
Authors: Thurlow Lance R. , Thomas Vinai Chittezham , Narayanan Sanjeev , Olson Sally , Fleming Sherry D. , Hancock Lynn E.
Published: August 2010

The Gram-positive pathogenEnterococcus faecalisis a leading agent of nosocomial infections, including urinary tract infections, surgical site infections, and bacteremia. Among the infections caused byE. faecalis, endocarditis remains a serious clinical manifestation and unique in that it is commonly acquired in a community setting. Infective endocarditis is a complex disease, with many host and microbial components contributing to the formation of bacterial biofilm-like vegetations on the aortic valve and adjacent areas within the heart. In the current study, we compared the pathogenic potential of the vancomycin-resistantE. faecalisV583 and three isogenic protease mutants (ΔgelE, ΔsprE, and ΔgelEΔsprEmutants) in a rabbit model of enterococcal endocarditis. The bacterial burdens displayed by GelE−mutants (ΔgelEand ΔgelEΔsprEmutants) in the heart were significantly lower than those of V583 or the SprE−mutant. Vegetations on the aortic valve infected with GelE−mutants (ΔgelEand ΔgelEΔsprEmutants) also showed a significant increase in deposition of fibrinous matrix layer and increased chemotaxis of inflammatory cells. In support of a role for proteolytic modulation of the immune response toE. faecalis, we also demonstrate that GelE can cleave the anaphylatoxin complement C5a and that this proteolysis leads to decreased neutrophil migrationin vitro.In vivo, a decreased heterophil (neutrophil-like cell) migration was observed at tissue sites infected with GelE-producing strains but not at those infected with SprE-producing strains. Taken together, these observations suggest that of the two enterococcal proteases, gelatinase is the principal mediator of pathogenesis in endocarditis.