bluuebunny/crossref_metadata_2025 huggingface dataset:
AlGaN/GaN high electron mobility transistors on 100 mm silicon substrates by plasma molecular beam epitaxy
Authors: Hoke W. E. , Kennedy T. D. , Mosca J. J. , Kerr A. J. , Torabi A. , Davis-Hearns S. , LaRoche J. R.
Published: February 2011

GaN high electron mobility transistor (HEMT) structures have been grown by plasma molecular beam epitaxy on 100 mm diameter ⟨111⟩ silicon substrates. Crack-free films with thicknesses of up to 1.7 μm were deposited without the use of strain-relaxing buffer layers. X-ray measurements indicate high structural uniformity and the Pendellosung oscillations are observed due to the abruptness of the AlGaN/GaN interface. Capacitance-voltage measurements display a sharp pinch-off with a depleted GaN buffer layer and no measurable charge accumulation at the substrate-epi interface. Transmission line measurements on the GaN HEMT buffer and substrate indicate a loss of less than 0.2 dB/mm up to 20 GHz. An average sheet resistance of 443 Ω/sq with a standard deviation of 0.8% and a mobility of 1600 cm2/V s were obtained for an Al0.25Ga0.75N/GaN HEMT. Transistors were fabricated with a current density of 1.2 A/mm and a transconductance of 290 mS/mm which is quite comparable to GaN HEMTs on SiC.
Tumor control probability in radiation treatment
Authors: Zaider Marco , Hanin Leonid
Published: February 2011

Patients undergoing radiation therapy (and their physicians alike) are concerned with theprobability of cure(long‐term recurrence‐free survival, meaning the absence of a detectable or symptomatic tumor). This is not what current practice categorizes as “tumor control (TC);” instead, TC is taken to mean the extinction of clonogenic tumor cells at the end of treatment, a sufficient but not necessary condition for cure. In this review, we argue that TC thus defined has significant deficiencies. Most importantly, (1) it is an unobservable event and (2) elimination ofallmalignant clonogenic cells is, in some cases, unnecessary. In effect, within the existing biomedical paradigm, centered on the evolution of clonogenic malignant cells, full information about the long‐term treatment outcome is contained in the distributionof the number of malignant cells m that remain clonogenic at the end of treatment and the birth and death rates of surviving tumor cells after treatment. Accordingly, plausible definitions of tumor control are invariably traceable to. Many primary cancers, such as breast and prostate cancer, are not lethalper se; they kill through metastases. Therefore, an object of tumor control in such cases should be the prevention of metastatic spread of the disease. Our claim, accordingly, is that improvements in radiation therapy outcomes require a twofold approach: (a) Establish a link between survival time, where the events of interest are local recurrence or distant (metastatic) failure (cancer‐free survival) or death (cancer‐specific survival), and the distributionand (b) linkto treatment planning (modality, total dose, and schedule of radiation) and tumor‐specific parameters (initial number of clonogens, birth and spontaneous death rates during the treatment period, and parameters of the dose‐response function). The biomedical, mathematical, and practical aspects of implementing this program are discussed.
Development of a physical 3D anthropomorphic breast phantom
Authors: Carton Ann‐Katherine , Bakic Predrag , Ullberg Christer , Derand Helen , Maidment Andrew D. A.
Published: February 2011

Purpose:

Develop a technique to fabricate a 3D anthropomorphic breast phantom with known ground truth for image quality assessment of 2D and 3D breast x‐ray imaging systems.

Methods:

The phantom design is based on an existing computer model that can generate breast voxel phantoms of varying composition, size, and shape. The physical phantom is produced in two steps. First, the portion of the voxel phantom consisting of the glandular tissue, skin, and Cooper's ligaments is separated into sections. These sections are then fabricated by high‐resolution rapid prototyping using a single material with 50% glandular equivalence. The remaining adipose compartments are then filled using an epoxy‐based resin (EBR) with 100% adipose equivalence. The phantom sections are stacked to form the physical anthropomorphic phantom.

Results:

The authors fabricated a prototype phantom corresponding to a 450 ml breast with 45% dense tissue, deformed to a 5 cm compressed thickness. Both the rapid prototype (RP) and EBR phantom materials are radiographically uniform. The coefficient of variation (CoV) of the relative attenuation between RP and EBR phantom samples was and the CoV of the signal intensity within RP and EBR phantom samples was on average. Digital mammography and reconstructed digital breast tomosynthesis images of the authors' phantom were reviewed by two radiologists; they reported that the images are similar in appearance to clinical images, noting there are still artifacts from air bubbles in the EBR.

Conclusions:

The authors have developed a technique to produce 3D anthropomorphic breast phantoms with known ground truth, yielding highly realistic x‐ray images. Such phantoms may serve both qualitative and quantitative performance assessments for 2D and 3D breast x‐ray imaging systems.
An anthropomorphic phantom for quantitative evaluation of breast MRI
Authors: Freed Melanie , de Zwart Jacco A. , Loud Jennifer T. , El Khouli Riham H. , Myers Kyle J. , Greene Mark H. , Duyn Jeff H. , Badano Aldo
Published: February 2011

Purpose:

In this study, the authors aim to develop a physical, tissue‐mimicking phantom for quantitative evaluation of breast MRI protocols. The objective of this phantom is to address the need for improved standardization in breast MRI and provide a platform for evaluating the influence of image protocol parameters on lesion detection and discrimination. Quantitative comparisons between patient and phantom image properties are presented.

Methods:

The phantom is constructed using a mixture of lard and egg whites, resulting in a random structure with separate adipose‐ and glandular‐mimicking components. and relaxation times of the lard and egg components of the phantom were estimated at 1.5 T from inversion recovery and spin‐echo scans, respectively, using maximum‐likelihood methods. The image structure was examined quantitatively by calculating and comparing spatial covariance matrices of phantom and patient images. A static, enhancing lesion was introduced by creating a hollow mold with stereolithography and filling it with a gadolinium‐doped water solution.

Results:

Measured phantom relaxation values fall within 2 standard errors of human values from the literature and are reasonably stable over 9 months of testing. Comparison of the covariance matrices of phantom and patient data demonstrates that the phantom and patient data have similar image structure. Their covariance matrices are the same to within error bars in the anterior‐posterior direction and to within about two error bars in the right‐left direction. The signal from the phantom's adipose‐mimicking material can be suppressed using active fat‐suppression protocols. A static, enhancing lesion can also be included with the ability to change morphology and contrast agent concentration.

Conclusions:

The authors have constructed a phantom and demonstrated its ability to mimic human breast images in terms of key physical properties that are relevant to breast MRI. This phantom provides a platform for the optimization and standardization of breast MRI imaging protocols for lesion detection and characterization.
Classification of echolocation clicks from odontocetes in the Southern California Bight
Authors: Roch Marie A. , Klinck Holger , Baumann-Pickering Simone , Mellinger David K. , Qui Simon , Soldevilla Melissa S. , Hildebrand John A.
Published: February 2011

This study presents a system for classifying echolocation clicks of six species of odontocetes in the Southern California Bight: Visually confirmed bottlenose dolphins, short- and long-beaked common dolphins, Pacific white-sided dolphins, Risso’s dolphins, and presumed Cuvier’s beaked whales. Echolocation clicks are represented by cepstral feature vectors that are classified by Gaussian mixture models. A randomized cross-validation experiment is designed to provide conditions similar to those found in a field-deployed system. To prevent matched conditions from inappropriately lowering the error rate, echolocation clicks associated with a single sighting are never split across the training and test data. Sightings are randomly permuted before assignment to folds in the experiment. This allows different combinations of the training and test data to be used while keeping data from each sighting entirely in the training or test set. The system achieves a mean error rate of 22% across 100 randomized three-fold cross-validation experiments. Four of the six species had mean error rates lower than the overall mean, with the presumed Cuvier’s beaked whale clicks showing the best performance (<2% error rate). Long-beaked common and bottlenose dolphins proved the most difficult to classify, with mean error rates of 53% and 68%, respectively.
The effect of coupling on bubble fragmentation acoustics
Authors: Czerski Helen , Deane Grant B.
Published: February 2011

Understanding the formation and evolution of bubble populations is important in a wide range of situations, including industrial processes, medical applications, and ocean science. Passive acoustical techniques can be used to track changes in the population, since each bubble formation or fragmentation event is likely to produce sound. This sound potentially contains a wealth of information about the fragmentation process and the products, but to fully exploit these data it is necessary to understand the physical processes that determine its characteristics. The focus of this paper is binary fragmentation, when turbulence causes one bubble to split into two. Specifically, the effect that bubble-bubble coupling has on the sound produced is examined. A numerical simulation of the acoustical excitation of fragmenting bubbles is used to generate model acoustic signals, which are compared with experimental data. A frequency range with a suppressed acoustic output which is observed in the experimental data can be explained when coupling is taken into account. In addition, although the driving mechanism of neck collapse is always consistent with the data for the larger bubble of the newly formed pair, a different mechanism must be driving the smaller bubble in some situations.
Determining the direction to a sound source in air using vector sound-intensity probes
Authors: Hickling R. , Brown A. W.
Published: February 2011

This paper is concerned with probes for measuring vector sound intensity in air using the minimum number of sound-pressure sensors. The probes consist of an arrangement of four small microphones at the vertices of a regular tetrahedron. They are connected to a digital signal processor, which determines the sound-intensity vector, using the cross-spectral formulation based on finite-difference approximations. Determining the direction of a sound source is an obvious application. To do this accurately the probes should be omnidirectional. This implies that the microphones in the probe have to be omnidirectional and to have the same response. Results in the paper show that the direction of a sound source can be determined with an accuracy of a few degrees. Two types of probes are described. One measures the sound-intensity vector in three-dimensional space. The other measures the vector in a half space such as would occur above the ground or in front of a wall.
A method for evaluating the relation between sound source segregation and masking
Authors: Lutfi Robert A. , Liu Ching-Ju
Published: February 2011

Sound source segregation refers to the ability to hear as separate entities two or more sound sources comprising a mixture. Masking refers to the ability of one sound to make another sound difficult to hear. Often in studies, masking is assumed to result from a failure of segregation, but this assumption may not always be correct. Here a method is offered to identify the relation between masking and sound source segregation in studies and an example is given of its application.
Perceptual assimilation of Dutch vowels by Peruvian Spanish listeners
Authors: Escudero Paola , Williams Daniel
Published: February 2011

Many cross-language and L2 speech perception studies have been conducted on English sounds and a limited number of speakers or synthetic tokens have been used for auditory stimuli. The Spanish listeners of the present study were presented with natural tokens of Dutch vowels produced by males and females selected from the corpus reported in Adank et al. [(2004) J. Acoust. Soc. Am. 116, 1729–1738]. The results show that single category assimilations are common and that certain Dutch vowels frequently assimilate to Spanish diphthongs. Predictions are made for Spanish learners’ initial stage in the acquisition of the Dutch vowel system.
Free from Transcription
Authors: Foley John F.
Published: February 2011

Circadian rhythms in humans and algae can occur without the need for transcription-translation feedback control.
Are You Experienced?
Authors: Wong Wei
Published: February 2011

In naïve and experienced human T cells, activation of the TCR elicits different signaling pathways.
Voriconazole-Induced Inhibition of the Fungicidal Activity of Amphotericin B in
Candida
Strains with Reduced Susceptibility to Voriconazole: an Effect Not Predicted by the MIC Value Alone
Authors: Lignell Anders , Löwdin Elisabeth , Cars Otto , Sanglard Dominique , Sjölin Jan
Published: February 2011

An antagonistic effect of voriconazole on the fungicidal activity of sequential doses of amphotericin B has previously been demonstrated in
Candida albicans
strains susceptible to voriconazole. Because treatment failure and the need to switch to other antifungals are expected to occur more often in infections that are caused by resistant strains, it was of interest to study whether the antagonistic effect was still seen in
Candida
strains with reduced susceptibility to voriconazole. With the hypothesis that antagonism will not occur in voriconazole-resistant strains,
C. albicans
strains with characterized mechanisms of resistance against voriconazole, as well as
Candida glabrata
and
Candida krusei
strains with differences in their degrees of susceptibility to voriconazole were exposed to voriconazole or amphotericin B alone, to both drugs simultaneously, or to voriconazole followed by amphotericin B in an
in vitro
kinetic model. Amphotericin B administered alone or simultaneously with voriconazole resulted in fungicidal activity. When amphotericin B was administered after voriconazole, its activity was reduced (median reduction, 61%; range, 9 to 94%). Levels of voriconazole-dependent inhibition of amphotericin B activity differed significantly among the strains but were not correlated with the MIC values (correlation coefficient, −0.19;
P
= 0.65). Inhibition was found in
C. albicans
strains with increases in
CDR1
and
CDR2
expression but not in the strain with an increase in
MDR1
expression. In summary, decreased susceptibility to voriconazole does not abolish voriconazole-dependent inhibition of the fungicidal activity of amphotericin B in voriconazole-resistant
Candida
strains. The degree of interaction could not be predicted by the MIC value alone.
Contribution of N-Glucuronidation to Efavirenz Elimination
In Vivo
in the Basal and Rifampin-Induced Metabolism of Efavirenz
Authors: Cho Doo-Yeoun , Ogburn Evan T. , Jones David , Desta Zeruesenay
Published: February 2011

In this study, the contribution of efavirenz N-glucuronidation to efavirenz elimination
in vivo
was assessed. In a two-period placebo-controlled crossover trial design, a single 600-mg oral dose of efavirenz was administered to healthy volunteers (
n
= 10) pretreated with placebo pills or 600 mg/day rifampin orally for 10 days. Urine and plasma concentrations of efavirenz and 8-hydroxyefavirenz were measured by the liquid chromatography-tandem mass spectrometry method after enzymatic hydrolysis with β-glucuronidase (conjugated and unconjugated) and without enzymatic hydrolysis (unconjugated). Pharmacokinetic parameters of efavirenz within the placebo- or rifampin-treated group obtained after enzymatic hydrolysis did not show any statistically significant difference compared with those obtained without enzymatic hydrolysis (
P
> 0.05; paired
t
test, two-tailed). The amount of efavirenz excreted over 12 h was significantly larger after enzymatic hydrolysis in both the placebo (
P
= 0.007) and rifampin (
P
= 0.0001) treatment groups, supporting the occurrence of direct N-glucuronidation of efavirenz, but the relevance of this finding is limited because the amount of efavirenz excreted as unchanged or conjugated in urine is less than 1% of the dose administered. In both the placebo- and rifampin-treated groups, plasma concentrations of 8-hydroxyefavirenz and the amount excreted over 12 h were significantly larger (
P
< 0.00001) after enzymatic hydrolysis than without enzymatic hydrolysis. These findings suggest that although the occurrence of direct efavirenz N-glucuronidation is supported by the urine data, the abundance of efavirenz
N
-glucuronide in plasma is negligible and that the contribution of the N-glucuronidation pathway to the overall clearance of efavirenz seems minimal.
Intracellular Nucleotide Levels during Coadministration of Tenofovir Disoproxil Fumarate and Didanosine in HIV-1-Infected Patients
Authors: Hawkins Trevor , Veikley Wenoah , Durand-Gasselin Lucie , Babusis Darius , Reddy Y. Sunila , Flaherty John F. , Ray Adrian S.
Published: February 2011

Studies were conducted to determine if there is a mechanistic basis for reports of suboptimal virologic responses and concerns regarding the safety of regimens containing the combination of tenofovir (TFV) disoproxil fumarate (TDF) and didanosine (ddI) by assessing the pharmacokinetic consequences of coadministration of these drugs on intracellular nucleotides. This was a prospective and longitudinal study in HIV-1-infected patients of adding either TDF or ddI to a stable antiretroviral regimen containing the other drug. Intracellular concentrations of the nucleotide analogs TFV diphosphate (TFV-DP) and ddATP and the endogenous purine nucleotides dATP and 2′-dGTP in peripheral blood mononuclear cells were measured. A total of 16 patients were enrolled into the two study arms and a study extension. Intracellular TFV-DP concentrations (median, 120 fmol/106cells) and ddATP concentrations (range, 1.50 to 7.54 fmol/106cells in two patients) were unaffected following addition of ddI or TDF to a stable regimen containing the other drug. While coadministration of ddI and TDF for 4 weeks did not appear to impact dATP or dGTP concentrations, cross-sectional analysis suggested that extended therapy with ddI-containing regimens, irrespective of TDF coadministration, may decrease dATP and ddATP concentrations. Addition of TDF or ddI to a stable regimen including the other drug, in the context of ddI dose reduction, did not adversely affect the concentration of dATP, dGTP, TFV-DP, or ddATP. The association between longer-term ddI therapy and reduced intracellular nucleotide concentrations and this observation's implication for the efficacy and toxicity of ddI-containing regimens deserve further study.
Pharmacokinetic Properties of Conventional and Double-Dose Sulfadoxine-Pyrimethamine Given as Intermittent Preventive Treatment in Infancy
Authors: Salman Sam , Griffin Susan , Kose Kay , Pitus Nolene , Winmai Josephine , Moore Brioni , Siba Peter , Ilett Kenneth F. , Mueller Ivo , Davis Timothy M. E.
Published: February 2011

Intermittent preventive treatment in infancy (IPTi) entails routine administration of antimalarial treatment doses at specified times in at-risk infants. Sulfadoxine-pyrimethamine (SDX/PYR) is a combination that has been used as first-line IPTi. Because of limited pharmacokinetic data and suggestions that higher milligram/kilogram pediatric doses than recommended should be considered, we assessed SDX/PYR disposition, randomized to conventional (25/1.25 mg/kg of body weight) or double (50/2.5 mg/kg) dose, in 70 Papua New Guinean children aged 2 to 13 months. Blood samples were drawn at baseline, 28 days, and three time points randomly selected for each infant at 4 to 8 h or 2, 5, 7, 14, or 21 days. Plasma SDX, PYR, and N
4
-acetylsulfadoxine (NSX, the principal metabolite of SDX) were assayed by high-performance liquid chromatography (HPLC). Using population modeling incorporating hepatic maturation and cystatin C-based renal function, two-compartment models provided best fits for PYR and SDX/NSX plasma concentration profiles. The area under the plasma concentration-time curve from 0 h to infinity (AUC
0-∞
) was greater with the double dose versus the conventional dose of PYR (4,915 versus 2,844 μg/day/liter) and SDX (2,434 versus 1,460 mg/day/liter). There was a 32% reduction in SDX relative bioavailability with the double dose but no evidence of dose-dependent metabolism. Terminal elimination half-lives (15.6 days for PYR, 9.1 days for SDX) were longer than previously reported. Both doses were well tolerated without changes in hemoglobin or hepatorenal function. Five children in the conventional and three in the double-dose group developed malaria during follow-up. These data support the potential use of double-dose SDX/PYR in infancy, but further studies should examine the influence of hepatorenal maturation in very young infants.
Role of VltAB, an ABC Transporter Complex, in Viologen Tolerance in
Streptococcus mutans
Authors: Biswas Saswati , Biswas Indranil
Published: February 2011

Streptococcus mutans
, a Gram-positive organism, is the primary causative agent in the formation of dental caries in humans. To persist in the oral cavity,
S. mutans
must be able to tolerate rapid environmental fluctuations and exposure to various toxic chemicals. However, the mechanisms underlying the ability of this cariogenic pathogen to survive and proliferate under harsh environmental conditions remain largely unknown. Here, we wanted to understand the mechanisms by which
S. mutans
withstands exposure to methyl viologen (MV), a quaternary ammonium compound (QAC) that generates superoxide radicals in the cell. To elucidate the essential genes for MV tolerance, screening of ∼3,500 mutants generated by IS
S1
mutagenesis, revealed 15 MV-sensitive mutants. Among them, five and four independent insertions had occurred in SMU.905 and SMU.906 genes, respectively. These two genes are appeared to be organized in an operon and encode a putative ABC transporter complex; we designated the genes as
vltA
and
vltB
, for

v

io

l

ogen

t

ransporter. To verify our results,
vltA
was deleted by using an antibiotic resistance marker; the mutant was just as sensitive to MV as the IS
S1
insertion mutants. Furthermore,
vltA
and
vltB
mutants were also sensitive to other viologen compounds such as benzyl and ethyl viologens. Complementation assays were also carried out to confirm the role of VltA and VltB in viologen tolerance. Sensitivity to various drugs, including a wide range of QACs, was evaluated. It appears that a functional VltA is also required for full resistance toward acriflavin, ethidium bromide, and safranin; all are well-known QACs. These results indicate that VltA/B constitute a heterodimeric multidrug efflux pump of the ABC family. BLAST-P analysis suggests that homologs of VltA/B are widely present in streptococci, enterococci, and other important Gram-positive pathogens.
Impact of the N348I Mutation in HIV-1 Reverse Transcriptase on Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Non-Subtype B HIV-1
Authors: McCormick Adele L. , Parry Chris M. , Crombe Anne , Goodall Ruth L. , Gupta Ravindra K. , Kaleebu Pontiano , Kityo Cissy , Chirara Michael , Towers Greg J. , Pillay Deenan
Published: February 2011

We investigated the effect of N348I alone and with M184V on nonnucleoside reverse transcriptase inhibitor (NNRTI) drug susceptibility and replicative capacity in B and non-B HIV-1 isolates. N348I reduced the susceptibility to all NNRTI drugs across subtypes. The replication capacity of all viruses in a variety of cell lines was impaired by N348I. Interestingly, the N348I and M184V double mutation compensated for the reduced NNRTI drug susceptibility observed in the N348I single mutant and marginally improved viral replicative capacity.
Dose-Dependent Activity of Pyrazinamide in Animal Models of Intracellular and Extracellular Tuberculosis Infections
Authors: Ahmad Zahoor , Fraig Mostafa M. , Bisson Gregory P. , Nuermberger Eric L. , Grosset Jacques H. , Karakousis Petros C.
Published: February 2011

Recentin vitropharmacokinetic data suggest that the currently recommended dose of pyrazinamide may be suboptimal for killing intracellular bacilli in humans. We evaluated a range of pyrazinamide doses against intracellular and extracellularMycobacterium tuberculosisin chronically infected mice and guinea pigs, respectively. Antibiotics were given five times weekly for 4 weeks beginning 28 days after infection. Human-equivalent doses of isoniazid reduced lung bacterial counts 10-fold in each species. Pyrazinamide given at 1/4 and 1/2 the human-equivalent dose was minimally active, while human-equivalent doses reduced lung bacterial counts by ∼1.0 log10in each species. Doubling the human-equivalent dose of pyrazinamide reduced the lung bacillary burden by 1.7 and 3.0 log10in mice and guinea pigs, respectively. As in humans and mice, pyrazinamide showed significant synergy with rifampin in guinea pigs. Clinical studies are warranted to investigate the sterilizing activity and tolerability of higher doses of pyrazinamide in combination tuberculosis regimens.
Novel HIV-1 Protease Inhibitors (PIs) Containing a Bicyclic P2 Functional Moiety, Tetrahydropyrano-Tetrahydrofuran, That Are Potent against Multi-PI-Resistant HIV-1 Variants
Authors: Ide Kazuhiko , Aoki Manabu , Amano Masayuki , Koh Yasuhiro , Yedidi Ravikiran S. , Das Debananda , Leschenko Sofiya , Chapsal Bruno , Ghosh Arun K. , Mitsuya Hiroaki
Published: February 2011

We identified GRL-1388 and -1398, potent nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) containing a bicyclic P2 functional moiety, tetrahydropyrano-tetrahydrofuran (Tp-THF). GRL-1388 was as potent as darunavir (DRV) against various drug-resistant HIV-1 laboratory strains with 50% effective concentration (EC
50
s) of 2.6 to 32.6 nM. GRL-1398 was significantly more potent against such variants than DRV with EC
50
s of 0.1 to 5.7 nM. GRL-1388 and -1398 were also potent against multiple-PI-resistant clinical HIV-1 variants (
CL
HIV-1
MDR
) with EC
50
s ranging from 2.7 to 21.3 nM and from 0.3 to 4.8 nM, respectively. A highly DRV-resistant HIV-1 variant selected
in vitro
remained susceptible to GRL-1398 with the EC
50
of 21.9 nM, while the EC
50
of DRV was 214.1 nM. When HIV-1
NL4-3
was selected with GRL-1398, four amino acid substitutions—leucine to phenylalanine at a position 10 (L10F), A28S, L33F, and M46I—emerged, ultimately enabling the virus to replicate in the presence of >1.0 μM the compound beyond 57 weeks of selection. When a mixture of 10 different
CL
HIV-1
MDR
strains was selected, the emergence of resistant variants was more substantially delayed with GRL-1398 than with GRL-1388 and DRV. Modeling analyses revealed that GRL-1398 had greater overall hydrogen bonding and hydrophobic interactions than GRL-1388 and DRV and that GRL-1388 and -1398 had hydrogen bonding interactions with the main chain of the active-site amino acids (Asp29 and Asp30) of protease. The present findings warrant that GRL-1398 be further developed as a potential drug for treating individuals with HIV-1 infection.
Genomic Analysis of
Acinetobacter baumannii
A118 by Comparison of Optical Maps: Identification of Structures Related to Its Susceptibility Phenotype
Authors: Ramirez Maria Soledad , Adams Mark D. , Bonomo Robert A. , Centrón Daniela , Tolmasky Marcelo E.
Published: February 2011

Acinetobacter baumannii
A118, a naturally competent clinical isolate, is unusually susceptible to several antibiotics. Comparison of the optical map of strain A118 with
in silico
-generated restriction maps of sequenced genomes and sequence analyses showed that the AbaR region, commonly found inserted within the
comM
gene in other isolates, is missing in strain A118, which could in part explain the susceptible phenotype exhibited by this isolate. These comparative studies also showed differences in regions where genes coding for functions that may be involved in drug resistance or susceptibility are located. Further sequencing demonstrated that
cat
and
bla
ADC
, named
bla
ADC-55
, are present but that a
tet
(A) gene usually found in other strains is not. In addition,
carO
and
pbp2
, which may play a role in susceptibility to carbapenems, are present in strain A118. These findings support the idea that
A. baumannii
strains possess multiple mechanisms that contribute to antibiotic resistance, and the presence of some of them is not sufficient for a resistant phenotype. The results shown here indicate that optical mapping is a useful tool for preliminary comparative genomic analysis.
Antibodies Contribute to Effective Vaccination against Respiratory Infection by Type A
Francisella tularensis
Strains
Authors: Mara-Koosham Gopi , Hutt Julie A. , Lyons C. Rick , Wu Terry H.
Published: February 2011

Pneumonic tularemia is a life-threatening disease caused by inhalation of the highly infectious intracellular bacterium
Francisella tularensis
. The most serious form of the disease associated with the type A strains can be prevented in experimental animals through vaccination with the attenuated live vaccine strain (LVS). The protection is largely cell mediated, but the contribution of antibodies remains controversial. We addressed this issue in a series of passive immunization studies in Fischer 344 (F344) rats. Subcutaneous LVS vaccination induced a robust serum antibody response dominated by IgM, IgG2a, and IgG2b antibodies. Prophylactic administration of LVS immune serum or purified immune IgG reduced the severity and duration of disease in naïve rats challenged intratracheally with a lethal dose of the virulent type A strain SCHU S4. The level of resistance increased with the volume of immune serum given, but the maximum survivable SCHU S4 challenge dose was at least 100-fold lower than that shown for LVS-vaccinated rats. Protection correlated with reduced systemic bacterial growth, less severe histopathology in the liver and spleen during the early phase of infection, and bacterial clearance by a T cell-dependent mechanism. Our results suggest that treatment with immune serum limited the sequelae associated with infection, thereby enabling a sterilizing T cell response to develop and resolve the infection. Thus, antibodies induced by LVS vaccination may contribute to the defense of F344 rats against respiratory infection by type A strains of
F. tularensis
.
Identification of
Vibrio cholerae
Type III Secretion System Effector Proteins
Authors: Alam Ashfaqul , Miller Kelly A. , Chaand Mudit , Butler J. Scott , Dziejman Michelle
Published: February 2011

AM-19226 is a pathogenic O39 serogroup
Vibrio cholerae
strain that lacks the typical virulence factors for colonization (toxin-coregulated pilus [TCP]) and toxin production (cholera toxin [CT]) and instead encodes a type III secretion system (T3SS). The mechanism of pathogenesis is unknown, and few effector proteins have been identified. We therefore undertook a survey of the open reading frames (ORFs) within the ∼49.7-kb T3SS genomic island to identify potential effector proteins. We identified 15 ORFs for their ability to inhibit growth when expressed in yeast and then used a β-lactamase (TEM1) fusion reporter system to demonstrate that 11 proteins were
bona fide
effectors translocated into HeLa cells
in vitro
in a T3SS-dependent manner. One effector, which we named VopX (A33_1663), is conserved only in
V. cholerae
and
Vibrio parahaemolyticus
T3SS-positive strains and has not been previously studied. A
vopX
deletion reduces the ability of strain AM-19226 to colonize
in vivo
, and the bile-induced expression of a
vopX-lacZ
transcriptional fusion
in vitro
is regulated by the T3SS-encoded transcriptional regulators VttR
A
and VttR
B
. An
RLM1
yeast deletion strain rescued the growth inhibition induced by VopX expression, suggesting that VopX interacts with components of the cell wall integrity mitogen-activated protein kinase (MAPK) pathway. The collective results show that the
V. cholerae
T3SS encodes multiple effector proteins, one of which likely has novel activities that contribute to disease via interference with eukaryotic signaling pathways.
Natural Antibodies against Several Pneumococcal Virulence Proteins in Children during the Pre-Pneumococcal-Vaccine Era: the Generation R Study
Authors: Lebon Ankie , Verkaik Nelianne J. , Labout Joost A. M. , de Vogel Corné P. , Hooijkaas Herbert , Verbrugh Henri A. , van Wamel Willem J. B. , Jaddoe Vincent W. V. , Hofman Albert , Hermans Peter W. M. , Ma Jiangtao , Mitchell Tim J. , Moll Henriette A. , van Belkum Alex
Published: February 2011

The currently available pneumococcal vaccines do not protect against all serotypes of
Streptococcus pneumoniae
. A shift toward nonvaccine serotypes causing colonization and invasive disease has occurred, and studies on protein-based vaccines have been undertaken. We assessed the association between specific antibodies against pneumococcal virulence proteins and colonization and respiratory tract infections (RTIs). Additionally, we assessed the extent to which colonization induces a humoral immune response. Nasopharyngeal swabs collected from children at 1.5, 6, 14, and 24 months of age were cultured for pneumococcus. Serum samples were obtained at birth and at 6, 14, and 24 months (
n
= 57 children providing 177 serum samples). Data were collected prior to the pneumococcal vaccine era. IgG, IgA, and IgM levels against 17 pneumococcal protein vaccine candidates were measured using a bead-based flow cytometry technique (xMAP; Luminex Corporation). Information regarding RTIs was questionnaire derived. Levels of IgG against all proteins were high in cord blood, decreased in the first 6 months and increased again thereafter, in contrast to the course of IgA and IgM levels. Specific antibodies were induced upon colonization. Increased levels of IgG against BVH-3, NanA, and SP1003 at 6 months, NanA, PpmA, PsaA, SlrA, SP0189, and SP1003 at 14 months, and SlrA at 24 months were associated with a decreased number of RTIs in the third year of life but not with colonization. Maternal antipneumococcal antibodies did not protect against pneumococcal colonization and infection. Certain antibodies against pneumococcal virulence proteins, some of which are induced by colonization, are associated with a decreased number of RTIs in children. This should be taken into account in future pneumococcal vaccine studies.
Microbial Communities of the Upper Respiratory Tract and Otitis Media in Children
Authors: Laufer Alison S. , Metlay Joshua P. , Gent Janneane F. , Fennie Kristopher P. , Kong Yong , Pettigrew Melinda M.
Published: February 2011

Streptococcus pneumoniae
asymptomatically colonizes the upper respiratory tract of children and is a frequent cause of otitis media. Patterns of microbial colonization likely influence
S. pneumoniae
colonization and otitis media susceptibility. This study compared microbial communities in children with and without otitis media. Nasal swabs and clinical and demographic data were collected in a cross-sectional study of Philadelphia, PA, children (6 to 78 months) (
n
= 108) during the 2008-2009 winter respiratory virus season. Swabs were cultured for
S. pneumoniae
. DNA was extracted from the swabs; 16S rRNA gene hypervariable regions (V1 and V2) were PCR amplified and sequenced by Roche/454 Life Sciences pyrosequencing. Microbial communities were described using the Shannon diversity and evenness indices. Principal component analysis (PCA) was used to group microbial community taxa into four factors representing correlated taxa. Of 108 children, 47 (44%) were colonized by
S. pneumoniae
, and 25 (23%) were diagnosed with otitis media. Microbial communities with
S. pneumoniae
were significantly less diverse and less even. Two PCA factors were associated with a decreased risk of pneumococcal colonization and otitis media, as follows: one factor included potentially protective flora (
Corynebacterium
and
Dolosigranulum
), and the other factor included
Propionibacterium
,
Lactococcus
, and
Staphylococcus
. The remaining two PCA factors were associated with an increased risk of otitis media. One factor included
Haemophilus
, and the final factor included
Actinomyces
,
Rothia
,
Neisseria
, and
Veillonella
. Generally, these taxa are not considered otitis media pathogens but may be important in the causal pathway. Increased understanding of upper respiratory tract microbial communities will contribute to the development of otitis media treatment and prevention strategies.

IMPORTANCE
Otitis media (middle ear infection) is the most common reason for pediatric sick visits in the United States.
Streptococcus pneumoniae
is a leading otitis media pathogen.
S. pneumoniae
must colonize the upper respiratory tract and compete with a complex community of nonpathogenic bacteria before infecting the middle ear. We compared microbial communities in the upper respiratory tract of children who had otitis media and those who did not. Members of the normal flora, i.e.,
Corynebacterium
and
Dolosigranulum
, were protective for
S. pneumoniae
colonization and otitis media. As expected, the genera
Haemophilus
was associated with otitis media. Surprisingly,
Actinomyces
,
Rothia
,
Neisseria
, and
Veillonella
were associated with an increased risk of otitis media. These bacteria are not otitis media pathogens but may be associated with antibiotic use or involved in the causal pathway to disease. Increased understanding of upper respiratory tract microbial communities will lead to new ways to prevent middle ear infections, including probiotics.
Attitudes to perinatal postmortem: parental views about research participation: Table 1
Authors: Breeze Andrew C G , Statham Helen , Hackett Gerald A , Jessop Flora A , Lees Christoph C
Published: February 2011

Objective

To study parental attitudes to participating in questionnaire research about perinatal postmortem immediately after late miscarriage, stillbirth and termination for fetal abnormality.

Design

Prospective self-completion questionnaire.

Setting

UK fetal medicine and delivery unit.

Patients

35 women and their partners after second or third trimester pregnancy loss, making decisions about having a postmortem.

Methods

Participants were asked to complete a questionnaire about postmortem decision-making which included questions about their attitudes to taking part in research. Prior to giving full approval for the study, the Research Ethics Committee (REC) requested feedback after 10 questionnaires had been returned.

Results

Responses from the first 10 participants were positive about the research and the REC allowed the study to continue. 31 questionnaires were received from parents of 17 babies (49% of those asked; 16 from mothers, 15 from fathers). Of the 22 participants who answered a question about the impact of participating in this research, 73% stated that completing the questionnaire had helped them feel better about the decision whether or not to consent to postmortem and none reported any adverse effect of completing the questionnaire. Additional comments made by 19 participants supported this finding.

Conclusion

Research into this sensitive area of perinatal medicine where there is a poor outcome is possible and is indeed well received by many parents. RECs should not automatically take a negative stance towards studies of this type.
AREA SPECTRUM OF THE EXTREME REISSNER–NORDSTRÖM BLACK HOLE
Authors: GUO GUANGHAI , GUO JUN
Published: February 2011

Motivated by the new interpretation on quasinormal modes by Maggiore, we investigate the quantization of the extreme Reissner–Nordström black hole in the four-dimensional spacetime. Following Kunstatter's method, we derive the equally spaced area spectrum and the entropy, however the spacing differs from Setare's result via Hod's proposal. Moreover, our result is in full agreement with Bekenstein's result as well as the claim that black hole's area is equidistant in Einstein's Gravity theory by Wei et al.
ACOUSTIC BAND GAP FORMATION IN METAMATERIALS
Authors: ELFORD D. P. , CHALMERS L. , KUSMARTSEV F. , SWALLOWE G. M.
Published: February 2011

We present several new classes of metamaterials and/or locally resonant sonic crystal that are comprised of complex resonators. The proposed systems consist of multiple resonating inclusion that correspond to different excitation frequencies. This causes the formation of multiple overlapped resonance band gaps. We demonstrate theoretically and experimentally that the individual band gaps achieved, span a far greater range (≈ 2kHz) than previously reported cases. The position and width of the band gap is independent of the crystal's lattice constant and forms in the low frequency regime significantly below the conventional Bragg band gap. The broad envelope of individual resonance band gaps is attractive for sound proofing applications and furthermore the devices can be tailored to attenuate lower or higher frequency ranges, i.e., from seismic to ultrasonic.
DYNAMICAL SPATIALLY RESOLVED RESPONSE FUNCTION OF FINITE 1-D NANO PLASMAS
Authors: RAITZA THOMAS , REINHOLZ HEIDI , RÖPKE GERD
Published: February 2011

The dynamical response of one dimensional chains containing 55 till 309 atoms is investigated using a restricted molecular dynamics simulation scheme. The total momentum correlation function of an electron cloud shows resonances that are related to different collective excitation modes of the nano plasma. Spatially resolved cross correlation functions are calculated to deduce the spatial structure and strength of these resonance modes. The dependence of the corresponding resonance frequencies on temperature, density and chain size is investigated. The width of the resonances is analyzed in terms of a mode dependent collision frequency.
LIGHT CLUSTERS IN NUCLEAR MATTER
Authors: RÖPKE GERD
Published: February 2011

Nuclei in dense matter are influenced by the medium. In the cluster mean-field approximation, an effective Schrodinger equation for the A-nucleon cluster is obtained accounting for the effects of the surrounding medium, such as self-energy and Pauli blocking. Similar to the single-baryon states (free protons and neutrons), the light elements (A ≤ 4) are treated as quasiparticles. Fit formulae are given for the quasiparticle shifts as function of temperature, density, asymmetry, and momentum. Composition, quantum condensates and thermodynamic functions are considered. The relevance for nuclear structure, heavy ion collisions and supernova astrophysics is shown.
MAGNETIC ORDERING OF ANTIFERROMAGNETS ON A SPATIALLY ANISOTROPIC TRIANGULAR LATTICE
Authors: BISHOP R. F. , LI P. H. Y. , FARNELL D. J. J. , CAMPBELL C. E.
Published: February 2011

We study the spin-1/2 and spin-1 [Formula: see text] Heisenberg antiferromagnets (HAFs) on an infinite, anisotropic, two-dimensional triangular lattice, using the coupled cluster method. With respect to an underlying square-lattice geometry the model contains antiferromagnetic (J1 > 0) bonds between nearest neighbours and competing [Formula: see text] bonds between next-nearest-neighbours across only one of the diagonals of each square plaquette, the same diagonal in each square. In a topologically equivalent triangular-lattice geometry the model has two sorts of nearest-neighbour bonds, with [Formula: see text] bonds along parallel chains and with J1 bonds providing an interchain coupling. The model thus interpolates between an isotropic HAF on the square lattice at one extreme (κ = 0) and a set of decoupled chains at the other (κ → ∞), with the isotropic HAF on the triangular lattice in between at κ = 1. For the spin-1/2 [Formula: see text] model, we find a weakly first-order (or possibly second-order) quantum phase transition from a Néel-ordered state to a helical state at a first critical point at κc1 = 0.80 ± 0.01, and a second critical point at κc2 = 1.8 ± 0.4 where a first-order transition occurs between the helical state and a collinear stripe-ordered state. For the corresponding spin-1 model we find an analogous transition of the second-order type at κc1 = 0.62 ± 0.01 between states with Néel and helical ordering, but we find no evidence of a further transition in this case to a stripe-ordered phase.
THE SU(2) SEMI QUANTUM SYSTEMS DYNAMICS AND THERMODYNAMICS
Authors: SARRIS C. M. , PROTO A. N.
Published: February 2011

The dynamical description of a semi quantum nonlinear systems whose classical limit is not chaotic is still an open question. These systems are characterized by mixing a classical system with a quantum-mechanical one. As some of them lead to an irregular dynamics, the name "semi quantum chaos" arises. In this contribution we study two different Hamiltonians through the Maximum Entropy Principle Approach (MEP). Taking advantage of the MEP formalism, it can be clearly established that the Hamiltonians belonging to the SU(2) Lie algebra have common properties and a common treatment can be developed for them. These Hamiltonians resemble a quantum spin system coupled to a classical cavity. In the present contribution, we show that all of them share the generalized uncertainty principle as an invariant of the motion and other invariants as well. Two different classical potentials V(q) have been studied. Their specific heat are evaluated in terms of the extensive (mean values) and the intensive (Lagrange multipliers) variables. The main result of the present contribution is to show that the specific heat of these systems can be fixed independently of the temperature by setting only the initial conditions on the extensive or intensive variables, as well as the value of the quantum-classical coupling parameter. It could be possible to infer that this result can be extended to generalized forms for the V(q) classical potential.
SPECTRAL PROPERTIES OF MOLECULAR OLIGOMERS: A NON-MARKOVIAN QUANTUM STATE DIFFUSION APPROACH
Authors: RODEN JAN , STRUNZ WALTER T. , EISFELD ALEXANDER
Published: February 2011

Absorption spectra of small molecular aggregates (oligomers) are considered. The dipole-dipole interaction between the monomers leads to shifts of the oligomer spectra with respect to the monomer absorption. The line-shapes of monomer as well as oligomer absorption depend strongly on the coupling to vibrational modes. Using a recently developed approach [Roden et al., PRL 103, 058301] we investigate the length dependence of spectra of one-dimensional aggregates for various values of the interaction strength between the monomers. It is demonstrated, that the present approach is well suited to describe the occurrence of the J- and H-bands.
KINETIC ENERGY FUNCTIONALS: EXACT ONES FROM ANALYTIC MODEL WAVE FUNCTIONS AND APPROXIMATE ONES IN ORBITAL-FREE MOLECULAR DYNAMICS
Authors: KARASIEV VALENTIN V. , LOPEZ XABIER , UGALDE JESUS M. , LUDEÑA EDUARDO V.
Published: February 2011

We consider the problem of constructing kinetic energy functionals in density functional theory. We first discuss the functional generated through the application of local-scaling transformations to the exact analytic wavefunctions for the Hookean model of 4He (a finite mass three-particle system), and contrast this result with a previous one for ∞He (infinite mass system). It is shown that an exact non-Born-Oppenheimer treatment not only leads to mass-correction terms in the kinetic energy, but to a basically different functional expression. In addition, we report and comment on some recently advanced approximate kinetic energy functionals generated in the context of the constraint-based approach to orbital-free molecular dynamics. The positivity and non-singularity of a new family of kinetic energy functionals specifically designed for orbital-free molecular dynamics is discussed. Finally, we present some conclusions.