bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-Dimensional FSI Simulation of Closing Dynamics of a Tilting Disk Mechanical Heart Valve
Authors: Govindarajan V. , Udaykumar H. S. , Herbertson L. H. , Deutsch S. , Manning K. B. , Chandran K. B.
Published: March 2010

The fluid dynamics during valve closure resulting in high shear flows and large residence times of particles has been implicated in platelet activation and thrombus formation in mechanical heart valves. Our previous studies with bileaflet valves have shown that large shear stresses induced in the gap between the leaflet edge and valve housing results in relatively high platelet activation levels, whereas flow between the leaflets results in shed vortices not conducive to platelet damage. In this study we compare the result of closing dynamics of a tilting disk valve with that of a bileaflet valve. The two-dimensional fluid-structure interaction analysis of a tilting disk valve closure mechanics is performed with a fixed grid Cartesian mesh flow solver with local mesh refinement, and a Lagrangian particle dynamic analysis for computation of potential for platelet activation. Throughout the simulation the flow remains in the laminar regime, and the flow through the gap width is marked by the development of a shear layer, which separates from the leaflet downstream of the valve. Zones of recirculation are observed in the gap between the leaflet edge and valve housing on the major orifice region of the tilting disk valve and are seen to be migrating toward the minor orifice region. Jet flow is observed at the minor orifice region and a vortex is formed, which sheds in the direction of fluid motion, as observed in experiments using PIV measurements. The activation parameter computed for the tilting disk valve at the time of closure was found to be 2.7 times greater than that of the bileaflet mechanical valve and was found to be in the vicinity of the minor orifice region, mainly due to the migration of vortical structures from the major to the minor orifice region during the leaflet rebound of the closing phase.
Measurement and Optimization of Minimally Invasive Intervention Device Design Fitness Using a Multiobjective Weighted Isotropy Index
Authors: Hammond Frank L. , Shimada Kenji , Zenati Marco A.
Published: March 2010

The recent transition from multiple-port to single-port systems in minimally invasive intervention (MII) procedures has created a need for more flexible, dexterous robotic manipulation devices capable of spanning an entire surgical workspace without the risk of collateral damage. The design of such devices requires a careful balance of the mechanical complexity needed to facilitate clinical functionality and the cost of manufacturing and operating the device. This paper presents a novel metric for measuring the design fitness of kinematically redundant robotic MII devices and for optimizing them to achieve that balance. The proposed fitness metric rewards designs that are conducive to collision avoidance and energy conservation while penalizing those with exorbitant design complexities that adversely affect the economic feasibility of an MII system. The authors’ metric is used here to design a kinematically redundant, single-port MII device capable of accessing the cardiothoracic cavity through a single subxiphoid port and reaching several regions of interest, consistent with procedures such as epicardial ablation and therapeutic substance injection, with minimal physiologic disturbance. The design of this device is determined by a morphological optimization process, which searches a discrete mechanical design parameter space, consisting of linkage parts, part dimensions, and actuator types, using genetic algorithms. The execution of specific surgical maneuvers is simulated for each candidate MII device design, and the design is improved until the fitness metric is maximized. The results of this optimization study demonstrate that redesigning a 20 degree-of-freedom (DOF) MII device using the proposed metric decreased the DOF in the design by 45% while ensuring near-optimal levels of kinematic flexibility. The results also demonstrate the ability of the fitness metric to elucidate the relationship between functionality and complexity and to produce suitable device designs over a broad range of performance and cost goals. The authors conclude that this new design fitness metric, while heuristic in nature, holds the potential to improve both the clinical value and the economy of a wide variety of single-port MII devices, including those used in cardiothoracic surgery.
Broadening of intersubband transitions in InGaN/AlInN multiquantum wells
Authors: Cywiński G. , Gładysiewicz M. , Kudrawiec R. , Kryśko M. , Feduniewicz-Żmuda A. , Siekacz M. , Sawicka M. , Wolny P. , Smalc-Koziorowska J. , Nevou L. , Tchernycheva M. , Julien F. H. , Misiewicz J. , Skierbiszewski C.
Published: March 2010

In this article, the authors report on growth of InGaN/AlInN multiquantum wells (MQWs) by rf-plasma-assisted molecular beam epitaxy on (0001) GaN substrates. Intersubband transitions in InGaN/AlInN MQWs with widths varying from 1.3 to 1.8 nm has been studied experimentally and analyzed theoretically within the electron effective mass approximation. The intersubband absorption between the first and the second electron levels was observed at the wavelength of ∼1.3–1.6 μm. The broadening of intersubband absorption for this system has been found to be much larger than for indium free system (i.e., GaN/AlN MQWs). In addition, it has been found that the broadening increases from ∼280 to ∼390 meV when the nominal quantum well (QW) width decreased from 1.8 to 1.3 nm. On the basis of theoretical calculations combined with the transmission electron microscopy analysis, it has been concluded that the observed broadening of intersubband absorption is due to the QW width fluctuations. It has been estimated that the maximal width fluctuations in these MQWs are equal to ∼2 monolayers. Such a significant QW width fluctuation appears in this system because of the incorporation of indium atoms.
Modulated beam mass spectrometer studies of a Mark V Veeco cracker
Authors: Campion R. P. , Foxon C. T. , Bresnahan R. C.
Published: March 2010

Mass spectrometer studies provide a powerful means to evaluate both the major species coming from a Knudsen source used for molecular beam epitaxy and also impurities, which may be detrimental to device performance. To distinguish signals from the source from those due to background gases in the ultrahigh vacuum system it is essential to have direct line of sight from the source to the ionizer of the mass spectrometer. For condensable species this criterion combined with a liquid nitrogen cryopanel is sufficient to ensure the species detected come from the source. However, for volatile species, such as arsenic, this is not the case and to adequately identify material from the source it is necessary to use modulated beam mass spectrometer studies as has previously been demonstrated in studies of the evaporation of GaAs [C. T. Foxon et al., J. Phys. Chem. Solids 34, 1693 (1973)]. The authors have recently constructed a new version of this apparatus using a Hiden HAL IV mass spectrometer, which has both pre and postfilters to improve transmission and sensitivity at high mass numbers. The new apparatus has several improvements compared to the original system used by one of the authors. In particular, in addition to the improved intrinsic sensitivity of the mass spectrometer, it is now possible to tune the electron ionization energy to a low enough value to prevent cracking of species within the ionizer of the mass spectrometer, thus simplifying the interpretation of the data. This new system has been used to study the performance of a Veeco Mark V arsenic valved cracker equipped with a variety of different baffles. In all cases, at a sufficiently high temperature of the hot (cracker) zone, complete decomposition of the arsenic from tetramers (As4) to dimers (As2) is achieved. Surprisingly, the source with an open tube achieves significant cracking at very low cracker temperatures. In this case the flux would not be sufficiently uniform over the area of a growth sample, so additional beam forming apertures or a series of baffle plates are typically used to alleviate this situation. With such apertures or baffles present, complete decomposition can also be achieved, but at a slightly higher operating temperature, suggesting some recombination takes place. In this article, the authors concentrate on baffle assemblies that will be familiar to users of most of the current models of cracker in service today. Aperture plates of various designs will be the subject of future work.
Low work function nanometer-order controlled transfer mold field-emitter arrays
Authors: Nakamoto Masayuki , Moon Jonghyun , Shiratori Koji
Published: March 2010

Extremely sharp and uniform field-emitter arrays (FEAs) with low work function and environmentally resistant emitter materials, such as TiN and Au, have been fabricated by a transfer metal mold FEA fabrication method to realize highly efficient, highly reliable, and low-cost vacuum nanoelectronic devices and aerospace nanodevices for electric propulsion engines. The tip radii can be linearly controlled from 2.5 to 52.5 nm by changing the thickness of the emitter materials. For the first time, turn-on electric fields of the transfer metal mold FEAs have been controlled by changing tip radii. Control of turn-on field is one of requirements for realizing vacuum nanoelectronic devices, such as field-emission displays, aerospace devices, and so on. The transfer metal mold fabrication method is useful for controlling the turn-on fields and tip radii and conductive to changing emitter materials while maintaining sharp and uniform emitter shapes.
Addressing Science Teacher Needs
Authors: Moreno Nancy P. , Erdmann Deanne B.
Published: March 2010

A pair of Web sites enhances teachers' content knowledge and teaching repertoire through asynchronous approaches.
Major Galaxy Mergers and the Growth of Supermassive Black Holes in Quasars
Authors: Treister Ezequiel , Natarajan Priyamvada , Sanders David B. , Urry C. Megan , Schawinski Kevin , Kartaltepe Jeyhan
Published: March 2010

Dusty Quasars

Quasars are energetic sources thought to be fueled by matter accreting onto black holes a billion times more massive than the Sun. Some quasars are difficult to detect because of surrounding clouds of gas and dust, so much so that this population of objects has remained elusive. Based on a compilation of x-ray, optical, and mid-infrared data,

Treister
et al.

(p.
600
, published online 25 March; see the Perspective by

Primack

) show that the evolution of quasars across cosmic time occurs during mergers of gas-rich galaxies, with an obscured phase preceding an unobscured state by about 100 million years. Other objects have been detected in diverse wavebands, including ultraluminous infrared galaxies, which are known to be the product of similar gas-rich mergers of massive galaxies.
Anomalous Expansion of Attractively Interacting Fermionic Atoms in an Optical Lattice
Authors: Hackermüller Lucia , Schneider Ulrich , Moreno-Cardoner Maria , Kitagawa Takuya , Best Thorsten , Will Sebastian , Demler Eugene , Altman Ehud , Bloch Immanuel , Paredes Belén
Published: March 2010

Fermion Behavior in an Optical Lattice

Due to their extreme tunability, optical lattices loaded with fermions and bosons are expected to act as quantum simulators, answering complicated many-body physics questions beyond the reach of theory and computation. Some of these many-body states, such as the Mott insulator and the superfluid, have been achieved in bosonic optical lattices by simply changing the characteristic depth of the lattice potential wells. Now,

Hackermüller
et al.

(p.
1621
) describe an unusual effect in an optical lattice loaded with fermions: When the strength of the attraction between the fermions is increased adiabatically, instead of contracting, the gas expands in order to preserve entropy.
Evolutionary Trade-Offs in Plants Mediate the Strength of Trophic Cascades
Authors: Mooney Kailen A. , Halitschke Rayko , Kessler Andre , Agrawal Anurag A.
Published: March 2010

Trophic Trade-Offs

There have been many attempts to document and explain the effects of predators on plant biomass in so-called “trophic cascades.” Theory suggests that fast-growing plants are relatively undefended and suffer more from herbivory, which implies a functional trade-off between investment in traits relating to growth and defensive strategies.

Mooney
et al.

(p.
1642
; see the Perspective by

Hambäck

) compared responses to fertilization and aphid predators in 16 milkweed species. As predicted, interspecific variation in the strength of top-down control in terms of a tradeoff with growth was observed.
The Wnt/β-Catenin Pathway Is Required for the Development of Leukemia Stem Cells in AML
Authors: Wang Yingzi , Krivtsov Andrei V. , Sinha Amit U. , North Trista E. , Goessling Wolfram , Feng Zhaohui , Zon Leonard I. , Armstrong Scott A.
Published: March 2010

A Pathway to Leukemia

Leukemia is initiated and maintained by a small number of self-renewing cells called leukemia stem cells (LSCs), which share properties with hematopoietic stem cells (HSCs), the self-renewing cells that produce healthy blood cells.

Wang
et al.

(p.
1650
) studied mouse models of acute myelogenous leukemia (AML), a disease that is often refractory to existing therapies. Activation of the Wnt/β-catenin signaling pathway was required for efficient oncogene-mediated conversion of HSCs into LSCs. This pathway is among the most well studied signaling pathways in cell biology, setting the stage for testing of β-catenin signaling antagonists in preclinical models of AML.
Less Costly Catalysts for Controlling Engine Emissions
Authors: Parks James E.
Published: March 2010

Perovskite oxide catalysts may be able to control emissions from more fuel-efficient internal combustion engines and replace expensive noble metals.
A Southern Tyrant Reptile
Authors: Benson Roger B. J. , Barrett Paul M. , Rich Tom H. , Vickers-Rich Pat
Published: March 2010

Fossil evidence indicates that tyrannosaurs also inhabited the southern continents in the late Early Cretaceous period.
Fishing for the Universe
Authors: Lang Rafael F.
Published: March 2010

After analysis of a year-long detection experiment, resolution of the dark matter mystery may be near.
Refugee Receptors Switch Sides
Authors: Dorn Gerald W.
Published: March 2010

Disrupted localization of β2adrenergic receptors in cardiac cells may contribute to heart failure.
Latest Prize Bolsters Templeton's Shift to Mainstream
Authors: Bhattacharjee Yudhijit
Published: March 2010

This week, the Templeton Foundation awarded its annual $1.5 million Templeton Prize to Francisco Ayala, a priest-turned-biologist who for decades has campaigned against the teaching of creationism and intelligent design in the science classroom.
Immunology Uncaged
Authors: Leslie Mitch
Published: March 2010

An immunologist argues that to move beyond mice and galvanize clinical research, his field needs its own version of the Human Genome Project.
Mission: Irreplaceable?
Authors: Service Robert F.
Published: March 2010

Scientists are scrambling to develop substitutes for scarce elements critical to industry. But the myriad uses of the elements make the effort an uphill struggle.
Widespread Circulation of Echovirus Type 13 Demonstrated by Increased Seroprevalence in Toyama, Japan, between 2000 and 2003
Authors: Iwai Masae , Yoshida Hiromu , Obara Mayumi , Horimoto Eiji , Nakamura Kazuya , Takizawa Takenori , Kurata Takeshi , Mizuguchi Mineyuki , Daikoku Tohru , Shiraki Kimiyasu
Published: March 2010

To confirm the magnitude of an echovirus type 13 (E13) outbreak in 2002 and to evaluate whether genetic and antigenic changes in E13 influenced the occurrence of the outbreak, we measured titers of neutralizing (NT) antibody against the Toyama, 2002-240-SF, and prototype Del Carmen E13 strains among inhabitants of Toyama before and after 2002. The rate of positivity for NT antibodies against both 2002-240-SF and Del Carmen in 2003 made a remarkable upturn in children 0 to 14 years old, compared to that in 2000. Titers of NT antibody against strain 2002-240-SF of inhabitants were slightly higher than those against Del Carmen, whereas anti-E13 rabbit serum raised against either strain Del Carmen or 2002-240-SF showed almost the same titer of NT antibody against both strains. These data indicate that the antigenic properties of the strains may be slightly different. Differences in amino acids between strains 2002-240-SF and Del Carmen in the VP4, VP2, VP3, and VP1 regions may affect both antigenic and receptor binding properties, even though they do not seem to be significant enough to escape widespread immunity. One of the factors of the outbreak was thought to be the increase in susceptibility in the young generation.
Staphylococcus aureus
Exotoxins Are Present
In Vivo
in Tampons
Authors: Schlievert Patrick M. , Nemeth Kimberly A. , Davis Catherine C. , Peterson Marnie L. , Jones Bruce E.
Published: March 2010

Staphylococcal toxic shock syndrome toxin 1 (TSST-1) is the cause of menstrual toxic shock syndrome (mTSS) associated with vaginal colonization by
Staphylococcus aureus
. In this pilot study, we measured TSST-1 and alpha-toxin, another exotoxin, on used tampons from four healthy women with
S. aureus
on tampons and from two women with tampon-associated mTSS. Tampons from all six women were sectioned into approximately 0.5-cm
3
pieces, some containing menstrual blood and some lacking menstrual blood. The pH of tampon sections with or without menstrual blood was neutral.
S. aureus
CFU were present in tampon sections at approximately equivalent counts (total counts were 1 × 10
8
to 2 × 10
9
CFU/tampon). TSST-1 (2 to 80 μg/tampon) and alpha-toxin (28 to 30 μg/tampon) were present only in the sections containing little or no menstrual blood (low hemoglobin density). In the tampons from TSS patients, the cytokine gamma interferon (IFN-γ) was detected only in menstrual-blood-containing sections, whereas the chemokines macrophage inflammatory protein 3α and interleukin-8 were detected in all sections. Thus, IFN-γ was being produced systemically, whereas the chemokines were being produced both locally by epithelial cells and systemically. The data show that
S. aureus
exotoxins can be identified in tampons
ex vivo
in sites with low hemoglobin density.
Multicenter Evaluation of the LightCycler Methicillin-Resistant
Staphylococcus aureus
(MRSA) Advanced Test as a Rapid Method for Detection of MRSA in Nasal Surveillance Swabs
Authors: Peterson Lance R. , Liesenfeld Oliver , Woods Christopher W. , Allen Stephen D. , Pombo David , Patel Parul A. , Mehta Maitry S. , Nicholson Bradly , Fuller DeAnna , Onderdonk Andrew
Published: March 2010

The rate of methicillin-resistant
Staphylococcus aureus
(MRSA) infection continues to rise in many health care settings. Rapid detection of MRSA colonization followed by appropriate isolation can reduce transmission and infection. We compared the performance of the new Roche LightCycler MRSA advanced test to that of the BD GeneOhm MRSA test and culture. Double-headed swabs were used to collect anterior nasal specimens from each subject. For both tests, DNA was extracted and real-time PCR was performed according to manufacturer's instructions. For culture, one swab of the pair was plated directly to CHROMagar MRSA. The swab paired with the BD GeneOhm MRSA test was also placed into an enrichment broth and then plated to CHROMagar MRSA. Colonies resembling staphylococci were confirmed as
S. aureus
by standard methods. Discrepant specimens had further testing with additional attempts to grow MRSA as well as sample amplicon sequencing. Agreement between results for the two swabs was 99.3% for those with valid results. A total of 1,402 specimens were tested using direct culture detection of MRSA as the gold standard; 187 were culture positive for MRSA. The LightCycler MRSA advanced test had relative sensitivity and specificity of 95.2% (95% confidence interval [CI]: 91.1% to 97.8%) and 96.4% (95% CI: 95.2% to 97.4%), respectively. The BD GeneOhm assay had relative sensitivity and specificity of 95.7% (95% CI: 91.7% to 98.1%) and 91.7% (95% CI: 90.0% to 93.2%), respectively. Following discrepancy analysis, the relative sensitivities of the LightCycler MRSA advanced test and the BD GeneOhm MRSA assay were 92.2 and 93.2%, respectively; relative specificities were 98.9 and 94.2%, respectively. Specificity was significantly better (
P
< 0.001) with the LightCycler MRSA advanced test. The sensitivity of direct culture was 80.4%. The LightCycler MRSA advanced test is a useful tool for sensitive and rapid detection of MRSA nasal colonization.
Evaluation of Blood Agar Microtiter Plates for Culturing
Leishmania
Parasites To Titrate Parasite Burden in Spleen and Peripheral Blood of Patients with Visceral Leishmaniasis
Authors: Maurya Radheshyam , Mehrotra Sanjana , Prajapati Vijay Kumar , Nylén Susanne , Sacks David , Sundar Shyam
Published: March 2010

Serial dilution of blood and spleen biopsy specimens, plated on Novy-MacNeal-Nicolle (NNN) blood agar using microtiter culture plates, is a sensitive and reproducible method for detection and growth of
Leishmania
parasites. Plates could be easily monitored, and growth could be rapidly detected. Moreover, parasite number may be estimated using this technique.
Enhanced Discrimination of Highly Clonal ST22-Methicillin-Resistant
Staphylococcus aureus
IV Isolates Achieved by Combining
spa
,
dru
, and Pulsed-Field Gel Electrophoresis Typing Data
Authors: Shore Anna C. , Rossney Angela S. , Kinnevey Peter M. , Brennan Orla M. , Creamer Eilish , Sherlock Orla , Dolan Anthony , Cunney Robert , Sullivan Derek J. , Goering Richard V. , Humphreys Hilary , Coleman David C.
Published: March 2010

ST22-methicillin-resistant
Staphylococcus aureus
type IV (ST22-MRSA-IV) is endemic in Irish hospitals and is designated antibiogram-resistogram type-pulsed-field group (AR-PFG) 06-01. Isolates of this highly clonal strain exhibit limited numbers of pulsed-field gel electrophoresis (PFGE) patterns and
spa
types. This study investigated whether combining PFGE and
spa
typing with DNA sequencing of the staphylococcal cassette chromosome
mec
element (SCC
mec
)-associated direct repeat unit (
dru
typing) would improve isolate discrimination. A total of 173 MRSA isolates recovered in one Irish hospital during periods in 2007 and 2008 were investigated using antibiogram-resistogram (AR), PFGE,
spa
,
dru
, and SCC
mec
typing. Isolates representative of each of the 17 pulsed-field group 01 (PFG-01)
spa
types identified underwent multilocus sequence typing, and all isolates were ST22. Ninety-seven percent of isolates (168 of 173) exhibited AR-PFG 06-01 or closely related AR patterns, and 163 of these isolates harbored SCC
mec
type IVh. The combination of PFGE,
spa
, and
dru
typing methods significantly improved discrimination of the 168 PFG-01 isolates, yielding 65 type combinations with a Simpson's index of diversity (SID) of 96.53, compared to (i) pairwise combinations of s
pa
and
dru
typing,
spa
and PFGE typing, and
dru
and PFGE typing, which yielded 37, 44, and 43 type combinations with SIDs of 90.84, 91.00, and 93.57, respectively, or (ii) individual
spa
,
dru
, and PFGE typing methods, which yielded 17, 17, and 21 types with SIDs of 66.9, 77.83, and 81.34, respectively. Analysis of epidemiological information for a subset of PFG-01 isolates validated the relationships inferred using combined PFGE,
spa
, and
dru
typing data. This approach significantly enhances discrimination of ST22-MRSA-IV isolates and could be applied to epidemiological investigations of other highly clonal MRSA strains.
Comparison of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Etest Methods with the CLSI Broth Microdilution Method for Echinocandin Susceptibility Testing of
Candida
Species
Authors: Pfaller M. A. , Castanheira M. , Diekema D. J. , Messer S. A. , Moet G. J. , Jones R. N.
Published: March 2010

The antifungal broth microdilution (BMD) method of the European Committee on Antibiotic Susceptibility Testing (EUCAST) and the Etest agar diffusion method were compared with the Clinical and Laboratory Standards Institute (CLSI) BMD method M27-A3 for anidulafungin, caspofungin, and micafungin susceptibility testing of 133 clinical isolates of
Candida
species. The isolates were characterized for the presence or absence of
fks1
and/or
fks2
gene mutations and included 34 isolates of
C. glabrata
(4 mutant strains), 32 of
C. albicans
(1 mutant strain), 25 of
C. parapsilosis
, 19 of
C. guilliermondii
, 12 of
C. tropicalis
(2 mutant strains), and 11 of
C. krusei
. Excellent essential agreement (EA; within 2 dilutions) between the CLSI and EUCAST and CLSI and Etest MIC results was observed. The overall EA between the EUCAST and CLSI results ranged from 89.5% (caspofungin) to 99.2% (micafungin), whereas the EA between the Etest and CLSI results ranged from 90.2% (caspofungin) to 93.2% (anidulafungin). The categorical agreement (CA) between methods for each antifungal agent was assessed using previously determined epidemiological cutoff values (ECVs). Excellent CA (>90%) was observed for all comparisons between the EUCAST and CLSI results with the exceptions of
C. glabrata
and caspofungin (85.3%) and
C. krusei
and caspofungin (54.5%). The CA between the Etest and CLSI results was also excellent for all comparisons, with the exception of
C. krusei
and caspofungin (81.8%). All three methods were able to differentiate wild-type (WT) strains from those with
fks
mutations. With anidulafungin as the test reagent, the CLSI method identified 5 of 7 mutant strains, whereas the EUCAST method and the Etest identified 6 of 7 mutant strains. With either caspofungin or micafungin as the test reagent, the CLSI method identified all 7 mutant strains and the EUCAST method identified 6 of 7 mutant strains. The Etest identified all 7 mutant strains using caspofungin as the reagent. All three test methods showed a high level of agreement and of ability to distinguish
fks
mutant strains of
Candida
species from WT strains using each of the echinocandins.
Human Picobirnaviruses Identified by Molecular Screening of Diarrhea Samples
Authors: van Leeuwen Marije , Williams Marisol M. W. , Koraka Penelope , Simon James H. , Smits Saskia L. , Osterhaus Albert D. M. E.
Published: March 2010

The global threat of (re)emerging infectious viruses requires a more effective approach regarding virus surveillance and diagnostic assays, as current diagnostics are often virus species specific and not able to detect highly divergent or unknown viruses. A systematic exploration of viruses that infect humans is the key to effectively counter the potential public health threat caused by new and emerging infectious diseases. The human gut is a known reservoir of a wide variety of microorganisms, including viruses. In this study, Dutch clinical diarrhea samples for which no etiological agent could be identified by available cell culture, serological, or nucleic acid-based tests were gathered. Large-scale molecular RNA virus screening based on host nucleic acid depletion, sequence-independent amplification, and sequencing of partially purified viral RNA from a limited number of clinical diarrhea samples revealed four eukaryotic virus species. Among the detected viruses were a rhinovirus and a new picobirnavirus variant. In total, ∼20% of clinical diarrhea samples contained human picobirnavirus sequences. The Dutch picobirnaviruses belonged to different phylogenetic clades and did not group with other picobirnaviruses according to year of isolation or host species. Interestingly, the average age of patients infected with picobirnavirus was significantly higher than that of uninfected patients. Our data show that sequence-independent amplification of partially purified viral RNA is an efficient procedure for identification of known and highly divergent new RNA viruses in clinical diarrhea samples.
A Five-Year Longitudinal Analysis of Sooty Mangabeys Naturally Infected with Simian Immunodeficiency Virus Reveals a Slow but Progressive Decline in CD4+T-Cell Count Whose Magnitude Is Not Predicted by Viral Load or Immune Activation
Authors: Taaffe Jessica , Chahroudi Ann , Engram Jessica , Sumpter Beth , Meeker Tracy , Ratcliffe Sarah , Paiardini Mirko , Else James , Silvestri Guido
Published: March 2010

Natural simian immunodeficiency virus (SIV) infection in sooty mangabeys (SMs) typically does not result in AIDS, despite high-level viremia and significant depletion of mucosal CD4+T cells. Here, we report the results of the first longitudinal study of a large cohort of SMs naturally infected with SIV (n= 78) housed at the Yerkes National Primate Research Center from which samples were obtained three times over a 5-year period. In this study, we observed (i) no signs of simian AIDS, (ii) stable SIV loads, (iii) a slow but progressive decline in CD4+T-cell counts (from a mean of 1,067.0 cells/mm3at time point 1 to 764.8 cells/mm3at time point 3) and increases in the numbers of animals with CD4+T-cell levels below 500 and 200 cells/mm3(from 8 to 28 of 78 and from 1 to 4 of 78, respectively), (iv) progressive declines in percentages of naïve CD4+and CD8+T cells (from 37.7 to 24.8% and from 21.0 to 13.0%, respectively), and (v) stably low levels of activated/proliferating T cells as well as CD4+CCR5+T cells. Since the level of total CD4+T cells and the fraction of naïve T cells in SIV-uninfected SMs also declined, it is possible that some of these observations are related to aging, as the SIV-infected animals were significantly older than the uninfected animals. In contrast to the decline in CD4+T cell counts in individuals infected with human immunodeficiency virus (HIV), the decline in CD4+T cell counts in SMs naturally infected with SIV over a 5-year period was not predicted by either plasma viremia or levels of T-cell activation. Taken together, these results confirm that natural SIV infection is nonprogressive from a clinical, virological, and immunological point of view and that stable levels of viremia associated with persistently low-level immune activation represent key differences from the natural course of HIV infection in humans.
Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization
Authors: Binley James M. , Ban Yih-En Andrew , Crooks Emma T. , Eggink Dirk , Osawa Keiko , Schief William R. , Sanders Rogier W.
Published: March 2010

Complex N-glycans flank the receptor binding sites of the outer domain of HIV-1 gp120, ostensibly forming a protective “fence” against antibodies. Here, we investigated the effects of rebuilding this fence with smaller glycoforms by expressing HIV-1 pseudovirions from a primary isolate in a human cell line lacking
N
-acetylglucosamine transferase I (GnTI), the enzyme that initiates the conversion of oligomannose N-glycans into complex N-glycans. Thus, complex glycans, including those that surround the receptor binding sites, are replaced by fully trimmed oligomannose stumps. Conversely, the untrimmed oligomannoses of the silent domain of gp120 are likely to remain unchanged. For comparison, we produced a mutant virus lacking a complex N-glycan of the V3 loop (N301Q). Both variants exhibited increased sensitivities to V3 loop-specific monoclonal antibodies (MAbs) and soluble CD4. The N301Q virus was also sensitive to “nonneutralizing” MAbs targeting the primary and secondary receptor binding sites. Endoglycosidase H treatment resulted in the removal of outer domain glycans from the GnTI- but not the parent Env trimers, and this was associated with a rapid and complete loss in infectivity. Nevertheless, the glycan-depleted trimers could still bind to soluble receptor and coreceptor analogs, suggesting a block in post-receptor binding conformational changes necessary for fusion. Collectively, our data show that the antennae of complex N-glycans serve to protect the V3 loop and CD4 binding site, while
N
-glycan stems regulate native trimer conformation, such that their removal can lead to global changes in neutralization sensitivity and, in extreme cases, an inability to complete the conformational rearrangements necessary for infection.
Membrane Insertion and Biogenesis of the
Turnip Crinkle Virus
p9 Movement Protein
Authors: Martínez-Gil Luis , Johnson Arthur E. , Mingarro Ismael
Published: March 2010

Plant viral infection and spread depends on the successful introduction of a virus into a cell of a compatible host, followed by replication and cell-to-cell transport. The movement proteins (MPs) p8 and p9 of
Turnip crinkle virus
are required for cell-to-cell movement of the virus. We have examined the membrane association of p9 and found that it is an integral membrane protein with a defined topology in the endoplasmic reticulum (ER) membrane. Furthermore, we have used a site-specific photo-cross-linking strategy to study the membrane integration of the protein at the initial stages of its biosynthetic process. This process is cotranslational and proceeds through the signal recognition particle and the translocon complex.
In Vitro
Reconstitution Reveals Key Intermediate States of Trimer Formation by the Dengue Virus Membrane Fusion Protein
Authors: Liao Maofu , Martín Claudia Sánchez-San , Zheng Aihua , Kielian Margaret
Published: March 2010

The flavivirus dengue virus (DV) infects cells through a low-pH-triggered membrane fusion reaction mediated by the viral envelope protein E. E is an elongated transmembrane protein with three domains and is organized as a homodimer on the mature virus particle. During fusion, the E protein homodimer dissociates, inserts the hydrophobic fusion loop into target membranes, and refolds into a trimeric hairpin in which domain III (DIII) packs against the central trimer. It is clear that E refolding drives membrane fusion, but the steps in hairpin formation and their pH requirements are unclear. Here, we have used truncated forms of the DV E protein to reconstitute trimerization
in vitro
. Protein constructs containing domains I and II (DI/II) were monomeric and interacted with membranes to form core trimers. DI/II-membrane interaction and trimerization occurred efficiently at both neutral and low pH. The DI/II core trimer was relatively unstable and could be stabilized by binding exogenous DIII or by the formation of mixed trimers containing DI/II plus E protein with all three domains. The mixed trimer had unoccupied DIII interaction sites that could specifically bind exogenous DIII at either low or neutral pH. Truncated DV E proteins thus reconstitute hairpin formation and define properties of key domain interactions during DV fusion.
High-Resolution X-Ray Structure and Functional Analysis of the Murine Norovirus 1 Capsid Protein Protruding Domain
Authors: Taube Stefan , Rubin John R. , Katpally Umesh , Smith Thomas J. , Kendall Ann , Stuckey Jeanne A. , Wobus Christiane E.
Published: March 2010

Murine noroviruses (MNV) are closely related to the human noroviruses (HuNoV), which cause the majority of nonbacterial gastroenteritis. Unlike HuNoV, MNV grow in culture and in a small-animal model that represents a tractable model to study norovirus biology. To begin a detailed investigation of molecular events that occur during norovirus binding to cells, the crystallographic structure of the murine norovirus 1 (MNV-1) capsid protein protruding (P) domain has been determined. Crystallization of the bacterially expressed protein yielded two different crystal forms (Protein Data Bank identifiers [PDB ID], 3LQ6 and 3LQE). Comparison of the structures indicated a large degree of structural mobility in loops on the surface of the P2 subdomain. Specifically, the A′-B′ and E′-F′ loops were found in open and closed conformations. These regions of high mobility include the known escape mutation site for the neutralizing antibody A6.2 and an attenuation mutation site, which arose after serial passaging in culture and led to a loss in lethality in STAT1
−/−
mice, respectively. Modeling of a Fab fragment and crystal structures of the P dimer into the cryoelectron microscopy three-dimensional (3D) image reconstruction of the A6.2/MNV-1 complex indicated that the closed conformation is most likely bound to the Fab fragment and that the antibody contact is localized to the A′-B′ and E′-F′ loops. Therefore, we hypothesize that these loop regions and the flexibility of the P domains play important roles during MNV-1 binding to the cell surface.
Cellular and Viral Control over the Initial Events of Human Cytomegalovirus Experimental Latency in CD34+Cells
Authors: Saffert Ryan T. , Penkert Rhiannon R. , Kalejta Robert F.
Published: March 2010

Human cytomegalovirus (HCMV) persists for the life of its host by establishing a latent infection. The identification of viral and cellular determinants of latency is the first step toward developing antiviral treatments that target and might clear or control the reservoir of latent virus. HCMV latency is established in CD34+cells when expression of viral immediate early (IE) proteins that initiate lytic infection is silenced. Viral IE gene expression during lytic infection is controlled by a cellular intrinsic immune defense mediated by promyelocytic leukemia nuclear body (PML-NB) proteins such as Daxx and histone deacetylases (HDACs). This defense is inactivated at the start of lytic infection by the HCMV virion tegument protein pp71, which upon viral entry traffics to the nucleus and induces Daxx degradation. Here we show that a similar defense is present, active, and not neutralized during experimental latency in CD34+cells infectedin vitrobecause tegument-delivered pp71 remains in the cytoplasm. Artificial inactivation of this defense by HDAC inhibition or Daxx knockdown rescues viral IE gene expression upon infection of CD34+cells with a laboratory-adapted viral strain but not with clinical strains. Interestingly, coinfection of CD34+cells with clinical viral strains blocked the ability of an HDAC inhibitor to activate IE1 and early protein expression during infection with a laboratory-adapted strain. This suggests that in addition to the intrinsic defense, HCMV clinical strains contribute an HDAC-independent,trans-acting dominant means of control over viral gene expression during the early stages of experimental HCMV latency modeledin vitroin CD34+cells.
Bioethics and professionalism in popular television medical dramas
Authors: Czarny Matthew J , Faden Ruth R , Sugarman Jeremy
Published: March 2010

Television medical dramas sometimes depict medical professionalism and bioethical issues, but their nature and extent are unclear. The authors systematically analysed the bioethical and professionalism content of one season each ofGrey's AnatomyandHouse M.D., two of the most popular current television medical dramas. The results indicate that these programmes are rife with powerful portrayals of bioethical issues and egregious deviations from the norms of professionalism and contain exemplary depictions of professionalism to a much lesser degree.
Some principles of Islamic ethics as found in Harrisian philosophy
Authors: Aksoy Sahin
Published: March 2010

John Harris is one of the prominent philosophers and bioethicists of our time. He has published tens of books and hundreds of papers throughout his professional life. This paper aims to take a ‘deep-look’ at Harris' works to argue that it is possible to find some principles of Islamic ethics in Harrisian philosophy, namely in his major works, as well as in his personal life.

This may be surprising, or thought of as a ‘big’ and ‘groundless’ claim, since John Harris has nothing to do with any religion in his intellectual works. The major features of Harrisian philosophy could be defined as consequentialism or utilitarianism with liberal overtones. Despite some significant and fundamental differences in the application of principles (ie, abortion, euthanasia), the similarities between the major principles in Harrisian philosophy and Islamic ethics are greater at some points than the similarities between Islamic ethics and some other religious ethics (ie, Christian, Judaism).

In this study I compare Harrisian teachings with major Islamic principles on ‘Responsibility’, ‘Side-effects and Double-effects’, ‘Equality’, ‘Vicious choice, guilt and innocence’, ‘Organ transplantation and property rights’ and ‘Advance directives’.
Dutch experience of monitoring active ending of life for newborns: Table 1
Authors: Buiting Hilde M , Karelse Maartje A C , Brouwers Hens A A , Onwuteaka-Philipsen Bregje D , van der Heide Agnes , van Delden Johannes J M
Published: March 2010

Introduction

In 2007, a national review committee was instituted in The Netherlands to review cases of active ending of life for newborns. It was expected that 15–20 cases would be reported. To date, however, only one case has been reported to this committee. Reporting is essential to obtain societal control and transparency; the possible explanations for this lack of reporting were therefore explored.

Methods

Data on end-of-life decision-making were scrutinised from Dutch nation-wide studies (1995, 2001 and 2005), before institution of the committee. Physicians received a questionnaire about their medical decision-making for stratified samples of deceased infants up to 1 year, drawn from the central death registry.

Results

In 2005, 58% of all deaths were preceded by an end-of-life decision, compared with 68% in 2001 and 62% in 1995. The use of drugs with a possible life-shortening effect tended to be lower. In 2005, all four cases in the study in which an infants' life was actively ended were preceded by a decision to forego life-prolonging treatment. In three cases, the infant's life expectancy was short; one case involved a longer life expectancy.

Discussion

The expected number of cases is probably an overestimation due to changes in medical practice such as the tendency to attribute less life-shortening effects to opioids. The lack of reports is probably also associated with requirements in the regulation; it may be difficult to fulfil them due either to time constraints or the nature of the suffering that is addressed. If societal control of active ending of life is considered useful, changes in the regulation may be needed.
Towards a practical definition of professional behaviour
Authors: Rogers Wendy , Ballantyne Angela
Published: March 2010

Context

Professionalism remains a challenging part of the medical curriculum to define, teach and evaluate. We suggest that one way to meet these challenges is to clarify the definition of professionalism and distinguish this from medical ethics.

Methods

Our analysis is two staged. First, we reviewed influential definitions of professionalism and separated elements relating to (a) ethico-legal competencies, (b) clinical competence and (c) professionalism. In reference to professionalism, we then distinguished between aspirational virtues/values and specific behaviours. From these, we develop a working definition of medical professional behaviour consisting of six domains of behaviour: responsibility; relationships with and respect for patients; probity and honesty; self awareness and capacity for reflection; collaboration and team work; and care of colleagues. Second, we tested this working definition against empirical data concerning disciplinary action against practising doctors using (a) sources in the literature and (b) an original analysis of complaints received by the Medical Board of South Australia.

Conclusion

Our empirical analysis supports the relevance of four of the six potential domains: responsibility; relationships with and respect for patients; probity and honesty; self awareness and capacity for reflection. There are additional reasons for retaining ‘collaboration and team work’ in the medical professional behaviour curriculum but ‘care of colleagues’ may be better addressed in the ethico-legal curriculum. Our definition of professional behaviour is consistent with the theoretical literature, captures behaviours that predict future complaints against practitioners and is consistent with current complaints about professionalism in South Australian practitioners. This definition can further the teaching and assessing of professional behaviour in medical schools.
Patterns and magnitude of Zn:Ca in otoliths support the recent phylogenetic typology of Salmoniformes and their sister groups
Authors: Limburg Karin E. , Elfman Mikael
Published: March 2010

Fish otolith chemistries are used to associate fishes with specific environments. However, otolith chemistry may also have potential as a tool in phylogenetic research, as demonstrated here in salmoniform fishes and related taxa. Two-dimensional maps of Zn:Ca otolith chemistry displayed annual oscillations in magnitude in members of the Salmoniformes (with salmons differing from whitefishes). These are also detectable in esocids, but not strongly in osmerids or in more distantly related taxa. Further, Zn:Ca magnitudes were highest in salmonids and declined in other taxa: salmonids (salmons, grayling, and whitefishes) > esocids > osmerids > other. We performed spatial analysis on sagittal section Zn:Ca maps, dividing them into five zones and obtaining means within each zone, as well as grand means. Discriminant function analysis of the different otolith zones was better able to separate taxonomic groups, but showed pike grouping more closely with salmonids and osmerids with the out-group. Zn:Ca incorporation in otoliths may be a trait under phylogenetic control, and recent re-ordering of the systematics of Salmoniformes and their sister groups may be supported by otolith Zn:Ca chemistry.
The role of dispersal and retention in the early life stages of shrimp in a lowland river
Authors: Price Amina E. , Humphries Paul
Published: March 2010

This study investigated the importance of dispersal and retention processes during early ontogeny for three caridean shrimp species that complete their entire life history in freshwater. Directional traps were used to examine the small-scale movement patterns of shrimp into and out of nursery habitat patches (slackwaters) in a small lowland river in southeastern Australia. Movement patterns provided evidence for two contrasting life history based dispersal and retention strategies. For the two smaller atyid species, Paratya australiensis and Caridina mccullochi , the majority of larvae remained within the slackwater in which they were hatched until the final stage of development, at which point dispersal, either among slackwaters or out of slackwaters to faster-flowing pool and run habitats, occurred. For the larger palaemonid species, Macrobrachium australiense , larvae were hatched into slackwaters and dispersal occurred predominately during the first stage of larval development and then decreased as development progressed. Despite the differences in dispersal strategies among species, movement was mostly associated with a particular larval stage and thus emphasizes the importance of retention during critical developmental periods and of the potential impact that flow alteration could have on these and other species with similar life histories.