bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet transfusions from D+ donors to D− patients: a 10‐year follow‐up study of 1014 patients
Authors: Cid Joan , Carbassé Gloria , Pereira Arturo , Sanz Cristina , Mazzara Roberto , Escolar Ginés , Lozano Miguel
Published: December 2010

BACKGROUND: Current guidelines recommend that platelets (PLTs) from D− donors should be given to D− patients. However, such evidence comes from studies with a limited number of included patients that reported an incidence of anti‐D alloimmunization to be up to 19%. We thus decided to extend these findings by examining anti‐D alloimmunization at our institution, where PLT transfusions from D+ donors are transfused to D− patients because of logistic constraints.

STUDY DESIGN AND METHODS: From April 1999 to December 2009, we retrospectively reviewed the clinical and transfusion records of all D− patients who received PLT transfusions from D+ donors at our hospital. PLT concentrates (PCs) were obtained from apheresis and from whole blood donations. RhIG was not administered after the transfusion of PCs from D+ donors. The antibody screen test to detect anti‐D was performed by low‐ionic‐strength solution indirect antiglobulin test using the gel test.

RESULTS: Our series comprises 1014 D− patients who received 5128 PLT transfusions from D+ donors (89% were pooled PCs). We had 315 (31.1%) patients who had a blood sample to analyze the presence of anti‐D 4 or more weeks after the first D+ PLT transfusion with a median follow‐up of 29 weeks (range, 4‐718 weeks). Anti‐D developed in 12 (3.8%) of these 315 patients.

CONCLUSIONS: The frequency of anti‐D alloimmunization of D− patients after receiving pooled PCs from D+ donors is low. The transfusion of D‐incompatible pooled PCs without immunoprophylaxis to D− men or D− women without childbearing potential seems a reasonable and safe alternative.
Sustainability as a Conceptual Focus for Public Administration
Authors: Fiorino Daniel J.
Published: December 2010

This article argues that sustainability should define the conceptual focus for the field of public administration in the coming decade. Sustainability involves three systems: environmental, economic, and political/social systems. The challenge of governance, and thus of public administration, is to sustain each of these systems on its own while maintaining an appropriate balance among them. The article defines the sustainability concept, and its environmental component in particular, in ways that are relevant to public administration; assesses the validity of the concept in terms of the interrelationships and interdependencies among the three systems; and suggests the implications for the field. By integrating knowledge and study of the environmental system with the traditional competence in the political/social and economic systems that is expected in the field, public administrators may achieve a more theoretically complete and empirically valid foundation for education, research, and practice.

And just as many apparently insoluble problems have eluded solution until someone discovered the “right” way to view them, so it may be that our failure to cope adequately with certain large and complex problems of our time is a consequence of failure to see the unifying elements in the complexity.

—Lynton K. Caldwell, 1963
Governance Infrastructures in 2020
Authors: Johnston Erik
Published: December 2010

A governance infrastructure is the collection of technologies and systems, people, policies, practices, and relationships that interact to support governing activities. Information technology, especially communication and computational technologies, continues to augment society’s ability to organize, interact, and govern. As we think about the future of governance, this article challenges us to move beyond questions of how to best manage government institutions to how to design smart governance systems with the appropriate incentives and rules to harness and coordinate the enthusiasm and capabilities of those governed. This article anticipates how the interaction of technology and society can be leveraged to mindfully design an interaction‐defined, participation‐based governance infrastructure to return power to the people while increasing accountability. Supporting examples of such governance approaches already exist and are regularly emerging in distributed organizations, online communities, nonprofits, and governments.
Governing Cities in the Coming Decade: The Democratic and Regional Disconnects
Authors: Barnes William R.
Published: December 2010

How will cities be governed in 2020? The answer will depend to a significant degree on reducing two “disconnects”: one between municipal government and its citizenry, and the other between municipal government and its region. Elected, managerial, and intellectual leaders need to strengthen their understanding, capacities, and skills regarding public engagement and regional engagement across jurisdictional boundaries. Enhanced performance of these functions will improve cities’ ability to address problems and seize opportunities in the decade ahead.
The Future of Local Government: Twenty‐First‐Century Challenges
Authors: Warner Mildred E.
Published: December 2010

Local governments in the twenty‐first century face challenges regarding service delivery, finance, the workforce, and citizen engagement. While privatization was a major innovation in the last decades of the twentieth century, lack of costs savings and the loss of public values in market provision are prompting reversals in privatization, increases in regulation, and new approaches to government enterprise. The twenty‐first century must focus on rebuilding the capacity of local governments to finance critical infrastructure, attract and retain a skilled labor force, and engage citizen in designing innovative solutions to address public problems. Innovations in public service delivery will move beyond public private partnerships to models that more effectively balance accountability, equity, and efficiency concerns.
Governance, Structure, and Democracy: Luther Gulick and the Future of Public Administration
Authors: Meier Kenneth J.
Published: December 2010

Luther Gulick was both an academic and a reformer. In the latter role, he thought seriously about what the future of public administration might look like. This essay examines his work as a lens through which to view the future of public administration in 2020. Gulick suggests that public administration needs a governance orientation to link scholarship with the realities of practice, a recognition of the bias of structures, a stress on the informal elements of organization, additional research on almost every question, a recognition of the importance of ethics, a stress on the importance of context, and a fundamental appreciation of the role that public management plays in fostering democracy.
Morphologic and Molecular Data Suggest that Lynnella semiglobulosa n. g., n. sp. Represents a New Family within the Subclass Choreotrichia (Ciliophora, Spirotrichea)
Authors: LIU WEIWEI , YI ZHENZHEN , LIN XIAOFENG , AL‐RASHEID KHALED A. S.
Published: December 2010

ABSTRACT. The morphology, morphogenesis, and phylogeny of an undescribed oligotrich sensu lato (s. lat.) ciliate, Lynnella semiglobulosa n. g., n. sp., found in Daya Bay, southern China, were investigated. This species shares some features with both oligotrichs sensu stricto and choreotrichs, but most morphological and morphogenetic characters as well as the phylogenetic analysis suggest that it should be assigned into subclass Choreotrichia temporarily. Lynnella semiglobulosa is distinguished from members of all known genera and families of the subclass Choreotrichia by a unique combination of characteristics of the buccal and somatic ciliatures. Thus, a new family Lynnellidae n. fam. and a new genus Lynnella n. g. are proposed for it. The new family is distinguished by an open adoral zone of membranelles (AZM) in which, however, there are no ventral membranelles; the distal and proximal portions of the new adoral zone lie close to each other forming an open circle in stomatogenesis. The new genus Lynnella is characterized by possessing two longitudinally oriented somatic kineties, one dorsal and one ventral, several proximal membranelles progressively lengthened toward the proximal end of adoral zone, and two macronuclear nodules. In phylogenetic analyses based on small subunit rRNA gene sequences, L. semiglobulosa clustered basally to all choreotrichs, but with relatively weak support; nevertheless, the possibility of a relationship with the subclass Oligotrichia was not rejected by the approximately unbiased nor Shimodaira–Hasegawa test. Based on morphological, morphogenetic, and molecular evidence of L. semiglobulosa, it is confirmed that the open AZM should be a plesiomorphic character of oligotrichs s. lat. as suggested previously.
Improved pre‐osteoblast response and mechanical compatibility of ultrafine‐grained Ti–13Nb–13Zr alloy
Authors: Park Chan Hee , Lee Chong Soo , Kim Youn‐Jeong , Jang Je‐Hee , Suh Jo‐Young , Park Jin‐Woo
Published: December 2010

Objective: Metallic implantation materials having high yield strength, low elastic modulus, and non‐cytotoxic alloying elements would be advantageous for the long‐term stability of implants. This study assessed the surface and mechanical properties, and also in vitro osteoconductivity of ultrafine‐grained (UFG) Ti–13Nb–13Zr alloy produced by dynamic globularization without any severe deformation for future biomedical applications as an endosseous implant material.

Material and methods: The surface characteristics and mechanical properties were investigated by orientation image microscopy, contact angle measurements, optical profilometry, and uniaxial tension tests. Mouse calvaria‐derived pre‐osteoblastic cell (MC3T3‐E1) attachment, spreading, viability, alkaline phosphatase (ALP) activity, and quantitative analysis of osteoblastic gene expression on UFG Ti–13Nb–13Zr alloy were compared with coarse‐grained (CG) Ti–13Nb–13Zr and CG Ti–6Al–4V alloys.

Results: Dynamic globularized Ti–13Nb–13Zr alloy has an ultrafine grain size (0.3 μm) and an excellent combination of yield strength and elastic modulus compared with CG alloys, which displayed significantly lower water contact angles compared with CG alloys (P<0.05). The UFG and CG Ti–13Nb–13Zr alloys displayed significantly increased cellular attachment compared with CG Ti–6Al–4V alloy (P<0.05). The UFG Ti–13Nb–13Zr supported better cell spreading and more numerous focal adhesions. ALP activity (P<0.05) and mRNA expressions of the osteoblast transcription factor genes (osterix, Runx2) and marker gene for osteoblast differentiation (osteocalcin) were markedly increased in cells grown on the UFG substrate compared with CG substrates at early incubation timepoints.

Conclusion: Enhanced pre‐osteoblast response to UFG Ti–13Nb–13Zr substrate is attributable to the non‐cytotoxic alloying elements and the submicron scale grain size contributes to the superior surface hydrophilicity and abundant grain boundaries favorable for cell behavior. These findings indicate that dynamic globularized UFG Ti–13Nb–13Zr alloy is promising for load‐bearing endosseous implant material because of excellent mechanical and biological compatibilites.

To cite this article:
 Park CH, Lee CS, Kim Y‐J, Jang J‐H, Suh J‐Y, Park J‐W. Improved pre‐osteoblast response and mechanical compatibility of ultrafine‐grained Ti–13Nb–13Zr alloy. Clin. Oral Impl. Res. 22, 2011; 735–742 doi: 10.1111/j.1600‐0501.2010.02053.x
Barriers to translating evidence‐based breastfeeding information into practice
Authors: Brodribb Wendy
Published: December 2010

There is strong evidence that using breastmilk substitutes disadvantages the infant, mother and community as a whole. There is also increasing evidence regarding the lactation process, breastfeeding inhibitors and enablers, and breastfeeding management options. However, there appears to be a gap between this evidence base and practice with breastfeeding rates being unacceptably low, especially following hospital discharge. This paper discusses barriers to the implementation of breastfeeding best practice using a framework of the research‐to‐practice pipeline: acceptance, applicable, available and able, acted upon, agreed to and adhered to. As blocks or restrictions to the flow of information or evidence may occur at any point along the pathway, researchers designing interventions to increase breastfeeding rates need to consider using multi‐strategy interventions and target collaborative care across professions.

Conclusion:  Barriers to implementing evidence‐based breastfeeding practices are common and wide ranging. These barriers should be considered when developing new breastfeeding services and research programmes.
Irradiance Differences in the Violet (405 nm) and Blue (460 nm) Spectral Ranges among Dental Light‐Curing Units
Authors: PRICE RICHARD B.T. , LABRIE DANIEL , RUEGGEBERG FREDERICK A. , FELIX CHRISTOPHER M.
Published: December 2010

Problem:  Previous studies identified nonuniformity in the irradiance at the tip end of a variety of dental light‐curing units (LCUs) and correlated those differences with potential clinical implications, but the spectral dependence of the irradiance uniformity has not yet been addressed.

Purpose:  This study examined the irradiance uniformity across emitting tips of LCUs at two emission wavelengths, 405 and 460 nm. Two broadband emission light units (quartz‐tungsten‐halogen [QTH] and plasma arc [PAC]), and four commercial light‐emitting diode (LED)‐type LCUs were examined.

Materials and Methods:  The spectral radiant power from six LCUs was measured using a laboratory grade spectroradiometer (Ocean Optics, Dunedin, FL, USA). The spatial and spectral characteristics of irradiance across the emitting tips of these light units were recorded through 10‐nm wide bandpass filters (centered at 405 nm [violet] or 460 nm [blue]) using a laser beam analyzer (Ophir‐Spiricon, Logan, UT, USA). Irradiance distributions were reported using two‐dimensional contour and three‐dimensional isometric color‐coded images. Irradiance uniformity at the tip end was determined using the Top Hat Factor (THF) for each filtered wavelength.

Results:  Irradiance distributions from the QTH and PAC units were uniformly distributed across the tip end of the light guide, and THF values, measured through the 405 and 460‐nm filters, were not significantly different. However, the three polywave LED units delivered non‐uniform irradiance distributions with THF values differing significantly between the 405 and 460‐nm emission wavelengths for each unit. Areas of nonuniformity were attributed to the locations of the various types of LED chips within the LCUs.

Conclusion:  All three polywave LED units delivered a nonuniform irradiance distribution across their emitting tip ends at the two important emission wavelengths of 405 nm and 460 nm, whereas the broadband light sources (QTH and PAC) showed no evidence of spectral inhomogeneity at these wavelengths.

CLINICAL SIGNIFICANCE

Since the rate and extent of polymerization of photo activated restorative materials is highly dependent on delivering radiant energy at specific wavelengths, the nonuniform spectral distribution across the emitting tips of polywave light‐emitting diode curing lights may affect the resulting properties of some photocured resins and their potential for long‐term clinical success.

(J Esthet Restor Dent 22:363–378, 2010)
Influence of Bleaching Agents on Surface Roughness of Sound or Eroded Dental Enamel Specimens
Authors: AZRAK BIRGÜL , CALLAWAY ANGELIKA , KURTH PETRA , WILLERSHAUSEN BRITA
Published: December 2010

Purpose:  The aim of the present in vitro study was to assess the effect of bleaching agents on eroded and sound enamel specimens.

Materials and Methods:  Enamel specimens prepared from human permanent anterior teeth were incubated with different bleaching agents containing active ingredients as 7.5 or 13.5% hydrogen peroxide or 35% carbamide peroxide, ranging in pH from 4.9 to 10.8. The effect of the tooth whitening agents on surface roughness was tested for sound enamel surfaces as well as for eroded enamel specimens. To provoke erosive damage, the enamel specimens were incubated for 10 hours with apple juice (pH = 3.4). Afterwards, pretreated and untreated dental slices were incubated with one of the bleaching agents for 10 hours. The surface roughness (Ra) of all enamel specimens (N = 80) was measured using an optical profilometric device. A descriptive statistical analysis of the Ra values was performed.

Results:  The study demonstrated that exposure to an acidic bleaching agent (pH = 4.9) resulted in a higher surface roughness (p = 0.043) than treatment with a high peroxide concentration (pH = 6.15). If the enamel surface was previously exposed to erosive beverages, subsequent bleaching may enhance damage to the dental hard tissue.

Conclusion:  Bleaching agents with a high concentration of peroxide or an acidic pH can influence the surface roughness of sound or eroded enamel.

CLINICAL SIGNIFICANCE

Patients with erosive defects who wish to receive a tooth bleaching treatment must be informed about possible complications and damage to the tooth surface. However, extrapolation of in vitro results to clinical situations is limited.

(J Esthet Restor Dent 22:391–401, 2010)
Identification of the primary mechanism of complement evasion by the periodontal pathogen, Treponema denticola
Authors: McDowell J.V. , Frederick J. , Miller D.P. , Goetting‐Minesky M.P. , Goodman H. , Fenno J.C. , Marconi R.T.
Published: December 2010

Treponema denticola, a periodontal pathogen, binds the complement regulatory protein Factor H (FH). Factor H binding protein B (FhbB) is the sole FH binding protein produced by T. denticola. The interaction of FhbB with FH is unique in that FH is bound to the cell and then cleaved by the T. denticola protease, dentilisin. A ∼ 50‐kDa product generated by dentilisin cleavage is retained at the cell surface. Until this study, a direct role for the FhbB–FH interaction in complement evasion and serum sensitivity had not been demonstrated. Here we assess the serum resistance of T. denticola strain 35405 (Td35405wt) and isogenic mutants deficient in dentilisin (Td35405‐CCE) and FhbB production (Td35405ΔfhbB), respectively. Both dentilisin and FhbB have been postulated to be key virulence factors that mediate complement evasion. Consistent with conditions in the subgingival crevice, an environment with a significant concentration of complement, Td35405wt was resistant to serum concentrations as high as 25%. Deletion of fhbB (Td35405ΔfhbB), which resulted in the complete loss of FH binding ability, but not inactivation of dentilisin activity (Td35405‐CCE), rendered T. denticola highly sensitive to 25% human serum with 80% of the cells being disrupted after 4 h of incubation. Heat treatment of the serum to inactivate complement confirmed that killing was mediated by complement. These results indicate that the FH–FhbB interaction is required for serum resistance whereas dentilisin is not. This report provides new insight into the novel complement evasion mechanisms of T. denticola.
Large Eddy Simulation of Turbulent-Cavitation Interactions in a Venturi Nozzle
Authors: Dittakavi Nagendra , Chunekar Aditya , Frankel Steven
Published: December 2010

Large eddy simulation of turbulent cavitating flow in a venturi nozzle is conducted. The fully compressible Favre-filtered Navier–Stokes equations are coupled with a homogeneous equilibrium cavitation model. The dynamic Smagorinsky subgrid-scale turbulence model is employed to close the filtered nonlinear convection terms. The equations are numerically integrated in the context of a generalized curvilinear coordinate system to facilitate geometric complexities. A sixth-order compact finite difference scheme is employed for the Navier–Stokes equations with the AUSM+-up scheme to handle convective terms in the presence of large density gradients. The stiffness of the system due to the incompressibility of the liquid phase is addressed through an artificial increase in the Mach number. The simulation predicts the formation of a vapor cavity at the venturi throat with an irregular shedding of the small scale vapor structures near the turbulent cavity closure region. The vapor formation at the throat is observed to suppress the velocity fluctuations due to turbulence. The collapse of the vapor structures in the downstream region is a major source of vorticity production, resulting into formation of hair-pin vortices. A detailed analysis of the vorticity transport equation shows a decrease in the vortex-stretching term due to cavitation. A substantial increase in the baroclinic torque is observed in the regions where the vapor structures collapse. A spectra of the pressure fluctuations in the far-field downstream region show an increase in the acoustic noise at high frequencies due to cavitation.
Study on the Cure Kinetic Behavior of Thermosetting Polyurethane Solids and Foams: Effect of Temperature, Density, and Carbon Nanofiber
Authors: Saha Mrinal C. , Barua Bipul , Mohan Sriram
Published: December 2010

Cure kinetic behavior was studied for both thermosetting polyurethane (PU) solids and foams. The effects of cure temperature, foam density, and carbon nanofiber (CNF) contents were examined. Cure studies were performed experimentally by measuring the evolution of complex shear modulus as a function of time using an advanced polymer analyzer operating in dynamic shear mode. Isothermal cure behavior of PU solid and foams was investigated at four different temperatures, namely, 25°C, 45°C, 60°C, and 80°C and at three different amounts of CNF, namely, 0.01%, 0.05%, and 0.1% by weight. The cure data were analyzed by using an autocatalytic cure kinetic model. The cure behavior of both solid and foam was found to be temperature dependent. Addition of CNF was also found to affect the cure behavior of the PU foam. It was observed that the PU foam with 0.1% CNF shows the highest polymerization reaction compared with the neat foam. It was also observed that the reaction rate constants follow an Arrhenius dependence on temperature, whereas the reaction orders remain fairly constant. A simple predictive model using the reaction orders indicated that the maximum cure reaction rate was occurred at 37.5% conversion.
Dynamic Mechanical Analysis of Fly Ash Filled Polyurea Elastomer
Authors: Qiao Jing , Amirkhizi Alireza V. , Schaaf Kristin , Nemat-Nasser Sia
Published: December 2010

In this work, the material properties of a series of fly ash/polyurea composites were studied. Dynamic mechanical analysis was conducted to study the effect of the fly ash volume fraction on the composite’s mechanical properties, i.e., on the material’s frequency- and temperature-dependent storage and loss moduli. It was found that the storage and loss moduli of the composite both increase as the fly ash volume fraction is increased. The storage and loss moduli of the composites relative to those of pure polyurea initially increase significantly with temperature and then slightly decrease or stay flat, attaining peak values around the glass transition region. The glass transition temperature (measured as the temperature at the maximum value of the loss modulus) shifted toward higher temperatures as the fly ash volume fraction increased. Additionally, we present the storage and loss moduli master curves for these materials obtained through application of the time-temperature superposition on measurements taken at a series of temperatures.
Comparing Linear and Essentially Nonlinear Vibration-Based Energy Harvesting
Authors: Quinn D. Dane , Triplett Angela L. , Bergman Lawrence A. , Vakakis Alexander F.
Published: December 2010

This work considers the performance of a resonant vibration-based energy harvesting system utilizing a strongly nonlinear attachment. Typical designs serving as the basis for harvesting energy from ambient vibration typically employ a linear oscillator for this purpose, limiting peak harvesting performance to a narrow band of frequencies about the resonant frequency of the oscillator. Herein, in an effort to maximize performance over the broader band of frequency content typically observed in ambient vibration measurements, we employ an essentially nonlinear cubic oscillator in the harvesting device and show that, with proper design, significant performance gains can be realized as compared with a tuned linear attachment. However, we also show that the coexistence of multiple equilibria due to the nonlinearity can degrade system performance, as the system can be attracted to a low amplitude state that provides reduced harvested power. Finally, when multiple equilibria exist in the system, the basins of attraction for the stable states are determined and related to the expected response of the system.
Stall Inception Mechanism in an Axial Flow Fan Under Clean and Distorted Inflows
Authors: Salunkhe Pramod B. , Pradeep A. M.
Published: December 2010

The present paper describes the use of Morlet wavelet transform in understanding the stall inception mechanism in a single stage axial flow fan. Unsteady pressure data from wall mounted sensors were used in the wavelet transforms. This paper was carried out under undistorted and distorted inflow conditions as well as for slow throttle closure and throttle ramping. It was observed from the wavelet transforms that the stall inception under clean inflow (undistorted) and counter-rotating inflow distortions (in the direction opposing the rotor rotation) incur through short length-scale disturbances and through long length-scale disturbances under static and co-rotating inflow distortions (in the same direction of rotor rotation). Modal activity was observed to be insignificant under clean inflow while under static inflow distortion, long length-scale disturbances evolved due to interaction between rotor blades and the distorted sector, especially near the trailing edge of the distortion screen. The presence of a strong mode was observed under both co- and counter-rotating inflow distortions. With throttle ramping, stall inception occurs through long and short length-scale disturbances under co- and counter-rotating inflow distortions, respectively. Some preliminary flow characteristics were studied using a seven hole probe. A significant increase in flow angle and decrease in axial flow coefficient close to the rotor tip were observed under co-rotating inflow distortion as compared with counter-rotating inflow distortion.
Cytoplasmic Partitioning of P Granule Components Is Not Required to Specify the Germline in
C. elegans
Authors: Gallo Christopher M. , Wang Jennifer T. , Motegi Fumio , Seydoux Geraldine
Published: December 2010

Making a Germ Cell

When it comes to generating the germ line, animals fall into two classes: those, like mammals, which use inductive interactions to specify the germ line and those, like nematodes, which use germ plasm—a specialized egg cytoplasm that segregates asymmetrically in embryos. Germ plasm contains germ, or P, granules—RNA-protein aggregates that have been thought to harbor the germ line determinants. Now,

Gallo
et al.

(p.
1685
, published online 2 December) describe a
Caenorhabditis elegans
mutant that challenges this belief. The germ line still formed even when germ granule components were missegregated. Thus, even in animals with germ plasm, germ granules appear to be a consequence, not a cause, of germ cell specification.
Dynamic Metabolons
Authors: Møller Birger Lindberg
Published: December 2010

The assembly and disassembly of enzymes complexes may differentiate plant defense responses to insect attack and fungal infection.
Cryptic Links in the Ocean
Authors: Teske Andreas
Published: December 2010

Analysis of the bacterial communities in oxygen-depleted water columns reveals a new strategy how microbes link the nitrogen and sulfur cycles in the ocean.
The DNA Damage Road Map
Authors: Friedman Nir , Schuldiner Maya
Published: December 2010

Comparing maps of gene interactions offers insight into how yeast cells repair DNA damage.
Policy-Making Needs Science
Authors: Alberts Bruce
Published: December 2010

Over the long run, any nation that makes crucial decisions while ignoring science is doomed. Consider, for example, the decision about how much arsenic should be allowed in drinking water supplies. There is no one “right answer” to this or many other policy questions, but it is critical that national legislation be based on what science knows about potential harm. It is therefore disturbing that so many lawmakers elected to the new U.S. Congress reject the overwhelming scientific consensus with respect to human-induced climate change. It will be difficult to make wise choices with such attitudes. The question now facing the United States is not only how to effectively reinject the facts of climate science back into the core of this particular debate, but also how to ensure that good science underlies all legislative decisions.
Panel Explores New Funding Pact With Washington
Authors: Mervis Jeffrey
Published: December 2010

At an intense meeting last week at the National Academies in Washington, D.C., a blue-ribbon panel asked by Congress to recommend how the country's research universities can bolster the nation's well-being spent a day and a half in public discussion with several dozen leaders in higher education, followed by a day of private deliberations aimed at producing a final report next summer.
Usefulness of Mycobacterial Interspersed Repetitive-Unit Locus PCR Amplification in Rapid Diagnosis of Beijing Lineage Strain Infection among Pediatric Tuberculosis Patients
Authors: Liu Ruixi , Xing Linlin , Peng Ze , Zhang Yukun , Zhu Chaomin , Yang Zhenhua
Published: December 2010

We assessed the usefulness of mycobacterial interspersed repetitive-unit–variable-number tandem-repeat loci 26, 31, ETR-A, Mtub30, and Mtub02 and a deletion-targeted multiplex PCR in identifying pediatric
Mycobacterium tuberculosis
Beijing lineage strain infection. We found that the Beijing lineage isolates accounted for ∼62% (130/210) of the study isolates.
Use of Epidemiological Cutoff Values To Examine 9-Year Trends in Susceptibility of Aspergillus Species to the Triazoles
Authors: Pfaller M. , Boyken L. , Hollis R. , Kroeger J. , Messer S. , Tendolkar S. , Diekema D.
Published: December 2010

In the absence of clinical breakpoints, epidemiological cutoff values (ECVs) have been established to distinguish wild-type (WT) isolates of
Aspergillus
spp. from those that may harbor resistance mutations. Recently, the CLSI has developed ECVs for triazoles (itraconazole, posaconazole, and voriconazole) and common
Aspergillus
species. We applied the triazole ECVs to 1,789
Aspergillus
isolates collected from 63 centers worldwide from 2001 to 2009 to determine the frequency of non-WT strains of each species. Temporal trends were evaluated for
Aspergillus fumigatus
and
Aspergillus flavus
over the 9-year period for each drug. The collection included 1,312 isolates of
A. fumigatus
, 235 of
A. flavus
, 162 of
Aspergillus niger
, 64 of
Aspergillus terreus
, and 15 of
Aspergillus versicolor
. Using the ECVs, the percentages of non-WT isolates for itraconazole, posaconazole, and voriconazole, respectively, were as follows:
A. fumigatus
(2.0%, 3.5%, and 1.4%),
A. flavus
(0.8%, 5.1%, and 1.7%),
A. niger
(17.3%, 3.7%, and 0.6%),
A. terreus
(0.0%, 1.6%, and 3.2%), and
A. versicolor
(6.3%, 0.0%, and 0.0%). Among 49
Aspergillus
isolates for which itraconazole MICs were >2 μg/ml, the posaconazole and voriconazole MICs were greater than the ECVs for 14 and 12 isolates, respectively. The percentages of isolates for which MICs were greater than the ECVs ranged from 1.1 to 5.7% for posaconazole, 0.0 to 1.6% for voriconazole, and 0.7 to 4.0% for itraconazole. There was no consistent trend toward decreased susceptibility for any triazole and
A. fumigatus
or
A. flavus
over time. Decreased susceptibility among
Aspergillus
spp. was observed for each of the extended-spectrum triazoles and varied by species over the 9-year study period.
The C Proteins of Human Parainfluenza Virus Type 1 Limit Double-Stranded RNA Accumulation That Would Otherwise Trigger Activation of MDA5 and Protein Kinase R
Authors: Boonyaratanakornkit Jim , Bartlett Emmalene , Schomacker Henrick , Surman Sonja , Akira Shizuo , Bae Yong-Soo , Collins Peter , Murphy Brian , Schmidt Alexander
Published: December 2010

Human parainfluenza virus type 1 (HPIV1) is an important respiratory pathogen in young children, the immunocompromised, and the elderly. We found that infection with wild-type (WT) HPIV1 suppressed the innate immune response in human airway epithelial cells by preventing not only phosphorylation of interferon regulatory factor 3 (IRF3) but also degradation of IκBβ, thereby inhibiting IRF3 and NF-κB activation, respectively. Both of these effects were ablated by a F170S substitution in the HPIV1 C proteins (F170S) or by silencing the C open reading frame [P(C−)], resulting in a potent beta interferon (IFN-β) response. Using murine knockout cells, we found that IFN-β induction following infection with either mutant relied mainly on melanoma-associated differentiation gene 5 (MDA5) rather than retinoic acid-inducible gene I (RIG-I). Infection with either mutant, but not WT HPIV1, induced a significant accumulation of intracellular double-stranded RNA (dsRNA). These mutant viruses directed a marked increase in the accumulation of viral genome, antigenome, and mRNA that was coincident with the accumulation of dsRNA. In addition, the amount of viral proteins was reduced compared to that of WT HPIV1. Thus, the accumulation of dsRNA might be a result of an imbalance in the N protein/genomic RNA ratio leading to incomplete encapsidation. Protein kinase R (PKR) activation and IFN-β induction followed the kinetics of dsRNA accumulation. Interestingly, the C proteins did not appear to directly inhibit intracellular signaling involved in IFN-β induction; instead, their role in preventing IFN-β induction appeared to be in suppressing the formation of dsRNA. PKR activation contributed to IFN-β induction and also was associated with the reduction in the amount of viral proteins. Thus, the HPIV1 C proteins normally limit the accumulation of dsRNA and thereby limit activation of IRF3, NF-κB, and PKR. If C protein function is compromised, as in the case of F170S HPIV1, the resulting PKR activation and reduction in viral protein levels enable the host to further reduce C protein levels and to mount a potent antiviral type I IFN response.
Insertion of MicroRNA Targets into the Flavivirus Genome Alters Its Highly Neurovirulent Phenotype
Authors: Heiss Brian L. , Maximova Olga A. , Pletnev Alexander G.
Published: December 2010

Flaviviruses such as West Nile, Japanese encephalitis, and tick-borne encephalitis (TBEV) viruses are important neurotropic human pathogens, causing a devastating and often fatal neuroinfection. Here, we demonstrate that incorporation into the viral genome of a target sequence for cellular microRNAs expressed in the central nervous system (CNS) enables alteration of the neurovirulence of the virus and control of the neuropathogenesis of flavivirus infection. As a model virus for this type of modification, we used a neurovirulent chimeric tick-borne encephalitis/dengue virus (TBEV/DEN4) that contained the structural protein genes of a highly pathogenic TBEV. The inclusion of just a single target copy for a brain tissue-expressed mir-9, mir-124a, mir-128a, mir-218, or let-7c microRNA into the TBEV/DEN4 genome was sufficient to prevent the development of otherwise lethal encephalitis in mice infected intracerebrally with a large dose of virus. Viruses bearing a complementary target for mir-9 or mir-124a were highly restricted in replication in primary neuronal cells, had limited access into the CNS of immunodeficient mice, and retained the ability to induce a strong humoral immune response in monkeys. This work suggests that microRNA targeting to control flavivirus tissue tropism and pathogenesis might represent a rational approach for virus attenuation and vaccine development.
Use of Single-Cycle Infectious Lymphocytic Choriomeningitis Virus To Study Hemorrhagic Fever Arenaviruses
Authors: Rodrigo W. W. Shanaka I. , de la Torre Juan C. , Martínez-Sobrido Luis
Published: December 2010

Several arenaviruses, chiefly Lassa virus (LASV) and Junin virus in West Africa and Argentina, respectively, cause hemorrhagic fever (HF) disease in humans that is associated with high morbidity and significant mortality. The investigation of antiviral strategies to combat HF arenaviruses is hampered by the requirement of biosafety level 4 (BSL-4) facilities to work with these viruses. These biosafety hurdles could be overcome by the use of recombinant single-cycle infectious arenaviruses. To explore this concept, we have developed a recombinant lymphocytic choriomeningitis virus (LCMV) (rLCMVΔGP/GFP) where we replaced the viral glycoprotein (GP) with the green fluorescent protein (GFP). We generated high titers of GP-pseudotyped rLCMVΔGP/GFP via genetic
trans
complementation using stable cell lines that constitutively express LCMV or LASV GPs. Replication of these GP-pseudotyped rLCMVΔGP/GFP viruses was restricted to GP-expressing cell lines. This system allowed us to rapidly and reliably characterize and quantify the neutralization activities of serum antibodies against LCMV and LASV within a BSL-2 facility. The sensitivity of the GFP-based microneutralization assay we developed was similar to that obtained with a conventionally used focus reduction neutralization (FRNT) assay. Using GP-pseudotyped rLCMVΔGP/GFP, we have also obtained evidence supporting the feasibility of this approach to identify and evaluate candidate antiviral drugs against HF arenaviruses without the need of BSL-4 laboratories.
Endometrial metaplasias and reactive changes: a spectrum of altered differentiation
Authors: Nicolae Alina , Preda Ovidiu , Nogales Francisco F
Published: December 2010

Endometrial metaplasias and changes (EMCs) are conditions frequently overlooked and misdiagnosed. The aim of this review is to update current issues and provide a classification with a practical clinicopathological approach. Hormonal or irritative stimuli are the main inducing factors of EMCs, although some metaplasias have a mutational origin. EMCs vary from reactive, degenerative lesions to those able to associate with malignancy or those having a preneoplastic potential. The most common types of EMCs are ciliated tubal metaplasia (CTM) and mucinous metaplasia (MM), which occur in simple and complex glands, and possibly these architectural changes hold the same prognostic significance as they do in hyperplastic endometrioid lesions. Immunohistochemically, CTM is positive for LhS28, bcl-2, PAX2 and p16INK4A. Complex CTM is likely to be a precursor of ciliated endometrioid-type carcinomas. MMs should be evaluated architecturally, taking into account that their atypicality is minimal. The differentiation between complex MM and mucinous carcinoma may be extremely difficult. Surface complex, papillary MM in endometrial polyps can be considered as benign. Intestinal-type endometrial MM is rare and its presence should prompt further investigation of associated lesions in the endocervix. Endometrial squamous metaplasia (ESS) is often linked to chronic irritative situations. It should be differentiated from secondary involvement by a human papilomavirus-related cervical lesion. Morular metaplasia is a mutational phenomenon with a distinct phenotype that helps to differentiate it from ESS. Morules are benign, hormonally inert structures that are often markers of complex endometrioid glandular architecture, and they are associated with an attenuated malignancy. Endometrial reactive changes are commonly associated with desquamation or hormonal imbalance. The frequent, p16INK4Apositive, benign surface papillary syncytial change may be misdiagnosed, in some cases, as surface serous adenocarcinoma. Eosinophilic, oxyphilic, oncocytic and clear cell changes are non-specific. Rare stromal metaplasias have little clinical significance and should be differentiated from implanted fetal or embryonal tissues.
Safety of a non‐adjuvanted therapeutic vaccine for the treatment of feline dermatophytosis
Authors: Westhoff D. , Orveillon F. X. , Farnow D. , Klös M‐C. , Elbers K.
Published: December 2010

The safety of a non‐adjuvanted inactivated fungal vaccine for the treatment of dermatophytosis in cats was investigated in two studies: a controlled laboratory study, and a placebo‐controlled double‐blind field study with a cross‐over design in Europe. In the laboratory study, two groups of 10 cats each were administered an intramuscular twofold overdose, followed by five single 1 ml doses, of either vaccine or control product at 14‐day intervals. In the field study, cats were treated with three intramuscular injections of 1 ml vaccine administered at 14‐day intervals, as recommended by the manufacturer. A total of 89 cats were enrolled in the field study and divided into two groups to receive either vaccine or placebo for the first three treatments, followed by the opposite product for the final three treatments. The cats enrolled in the two studies were 12 weeks of age or older, as recommended by the manufacturer. All the cats were monitored closely for possible injection site reactions, systemic reactions (including changes in rectal body temperature) and adverse events. The results from both studies showed no significant differences between the vaccinated cats and the control or placebo‐treated cats with regard to local or systemic reactions. A few mild to moderate local reactions were noted, but these were evenly distributed between the vaccinated and placebo‐treated cats and resolved within a few days. No severe or serious adverse events related to the vaccinations were observed.
LORENTZ VIOLATION EFFECTS ON ASTROPHYSICAL PROPAGATION OF VERY HIGH ENERGY PHOTONS
Authors: SHAO LIJING , MA BO-QIANG
Published: December 2010

Lorentz violation (LV) is predicted by some quantum gravity (QG) candidates, wherein the canonical energy–momentum dispersion relation, E2= p2+m2, is modified. Consequently, new phenomena beyond the standard model are predicted. In particular, the presence of LV highly affects the propagation of astrophysical photons with very high energies from distant galaxies. In this paper, we review the updating theoretical and experimental results on this topic. We classify the effects into three categories: (i) time lags between photons with different energies; (ii) a cutoff of photon flux above the threshold energy of photon decay, γ→e++e-; (iii) new patterns in the spectra of multi-TeV photons and EeV photons, due to the absorption of background lights. As we can see, the details of LV effects on astrophysical photons depend heavily on the "phase space" of LV parameters. From observational aspects, available and upcoming instruments can study these phenomena hopefully, and shed light onto LV issues and QG theories. The most recent progresses and constraints on the ultra-high energy cosmic rays (UHECRs) are also discussed.
PREPARATION AND CHARACTERIZATION OF TRANSPARENT CONDUCTIVE Ta-DOPED ITO FILMS BY ELECTRON-BEAM EVAPORATION
Authors: HUANG J. Y. , FAN G. H. , MEI T. , ZHENG S. W. , NIU Q. L. , LI S. T. , ZHANG Y.
Published: December 2010

Tantalum-doped indium tin oxide ( Ta -doped ITO) transparent conductive films are deposited on glass substrates by electron-beam evaporation. The effects of different Ta concentrations and annealing temperatures on the structural, morphologic, electrical, and optical properties of Ta -doped ITO films are investigated by X-ray diffraction (XRD), atomic force microscope (AFM), Hall measurement, and optical transmission spectroscopy. The obtained films are polycrystalline with a cubic bixbyite structure of indium oxide and preferentially oriented in the (222) crystallographic direction. The minimum resistivity of 1.54×10-4 Ω ·cm is obtained from the ITO film containing 0.2 wt% tantalum annealed at 500°C and the average optical transmittance is over 95% from 425 nm to 460 nm.
Calcium-activated K+ channels increase cell proliferation independent of K+ conductance
Authors: Millership Joanne E. , Devor Daniel C. , Hamilton Kirk L. , Balut Corina M. , Bruce Jason I. E. , Fearon Ian M.
Published: December 2010

The intermediate-conductance calcium-activated potassium channel (IK1) promotes cell proliferation of numerous cell types including endothelial cells, T lymphocytes, and several cancer cell lines. The mechanism underlying IK1-mediated cell proliferation was examined in human embryonic kidney 293 (HEK293) cells expressing recombinant human IK1 (hIK1) channels. Inhibition of hIK1 with TRAM-34 reduced cell proliferation, while expression of hIK1 in HEK293 cells increased proliferation. When HEK293 cells were transfected with a mutant (GYG/AAA) hIK1 channel, which neither conducts K+ ions nor promotes Ca2+ entry, proliferation was increased relative to mock-transfected cells. Furthermore, when HEK293 cells were transfected with a trafficking mutant (L18A/L25A) hIK1 channel, proliferation was also increased relative to control cells. The lack of functional activity of hIK1 mutants at the cell membrane was confirmed by a combination of whole cell patch-clamp electrophysiology and fura-2 imaging to assess store-operated Ca2+ entry and cell surface immunoprecipitation assays. Moreover, in cells expressing hIK1, inhibition of ERK1/2 and JNK kinases, but not of p38 MAP kinase, reduced cell proliferation. We conclude that functional K+ efflux at the plasma membrane and the consequent hyperpolarization and enhanced Ca2+ entry are not necessary for hIK1-induced HEK293 cell proliferation. Rather, our data suggest that hIK1-induced proliferation occurs by a direct interaction with ERK1/2 and JNK signaling pathways.
Soluble adenylyl cyclase mediates bicarbonate-dependent corneal endothelial cell protection
Authors: Li Shimin , Allen Kah Tan , Bonanno Joseph A.
Published: December 2010

Cyclic AMP produced from membrane receptor complex bound adenylyl cyclases is protective in corneal endothelial cells (CEC). CEC also express soluble adenylyl cyclase (sAC), which is localized throughout the cytoplasm. When activated by HCO3−, cAMP concentration ([cAMP]) increases by ∼50%. Here we ask if cAMP produced from sAC is also protective. We examined the effects of HCO3−, pH, phosphodiesterase 4 inhibition by rolipram, sAC inhibition by 2HE (2-hydroxyestradiol), and sAC small interfering RNA (siRNA) knockdown on basal and staurosporine-mediated apoptosis. HCO3− (40 mM) or 50 μM rolipram raised [cAMP] to similar levels and protected endothelial cells by 50% relative to a HCO3−-free control, whereas 2HE, which decreased [cAMP] by 40%, and H89 (PKA inhibitor) doubled the apoptotic rate. sAC expression was reduced by two-thirds in the absence of HCO3− and was reduced to 15% of control by sAC siRNA. Protection by HCO3− was eliminated in siRNA-treated cells. Similarly, caspase-3 activity and cytochrome c release were reduced by HCO3− and enhanced by 2HE or siRNA. Analysis of percent annexin V+ cells as a function of [cAMP] revealed an inverse, nonlinear relation, suggesting a protective threshold [cAMP] of 10 pmol/mg protein. Relative levels of phosphorylated cAMP response element binding protein and phosphorylated Bcl-2 were decreased in CEC treated with 2HE or siRNA, suggesting that HCO3−-dependent endogenous sAC activity can mobilize antiapoptotic signal transduction. Overall, our data suggest a new role for sAC in endogenous cellular protection.