bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural clues to the origin of refractory metal alloys as condensates of the solar nebula
Authors: HARRIES Dennis , BERG Thomas , LANGENHORST Falko , PALME Herbert
Published: October 2012

Abstract– Alloys of the refractory metals Re, Os, W, Ir, Ru, Mo, Pt, and Rh with small amounts of Fe and Ni are predicted to be one of the very first high‐temperature condensates in a cooling gas of solar composition. Recently, such alloy grains were found in acid‐resistant residues of the Murchison CM2 chondrite. We used focused ion beam (FIB) preparation to obtain electron‐transparent sections of 15 submicrometer‐sized refractory metal nuggets (RMNs) from the original Murchison residue. We studied their crystallography, microstructures, and internal compositional variations using transmission electron microscopy (TEM). Our results show that all RMNs studied have hexagonal close‐packed (hcp) crystal structures despite considerable variations of their bulk compositions. Crystallographic superstructures or signs of spinodal decomposition are absent and defect microstructures are scarce. Internally, RMNs are compositionally homogeneous, with no evidence for zoning patterns or heterogeneities due to exsolution. Many RMNs show well‐defined euhedral crystal shapes and all are nearly perfect single crystal. Our findings are consistent with a direct (near‐) equilibrium condensation of refractory metals into a single alloy at high temperature in the solar nebula as predicted by current condensation models. We suggest that this alloy is generally hcp structured due to an extended ε‐phase field in the relevant multicomponent alloy system. The high degree of structural perfection and compositional homogeneity is attributed to high defect energies, high formation temperatures, slow cooling rates, small grain sizes, and rapid internal diffusion.
The Suavjärvi impact structure, NW Russia
Authors: MASHCHAK Mikhail S. , NAUMOV Mikhail V.
Published: October 2012

Abstract– We present the geology and interpreted shock features of the Suavjärvi circular structure. Suavjärvi is a circular feature (illustrated by satellite imagery, topography, and magnetic data) located in the central part of the Karelian Craton (lat. 63°07′N, long. 33°23′E). To date, little information on the geologic and impact features of the Suavjärvi structure is available in the literature. The structure is characterized by gravity and magnetic lows and disruption of the regional magnetic fabric. In the northeastern and southwestern parts of the structure, several erosional remnants of highly disturbed rocks occur referred to as monomict and polymict megabreccia. These comprise blocks of both basement granitoids and supracrustal greenstone rocks. The impact origin of polymict megabreccia and therefore of the Suavjärvi structure is confirmed by observations of closely spaced planar microstructures at angles consistent with planes that have Miller indices indicative of impact shock effects, mostly of ω{10¯13}. The Suavjärvi is considered to be a remnant of a deeply eroded and metamorphosed impact structure, which has a diameter of 16 km and was formed during the Paleoproterozoic (older than 2.2 Ga); this is inferred from the age of the overlying volcanic‐sedimentary Jatulian sequence. Suavjärvi underwent regional metamorphism that resulted in obliteration or transformation of shock metamorphic effects. Massive sulfides occur within megabreccia; originating probably from postimpact redeposition of pre‐existing mineralization.
Disposal of unwanted medications: throw, bury, burn or just ignore?
Authors: Koshy Samuel
Published: October 2012

Objectives

The aim of this article is to highlight the relevance of proper disposal of unwanted medications.

Key findings

Proper disposal of unwanted medications is a global issue. The consequences of improper disposal are a major concern, as it has negative consequences on both human health and the environment. Pharmacists are in a key position to ensure proper disposal and reduce the generation of unwanted medications.

Conclusion

There is urgent need for awareness on a global scale, among the public and healthcare professionals, of the importance of proper disposal of unwanted medications. Research is required to assess pharmacists' attitudes and methods used for disposal from pharmacies.
Evaluation of subgingivally delivered 0.5% clarithromycin as an adjunct to nonsurgical mechanotherapy in the management of chronic periodontitis: a short‐term double blinded randomized control trial
Authors: Kathariya Rahul , Pradeep A.R. , Raghavendra N.M. , Gaikwad Rahul
Published: October 2012

Objective

As the risk involved with systemic antimicrobials (high doses, microbial resistance, adverse reactions, etc.) restricts their use and local delivery of antimicrobials into periodontal pockets improves periodontal health, this study was designed to investigate the effects of subgingivally delivered clarithromycin (CLM; 0.5%) as an adjunct to nonsurgical mechanotherapy in chronic periodontitis subjects.

Methods

Ninety‐eight patients were categorized into two treatment groups: scaling and root planing (SRP) plus 0.5% CLM (test; group 1) and SRP plus placebo (control; group 2). Clinical parameters included gingival index (GI), sulcus bleeding index (SBI), plaque index (PI), probing depth (PD), and periodontal attachment level (PAL), recorded at 4, 8 and 12 weeks. The concentration of 0.5% CLM in gingival fluid was estimated by reverse‐phase high pressure liquid chromatography. anova, the chi‐square test and the Scatterthwaite test were used for statistical analysis.

Results

Patients treated with SRP + CLM showed enhanced reductions in GI, SBI, and PD, and gains in PAL (P < 0.001) over time, as compared with the placebo group. However, no statistically significant differences were noted for PI. The mean concentration of CLM was detected in gingival crevicular fluid for up to 7 weeks, fulfilling the conditions for a controlled‐release device.

Conclusion

Adjunctive use of 0.5% CLM as a controlled drug delivery system enhanced the clinical outcome up to 3 months.
Identification of the minimal promoter for specific expression of the GABAρ1 receptor in retinal bipolar cells
Authors: Machuca‐Parra Arturo Israel , Miledi Ricardo , Martínez‐Torres Ataúlfo
Published: October 2012

γ‐aminobutyric acid (GABA)ρ receptors regulate rapid synaptic ion currents in the axon end of retinal ON bipolar neurons, acting as a point of control along the visual pathway. In the GABAρ1 subunit knock out mouse, inhibition mediated by this receptor is totally eliminated, showing its role in neural transmission in retina. GABAρ1 mRNA is expressed in mouse retina after post‐natal day 7, but little is known about its transcriptional regulation. To identify the GABAρ1 promoter, in silico analyses were performed and indicated that a 0.290‐kb fragment, flanking the 5′‐end of the GABAρ1 gene, includes putative transcription factor‐binding sites, two Inr elements, and lacks a TATA‐box. A rapid amplification of cDNA ends (RACE) assay showed three transcription start sites (TSS) clustered in the first exon. Luciferase reporter assays indicated that a 0.232‐kb fragment upstream from the ATG is the minimal promoter in transfected cell lines and in vitro electroporated retinae. The second Inr and AP1 site are important to activate transcription in secretin tumor cells (STC‐1) and retina. Finally, the 0.232‐kb fragment drives green fluorescent protein (GFP) expression to the inner nuclear layer, where bipolar cells are present. This first work paves the way for further studies of molecular elements that control GABAρ1 transcription and regulate its expression during retinal development.
What Is Graded Membership?
Authors: Decock Lieven , Douven Igor
Published: October 2012

It has seemed natural to model phenomena related to vagueness in terms of graded membership. However, so far no satisfactory answer has been given to the question of what graded membership is nor has any attempt been made to describe in detail a procedure for determining degrees of membership. We seek to remedy these lacunae by building on recent work on typicality and graded membership in cognitive science and combining some of the results obtained there with a version of the conceptual spaces framework.
Standardized Care Pathway Versus Conventional Approach in the Management of Patients Presenting with Faint at the University of Utah
Authors: SANDERS NATALIE A. , JETTER TAWNI L. , BRIGNOLE MICHELE , HAMDAN MOHAMED H.
Published: October 2012

Background

Despite the availability of guidelines, the evaluation of patients with faint continues to be inconsistent. The purpose of this study was to test the hypothesis that utilization of a new standardized‐care pathway (Faint‐Algorithm) reduces hospital admissions and improves diagnostic yield when compared to the conventional approach in the evaluation of patients with faint.

Methods

We reviewed the data of 154 consecutive patients presenting with faint to the Faint and Fall Clinic at the University of Utah (standardized group) and 100 patients previously evaluated for faint using the conventional approach (conventional group).

Results

Using a standardized approach, only 4% of patients were admitted when compared to 20% in the conventional group (P < 0.001). The rate of diagnosis at initial evaluation was similar between the groups; however, at 45 days, it was greater in the standardized group when compared to the conventional group (57% vs 45% in the total population, P = 0.09; 57% vs 39% in the outpatient subgroups, P = 0.02). The number of tests or consultations associated with additional charges was significantly lower in the standardized group when compared to the conventional group (1.9 ± 1.0 vs 2.6 ± 1.2, P = 0.001).

Conclusions

The use of a standardized approach in the evaluation of patients with faint decreased the number of hospital admissions and increased the rate of diagnosis at 45 days. This was achieved with less utilization of costly tests and consultations.
Strength Homogenization of Double-Porosity Cohesive-Frictional Solids
Authors: Ortega J. Alberto , Ulm Franz-Josef
Published: October 2012

The strength homogenization of cohesive-frictional solids influenced by the presence of two pressurized pore spaces of different characteristic sizes is addressed in this study. A two-scale homogenization model is developed based on limit analysis and the second-order method (SOM) in linear comparison composite theory, which resolves the nonlinear strength behavior through the use of linear comparison composites with optimally chosen properties. For the scale of the classical configuration of a porous solid, the formulation employs a compressible thermoelastic comparison composite to deliver closed-form expressions of strength criteria. Comparisons with numerical results reveal that the proposed homogenization estimates for drained conditions are adequate except for high triaxialities in the mean compressive strength regime. At the macroscopic scale of the double-porosity material, the SOM results are in agreement with strength criteria predicted by alternative micromechanics solutions for materials with purely cohesive solid matrices and drained conditions. The model predictions for the cohesive-frictional case show that drained strength development in granularlike composites is affected by the partitioning of porosity between micro- and macropores. In contrast, the drained strength is virtually equivalent for single- and double-porosity materials with matrix-inclusion morphologies. Finally, the second-order linear comparison composite approach confirms the applicability of an effective stress concept, previously proposed in the literature of homogenization of cohesive-frictional porous solids, for double-porosity materials subjected to similar pressures in the two pore spaces. For dissimilar pore pressures, the model analytically resolves the complex interplays of microstructure, solid properties, and volume fractions of phases, which cannot be recapitulated by the effective stress concept.
Poroelastic Analysis of Partial Freezing in Cohesive Porous Materials
Authors: Fen-Chong Teddy , Fabbri Antonin , Thiery Mickaël , Dangla Patrick
Published: October 2012

We revisit the poromechanics set up by Olivier Coussy for better understanding of the mechanical effect of partial freezing in cohesive porous materials. This approach proves to be able to quantitatively predict swelling even if the in-pore liquid does not expand when solidifying. In this case, dilation results from the so-called cryosuction process that dominates thermal shrinkage under cooling, as shown in our analysis conducted on the historical experiment run by Beaudoin and MacInnis (1974, “The Mechanism of Frost Damage in Hardened Cement Paste,” Cem. Concr. Res., 4, pp. 139–147) on benzene saturated 24-h old cement paste. Both mechanisms are also at work when freezing water saturated early age cement paste with air voids. In this case, the cryosuction process results in shrinkage and should be added to the thermal shrinkage, their respective amplitudes being temperature dependent but, a priori, of the same order of magnitude.
Impact of the Kinetics of Salt Crystallization on Stone Damage During Rewetting/Drying and Humidity Cycling
Authors: Desarnaud Julie , Bertrand François , Shahidzadeh-Bonn Noushine
Published: October 2012

In this study, we show that the key to understand why the same salt can cause damage in some conditions and not in others is the kinetics of crystallization. We present experiments assessing the impact of the recrystallization dynamics of sodium sulfate on damage observed in sandstone after repeated cycles of rewetting/drying and humidification/drying. Macroscopic and microscopic scale experiments using magnetic resonance imaging and phase contrast microscopy demonstrate that sodium sulfate that has both hydrated and anhydrous phases can lead to severe damage in sandstone during rewetting/drying cycles, but not during humidity cycling. During rewetting (a rapid process) in regions (pores) that are highly concentrated in salt, anhydrous microcrystals dissolve only partially, giving rise to a heterogeneous salt solution that is supersaturated with respect to the hydrated phase. The remaining anhydrous crystals then act as seeds for the formation of large amounts of hydrated crystals, creating grape-like structures that expand rapidly. These clusters can generate stresses larger than the tensile strength of the stone, leading to damage. On the other hand, with humidification (a slow process) and after complete deliquescence of salt crystals, the homogeneous sodium sulfate solution can reach high concentrations during evaporation without any nucleation, favoring the formation of isolated anhydrous crystals (thenardite). The crystallization of the anhydrous salt generates only very small stresses compared to the hydrated clusters and therefore causes hardly any damage to the stone.
Anisotropic Porochemoelectroelastic Solution for an Inclined Wellbore Drilled in Shale
Authors: Tran Minh H. , Abousleiman Younane N.
Published: October 2012

The porochemoelectroelastic analytical models have been used to describe the response of chemically active and electrically charged saturated porous media such as clay soils, shales, and biological tissues. However, existing studies have ignored the anisotropic nature commonly observed on these porous media. In this work, the anisotropic porochemoelectroelastic theory is presented. Then, the solution for an inclined wellbore drilled in transversely isotropic shale formations subjected to anisotropic far-field stresses with time-dependent down-hole fluid pressure and fluid activity is derived. Numerical examples illustrating the combined effects of porochemoelectroelastic behavior and anisotropy on wellbore responses are also included. The analysis shows that ignoring either the porochemoelectroelastic effects or the formation anisotropy leads to inaccurate prediction of the near-wellbore pore pressure and effective stress distributions. Finally, wellbore responses during a leak-off test conducted soon after drilling are analyzed to demonstrate the versatility of the solution in simulating complex down-hole conditions.
The Simultaneous Role of an Alveolus as Flow Mixer and Flow Feeder for the Deposition of Inhaled Submicron Particles
Authors: Henry F. S. , Haber S. , Haberthür D. , Filipovic N. , Milasinovic D. , Schittny J. C. , Tsuda A.
Published: October 2012

In an effort to understand the fate of inhaled submicron particles in the small sacs, or alveoli, comprising the gas-exchange region of the lung, we calculated the flow in three-dimensional (3D) rhythmically expanding models of alveolated ducts. Since convection toward the alveolar walls is a precursor to particle deposition, it was the goal of this paper to investigate the streamline maps’ dependence upon alveoli location along the acinar tree. On the alveolar midplane, the recirculating flow pattern exhibited closed streamlines with a stagnation saddle point. Off the midplane we found no closed streamlines but nested, funnel-like, spiral, structures (reminiscent of Russian nesting dolls) that were directed towards the expanding walls in inspiration, and away from the contracting walls in expiration. These nested, funnel-like, structures were surrounded by air that flowed into the cavity from the central channel over inspiration and flowed from the cavity to the central channel over expiration. We also found that fluid particle tracks exhibited similar nested funnel-like spiral structures. We conclude that these unique alveolar flow structures may be of importance in enhancing deposition. In addition, due to inertia, the nested, funnel-like, structures change shape and position slightly during a breathing cycle, resulting in flow mixing. Also, each inspiration feeds a fresh supply of particle-laden air from the central channel to the region surrounding the mixing region. Thus, this combination of flow mixer and flow feeder makes each individual alveolus an effective mixing unit, which is likely to play an important role in determining the overall efficiency of convective mixing in the acinus.
Investigation of the In Vitro Culture Process for Skeletal-Tissue-Engineered Constructs Using Computational Fluid Dynamics and Experimental Methods
Authors: Hossain Md. Shakhawath , Chen X. B. , Bergstrom D. J.
Published: October 2012

The in vitro culture process via bioreactors is critical to create tissue-engineered constructs (TECs) to repair or replace the damaged tissues/organs in various engineered applications. In the past, the TEC culture process was typically treated as a black box and performed on the basis of trial and error. Recently, computational fluid dynamics (CFD) has demonstrated its potential to analyze the fluid flow inside and around the TECs, therefore, being able to provide insight into the culture process, such as information on the velocity field and shear stress distribution that can significantly affect such cellular activities as cell viability and proliferation during the culture process. This paper briefly reviews the CFD and experimental methods used to investigate the in vitro culture process of skeletal-type TECs in bioreactors, where mechanical deformation of the TEC can be ignored. Specifically, this paper presents CFD modeling approaches for the analysis of the velocity and shear stress fields, mass transfer, and cell growth during the culture process and also describes various particle image velocimetry (PIV) based experimental methods to measure the velocity and shear stress in the in vitro culture process. Some key issues and challenges are also identified and discussed along with recommendations for future research.
Quantifying Effect of Intraplaque Hemorrhage on Critical Plaque Wall Stress in Human Atherosclerotic Plaques Using Three-Dimensional Fluid-Structure Interaction Models
Authors: Huang Xueying , Yang Chun , Canton Gador , Ferguson Marina , Yuan Chun , Tang Dalin
Published: October 2012

Recent magnetic resonance studies have indicated that intraplaque hemorrhage (IPH) may accelerate plaque progression and play an important role in plaque destabilization. However, the impact of hemorrhage on critical plaque wall stress (CPWS) and strain (CPWSn) has yet to be determined. The objective of this study was to assess the effect of the presence and size of IPH on wall mechanics. The magnetic resonance image (MRI) of one patient with histology-confirmed IPH was used to build eight 3D fluid-structure interaction (FSI) models by altering the dimensions of the existing IPH. As a secondary end point, the combined effect of IPH and fibrous cap thickness (FCT) was assessed. A volume curve fitting method (VCFM) was applied to generate a mesh that would guarantee numerical convergence. Plaque wall stress (PWS), strain (PWSn), and flow shear stress (FSS) were extracted from all nodal points on the lumen surface for analysis. Keeping other conditions unchanged, the presence of intraplaque hemorrhage caused a significant increase (27.5%) in CPWS; reduced FCT caused an increase of 22.6% of CPWS. Similar results were found for CPWSn. Furthermore, combination of IPH presence, reduced FCT, and increased IPH volume caused an 85% and 75% increase in CPWS and CPWSn, respectively. These results show that intraplaque hemorrhage has considerable impact on plaque stress and strain conditions and accurate quantification of IPH could lead to more accurate assessment of plaque vulnerability. Large-scale studies are needed to further validate our findings.
Chemistry of Cu(acac)2 on Ni(110) and Cu(110) surfaces: Implications for atomic layer deposition processes
Authors: Ma Qiang , Zaera Francisco
Published: October 2012

The thermal chemistry of copper(II)acetylacetonate, Cu(acac)2, on Ni(110) and Cu(110) single-crystal surfaces was probed under vacuum by using x-ray photoelectron spectroscopy (XPS) and temperature programmed desorption (TPD). Some data for acetylacetone (Hacac, CH3COCH2COCH3) adsorbed on Ni(110) are also reported as reference. Chemical transformations were identified in several steps covering a temperature range from 150 K to at least 630 K. The desorption of Hacac and a 3-oxobutanal (CH3COCH2CHO) byproduct was observed first at 150 and 180 K on Ni(110) and at 160 and 185 K on Cu(110), respectively. Partial loss of the acetylacetonate (acac) ligands and a likely change in adsorption geometry are seen next, with the possible production of HCu(acac), which desorbs at 200 and 235 K from the nickel and copper surfaces, respectively. Molecular Cu(acac)2 desorption is observed on both surfaces at approximately 300 K, probably from recombination of Cu(acac) and acac surface species. The remaining copper atoms on the surface lose their remaining acac ligands to the substrate and become reduced directly to metallic copper. At the same time, the organic ligands follow a series of subsequent surface reactions, probably involving several C–C bond-scissions, to produce other fragments, additional Hacac and HCu(acac) in the gas phase in the case of the copper surface, and acetone on nickel. A significant amount of acac must nevertheless survive on the surface to high temperatures, because Hacac peaks are seen in the TPD at about 515 and 590 K and the C 1s XPS split associated with acac is seen up to close to 500 K. In terms of atomic layer deposition processes, this suggests that cycles could be design to run at such temperatures as long as an effective hydrogenation agent is used as the second reactant to remove the surface acac as Hacac. Only a small fraction of carbon is left behind on Ni after heating to 800 K, whereas more carbon and additional oxygen remains on the surface in the case of Cu.
Performance comparison of high quantum efficiency and normal quantum efficiency photomultiplier tubes and position sensitive photomultiplier tubes for high resolution PET and SPECT detectors
Authors: Yamamoto Seiichi , Watabe Hiroshi , Kato Katsuhiko , Hatazawa Jun
Published: October 2012

Purpose:

Recently, photomultiplier tubes (PMTs) and position sensitive PMTs (PSPMTs) with higher quantum efficiencies (HQE) have been developed. However, it remains unclear whether they actually improve such performances as the energy and spatial resolution for PET and SPECT detectors.

Methods:

The authors evaluated the quantum efficiencies (QEs) for PMTs and PSPMTs and measured the energy resolution of a 3‐in. round HQE PMT combined with various scintillators and compared the results with a conventional normal quantum efficiency (NQE) PMT of the same type. The authors also measured the position and energy performance of a 2‐in. square HQE PSPMT combined with scintillator blocks and compared them with a NQE PSPMT of the same size.

Results:

The energy resolution of the 3‐in. round HQE PMT showed higher energy resolution than the NQE with all scintillators. The improvement of the energy resolution was smaller, for all measurements, than the expected value from the quantum efficiency of the PMT but was higher for the scintillators with smaller light outputs. The energy and position performance of the HQE PSPMT based block detectors showed higher position and energy performance than those with NQE.

Conclusions:

From these results, the authors conclude that both HQE PMT and PSPMT contribute to improve the energy and position performance for PET and SPECT detectors. Significant performance improvements will be expected in PET and SPECT systems by the use of the HQE PMTs or PSPMTs.
Quality assurance and independent dosimetry for an intraoperative x‐ray device
Authors: Eaton D. J.
Published: October 2012

Purpose:

Quality assurance is an essential component of accurate and safe radiotherapy delivery, and should include measurements which are independent of manufacturer‐provided calibration. However, the physical and dosimetric properties of the INTRABEAM compact mobile 50 kV x‐ray source are different from conventional kilovoltage therapy units and few reports describe methods for independent checks, frequencies, or tolerances for quality assurance tests.

Methods:

Based on the available evidence and local experience, methods are described for determination of the key dosimetric parameters: beam quality, output, isotropy, and depth doses. Internal system checks are also described, along with measurements of long‐term stability.

Results:

A small volume parallel plate ionization chamber in a liquid water tank is the gold standard for measurements with this unit, but solid water‐equivalent materials, thermoluminescent dosimeters and radiochromic film can all be used as practical alternatives with an accuracy of 5%–10%. The main cause of measurement uncertainty is positioning of the detector in the steep dose gradient, but energy dependence should also be considered.

Conclusions:

A quality assurance schedule with suggested tolerances is proposed, which includes both internal tests, before each treatment and on a monthly basis, and independent tests every year or after servicing or recalibration.
Response to Comment on “Conspecific Negative Density Dependence and Forest Diversity”
Authors: Johnson Daniel J. , Beaulieu Wesley T. , Bever James D. , Clay Keith
Published: October 2012

Dickie, Hurst, and Bellingham question some of the methods of our recent study on conspecific density dependence in forests. Here, we reanalyze our data set with the inclusion of joint absence plots of each species. We find that our results are robust to further analyses and that patterns of abundance and richness correlate with our measure of density dependence, supporting our original conclusions.
Measuring Solar Magnetism
Authors: de Wijn Alfred G.
Published: October 2012

How do you go about accurately measuring the magnetic field in the solar atmosphere?
Did Australopiths Climb Trees?
Authors: Larson Susan
Published: October 2012

The shoulder bones of a juvenile australopith resemble those of extant apes, suggesting that tree climbing continued to be important for these bipedal early human ancestors.
The Mood of a Worm
Authors: Emmons Scott W.
Published: October 2012

The behavioral effects of two hormones on the human brain are similar to those of a neuropeptide on sensory neurons in the worm.
Decoding the Neuronal Tower of Babel
Authors: McBain Chris J.
Published: October 2012

Identification of a postsynaptic protein in the hippocampus reveals how neurotransmitter release from one neuron is tailored to different target cells.
Social Media and the Elections
Authors: Metaxas Panagiotis T. , Mustafaraj Eni
Published: October 2012

Manipulation of social media affects perceptions of candidates and compromises decision-making.
Can Intellectual Property Save Drug Development?
Authors: FitzGerald Garret A.
Published: October 2012

Continually refining the focus of intellectual property during the drug development process should encourage productive collaborations and expedite the availability of new therapies.
Thriving on Common Ground
Authors: Alberts Bruce
Published: October 2012

A major U.S. election is imminent, with voting on 6 November (see the special news section on p. 456). A central issue dividing the two major political parties is how best to allocate scarce resources, as the country attempts to reduce its budget deficit without jeopardizing national prosperity. In last week's Editorial, John Hamre, a former U.S. Deputy Secretary of Defense, described how this challenge, coupled with the polarization of U.S. politics and a dogmatic refusal to compromise, has created “one of the most perilous conditions that I can remember in my professional life.”
*
To move forward, it is important to identify general principles for a successful future on which essentially all Americans can agree—principles that are also relevant for other nations.
An Adenovirus-Vectored Nasal Vaccine Confers Rapid and Sustained Protection against Anthrax in a Single-Dose Regimen
Authors: Zhang Jianfeng , Jex Edward , Feng Tsungwei , Sivko Gloria S. , Baillie Leslie W. , Goldman Stanley , Van Kampen Kent R. , Tang De-chu C.
Published: October 2012

Bacillus anthracis
is the causative agent of anthrax, and its spores have been developed into lethal bioweapons. To mitigate an onslaught from airborne anthrax spores that are maliciously disseminated, it is of paramount importance to develop a rapid-response anthrax vaccine that can be mass administered by nonmedical personnel during a crisis. We report here that intranasal instillation of a nonreplicating adenovirus vector encoding
B. anthracis
protective antigen could confer rapid and sustained protection against inhalation anthrax in mice in a single-dose regimen in the presence of preexisting adenovirus immunity. The potency of the vaccine was greatly enhanced when codons of the antigen gene were optimized to match the tRNA pool found in human cells. In addition, an adenovirus vector encoding lethal factor can confer partial protection against inhalation anthrax and might be coadministered with a protective antigen-based vaccine.
Antibody Responses to Mycobacterial Antigens in Children with Tuberculosis: Challenges and Potential Diagnostic Value
Authors: Achkar Jacqueline M. , Ziegenbalg Anke
Published: October 2012

The identification of easily detectable biomarkers for active tuberculosis (TB) is a global health priority. Such biomarkers would be of particular value in childhood TB, which poses greater diagnostic challenges than adult TB. Serum antibodies can be detected by simple formats that provide extremely rapid results. However, attempts to develop accurate serodiagnostic tests for TB have been unsuccessful. Whereas antibody responses to mycobacterial antigens in adult TB have been studied extensively and reviewed, the same cannot be said for serologic data in pediatric populations. Here we appraise studies on serological responses in childhood TB and discuss findings and limitations in the context of the developing immune system, the age range, and the spectrum of TB manifestations. We found that the antibody responses to mycobacterial antigens in childhood TB can vary widely, with sensitivities and specificities ranging from 14% to 85% and from 86% to 100%, respectively. We conclude that the limitations in serodiagnostic studies of childhood TB are manifold, thereby restricting the interpretation of currently available data. Concerns about the methodology used in published studies suggest that conclusions about the eventual value of serodiagnosis cannot be made at this time. However, the available data suggest a potential adjunctive value for serology in the diagnosis of childhood TB. Despite the difficulties noted in this field, there is optimism that the application of novel antigens and the integration of those factors which contribute to the serological responses in childhood TB can lead to useful future diagnostics.
Evaluation of the Speed-oligo Direct Mycobacterium tuberculosis Assay for Molecular Detection of Mycobacteria in Clinical Respiratory Specimens
Authors: Lara-Oya Ana , Mendoza-Lopez Pablo , Rodriguez-Granger Javier , Fernández-Sánchez Ana María , Bermúdez-Ruiz María Pilar , Toro-Peinado Inmaculada , Palop-Borrás Begoña , Navarro-Marí Jose María , Martínez-Lirola Miguel José
Published: October 2012

We present the first evaluation of a novel molecular assay, the Speed-oligo Direct
Mycobacterium tuberculosis
(SO-DMT) assay, which is based on PCR combined with a dipstick for the detection of mycobacteria and the specific identification of
M. tuberculosis
complex (MTC) in respiratory specimens. A blind evaluation was carried out in two stages: first, under experimental conditions on convenience samples comprising 20 negative specimens, 44 smear- and culture-positive respiratory specimens, and 11 sputa inoculated with various mycobacterium-related organisms; and second, in the routine workflow of 566 fresh respiratory specimens (4.9% acid-fast bacillus [AFB] smear positives, 7.6% MTC positives, and 1.8% nontuberculous mycobacteria [NTM] culture positives) from two
Mycobacterium
laboratories. SO-DMT assay showed no reactivity in any of the mycobacterium-free specimens or in those with mycobacterium-related organisms. Compared to culture, the sensitivity in the selected smear-positive specimens was 0.91 (0.92 for MTC and 0.90 for NTM), and there was no molecular detection of NTM in a tuberculosis case or vice versa. With respect to culture and clinical data, the sensitivity, specificity, and positive and negative predictive values for the SO-DMT system in routine specimens were 0.76 (0.93 in smear positives [1.0 for MTC and 0.5 for NTM] and 0.56 in smear negatives [0.68 for MTC and 0.16 for NTM]), 0.99, 0.85 (1.00 in smear positives and 0.68 in smear negatives), and 0.97, respectively. Molecular misidentification of NTM cases occurred when testing 2 gastric aspirates from two children with clinically but not microbiologically confirmed lung tuberculosis. The SO-DMT assay appears to be a fast and easy alternative for detecting mycobacteria and differentiating MTC from NTM in smear-positive respiratory specimens.
New Proteins for a New Perspective on Syphilis Diagnosis
Authors: Smith Brenden C. , Simpson Yvonne , Morshed Muhammad G. , Cowen Laura L. E. , Hof Rebecca , Wetherell Charmaine , Cameron Caroline E.
Published: October 2012

Syphilis is a sexually transmitted disease caused by
Treponema pallidum
subsp.
pallidum
; it can be effectively treated with penicillin yet remains prevalent worldwide, due in part to the shortcomings of current diagnostic tests. Here we report the production of soluble recombinant versions of three novel diagnostic candidate proteins, Tp0326, Tp0453, and a Tp0453-Tp0326 chimera. The sensitivities of these recombinant proteins were assessed by screening characterized serum samples from primary, secondary, and latent stages of infection (
n
= 169). The specificities were assessed by screening false positives identified with the standard diagnostic testing algorithm (
n
= 21), samples from patients with potentially cross-reactive infections (
Leptospira
spp.,
Borrelia burgdorferi
,
Helicobacter pylori
, Epstein-Barr virus, hepatitis B virus, hepatitis C virus, or cytomegalovirus) (
n
= 38), and samples from uninfected individuals (
n
= 11). The sensitivities of Tp0326, Tp0453, and the Tp0453-Tp0326 chimera were found to be 86%, 98%, and 98%, respectively, and the specificities were 99%, 100%, and 99%. In a direct comparison, the Captia syphilis (
T. pallidum
)-G enzyme immunoassay (Trinity Biotech) was used to screen the same serum samples and was found to have a sensitivity of 98% and a specificity of 90%. In particular, Tp0453 and the chimera exhibited superior accuracy in classifying analytical false-positive samples (100%, compared to 43% for the Captia assay). These findings identify Tp0453 and the Tp0453-Tp0326 chimera as novel syphilis-specific diagnostic candidates that surpass the performance of a currently available diagnostic enzyme immunoassay test for syphilis and that allow accurate detection of all stages of infection.
Sensitivity of the ISO 6579:2002/Amd 1:2007 Standard Method for Detection of Salmonella spp. on Mesenteric Lymph Nodes from Slaughter Pigs
Authors: Mainar-Jaime R. C. , Andrés S. , Vico J. P. , San Román B. , Garrido V. , Grilló M. J.
Published: October 2012

The ISO 6579:2002/Amd 1:2007 (ISO) standard has been the bacteriological standard method used in the European Union for the detection of
Salmonella
spp. in pig mesenteric lymph nodes (MLN), but there are no published estimates of the diagnostic sensitivity (Se) of the method in this matrix. Here, the Se of the ISO (Se
ISO
) was estimated on 675 samples selected from two populations with different
Salmonella
prevalences (14 farms with a ≥20% prevalence and 13 farms with a <20% prevalence) and through the use of latent-class models in concert with Bayesian inference, assuming 100% ISO specificity, and an
invA
-based PCR as the second diagnostic method. The Se
ISO
was estimated to be close to 87%, while the sensitivity of the PCR reached up to 83.6% and its specificity was 97.4%. Interestingly, the bacteriological reanalysis of 33 potential false-negative (PCR-positive) samples allowed isolation of 19 (57.5%) new
Salmonella
strains, improving the overall diagnostic accuracy of the bacteriology. Considering the usual limitations of bacteriology regarding Se, these results support the adequacy of the ISO for the detection of
Salmonella
spp. from MLN and also that of the PCR-based method as an alternative or complementary (screening) test for the diagnosis of pig salmonellosis, particularly considering the cost and time benefits of the molecular procedure.
Development of a Peptide Nucleic Acid Probe to Trichosporon Species and Identification of Trichosporonosis by Use of
In Situ
Hybridization in Formalin-Fixed and Paraffin-Embedded (FFPE) Sections
Authors: Shinozaki Minoru , Okubo Yoichiro , Sasai Daisuke , Nakayama Haruo , Murayama Somay Yamagata , Ide Tadashi , Wakayama Megumi , Ishiwatari Takao , Tochigi Naobumi , Nemoto Tetsuo , Shibuya Kazutoshi
Published: October 2012

In order to identify
Trichosporon
species in formalin-fixed and paraffin-embedded sections from which visual discrimination of non-
glabrata Candida
species is mostly ineffective but critical for the choice of antifungals, we tested the usefulness of a newly designed peptide nucleic acid probe (PNA) for
in situ
hybridization (ISH). Results confirmed the usefulness of ISH with our PNA probe in identifying
Trichosporon
species from
Candida albicans.
Characterizing the Picornavirus Landscape among Synanthropic Nonhuman Primates in Bangladesh, 2007 to 2008
Authors: Oberste M. Steven , Feeroz Mohammed M. , Maher Kaija , Nix W. Allan , Engel Gregory A. , Hasan Kamrul M. , Begum Sajeda , Oh Gunwha , Chowdhury Anwarul H. , Pallansch Mark A. , Jones-Engel Lisa
Published: October 2012

The term synanthropic describes organisms that thrive in human-altered habitats. Where synanthropic nonhuman primates (NHP) share an ecological niche with humans, cross-species transmission of infectious agents can occur. In Bangladesh, synanthropic NHP are found in villages, densely populated cities, religious sites, and protected forest areas. NHP are also kept as performing monkeys and pets. To investigate possible transmission of enteric picornaviruses between humans and NHP, we collected fecal specimens from five NHP taxa at16 locations in Bangladesh during five field sessions, from January 2007 to June 2008. Specimens were screened using real-time PCR assays for the generaEnterovirus,Parechovirus, andSapelovirus; PCR-positive samples were typed by VP1 sequencing. To compare picornavirus diversity between humans and NHP, the same assays were applied to 211 human stool specimens collected in Bangladesh in 2007 to 2008 for acute flaccid paralysis surveillance. Picornaviruses were detected in 78 of 677 (11.5%) NHP fecal samples. Twenty distinct human enterovirus (EV) serotypes, two bovine EV types, six human parechovirus serotypes, and one virus related to Ljungan virus were identified. Twenty-five additional enteroviruses and eight parechoviruses could not be typed. Comparison of the picornavirus serotypes detected in NHP specimens with those detected in human specimens revealed considerable overlap. Strikingly, no known simian enteroviruses were detected among these NHP populations. In conclusion, enteroviruses and parechoviruses may be transmitted between humans and synanthropic NHP in Bangladesh, but the directionality of transmission is unknown. These findings may have important implications for the health of both human and NHP populations.
SUMO-Conjugating Enzyme E2 UBC9 Mediates Viral Immediate-Early Protein SUMOylation in Crayfish To Facilitate Reproduction of White Spot Syndrome Virus
Authors: Chen An-Jing , Gao Lu , Wang Xian-Wei , Zhao Xiao-Fan , Wang Jin-Xing
Published: October 2012

Successful viruses have evolved superior strategies to escape host defenses or exploit host biological pathways. Most of the viral immediate-early (
ie
) genes are essential for viral infection and depend solely on host proteins; however, the molecular mechanisms are poorly understood. In this study, we focused on the modification of viral IE proteins by the crayfish small ubiquitin-related modifier (SUMO) and investigated the role of SUMOylation during the viral life cycle. SUMO and SUMO ubiquitin-conjugating enzyme 9 (UBC9) involved in SUMOylation were identified in red swamp crayfish (
Procambarus clarkii
). Both
SUMO
and
UBC9
were upregulated in crayfish challenged with white spot syndrome virus (WSSV). Replication of WSSV genes increased in crayfish injected with recombinant SUMO or UBC9, but injection of mutant SUMO or UBC9 protein had no effect. Subsequently, we analyzed the mechanism by which crayfish SUMOylation facilitates WSSV replication. Crayfish UBC9 bound to all three WSSV IE proteins tested, and one of these IE proteins (WSV051) was covalently modified by SUMO
in vitro
. The expression of viral
ie
genes was affected and that of late genes was significantly inhibited in
UBC9
-silenced or
SUMO
-silenced crayfish, and the inhibition effect was rescued by injection of recombinant SUMO or UBC9. The results of this study demonstrate that viral IE proteins can be modified by crayfish SUMOylation, prompt the expression of viral genes, and ultimately benefit WSSV replication. Understanding of the mechanisms by which viruses exploit host components will greatly improve our knowledge of the virus-host “arms race” and contribute to the development of novel methods against virulent viruses.
Transcriptional Profiling of Experimental CD8+Lymphocyte Depletion in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239
Authors: Bosinger Steven E. , Jochems Simon P. , Folkner Kathryn A. , Hayes Timothy L. , Klatt Nichole R. , Silvestri Guido
Published: October 2012

CD8+T cells inhibit virus replication in SIV-infected rhesus macaques. However, it is unclear to what extent the viral suppression mediated by CD8+T cells reflects direct killing of infected cells as opposed to indirect, noncytolytic mechanisms. In this study, we used functional genomics to investigate noncytolytic mechanisms ofin vivoviral suppression mediated by CD8+lymphocytes. Eight chronically SIVmac239-infected rhesus macaques underwent CD8+lymphocyte depletion, and RNA from whole blood was obtained prior to depletion, during the nadir of CD8+cell depletion, and after CD8+lymphocyte numbers had rebounded. We observed significant downregulation of the expression of genes encoding factors that can suppress SIV replication, including the CCR5-binding chemokine CCL5/RANTES and CCL4 and several members of the tripartite motif-containing (TRIM) family. Surprisingly, we also noted a strong, widespread downregulation of α- and θ-defensins with anti-HIV activity, which are not expressed by CD8+T cells. After cessation of depleting antibody treatment, we observed induction of a transcriptional signature indicative of B lymphocyte activation. Validation experiments demonstrated that animals during this period had elevated levels of B cells coupled with higher expression of the proliferative marker Ki67, indicating that CD8+depletion triggered a potent expansion of B cell numbers. Collectively, these data identify antiviral pathways perturbed byin vivoCD8+T cell depletion that may contribute to noncytolytic control of SIV replication.
Lymphotoxin Alpha-Deficient Mice Clear Persistent Rotavirus Infection after Local Generation of Mucosal IgA
Authors: Lopatin Uri , Blutt Sarah E. , Conner Margaret E. , Kelsall Brian L.
Published: October 2012

Rotavirus is a major cause of pediatric diarrheal illness worldwide. To explore the role of organized intestinal lymphoid tissues in infection by and immunity to rotavirus, lymphotoxin alpha-deficient (LTα−/−) mice that lack Peyer's patches and mesenteric lymph nodes were orally infected with murine rotavirus. Systemic rotavirus was cleared within 10 days in both LTα−/−and wild-type mice, and both strains developed early and sustained serum antirotavirus antibody responses. However, unlike wild-type mice, which resolved the intestinal infection within 10 days, LTα−/−mice shed fecal virus for approximately 50 days after inoculation. The resolution of fecal virus shedding occurred concurrently with induction of intestinal rotavirus-specific IgA in both mouse strains. Induction of intestinal rotavirus-specific IgA in LTα−/−mice correlated with the (late) appearance of IgA-producing plasma cells in the small intestine. This, together with the absence of rotavirus-specific serum IgA, implies that secretory rotavirus-specific IgA was produced locally. These findings indicate that serum IgG responses are insufficient and imply that local intestinal IgA responses are important for the clearance of rotavirus from intestinal tissues. Furthermore, they show that while LTα-dependent lymphoid tissues are important for the generation of IgA-producing B cells in the intestine, they are not absolutely required in the setting of rotavirus infection. Moreover, the induction of local IgA-producing B cell responses can occur late after infection and in an LTα-independent manner.