bluuebunny/crossref_metadata_2025 huggingface dataset:
Orpheus and Jupiter in the limelight: Farinelli and Caffarelli share the stage
Authors: Desler Anne
Published: August 2010

The two male sopranos Carlo Broschi Farinelli (17051782) and Gaetano Majorano Caffarelli (17101783) shared many similarities: the two most prominent exponents of the new, virtuosic Neapolitan style of singing were close in age, had a very similar educational background having studied
with Nicolo Porpora in Naples, and quickly climbed the career ladder to take only primo uomo roles. However, the singers were at very different points in their respective careers at the time of the productions in which they appeared together on stage, namely Siroe (Metastasio-Hasse)
at the Teatro Malvezzi in Bologna in 1733 and Merope (Zeno-Giacomelli), Artaserse (Metastasio, pasticcio) and Berenice (Salvi-Araja) at the Teatro San Grisostomo in Venice in 1734. Farinelli had already achieved international fame and was generally held to be the greatest
singer in Italy, whereas the slightly younger Caffarelli was still in the process of establishing himself at the very top, but loath to take secondary roles any more. As a result, their relationship was strained, according to Farinelli's correspondance with Count Sicinio Pepoli. The measures
Caffarelli took in Venice to challenge Farinelli's superiority apparently backfired, and contributed to the disastrous premiere of the first opera of the carnival Merope, which consequently was replaced at short notice with an Artaserse pasticcio with music by Hasse and Vinci.
An analysis of the two singers' roles in the operas in which they collaborated gives insights into mid-eighteenth-century opera production, and reveals both the dramatic and musical reasons for Farinelli's impact and popularity with the audience and Caffarelli's failure to outshine his older
colleague.
Musical semiotics in action: applying and debating Hatten's semiotics in a musico-dramatic context
Authors: Curry Ben
Published: August 2010

Robert Hatten's work on musical meaning and the classical style has become widely respected amongst music scholars. Hatten has applied theories of markedness and correlation almost exclusively to instrumental music, and one of the primary aims of this article is to investigate the usefulness of his analytical approach in the context of opera by way of an analysis of the opening section of the first duet in Act 3 of Mozart'sLe nozze di Figaro. Further to this aim, this article looks to explore the relationship of Hatten's work with the tradition of music analysis, thereby engaging with Scott Burnham's assertion that Hatten's work can be related to a wider shift in musicology away from theFormenlehretradition, which increasingly tended to treat [sonata] form ahistorically towards treatments of form that highlight a play of conventions (Burnham 2002: 903). This engagement will be carried out, in part, by reflecting on the analytical findings below with particular reference to the relationship they open up between libretto and music. This will, in turn, offer insight into wider musicological questions concerning the usefulness and limitations of formalist analysis in general. The article begins with a brief introduction to Hatten's application of markedness theory.
Evaluating the benefits of mammographic breast cancer screening
Authors: Kullmann Tamás , Misset Jean-Louis
Published: August 2010

Világszerte és Magyarországon is az egyik legelterjedtebb daganatoshalálozás-megelőzési program a mammográfiás emlőszűrés. Néhány évvel a szűrőprogram nemzetközi bevezetését követően az emlőrák okozta halálozás, majd az emlőrák előfordulása is csökkenni kezdett. A kedvező fordulatban a mammográfia által betöltött szerep jelentősége nem ismert. Egy szűrőprogram nyeresége többféle szempont szerint mérlegelhető. Egy figyelmen kívül hagyott mutató, az átlagos élettartam-nyereség más rendelkezésre álló adatokból kiszámítható. Mammográfiás szűrés esetén a nyereség korosztálytól függően legfeljebb 1–3 hét.
Hydraulic conductivity changes of a low-plasticity till subjected to freeze–thaw cycles
Authors: KONRAD J.-M.
Published: August 2010

This paper examines the influence of several freeze–thaw cycles on the hydraulic conductivity changes of a glacial till from Péribonka in Quebec, Canada. Samples reconstituted by consolidation of a slurry and by compaction at dry of optimum conditions were subjected to closed freezing and thaw as well as constant-head permeability tests. For saturated consolidated samples, the relationship between the logarithm of hydraulic conductivity and void ratio was linear for both unfrozen and thawed states. At a given void ratio, the increase of the hydraulic conductivity of the thawed soil was larger for compacted and unsaturated samples than for saturated consolidated samples. Actual freeze–thaw-induced hydraulic conductivity changes, however, may be offset by a decrease in void ratio during thaw consolidation. A general framework considering void ratio, water content, stress and hydraulic conductivity relationships is presented for Péribonka glacial till.
One-dimensional consolidation theories for layered soil and coupled and uncoupled solutions by the finite-element method
Authors: HUANG J. , GRIFFITHS D.V.
Published: August 2010

One-dimensional consolidation theories for layered soil have been re-examined. Coupled (settlement and excess pore pressure), uncoupled (excess pore pressure only) and the classical Terzaghi equation are solved by the finite-element method. By accounting only for changes in the coefficient of consolidation (cv), the classical Terzaghi approach is unable to satisfy the flow continuity conditions at the interface between layers.
Compression behaviour of reconstituted soils at high initial water contents
Authors: HONG Z.-S. , YIN J. , CUI Y.-J.
Published: August 2010

Oedometer tests starting from a very small effective vertical stress of 0·5 kPa were performed on three reconstituted clays with different liquid limits. The soils were prepared at various initial water contents, ranging from 0·7 to 2·0 times their corresponding liquid limits. It is observed that the e–log [Formula: see text] compression curves show an inverse ‘S' shape due to suction pressure resisting deformation, similar to that of soft natural clays caused by consolidation yield stress. The suction pressure [Formula: see text] of the reconstituted clays can be correlated with the ratio of initial void ratio to void ratio at liquid limit e0/eL. The suction pressure curve defined by a unique relationship between suction pressure [Formula: see text] and the normalised void ratio at suction pressure es/eLis also proposed to distinguish between the pre-suction and the post-suction states. In addition, Burland's concept of the intrinsic compression line is adopted for correlating the compression curves of various reconstituted clays at high initial water contents. It has been found that the void index is a powerful parameter for normalising the compression curves in the post-suction state. Nevertheless, it seems that Burland's intrinsic compression line slightly underestimates the void index at the low stresses considered in this study. An extended intrinsic compression line is then derived in order to better fit the data for stresses lower than 25 kPa.
Development of a generalised formula for dynamic active earth pressure
Authors: KIM W.-C. , PARK D. , KIM B.
Published: August 2010

The Mononobe–Okabe method is widely used in practice to estimate dynamic active earth pressure. The method, derived from Coulomb's theory, cannot account for the effect of cohesion and hence cannot be used for a cohesive backfill. In addition, the effect of wall adhesion and external load cannot be taken into account. This paper develops a new general formula for dynamic active earth pressure on a yielding wall. The strength of the formula is that it can take into account the effects of cohesion, wall adhesion and external load on dynamic active pressure, while remaining simple in form. The dynamic earth pressures calculated by the proposed formula, the Mononobe–Okabe method, and the graphical solution are compared for validation. The comparisons demonstrate the accuracy of the proposed formula. The formula is used in a parametric study to investigate the influence of cohesion, wall adhesion and external load. This study shows that the additional terms can significantly influence the calculated dynamic active earth pressure.
Yielding and plastic behaviour of Boom clay
Authors: SULTAN N. , CUI Y.-J. , DELAGE P.
Published: August 2010

An underground research laboratory (URL) has been excavated in a deposit of Boom clay at a depth of 223 m by the SCK-CEN Belgian organisation near the city of Mol. This URL is devoted to research into nuclear waste disposal. This paper presents the results of an investigation carried out in the triaxial apparatus on specimens that were trimmed from blocks extracted during excavation sequences in the URL. In order to characterise the mechanical behaviour of the natural Boom clay and to examine the effect of initial and induced anisotropy on its constitutive behaviour, two series of triaxial tests were carried out. Special attention was devoted to the yield behaviour and the effects of stress history. Experimental results showed a clear relation between the shape of yield curves and stress history. The yield curve of the clay in its initial state was oriented along the K0 line, illustrating the anisotropy of fabric that was generated during the soil deposition. Subsequent isotropic compression (up to 9 MPa) made the yield curve more and more oriented along the p′ axis. Based on these experimental results, an elasto-plastic model accounting for isotropic and anisotropic hardening in (p′:q) space was developed. The initial yield curve of the soil was taken inclined with respect to the p′ axis. The formulation proposed describes the change in shape, size and orientation of the yield curve, according to the stress history. Eight constitutive parameters were used to describe the anisotropic behaviour of the soil.
Measurements of transient ground movements below a ballasted railway line
Authors: PRIEST J.A. , POWRIE W. , YANG L. , GRABE P.J. , CLAYTON C.R.I.
Published: August 2010

This paper presents the results of a detailed investigation into the ground deformations that occur under a railway line during the passage of a train. Four horizontal boreholes were installed at different depths below a ballasted railway track. Ground deformations were measured using geophones at set distances from the centreline of the track within each borehole. The results show vertical displacements reducing with depth, from a maximum at the sleeper. Sleeper displacements are dominated by pairs of bogies at the ends of adjacent wagons (which have a frequency of loading 1 Hz), although the effects of individual bogies (2 Hz) and axles (6 Hz) are also apparent. Higher loading frequencies attenuate with depth so that at a depth of 0·780 m below the sleeper soffit no axles are visible within the displacement data and by a depth of 1·98 m only the combined effect of pairs of adjacent bogies is apparent. In contrast, longitudinal horizontal motion is greatest at a depth of 0·78 m below the sleeper soffit, and the longitudinal horizontal displacements at the sleeper and at a depth of 0·78 m are dominated by the individual axles (∼6 Hz). By a depth of 1·98 m, the longitudinal horizontal motion is dominated by the bogie pairs. A dynamic linear-elastic two-dimensional finite element model was developed and validated using the measured displacements.
Evaluation of the sand-cone method for determination of the in-situ density of soil
Authors: PARK S.-S.
Published: August 2010

A sand-cone method is commonly used to determine the density of compacted soils. The density of the compacted soil calculated from the sand-cone method could be correct, provided the calibration container has approximately the same size or volume and allows the sand to fall to approximately the same height as a test hole in the field. However, in most cases, the size or shape of the test hole is not exactly the same as that of the calibration container. This can result in a difference in the settlement or deposition of sand particles between the laboratory calibration and the field testing, which may cause an erroneous determination of the in-situ density. The sand-filling process is simulated in the laboratory and its effect on the determination of density is investigated. Artificially made holes with different depths and bottom shapes are prepared to simulate various shapes of the test hole in the field. Sands with different particle size distributions are used in the testing to examine how sand grain size influences the determination of density in the field. The error between the assumed and calculated densities is highly dependent on the types of sand used in the sand-cone method. This paper presents some guidelines for obtaining correct in-situ densities through the sand-cone method.
Gingival Overgrowth Among Patients Medicated With Cyclosporin A and Tacrolimus Undergoing Renal Transplantation: A Prospective Study
Authors: Paixão Caroline G. , Sekiguchi Ricardo T. , Saraiva Luciana , Pannuti Cláudio M. , Silva Hélio T. , Medina‐Pestana José O. , Romito Giuseppe A.
Published: August 2010

Background:The aim of this study is to make a longitudinal evaluation of the incidence and severity of gingival overgrowth (GO) induced by immunosuppressive agents, such as tacrolimus (Tcr) and cyclosporin A (CsA), in the absence of calcium channel blockers in patients undergoing renal transplantation (RT).

Methods:This longitudinal study is conducted in 49 patients with RT who were divided into a CsA group (n = 25) and Tcr group (n = 24). The individuals were assessed at four time intervals: before transplant and 30, 90, and 180 days after RTs. Demographic data and periodontal clinical parameters (plaque index, cemento‐enamel junction to the gingival margin, probing depth, clinical attachment level, bleeding on probing [BOP], and GO) were collected at all time intervals.

Results:The mean GO index was significantly lower in the Tcr group compared to the CsA group after 30 (P= 0.03), 90 (P= 0.004), and 180 (P= 0.01) days of immunosuppressive therapy. One hundred eighty days after RTs, a clinically significant GO was observed in 20.0% of individuals in the CsA group and 8.3% of individuals in the Tcr group. However, this difference was not statistically significant (P= 0.41). There was a reduction in periodontal clinical parameters regarding the time of immunosuppressive therapy for PI and BOP (P<0.001) in both groups.

Conclusion:Although there was no statistical difference in the incidences of clinically significant GO after 180 days of immunosuppressive therapy, it was observed that GO occurred later in the Tcr group, and the severity of GO in this group was lower than in patients who used CsA.
Smoking-Related Health Risks Among Persons With HIV in the Strategies for Management of Antiretroviral Therapy Clinical Trial
Authors: Lifson Alan R. , Neuhaus Jacqueline , Arribas Jose Ramon , van den Berg-Wolf Mary , Labriola Ann M. , Read Timothy R.H. ,   for the INSIGHT SMART Study Group
Published: August 2010

Objectives. We sought to determine smoking-related hazard ratios (HRs) and population-attributable risk percentage (PAR%) for serious clinical events and death among HIV-positive persons, whose smoking prevalence is higher than in the general population.

Methods. For 5472 HIV-infected persons enrolled from 33 countries in the Strategies for Management of Antiretroviral Therapy clinical trial, we evaluated the relationship between baseline smoking status and development of AIDS-related or serious non-AIDS events and overall mortality.

Results. Among all participants, 40.5% were current smokers and 24.8% were former smokers. Adjusted HRs were higher for current than for never smokers for overall mortality (2.4; P < .001), major cardiovascular disease (2.0; P = .002), non-AIDS cancer (1.8; P = .008), and bacterial pneumonia (2.3; P < .001). Adjusted HRs also were significantly higher for these outcomes among current than among former smokers. The PAR% for current versus former and never smokers combined was 24.3% for overall mortality, 25.3% for major cardiovascular disease, 30.6% for non-AIDS cancer, and 25.4% for bacterial pneumonia.

Conclusions. Smoking contributes to substantial morbidity and mortality in this HIV-infected population. Providers should routinely integrate smoking cessation programs into HIV health care.
Performance of an Experimental Wastewater Treatment High‐Rate Algal Pond in Subarctic Climate
Authors: Grönlund Erik , Hanæus Jörgen , Johansson Erica , Falk Stefan
Published: August 2010

A pilot‐scale experimental high‐rate algal pond (HRAP) was investigated in the subarctic mid‐Sweden region, at latitude 63°N. During autumn 2002, conditions included temperatures below 10°C and photosynthetic active radiation below 200 µE/m2·s. Biochemical oxygen demand was reduced by approximately 90% (approximately 40 g/m3), chemical oxygen demand by 65% (approximately 80 g/m3), total phosphorus by 20% (approximately 1 g/m3), and total nitrogen by 46% (approximately 15 g/m3), at a retention time of approximately 2.5 days. During autumn 2003, the performance of the HRAP appeared better with a more dense microalgae culture; however, as a result of poor settling of the microalgae, the reduction was considerably lower. A major difference between the years was the microalgae composition. In 2002, the large green algae Coelastrum dominated with Chlamydomonas, Scenedesmus, Lagerheimia, and the Cryptophyte Rhodomonas. In 2003, there was a total dominance of the very small green algae Chlorella, known to be difficult to settle. In batch growth experiments during spring 2002, doubling times of 4 to 6 days were achieved. The period of temperatures above 10°C and an insolation of more than approximately 270 uE/m2·s (125 Langleys), which is well‐documented as appropriate for HRAP function (Oswald, 1988a, 1988c), were measured to last for 4 to 4.5 months from early May to late September. However, the growth and treatment performance experiments indicated that a longer season may be possible—6.5 to 7 months, at best—from early April to late October.
Study on the Treatment of Wastewater Containing Mercury by Macromolecular Heavy Metal Flocculant Mercaptoacetyl Polyethyleneimine
Authors: Min Xu , Qing Chang , Jinjin Chen
Published: August 2010

A novel water‐soluble macromolecule heavy metal flocculant mercaptoacetyl polyethyleneimine (MAPEI) was synthesized by reacting polyethyleneimine (PEI) with thioglycolic acid (TGA). The removal of mercury ions (Hg2+) and turbidity from aqueous solutions by MAPEI was investigated. The MAPEI is efficient for the simultaneous removal of Hg2+ and turbidity. The highest removal ratio of mercury ions was above 95%. Factors were studied that could affect the process, such as pH, molecular weight of PEI, co‐existing ions, and so on, and the results show that, with the increase in pH or molecular weight of PEI, the removal rate increases; alkali metal and alkaline‐earth metal ions and chloride ions (C1−) and nitrate (NO3−) ions can promote the removal of Hg2+, while sulfate (SO42−) suppresses the process. In the process of treating wastewater containing both turbidity and mercury ions, both have a synergic removal effect with each other. Compared with TGA, MAPEI shows obvious advantages, including higher removal efficiency, larger flocs, and higher floc sedimentation velocity. In addition, compared with PEI, both PEI and MAPEI are almost equally not efficient for turbidity removal, but the presence of mercury ions can improve greatly the efficiency of MAPEI in the removal of turbidity.
Control of Partial Nitritation of Centrate in a Sequencing Batch Reactor
Authors: Miot Alexandre , Pagilla Krishna R.
Published: August 2010

This research identified suitable conditions for long‐term inhibition of nitrite‐oxidizer bacteria (NOB) in a sequencing batch reactor for the treatment of centrate by over‐nitrite pathways. The NOB were inhibited by free ammonia concentrations greater than 20 mg NH3‐N/L combined with a dissolved oxygen concentration less than 0.3 mg O2/L and a temperature of 30°C. The experiments were performed in a laboratory‐scale 2.5‐L reactor fed with synthetic and actual centrate from a full‐scale wastewater treatment plant (800 to 1500 mg NH4+‐N/L). The influence of influent‐alkalinity‐to‐ammonium ratio (AAR) on the effluent‐nitrite‐to‐ammonium ratio (NAR) also was investigated. The control of the effluent NAR was possible by adjusting the influent AAR when NOB inhibition was maintained and when total alkalinity depletion took place before the end of the cycle. The maximum nitritation rate of 860 mg NO2−‐N oxidized/L·d was obtained when the influent NH4+‐N concentration was 800 mg NH4+‐N/L and the hydraulic retention time was 1.7 days.
Strategies for Instructors on How to Improve Online Groupwork
Authors: Koh Myung Hwa , Barbour Michael , Hill Janette R.
Published: August 2010

Online groupwork is becoming an increasingly popular instructional strategy. Although researchers have questioned the benefits of groupwork in online learning environments, little empirical research has examined the challenges it presents. The purpose of this study was to investigate the experience of students involved in online groupwork to find strategies that could be implemented to assist students in completing online groupwork. The findings indicated that the strategies for the instructors included two areas: course design and groupwork process. The course design strategies include 1) providing multiple communication methods; 2) providing an overall plan for the class; 3) preparing for technology; and 4) building virtual team skills. The groupwork process strategies include 1) assisting group formation; 2) building a sense of connection; 3) being involved in group processes; and 4) evaluating group processes. Finally, this study suggested future research is needed in the conditions that facilitate effective group composition.
Learning in 3D Virtual Environments: Collaboration and Knowledge Spirals
Authors: Burton Brian G. , Martin Barbara N.
Published: August 2010

The purpose of this case study was to determine if learning occurred within a 3D virtual learning environment by determining if elements of collaboration and Nonaka and Takeuchi's (1995) knowledge spiral were present. A key portion of this research was the creation of a Virtual Learning Environment. This 3D VLE utilized the Torque Game Engine provided by Garage Games and a content pack created by BraveTree Productions, LLC. By creating this 3D didactic constructivist virtual environment, conversations were observed for collaborative and knowledge creation elements. Data for this mixed-design case study were gathered through three sources: the 3D virtual environment; a survey created by the researchers; and follow-up interviews. Findings revealed that the five forms of collaboration (Elementary Clarification, In-Depth Clarification, Inference, Judgment, and Application) amplified the knowledge creation process and indeed occurred within the virtual learning environment. It was also determined that all four modes for knowledge creation (socialization, externalization, combination, and internalization) were observed as well.
Political Dilemmas and the Institutional Foundation of Economic Development
Authors: Justesen Mogens K.
Published: August 2010

Differences in property rights institutions are often thought to contribute to explaining cross-national differences in economic development. If secure and universally enforced property rights help produce collectively beneficial economic results, the question is why there is so much variation in the institutions and rules that regulate property rights. Based on institutional analysis, the purpose of this article is to analyse why some states and governments establish and enforce property rights that are good for growth while others do not. The argument is that the incentive to enforce and protect property rights is shaped by particular political institutions, namely those that relate to the size of a governments supporting coalition and the extent of power sharing among veto players. The empirical analyses show that coalition institutions are strongly related to property rights while the impact of power sharing is less robust.
The Application of Net Neutrality to Wireless Networks Based on Network Architecture
Authors: Jordan Scott
Published: August 2010

There is considerable debate over whether and how net neutrality should apply to wireless networks. We address here whether differences between wired and wireless network technology merit different treatment with respect to net neutrality. The primary focus is on applications and traffic management, rather than device attachment. We first review the pertinent aspects of network architecture and discuss the main differences between wired and wireless networks, and find that wireless networks differ substantially from wired networks at the network layer and below. We then turn more specifically to how wired and wireless networks differ with respect to traffic management, and conclude that wireless networks require some different types of traffic management than wired networks. Finally, we turn to the question of how the differences in traffic management affect net neutrality, and find that despite the differences in traffic management, similar net neutrality concerns apply. Furthermore, we argue that since the differences lie in lower layers, net neutrality in both wired and wireless networks can be effectively accomplished by requiring an open interface between network and transport layers. We argue that this is a more streamlined and more effective solution that carving out a set of managed services.
The Essential Internet: Digital Exclusion in Low‐Income American Communities
Authors: Powell Alison , Bryne Amelia , Dailey Dharma
Published: August 2010

As the Internet, and broadband in particular, becomes a platform for social and political engagement, researchers investigate more carefully both the factors that drive broadband adoption and the barriers that constrain it. This paper reports on one of the only large‐scale qualitative studies of the barriers to broadband adoption in the United States, where 30% of the population lack broadband access. The primary research question asks: how can we qualitatively understand barriers to broadband adoption among low‐income communities? The study's community‐based approach, undertaken in four regions of the country, reveals the complex equilibrium of broadband adoption. Drawing from 170 interviews with broadband non‐adopters as well as community access providers and other intermediaries, this study finds that price is only one factor shaping home broadband adoption, and that libraries and other community organizations fill the gap between low home adoption and high demand for broadband. These intermediaries compensate for shortages in digital skills that also constitute barriers to adoption in a context where broadband is essential for gaining access to jobs, education, and e‐government. These three main findings suggest that low‐income people like our research participants are playing roles as actors in an ecology of broadband access games (Dutton et al. 2004). In particular, they are overcoming barriers to being online in order to participate in accessing services and gaining education. This is part of the process of defining broadband as an infrastructure for e‐democracy. The paper recommends a renewed focus on factors that sustain home access rather than drive demand, as well as support for community intermediaries in provisioning public broadband access within a context of skill shortages. It recommends further qualitative research to better understand the role of diverse populations in framing the value of broadband access.
Project RedCar: Cardiovascular Disease Risk Communication for People With Type 2 Diabetes Combining the Power of Electronic Health Records and Computer-Based Multimedia Technology
Authors: Roach Paris , Klindukhova Olena , Saha Chandan , Hudson Brenda , Cantrell Melissa , Marrero David
Published: August 2010

In Brief

Although cardiovascular disease (CVD) is the major cause of mortality in people with type 2 diabetes, CVD risk factors are undertreated in this population. The communication of individualized CVD risk to patients before clinical encounters may facilitate the discussion of CVD risk between patients and health care providers and lead to more timely therapeutic intensification. This article presents a CVD risk communication intervention designed for an urban primary care population, utilizing an electronic health record system. Preliminary analyses indicate that the intervention increases the likelihood of patients discussing CVD risk with their physicians and makes it easier for them to participate in these discussions.
Redesign of a Diabetes System of Care Using an All-or-None Diabetes Bundle to Build Teamwork and Improve Intermediate Outcomes
Authors: Bloom Frederick J. , Graf Thomas , Anderer Tammy , Stewart Walter F.
Published: August 2010

In Brief

Providing diabetes patients all of the care recommended by current guidelines is a clinical challenge. Geisinger Health System has designed a provider-led, team-based system of care to more consistently and reliably meet this challenge. This system of care uses an all-or-none bundle of diabetes measures and electronic health record tools to improve both process measures and intermediate diabetes outcomes.
Microfungi in Drinking Water: The Role of the Frog Litoria caerulea
Authors: Sammon Noel B. , Harrower Keith M. , Fabbro Larelle D. , Reed Rob H.
Published: August 2010

Microfungi were recovered from all parts of a municipal water distribution system in sub-tropical Australia even though virtually no colony-forming units were recovered from the treated water as it left the treatment plant. A study was then undertaken to determine the potential sources of the microfungal population in the distribution system. Observation of frogs (Litoria caerulea) using the internal infrastructure of a reservoir as diurnal sleeping places, together with observation of visible microfungal growth on their faecal pellets, led to an investigation of the possible involvement of this animal. Old faecal pellets were collected and sporulating fungal colonies growing on their surfaces were identified. Fresh faecal pellets were collected and analysed for microfungal content, and skin swabs were analysed for yeasts. It was found that the faeces and skin of L. caerulea carried large numbers of yeasts as well as spores of various filamentous fungal genera. While there are many possible sources of microfungal contamination of municipal drinking water supplies, this study has revealed that the Australian green tree frog L. caerulea is one of the important sources of filamentous microfungi and yeasts in water storage reservoirs in sub-tropical Australia where the animal is endemic.
Applications of Chemical Shift Imaging to Marine Sciences
Authors: Lee Haakil , Tikunov Andrey , Stoskopf Michael K. , Macdonald Jeffrey M.
Published: August 2010

The successful applications of magnetic resonance imaging (MRI) in medicine are mostly due to the non-invasive and non-destructive nature of MRI techniques. Longitudinal studies of humans and animals are easily accomplished, taking advantage of the fact that MRI does not use harmful radiation that would be needed for plain film radiographic, computerized tomography (CT) or positron emission (PET) scans. Routine anatomic and functional studies using the strong signal from the most abundant magnetic nucleus, the proton, can also provide metabolic information when combined with in vivo magnetic resonance spectroscopy (MRS). MRS can be performed using either protons or hetero-nuclei (meaning any magnetic nuclei other than protons or 1H) including carbon (13C) or phosphorus (31P). In vivo MR spectra can be obtained from single region ofinterest (ROI or voxel) or multiple ROIs simultaneously using the technique typically called chemical shift imaging (CSI). Here we report applications of CSI to marine samples and describe a technique to study in vivo glycine metabolism in oysters using 13C MRS 12 h after immersion in a sea water chamber dosed with [2-13C]-glycine. This is the first report of 13C CSI in a marine organism.
Synthesis and Application of a 2-[(4-Fluorophenyl)-sulfonyl]ethoxy Carbonyl(Fsec) Protected Glycosyl Donor in Carbohydrate Chemistry
Authors: Spjut Sara , Qian Weixing , Elofsson Mikael
Published: August 2010

The 2-[(4-fluorophenyl)sulfonyl]ethoxy carbonyl (Fsec) group for protection of hydroxyl groups has been designed, synthesized, and evaluated. Fsec-Cl was readily prepared in 91% yield over three steps and subsequently used to protect 4-fluorobenzyl alcohol in high yield. The Fsec group was cleaved from the resulting model compound under mild basic conditions e.g., 20% piperidine in DMF and was stable under acidic conditions, e.g., neat acetic acid. The Fsec group was used to protect the unreactive 4-OH in a galactose building block that was later used in the synthesis of 6-aminohexyl galabioside.
Design, Synthesis, and Biological Evaluation of Benzylamino-Methanone Based Cholesteryl Ester Transfer Protein Inhibitors
Authors: Sheikha Ghassan Abu , Abu Khalaf Reema , Melhem Areej , Albadawi Ghadeer
Published: August 2010

Cholesteryl ester transfer protein (CETP) is a glycoprotein involved in transporting lipoprotein particles and neutral lipids between high-density lipoprotein (HDL) and low density lipoproteins (LDL) and therefore its a proper target for treating dyslipidemia and related disorders. Guided by our previosuly-reported pharmacophore and QSAR models for CETP inhibition, we synthesized and bioassayed a series of benzylamino-methanones. The most potent illustrated 30% CETP inhibition at 10 μM.
Characterization of SNARE Cleavage Products Generated by Formulated Botulinum Neurotoxin Type-A Drug Products
Authors: Hunt Terrence , Rupp David , Shimizu Gary , Tam Karen , Weidler Julia , Xie Jack
Published: August 2010

The study evaluated substrate cleavage product(s) generated by three botulinum neurotoxin serotype A (BoNT/A) medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC) method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198–Ala199 (normal BoNT/A cleavage is Gln197–Arg198). Arg198–Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.
The Evolution of National Wastewater Management Regimes—the Case of Israel
Authors: Hophmayer-Tokich Sharon
Published: August 2010

In the state of Israel wastewater management (WWM), the legal responsibility of municipalities, was neglected for decades, resulting in pollution of the scarce water resources and the environment. This trend was reversed during the 1990s. This paper analyses the evolution process of the national WWM regime and its effect on WWM at the municipal level, and explains the paradigm shift. It is found that both the long-term neglect and the paradigm shift can be attributed to the central government’s policies regarding WWM rather than to the local authorities.
Proximal Events in 7,12-Dimethylbenz[a]anthracene-Induced, Stromal Cell-Dependent Bone Marrow B Cell Apoptosis: Stromal Cell–B Cell Communication and Apoptosis Signaling
Authors: Teague Jessica E. , Ryu Heui-Young , Kirber Michael , Sherr David H. , Schlezinger Jennifer J.
Published: August 2010

Intercellular communication is an essential process in stimulating lymphocyte development and in activating and shaping an immune response. B cell development requires cell-to-cell contact with and cytokine production by bone marrow stromal cells. However, this intimate relationship also may be responsible for the transfer of death-inducing molecules to the B cells. 7,12-Dimethylbenz[a]anthracene (DMBA), a prototypical polycyclic aromatic hydrocarbon, activates caspase-3 in pro/pre-B cells in a bone marrow stromal cell-dependent manner, resulting in apoptosis. These studies were designed to examine the hypothesis that an intrinsic apoptotic pathway is activated by DMBA and that the ultimate death signal is a DMBA metabolite generated by the stromal cells and transferred to the B cells. Although a loss of mitochondrial membrane potential did not occur in the DMBA/stromal cell-induced pathway, cytochrome c release was stimulated in B cells. Caspase-9 was activated, and formation of the apoptosome was required to support apoptosis, as demonstrated by the suppression of death in Apaf-1fog mutant pro-B cells. Investigation of signaling upstream of the mitochondria demonstrated an essential role for p53. Furthermore, DMBA-3,4-dihydrodiol-1,2-epoxide, a DNA-reactive metabolite of DMBA, was sufficient to upregulate p53, induce caspase-9 cleavage, and initiate B cell apoptosis in the absence of stromal cells, suggesting that production of this metabolite by the stromal cells and transfer to the B cells are proximal events in triggering apoptosis. Indeed, we provide evidence that metabolite transfer from bone marrow stromal cells occurs through membrane exchange, which may represent a novel communication mechanism between developing B cells and stromal cells.
IFN Regulatory Factor 3 Contributes to the Host Response during Pseudomonas aeruginosa Lung Infection in Mice
Authors: Carrigan Svetlana O. , Junkins Robert , Yang Yong Jun , MacNeil Adam , Richardson Christopher , Johnston Brent , Lin Tong-Jun
Published: August 2010

Pseudomonas aeruginosa is a major opportunistic pathogen. However, host defense mechanisms involved in P. aeruginosa lung infection remain incompletely defined. The transcription factor IFN regulatory factor 3 (IRF3) is primarily associated with host defense against viral infections, and a role of IRF3 in P. aeruginosa infection has not been reported previously. In this study, we showed that IRF3 deficiency led to impaired clearance of P. aeruginosa from the lungs of infected mice. P. aeruginosa infection induced IRF3 translocation to the nucleus, activation of IFN-stimulated response elements (ISRE), and production of IFN-β, suggesting that P. aeruginosa activates the IRF3–ISRE–IFN pathway. In vitro, macrophages from IRF3-deficient mice showed complete inhibition of CCL5 (RANTES) and CXCL10 (IP-10) production, partial inhibition of TNF, but no effect on CXCL2 (MIP-2) or CXCL1 (keratinocyte-derived chemokine) in response to P. aeruginosa stimulation. In vivo, IRF3-deficient mice showed complete inhibition of CCL5 production and partial or no effects on production of other cytokines and chemokines in the bronchoalveolar lavage fluids and lung tissues. Profiling of immune cells in the airways revealed that neutrophil and macrophage recruitment into the airspace was reduced, whereas B cell, T cell, NK cell, and NKT cell infiltration was unaffected in IRF3-deficient mice following P. aeruginosa lung infection. These data suggest that IRF3 regulates a distinct profile of cytokines and chemokines and selectively modulates neutrophil and macrophage recruitment during P. aeruginosa infection. Thus, IRF3 is an integral component in the host defense against P. aeruginosa lung infection.
P2Y2 Receptor Regulates VCAM-1 Membrane and Soluble Forms and Eosinophil Accumulation during Lung Inflammation
Authors: Vanderstocken Gilles , Bondue Benjamin , Horckmans Michael , Di Pietrantonio Larissa , Robaye Bernard , Boeynaems Jean-Marie , Communi Didier
Published: August 2010

ATP has been defined as a key mediator of asthma. In this study, we evaluated lung inflammation in mice deficient for the P2Y2 purinergic receptor. We observed that eosinophil accumulation, a distinctive feature of lung allergic inflammation, was defective in OVA-treated P2Y2-deficient mice compared with OVA-treated wild type animals. Interestingly, the upregulation of VCAM-1 was lower on lung endothelial cells of OVA-treated P2Y2−/− mice compared with OVA-treated wild type animals. Adhesion assays demonstrated that the action of UTP on leukocyte adhesion through the regulation of endothelial VCAM-1 was abolished in P2Y2-deficient lung endothelial cells. Additionally, the level of soluble VCAM-1, reported as an inducer of eosinophil chemotaxis, was strongly reduced in the bronchoalveolar lavage fluid (BALF) of P2Y2-deficient mice. In contrast, we observed comparable infiltration of macrophages and neutrophils in the BALF of LPS-aerosolized P2Y2+/+ and P2Y2−/− mice. This difference could be related to the much lower level of ATP in the BALF of LPS-treated mice compared with OVA-treated mice. Our data define P2Y2 as a regulator of membrane and soluble forms of VCAM-1 and eosinophil accumulation during lung inflammation.
Complement-Dependent Transport of Antigen into B Cell Follicles
Authors: Gonzalez Santiago F. , Lukacs-Kornek Veronika , Kuligowski Michael P. , Pitcher Lisa A. , Degn Søren E. , Turley Shannon J. , Carroll Michael C.
Published: August 2010

Since the original proposal by Fearon and Locksley (Fearon and Locksley. 1996. Science 272: 50–53) that the complement system linked innate and adaptive immunity, there has been a rapid expansion of studies on this topic. With the advance of intravital imaging, a number of recent papers revealed an additional novel pathway in which complement C3 and its receptors enhance humoral immunity through delivery of Ag to the B cell compartment. In this review, we discuss this pathway and highlight several novel exceptions recently found with a model influenza vaccine, such as mannose-binding lectin opsonization of influenza and uptake by macrophages, and the capture of virus by dendritic cells residing in the medullary compartment of peripheral lymph nodes.
Inflammatory Effects of Ex Vivo Human Th17 Cells Are Suppressed by Regulatory T Cells
Authors: Crome Sarah Q. , Clive Breanna , Wang Adele Y. , Kang Christine Y. , Chow Vickie , Yu Jie , Lai Amy , Ghahary Aziz , Broady Raewyn , Levings Megan K.
Published: August 2010

Th17 cells are proinflammatory cells associated with many immune-mediated diseases. Major factors limiting the study of human Th17 cells are the lack of an accepted method for their in vitro differentiation or for isolation of a homogenous population of Th17 cells that do not cosecrete IFN-γ. To overcome these hurdles, we established a novel method to isolate in vivo differentiated Th17 cells from peripheral blood by sorting CD161+CCR4+CCR6+CXCR3−CD4+ T cells. The resulting cells produce high levels of IL-17 but not IFN-γ, express high levels of retinoic acid-related orphan receptor variant 2, and maintain this phenotype upon expansion. Ex vivo Th17 cells exhibit a low cytotoxic potential and are hyporesponsive to polyclonal anti-CD3/anti-CD28 stimulation. Importantly, ex vivo Th17 cells were susceptible to suppression by both naive and memory regulatory T cells (Tregs), which inhibited production of IL-17, IL-22, and CXCL8. Moreover, Tregs suppressed the antifibrotic effects of Th17 cells in a wound-healing model. These findings provide new tools for the study of normal and pathological functions of bona fide Th17 cells in humans. They also provide new insight into the cross-talk between Th17 cells and immune and nonimmune cells, and they establish the paradigm that adoptive Treg-based therapies may effectively limit Th17-mediated inflammation.
Mucosal Anti-CD3 Monoclonal Antibody Attenuates Collagen-Induced Arthritis That Is Associated with Induction of LAP+ Regulatory T Cells and Is Enhanced by Administration of an Emulsome-Based Th2-Skewing Adjuvant
Authors: Wu Henry Yim , Maron Ruth , Tukpah Ann-Marcia , Weiner Howard L.
Published: August 2010

Mucosal (nasal or oral) administration of anti-CD3 mAb is effective in ameliorating animal models of autoimmunity (experimental autoimmune encephalomyelitis, diabetes, and lupus) by inducing LAP+ regulatory T cells. We tested this approach in an arthritis model using type II collagen. We found that nasal anti-CD3 was more effective than oral anti-CD3 in attenuating the development of arthritis. Nasal anti-CD3 induced a LAP+ regulatory T cell that secreted high levels of IL-10 and suppressed collagen-specific T cell proliferation and anti-collagen Ab production. However, neither nasal nor oral anti-CD3 attenuated disease when given to animals with ongoing arthritis, and this was associated with a lack of induction of LAP+ regulatory T cells. We found, however, that coadministration of a novel emulsome adjuvant, which enhances Th2 responses, resulted in the induction of LAP+ regulatory T cells and suppression of ongoing arthritis by both nasal and oral anti-CD3. Suppression of arthritis by mucosal anti-CD3 was associated with less joint damage, a decrease of TNF-α and IFN-γ mRNA expression in joints, and a reduction in anti-collagen Abs. These results demonstrate that mucosal anti-CD3 therapy may serve as a therapeutic approach in arthritis and that the biologic effect is enhanced by an emulsome-based adjuvant.
Pronounced Virus-Dependent Activation Drives Exhaustion but Sustains IFN-γ Transcript Levels
Authors: Mackerness Kathryn J. , Cox Maureen A. , Lilly Lauren M. , Weaver Casey T. , Harrington Laurie E. , Zajac Allan J.
Published: August 2010

During many chronic infections, the responding CD8 T cells become exhausted as they progressively lose their ability to elaborate key effector functions. Unlike prototypic memory CD8 cells, which rapidly synthesize IFN-γ following activation, severely exhausted T cells fail to produce this effector molecule. Nevertheless, the ontogeny of exhausted CD8 T cells, as well as the underlying mechanisms that account for their functional inactivation, remains ill defined. We have used cytokine reporter mice, which mark the transcription of IFN-γ mRNA by the expression of Thy1.1, to decipher how activation events during the early stages of a chronic infection dictate the development of exhaustion. We show that virus-specific CD8 T cells clearly respond during the early stages of chronic lymphocytic choriomeningitis virus infection, and that this early T cell response is more pronounced than that initially observed in acutely infected hosts. Thus, exhausted CD8 T cells appear to emerge from populations of potently activated precursors. Unlike acute infections, which result in massive expansion of the responding T cells, there is a rapid attenuation of further expansion during chronic infections. The exhausted T cells that subsequently emerge in chronically infected hosts are incapable of producing the IFN-γ protein. Surprisingly, high levels of the IFN-γ transcript are still present in exhausted cells, demonstrating that ablation of IFN-γ production by exhausted cells is not due to transcriptional silencing. Thus, posttranscription regulatory mechanisms likely disable this effector module.