bluuebunny/crossref_metadata_2025 huggingface dataset:
Seroprevalence of pertussis antitoxin (anti‐PT) in Sweden before and 10 years after the introduction of a universal childhood pertussis vaccination program
Authors: HALLANDER HANS O. , ANDERSSON MIKAEL , GUSTAFSSON LENNART , LJUNGMAN MARGARETHA , NETTERLID EVA
Published: November 2009

Hallander HO, Andersson M, Gustafsson L, Ljungman M, Netterlid E. Seroprevalence of pertussis antitoxin (anti‐PT) in Sweden before and 10 years after the introduction of a universal childhood pertussis vaccination program. APMIS 2009; 117: 912–22.

The prevalence of IgG ELISA antibodies against pertussis toxin (anti‐PT) was studied in two Swedish seroepidemiological studies. One was performed in 1997 when the new pertussis vaccination program was 1 year old (n = 3420). In 2007, when Pa vaccines had been used countrywide for 10 years in the universal child vaccination program, this study was repeated to analyze the effect of vaccination on anti‐PT prevalence (n = 2379). Before the statistical analysis of seroprevalence, children vaccinated within the last 2 years before the serosurveys were excluded. The results indicate a reduced exposure to Bordetella pertussis in the population. The proportion of sera without measurable anti‐PT antibodies increased significantly, aggregated over all comparable age groups, from 3.8% in people sampled in 1997 to 16.3% in people sampled in 2007. For cord blood, 1% was without measurable anti‐PT antibodies in 1997 compared to a significantly higher level, 12%, in 2007. With anti‐PT concentrations of ≥50 and ≥100 EU/ml as cutoff points for ‘recent infection’ the proportion above the cutoff points for younger children was significantly higher in 1997 than in 2007 at both cutoff points. For all adults, 20 years of age and older, the difference in proportions above the lower cutoff point was close to statistically significant, comparing 1997 with 2007. This was not the case at 100 EU/ml. In the 1997 samples of children, there was a significant downward trend of ‘recent infections’ at both cutoff points for three sampled age groups between 5 and 15 years of age from 21% at 5.0–5.5 years of age to 7% at 14.7–15.7 years for the lowest cutoff. In the 2007 samples of children, on the contrary, there was a significant continuous upward trend of ‘recent infections’, at both cutoff points, for four sampled age groups between 4 and 18 years of age – from 4% at 4–5 years of age to 16% at 17–18 years at the lowest cutoff. The continuous increase, with age of children with high anti‐PT concentrations, supports the recent change in the general Swedish childhood vaccination program to include a pre‐school booster at 5–6 years and a school‐leaving booster at 14–16 years of age.
Delineating the impact of neuroantigen vs genetic diversity on MP4‐induced EAE of C57BL/6 and B6.129 mice
Authors: KUERTEN STEFANIE , RODI MICHAEL , JAVERI SITA , GRUPPE TRAUGOTT L. , TARY‐LEHMANN MAGDALENA , LEHMANN PAUL V. , ADDICKS KLAUS
Published: November 2009

Kuerten S, Rodi M, Javeri S, Gruppe TL, Tary‐Lehmann M, Lehmann PV, Addicks K. Delineating the impact of neuroantigen vs genetic diversity on MP4‐induced EAE of C57BL/6 and B6.129 mice. APMIS 2009; 117: 923–35.

MBP‐PLP fusion protein (MP4)‐induced experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis (MS) that encompasses both a time‐dependent attack on central nervous system (CNS) regions and a B cell component, mirroring important features of human multiple sclerosis. Comparing C57BL/6 with B6.129 mice immunized with MP4, we point out similarities regarding these hallmarks and thus propose that they are largely dependent on the nature of the MP4 antigen itself, while differences between the two strains suggest that additional fine‐tuning is brought about by the genetic repertoire of the animal. Overall, our data imply that (i) the interplay between both the antigenic trigger and genetic variables can define the outcome of MP4‐induced autoimmune encephalomyelitis in C57BL/6 and B6.129 mice and (ii) that MP4 is not only a strong neuroantigen when it comes to reproducing the dynamics in effector mechanisms as is typical of the disease but also a promising agent for studying interindividual heterogeneity derived from genetic diversity in EAE/MS.
Primary human acute myelogenous leukemia cells release matrix metalloproteases and their inhibitors: release profile and pharmacological modulation
Authors: Reikvam Håkon , Hatfield Kimberley J. , Øyan Anne M. , Kalland Karl H. , Kittang Astrid O. , Bruserud Øystein
Published: November 2009

Objectives: Angiogenesis seems important for both leukemogenesis and chemosensitivity in acute myelogenous leukemia (AML). Angiogenesis is regulated by the balance between pro‐ and antiangiogenic cytokines, which also indicates an important role of matrix metalloproteases (MMPs) and their natural inhibitors, tissue inhibitors of metalloproteases (TIMPs). We investigated the constitutive release of MMPs and TIMPs for a large group of consecutive AML patients. Methods: AML cells were cultured in vitro either alone or together with microvascular endothelial cells, and levels of MMPs and TIMPs were determined in culture supernatants. Results: AML cells showed constitutive release of several MMPs and TIMPs. For all patients, detectable MMP‐10 release was observed, and most patients showed detectable release of at least one additional MMP, usually MMP‐9 or MMP‐2. A significant correlation was found between MMP‐9 and TIMP‐1 release and the release of several CCL and CXCL chemokines. MMP‐9 release was higher for AML cells with monocytic differentiation corresponding to the FAB‐subtype M4/M5 AML; it was mainly released in its inactive form, but endogenously active MMP‐9 could be detected even in the presence of the constitutively released TIMP‐1/2. Endothelial cells released relatively high levels of MMP‐10, and these levels were further increased by coculture with AML cells. Patients achieving complete hematological remission after only one induction cycle showed relatively low constitutive MMP‐2 release. Conclusion: We conclude that primary human AML cells show constitutive release of both MMPs and TIMPs, and this release may be important for leukemogenesis and possibly also for chemosensitivity.
Erythema leprosum – after treatment of Lepromatous Leprosy
Authors: Eickelmann Mareike , Steinhoff Martin , Metze Dieter , Tomimori‐Yamashita Jane , Sunderkötter Cord
Published: November 2009

Leprosy is usually well‐controlled by multidrug therapy (MDT). However, in case of noncompliance or leprosy reactions, it may present a therapeutically challenge. A 33‐year‐old Brazilian woman with lepromatous leprosy was treated with MDT for one year, but then discontinued therapy because she wanted to have children. Eight weeks after stopping her medications, she developed a severe and recalcitrant erythema (nodosum) leprosum (ENL) which presented histologically with thrombosed small veins and neutrophilic inflammation in fat septa, but without arteritis. During her pregnancy and ensuing lactation period, glucocorticoids were the only suitable drug. With the use of the shortened WHO/MDT regimen (one year vs. two years of treatment), ENL will probably be seen more often after the end of leprosy therapy. It needs to be rapidly recognized and treated to avoid damage to eyes or kidneys.
A strategy for discovery of cancer glyco‐biomarkers in serum using newly developed technologies for glycoproteomics
Authors: Narimatsu Hisashi , Sawaki Hiromichi , Kuno Atsushi , Kaji Hiroyuki , Ito Hiromi , Ikehara Yuzuru
Published: November 2009

Detection of cancer at early stages that can be treated through surgery is a difficult task. One methodology for cancer biomarker discovery exploits the fact that glycoproteins produced by cancer cells have altered glycan structures, although the proteins themselves are common, ubiquitous, abundant, and familiar. However, as cancer tissue at the early stage probably constitutes less than 1% of the normal tissue in the relevant organ, only 1% of the relevant glycoproteins in the serum should have altered glycan structures. Here, we describe our strategy to approach the detection of these low‐level glycoproteins: (a) a quantitative real‐time PCR array for glycogenes to predict the glycan structures of secreted glycoproteins; (b) analysis by lectin microarray to select lectins that distinguish cancer‐related glycan structures on secreted glycoproteins; and (c) an isotope‐coded glycosylation site‐specific tagging high‐throughput method to identify carrier proteins with the specific lectin epitope. Using this strategy, we have identified many glycoproteins containing glycan structures that are altered in cancer cells. These candidate glycoproteins were immunoprecipitated from serum using commercially available antibodies, and their glycan alteration was examined by a lectin microarray. Finally, they were analyzed by multistage tandem MS.
Functional polymorphism of cytotoxic T‐lymphocyte antigen 4 and nasopharyngeal carcinoma susceptibility in a Chinese population
Authors: Xiao M. , Qi F. , Chen X. , Luo Z. , Zhang L. , Zheng C. , Hu S. , Jiang X. , Zhou M. , Tang J.
Published: November 2009

Cytotoxic T‐lymphocyte antigen 4 (CTLA‐4; CD152) is a secondary receptor of B7 (CD80 and CD86) and shares homology with the CD28 receptor. Although the structures of CTLA‐4 and CD28 are very similar, they deliver different costimulatory signals. A functional polymorphism in CTLA‐4 exon 1 position +49 that can affect the T‐cell response has been reported by several groups. Previous case–control studies also revealed this polymorphism contribute to the risk of autoimmune diseases and common cancers. However, the relationship between CTLA‐4 functional polymorphism and nasopharyngeal carcinoma (NPC) susceptibility has not yet been explored. In this study, we performed a case–control study in a Chinese population. Our result showed that the CTLA‐4 +49 A>G polymorphism is associated with NPC susceptibility. The subjects carrying the CTLA‐4 +49 AA genotype have a ∼1.8‐fold increased risk of NPC (adjust OR 1.83; 95% CI, 1.16–2.93) when compared with the GG genotype.
Differences in soil carbon storage due to mowing, burning and uncontrolled management practices of a grassland at the foot of Mount Sanbe, Japan
Authors: Shimoda Seiji , Takahashi Yoshitaka
Published: November 2009

To investigate how grassland management practices influence soil carbon pools, we compared soil carbon, its stable isotopic composition (δ13C) and plant root mass among three management areas (17 years of mowing, 17 years of burning, and 10 years of no control) in a secondary grassland at the foot of Mount Sanbe (35°07′N, 132°36′E). The influence of the management practices on soil carbon was limited to the top 5 cm, namely, soil carbon content and δ13C in this layer were higher in the mowed area (5.3 kg C m–2 and −16.4‰) compared to the burned (4.4 kg C m–2 and −17.7‰) and uncontrolled (4.3 kg C m–2 and −18.0‰) areas. Root biomass below 5‐cm depth was significantly lower in the mowed area (266 g m–2) than in the burned and uncontrolled areas (1135 and 967 g m–2). The results indicate that management practices for less than 20 years have little effects on soil carbon in deep layers (<5 cm), though deeper distribution of roots in the burned and uncontrolled areas has a potential to supply carbon in the future.
Effect of distance from farm periphery on the risk of forage damage by sika deer (Cervus nippon)
Authors: Tsukada Hideharu , Fukasawa Michiru , Kosako Takami , Nakamura Yoshio , Hanafusa Yasuko
Published: November 2009

The foraging behavior of deer can be influenced by both food availability and the “critical distance” from protective vegetation cover. The effect of the distance from the farm periphery on the risk of forage damage by sika deer was investigated in a public pasture in Tochigi Prefecture in central Japan from May to November 2006 and in May 2007. The risk of forage damage by sika deer, evaluated by deer pellet group density, was compared along three line transects at different distances from the farm periphery (10, 110 and 210 m) and among 18 paddocks at different distances from the farm periphery. Deer pellet group abundance in the line transects did not differ significantly with the distance from the periphery but decreased significantly with the distance from the nearest escape cover. The transect‐based deer pellet abundance was more significantly influenced by other factors such as paddock identity and survey month in a generalized linear model. Deer pellet group abundance in the paddocks showed a significant albeit weak negative correlation with distance from the periphery in May 2007, but not in November 2006. The paddock‐based deer pellet abundance was more influenced by sward height than by the distance from the periphery in a generalized linear model. Furthermore, a high density of deer pellet groups was exclusively observed in the paddock just after pasture renovation. These results show that the foraging behavior of sika deer was influenced partially by the distance from the nearest escape cover but largely by other factors such as herbage quality and seasonality.
Effects of ruminal and abomasal digestion on seed germinability of Japanese wild plants
Authors: Obara Michihiro , Ogura Shin‐ichiro , Shishido Tetsuro , Sugawara Kazuo
Published: November 2009

Effects of ruminal and abomasal digestion on seed germinability were investigated for Dactylis glomerata, Anthoxanthum odoratum, Zoysia japonica, Trifolium repens and Carex albata for varying in vitro incubation periods. Seed surface characteristics were examined by scanning electronic microscopy (SEM) following ruminal digestion. Abomasal digestion, but not ruminal digestion, reduced the germinability of D. glomerata seed (P < 0.001). For A. odoratum, ruminal digestion reduced germinability (P < 0.001), whereas for Z. japonica and T. repens, both ruminal and abomasal digestion (P < 0.001) decreased germinability. In contrast, both ruminal and abomasal digestion increased germination rates for C. albata seeds with a significant interaction (P < 0.001). SEM observations indicated few ruminal bacteria attached to the seed surface of C. albata, whereas bacterial attachments were numerous for other species. These results indicate the resistance of C. albata seed surface to microbial digestion and enhancement of seed germinability by abomasal digestion.
Synthesis, Characterization, and Spectroscopic Analysis of NdxY1−xTiNbO6 Microwave Ceramics
Authors: Joseph Shyla , Suresh Madukayil Kunjoonju , Thomas Jijimon Kumpukkatu , John Annamma , Solomon Sam
Published: November 2009

Solid solutions of NdxY1−xTiNbO6 ceramics were prepared through the solid‐state ceramic route. The materials were calcined at 1250°C and sintered in the range 1400–1550°C. The structure of the system was analyzed using the X‐ray diffraction and vibrational spectroscopic analysis. The morphology and the sintering behavior of the samples were analyzed using scanning electron microscopy. The dielectric constant (ɛr), temperature coefficient of resonant frequency (τf), and the unloaded quality factor (Qu) were measured in the microwave frequency region using the cavity resonator method. The ɛr and τf increased with an increase in the concentration of Nd in the solid solutions. Nearly zero temperature coefficient of resonant frequency was obtained for the Nd0.6Y0.4TiNbO6 ceramic. Samples are of high quality factor and are useful for microwave applications.
The virtues of frugality — why cosmological observers should release their data slowly
Authors: Starkman Glenn D. , Trotta Roberto , Vaudrevange Pascal M.
Published: November 2009

Cosmologists will soon be in a unique position. Observational noise will gradually be replaced by cosmic variance as the dominant source of uncertainty in an increasing number of observations. We reflect on the ramifications for the discovery and verification of new models. If there are features in the full data set that call for a new model, there will be no subsequent observations to test that model's predictions. We give specific examples of the problem by discussing the pitfalls of model discovery by prior adjustment in the context of dark energy models and inflationary theories. We show how the gradual release of data can mitigate this difficulty, allowing anomalies to be identified and new models to be proposed and tested. We advocate that observers plan for the frugal release of data from future cosmic-variance-limited observations.
On Geographic and geography
Authors: Johnston Ron
Published: November 2009

New Zealand Geographic is one of a number of geographical magazines published in the English‐speaking world that make little or no reference to work by academic geographers. It recently launched a New Zealand Geographic Trust to promote research into ‘New Zealand's life, culture and sciences’ and collaborated with four other publishers of geographical magazines to raise awareness of climate change: the work of academic geographers is again ignored. This exclusion of academic and school geography from such enterprises raises important issues regarding the discipline's public profile in New Zealand and suggests the need for greater public engagement activity by the country's geographers.
Spatial history of kauri driving dam placement in the Kauaeranga Valley, Coromandel Peninsula
Authors: Napier Aaron , Boswijk Gretel , Brierley Gary
Published: November 2009

Understanding past anthropogenic influences on fluvial systems is an integral part of riverine research. In this paper the spatial history of kauri driving dam placement from the 1870s to the 1930s is studied using oral histories, historic documents and GIS in an attempt to assess the accuracy of historical accounts in reference to dam position in the landscape and assess the relationship of dam position to landscape features and characteristics. GIS results supported historical documentation showing that key factors influencing dam placement were location to kauri, geomorphic impediments to transport, slope and distance to deep water for rafting.
Grassland revolutions in New Zealand: Disaggregating a national story
Authors: Winder Gordon M.
Published: November 2009

The grassland revolution is a national story but the intensification of New Zealand pastoral agriculture was made possible by many changes in farm practice, and application varied within New Zealand. This paper identifies aggregation issues in the narrative and explores their implications for any reassessment of the revolution. Data from six counties are analysed to illustrate some of the varied experiences across New Zealand farm districts. The paper redirects attention to local‐ and farm‐scale studies as a way to investigate the significance of the diverse drivers of pastoral productivity, their timing and effects.
The new blackbirds? Vanuatu guestworkers in New Zealand
Authors: Hammond Jeremy , Connell John
Published: November 2009

An agricultural guestworker scheme for Pacific island states began in New Zealand in 2007 to remedy domestic agricultural labour shortages. Vanuatu was one of the first countries to take advantage of the scheme. After a pilot venture in 2007 greater numbers of workers were recruited in 2008. In Tanna, the recruits, though mainly male, represented a cross‐section of the population. Their objectives were income generation for education fees, house building and eventually small business development. Early returnees acquired significant capital and met some of these objectives. The scheme has benefited both countries and the first generation of guestworkers.
What's on top for geography teachers? National Certificate of Educational Achievement and the prioritization of professional development
Authors: Taylor Mike
Published: November 2009

Geography teachers' work is influenced by multiple education policy initiatives. Professional development opportunities emerge to support these policy changes and associated compliance issues. This paper reports the results of a survey in which geography teachers self‐reported their knowledge and prioritized professional development needs. The data indicate that some compliance issues associated with assessment policy reform have largely been resolved, while more substantive assessment and course design issues continue to be prioritized for professional development. However, professional development that continues to focus on assessment reform may marginalize geography teachers' engagement with concurrent curriculum and pedagogical policy initiatives.
Recursivity in Legal Change: Lawyers and Reforms of China's Criminal Procedure Law
Authors: Liu Sida , Halliday Terence C.
Published: November 2009

This article employs a new framework for legal change, the recursivity of law, to explain why China's criminal procedure law has cycled through numerous reforms between 1979 and 2008 without improving the conditions of lawyers' criminal defense work. The authors argue that Chinese lawyers' difficulties in criminal defense have deep roots in the recursive nature of the criminal procedure reforms. In particular, those difficulties were produced by interactions of the four mechanisms of recursivity (indeterminacy of law, contradictions, diagnostic struggles, and actor mismatch) in both lawmaking and implementation. The empirical analysis shows that these mechanisms are linked in pairs and in sequence. This logic of change offers an integrated interdisciplinary approach to the enactment and implementation of law in other times, places, and areas of law.
The USA's Reaction to the Bolivian Revolution of 1952: Pragmatism and the Inter‐American System
Authors: Murphey Oliver
Published: November 2009

Many historians view the Eisenhower administration's policies towards Latin America as dominated by a narrowly anti‐communist mindset and based on a limited understanding of Latin American nationalism. A closer examination of the administration's relationship with Bolivia's revolutionary regime challenges this over‐simplification. By nurturing Bolivian nationalism, while simultaneously pushing it towards more agreeable policy stances, the Eisenhower administration wanted to show nationalists across Latin America and beyond that there were benefits in co‐operating with the USA. Appreciating the importance and power of Third‐World nationalism in the post‐war era, Eisenhower sought to ensure that these emerging nations remained firmly in the Western camp economically and diplomatically. In Bolivia, this effort was ultimately unsuccessful. High aid levels and co‐operative policies proved insufficient to bring lasting prosperity and stability to Bolivia. Furthermore, although many officials recognised the importance of co‐opting regional nationalism, growing US influence on Bolivian domestic policy served to antagonise nationalist resentment. Bolivians and the many other Latin Americans continued to feel economic hardship and neglect, and were more influenced by polarising US interventions in Guatemala and Cuba than by seemingly benevolent US policies in Bolivia.
Cross‐Sectional Imaging Characteristics of Pituitary Adenomas, Invasive Adenomas and Adenocarcinomas in Dogs: 33 Cases (1988–2006)
Authors: Pollard Rachel E. , Reilly Christopher M. , Uerling Megan R. , Wood Farica D. , Feldman Edward C.
Published: November 2009

Background:Pituitary tumors in dogs can be adenomas, invasive adenomas, or adenocarcinomas. In people, invasive adenomas and pituitary adenocarcinomas carry a worse prognosis than adenomas.

Hypothesis/Objective:To identify differentiating features on cross‐sectional imaging in dogs with pituitary adenomas, invasive adenomas, and adenocarcinomas.

Animals:Thirty‐three dogs that had computed tomography (CT) or magnetic resonance imaging (MRI) performed and a necropsy diagnosis of pituitary adenoma (n= 20), invasive adenoma (n= 11), or adenocarcinoma (n= 2).

Methods:Medical records were retrospectively reviewed for signalment, history, and diagnosis. CT and MR images were reviewed for characteristics of pituitary tumors.

Results:Mean (± standard deviation) age for dogs with pituitary adenomas (10.6 ± 2.9 years) was greater than that of those with invasive adenomas (8.3 ± 2.7 years,P= .04). Eighteen out of 20 (90%) dogs with adenomas had contrast‐enhancing masses. Thirteen out of 20 (65%) had homogeneous enhancement. Mean adenoma height was 1.2 ± 0.7 cm. Eight out of 20 (40%) adenomas were round and 8/20 (40%) compressed surrounding brain. Eleven out of 11 dogs (100%) with invasive adenomas had contrast‐enhancing masses. Seven out of 11 (64%) masses were homogeneous. Mean invasive adenoma height was 1.8 ± 0.7 cm, which was significantly greater than adenomas (P= .03). Mass shape varied from round to oval to irregular. Six out of 11 (55%) masses compressed surrounding brain. Clinical and imaging features were variable for 2 dogs with adenocarcinomas.

Conclusions and Clinical Relevance:Invasive adenoma should be suspected if a dog with a pituitary tumor is <7.7 years of age and has a mass >1.9 cm in vertical height. Adenocarcinomas are uncommon and metastatic lesions were not seen with imaging.
Role of Latent Feline Leukemia Virus Infection in Nonregenerative Cytopenias of Cats
Authors: Stützer B. , Müller F. , Majzoub M. , Lutz H. , Greene C.E. , Hermanns W. , Hartmann K.
Published: November 2009

Background:Nonregenerative cytopenias such as nonregenerative anemia, neutropenia, and thrombocytopenia in cats with feline leukemia virus (FeLV) antigen are assumed to be caused by the underlying FeLV infection. In addition, cats with negative FeLV antigen‐test results that have cytopenias of unknown etiology often are suspected to suffer from latent FeLV infection that is responsible for the nonregenerative cytopenias.

Objective:The purpose of this study was to assess the role of latent FeLV infection by polymerase chain reaction (PCR) in bone marrow of cats with nonregenerative cytopenias that had negative FeLV antigen test results in blood.

Animals:Thirty‐seven cats were included in the patient group. Inclusion criteria were (1) nonregenerative cytopenia of unknown origin and (2) negative FeLV antigen test result. Antigenemia was determined by detection of free FeLV p27 antigen by ELISA in serum. Furthermore, 7 cats with positive antigen test results with nonregenerative cytopenia were included as control group I, and 30 cats with negative antigen test results without nonregenerative cytopenia were included as control group II.

Methods:Whole blood and bone marrow samples were tested by 2 different PCR assays detecting sequences of the envelope or long terminal repeat genes. FeLV immunohistochemistry was performed in bone marrow samples.

Results:Two of the 37 cats (5.4%) in the patient group were positive on the bone marrow PCR results and thus were latently infected with FeLV.

Conclusions and Clinical Importance:The findings of this study suggest that FeLV latency is rare in cats with nonregenerative cytopenias.
Sequential Plasma Lactate Concentrations as Prognostic Indicators in Adult Equine Emergencies
Authors: Tennent‐Brown B.S. , Wilkins P.A. , Lindborg S. , Russell G. , Boston R.C.
Published: November 2009

Background:Sequential lactate concentration ([LAC]) measurements have prognostic value in that hospitalized humans and neonatal foals that have a delayed return to normolactatemia have greater morbidity and case fatality rate.

Hypothesis:Prognosis for survival is decreased in horses with a delayed return to normal [LAC].

Animals:Two hundred and fifty adult horses presented for emergency evaluation excepting horses evaluated because of only ophthalmologic conditions, superficial wounds, and septic synovitis without systemic involvement.

Methods:Prospective observational study. [LAC] was measured at admission and then at 6, 12, 24, 48, and 72 hours after admission. The change in [LAC] over time ([LAC]ΔT) was calculated from changes in [LAC] between sampling points.

Results:Median [LAC] was significantly (P< .001) higher at admission in nonsurvivors (4.10 mmol/L [range, 0.60–18.20 mmol/L]) when compared with survivors (1.30 mmol/L [range, 0.30–13.90 mmol/L]) and this difference remained at all subsequent time points. The odds ratio for nonsurvival increased from 1.29 (95% confidence interval 1.17–1.43) at admission to 49.90 (6.47–384) at 72 hours after admission for every 1 mmol/L increase in [LAC]. [LAC]ΔTwas initially positive in all horses but became negative and significantly lower in nonsurvivors for the time periods between 24–72 hours (− 0.47,P= .001) and 48–72 hours (− 0.07,P= .032) when compared with survivors (0.00 at both time periods) consistent with lactate accumulation in nonsurvivors.

Conclusions and Clinical Importance:These results indicate that lactate metabolism is impaired in critically ill horses and [LAC]ΔTcan be a useful prognostic indicator in horses.
International Relations Studies in Korea: Retrospects and Prospects*
Authors: Kook Kim Hyung , Young Cho Yun
Published: November 2009

This paper aims at examining the research on theory and policy that has been funded by Korean international relations (IR) scholarships during the past 50 years.

In theoretical perspectives, lots of theoretical paradigms, including those of realists, liberals, constructivists, and radicals, have competed with each other in the field of Korean IR studies. Currently, the Korean IR scholarships no longer rely on just importing foreign thoughts and ideas. Now is the time to facilitate the process of appropriating the study of IR to the standards of Koreanization. First, it is desirable to pursue inter‐disciplinary research with historians. Second, such research cannot be completed within academic circles alone. Hundreds and hundreds of civilian sectors are raising their voices, especially in democratic environments. Scholars are required to have open‐mindedness to these demands. Third, we need to promote cooperation with other countries, including Japan and China, as South Korea needs to combine expertise on Korean issues with broader knowledge of the world in the contemporary era when global communications are more urgently needed than ever before.

With regard to policies, South Korea, in a state of national division, has constantly been faced with threats – military and political – from North Korea. The Korean IR scholarship is required to devote itself to finding proper ways to promote peace and prosperity on the Korean Peninsula. Thus, scholars of Korean IR are urged to continuously carry out their historical mission of offering wide‐ranging suggestions for external policies for the nation and the East Asian region.
Elementary properties of CaV1.3 Ca2+ channels expressed in mouse cochlear inner hair cells
Authors: Zampini Valeria , Johnson Stuart L. , Franz Christoph , Lawrence Neil D. , Münkner Stefan , Engel Jutta , Knipper Marlies , Magistretti Jacopo , Masetto Sergio , Marcotti Walter
Published: November 2009

Mammalian cochlear inner hair cells (IHCs) are specialized to process developmental signals during immature stages and sound stimuli in adult animals. These signals are conveyed onto auditory afferent nerve fibres. Neurotransmitter release at IHC ribbon synapses is controlled by L‐type CaV1.3 Ca2+ channels, the biophysics of which are still unknown in native mammalian cells. We have investigated the localization and elementary properties of Ca2+ channels in immature mouse IHCs under near‐physiological recording conditions. CaV1.3 Ca2+ channels at the cell pre‐synaptic site co‐localize with about half of the total number of ribbons present in immature IHCs. These channels activated at about −70 mV, showed a relatively short first latency and weak inactivation, which would allow IHCs to generate and accurately encode spontaneous Ca2+ action potential activity characteristic of these immature cells. The CaV1.3 Ca2+ channels showed a very low open probability (about 0.15 at −20 mV: near the peak of an action potential). Comparison of elementary and macroscopic Ca2+ currents indicated that very few Ca2+ channels are associated with each docked vesicle at IHC ribbon synapses. Finally, we found that the open probability of Ca2+ channels, but not their opening time, was voltage dependent. This finding provides a possible correlation between presynaptic Ca2+ channel properties and the characteristic frequency/amplitude of EPSCs in auditory afferent fibres.
Microstructure and temperature coefficient of resistance of thin cermet resistor films deposited from CrSi2–Cr–SiC targets by S-gun magnetron
Authors: Felmetsger Valery V.
Published: November 2009

Technological solutions for producing nanoscale cermet resistor films with sheet resistances above 1000Ω∕◻ and low temperature coefficients of resistance (TCR) have been investigated. 2–40nm thick cermet films were sputter deposited from CrSi2–Cr–SiC targets by a dual cathode dc S-gun magnetron. In addition to studying film resistance versus temperature, the nanofilm structural features and composition were analyzed using scanning electron microscopy, atomic force microscopy, high-resolution transmission electron microscopy, energy-dispersive x-ray spectroscopy, and electron energy loss spectroscopy. This study has revealed that all cermet resistor films deposited at ambient and elevated temperatures were amorphous. The atomic ratio of Si to Cr in these films was about 2 to 1. The film TCR displayed a significant increase when the deposited film thickness was reduced below 2.5nm. An optimized sputter process consisting of wafer degassing, cermet film deposition at elevated temperature with rf substrate bias, and a double annealing in vacuum, consisting of in situ annealing following the film sputtering and an additional annealing following the exposure of the wafers to air, has been found to be very effective for the film thermal stabilization and for fine tuning the film TCR. Cermet films with thicknesses in the range of 2.5–4nm deposited using this technique had sheet resistances ranging from 1800to1200Ω∕◻ and TCR values from −50ppm∕°C to near zero, respectively. A possible mechanism responsible for the high efficiency of annealing the cermet films in vacuum (after preliminary exposure to air), resulting in resistance stabilization and TCR reduction, is also discussed.
Ensuring Efficient Eating
Authors: Foley John F.
Published: November 2009

PPAR-δ in macrophages is required to efficiently clear apoptotic cells and to prevent autoimmune responses.
Staying on Track
Authors: Gough Nancy R.
Published: November 2009

Without STAT3 to limit Rac1 activity, cells move randomly.
Blocking Notch
Authors: Adler Elizabeth M.
Published: November 2009

A stabilized α-helical peptide penetrates cells to inhibit Notch signaling.
Picking a Promoter
Authors: Gough Nancy R.
Published: November 2009

Lysine monomethylation of the transcription factor NF-κB affects the stability of its interaction with specific gene promoters.
Outfoxing Immune Excess
Authors: Mueller Kristen
Published: November 2009

Suppressor T cells regulate different classes of immune responses through induction of specific transcription factors.
VIM-19, a Metallo-β-Lactamase with Increased Carbapenemase Activity from
Escherichia coli
and
Klebsiella pneumoniae
Authors: Rodriguez-Martinez Jose-Manuel , Nordmann Patrice , Fortineau Nicolas , Poirel Laurent
Published: November 2009

Two carbapenem-resistant isolates, one
Escherichia coli
isolate and one
Klebsiella pneumoniae
isolate, recovered from an Algerian patient expressed a novel VIM-type metallo-β-lactamase (MBL). The identified
bla
VIM-19
gene was located on a ca. 160-kb plasmid and located inside a class 1 integron in both isolates. VIM-19 differed from VIM-1 by the Asn215Lys and Ser228Arg substitutions, increasing its hydrolytic activity toward carbapenems. Site-directed mutagenesis experiments showed that both substitutions were necessary for the increased carbapenemase activity of VIM-19. This study indicates that MBLs with enhanced activity toward carbapenems may be obtained as a result of very few amino acid substitutions.
Anti-
Clostridium difficile
Potential of Tetramic Acid Derivatives from
Pseudomonas aeruginosa
Quorum-Sensing Autoinducers
Authors: Ueda Chihiro , Tateda Kazuhiro , Horikawa Manabu , Kimura Soichiro , Ishii Yoshikazu , Nomura Kaoru , Yamada Kanako , Suematsu Takashi , Inoue Yasuhisa , Ishiguro Masaji , Miyairi Shinichi , Yamaguchi Keizo
Published: November 2009

We have examined the potential bactericidal activities of several tetramic acids derived from
Pseudomonas
autoinducers against
Clostridium difficile
, a cause of antibiotic-associated pseudomembranous colitis. Clinical isolates of
C. difficile
(
n
= 4) were incubated in broth with a chemically synthesized
Pseudomonas
autoinducer and its tetramic acid derivatives. The structure-activity relationship and the mechanisms of action were examined by a time-killing assay and by determination of the morphological/staining characteristics. The use of some tetramic acids derived from
N
-3-oxododecanoyl
l
-homoserine lactone resulted in more than 3-log reductions in the viability of
C. difficile
within 30 min at 30 μM. The outer membrane was suggested to be one of the targets for the bactericidal activity of tetramic acid, because disturbance of the bacterial outer surface was demonstrated by alteration of the Gram-staining characteristic and electron microscopy. The data for the tetramic acid derivatives demonstrate that the keto-enol structure and the length of the acyl side chain of tetramic acid may be essential for the antibacterial activity of this molecule. These results suggest the potential for tetramic acid derivatives to be novel agents with activity against
C. difficile
.
Fitness Costs and Stability of a High-Level Ciprofloxacin Resistance Phenotype in
Salmonella enterica
Serotype Enteritidis: Reduced Infectivity Associated with Decreased Expression of
Salmonella
Pathogenicity Island 1 Genes
Authors: O'Regan Edel , Quinn Teresa , Frye Jonathan G. , Pagès Jean-Marie , Porwollik Steffen , Fedorka-Cray Paula J. , McClelland Michael , Fanning Séamus
Published: November 2009

The fitness costs associated with high-level fluoroquinolone resistance were examined for phenotypically and genotypically characterized ciprofloxacin-resistant
Salmonella enterica
serotype Enteritidis mutants (104-cip and 5408-cip; MIC, >32 μg/ml). The stability of the fluoroquinolone resistance phenotype in both mutants was investigated to assess whether clones with better fitness could emerge in the absence of antibiotic selective pressure. Mutants 104-cip and 5408-cip displayed altered morphology on agar and by electron microscopy, reduced growth rates, motility and invasiveness in Caco-2 cells, and increased sensitivity to environmental stresses. Microarray data revealed decreased expression of virulence and motility genes in both mutants. Two clones, 104-revert and 1A-revertC2, with ciprofloxacin MICs of 3 and 2 μg/ml, respectively, were recovered from separate lineages of 104-cip after 20 and 70 passages, respectively, on antibiotic-free agar. All fitness costs, except motility, were reversed in 104-revert. Potential mechanisms associated with reversal of the resistance phenotype were examined. Compared to 104-cip, both 104-revert and 1A-revertC2 showed decreased expression of
acrB
and
soxS
but still overexpressed
marA
. Both acquired additional mutations in SoxR and ParC, and 1A-revertC2 acquired two mutations in MarA. The altered porin and lipopolysaccharide (LPS) profiles observed in 104-cip were reversed. In contrast, 5408-cip showed no reversal in fitness costs and maintained its high-level ciprofloxacin resistance for 200 passages on antibiotic-free agar. In conclusion, high-level ciprofloxacin resistance in
S
. Enteritidis is associated with fitness costs. In the absence of antibiotic selection pressure, isolates may acquire mutations enabling reversion to an intermediate-level ciprofloxacin resistance phenotype associated with less significant fitness costs.
Ceftobiprole Is Superior to Vancomycin, Daptomycin, and Linezolid for Treatment of Experimental Endocarditis in Rabbits Caused by Methicillin-Resistant
Staphylococcus aureus
Authors: Tattevin P. , Basuino L. , Bauer D. , Diep B. A. , Chambers H. F.
Published: November 2009

Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible
Staphylococcus aureus
endocarditis. However, methicillin-resistant
S. aureus
(MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (
P
< 0.05 for each comparison). In addition, the numbers of organisms in spleens and in kidneys were significantly lower in ceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (
P
< 0.05 for each comparison). Anti-MRSA beta lactam agents such as ceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.
Method for Screening Compounds That Influence Virulence Gene Expression in
Staphylococcus aureus
Authors: Nielsen Anita , Nielsen Kristian F. , Frees Dorte , Larsen Thomas O. , Ingmer Hanne
Published: November 2009

We present a simple assay to examine effects of compounds on virulence gene expression in the human pathogen
Staphylococcus aureus
. The assay employs transcriptional reporter strains carrying
lacZ
fused to central virulence genes. Compounds affecting virulence gene expression and activity of the
agr
locus are scored based on color change in the presence of a chromogenic β-galactosidase substrate. The assay can be used to screen for novel antivirulence compounds from many different sources, such as fungi, as demonstrated here.
Characteristics and Population Dynamics of MosaicpenAAllele-ContainingNeisseria gonorrhoeaeIsolates Collected in Sydney, Australia, in 2007-2008
Authors: Tapsall John W. , Ray Sanghamitra , Limnios Athena
Published: November 2009

Eighteen hundredNeisseria gonorrhoeaeisolates collected in Sydney, Australia, in 2007 and 2008 were examined for mosaicpenAalleles that mediated cephalosporin resistance, and the genotypes of the isolates were evaluated. In 2008, there were substantial increases in numbers (from 15 to 85) and proportions (from 1.5 to 10.3%) of mosaic-containing gonococci and major shifts in genotypic patterns, with 10 new genotypes representing 74 of the 85 mosaic-containing isolates and genotypes detected between 2001 and 2005 having disappeared. Enhanced surveillance of gonococcal resistance to cephalosporins is necessary.
Porphyromonas gingivalis
Ferrous Iron Transporter FeoB1 Influences Sensitivity to Oxidative Stress
Authors: Anaya-Bergman Cecilia , He Jia , Jones Kevin , Miyazaki Hiroshi , Yeudall Andrew , Lewis Janina P.
Published: November 2009

Porphyromonas gingivalis
FeoB1 is a ferrous iron transporter. Analysis of parental and
feoB1
-deficient strains of the periodontal pathogen revealed that the
feoB1
-deficient mutant strain had an increased ability to survive oxidative stress. Specifically, survival of the mutant strain was increased 33% with exposure to peroxide and 5% with exposure to atmospheric oxygen compared to the parental strain. Interestingly, the ability to survive intracellularly also increased fivefold in the case of the
feoB1
-deficient mutant. Our data suggest that although the FeoB1 protein is required for ferrous iron acquisition in
P. gingivalis
, it also has an adverse effect on survival of the bacterium under oxidative stress conditions. Finally, we show that
feoB1
expression is not iron dependent and is dramatically reduced in the presence of host cells, consistent with the observed deleterious role it plays in bacterial survival.
Ferredoxin Is Involved in Secretion of Cytotoxic Necrotizing Factor 1 across the Cytoplasmic Membrane in
Escherichia coli
K1
Authors: Yu Hao , Kim Kwang Sik
Published: November 2009

We previously showed that cytotoxic necrotizing factor 1 (CNF1) contributes to
Escherichia coli
K1 invasion of human brain microvascular endothelial cells (HBMEC) and interacts with the receptor on the surface of HBMEC. CNF1 is the cytoplasmic protein, and it remains incompletely understood how CNF1 is secreted across the inner and outer membranes in
E. coli
K1. In order to investigate the genetic determinants for secretion of CNF1 in
E. coli
K1, we performed Tn
5
mutagenesis screening by applying β-lactamase as a reporter to monitor secretion of CNF1. We identified a Tn
5
mutant that exhibited no β-lactamase activity in the culture supernatant and in which the mutated gene encodes a ferredoxin gene (
fdx
). In the
fdx
deletion mutant, there was no evidence of translocation of CNF1 into HBMEC. Western blot analysis of the
fdx
deletion mutant revealed that ferredoxin is involved in translocation of CNF1 across the cytoplasmic membrane. The
fdx
mutant exhibited significantly decreased invasion of HBMEC, similar to the decreased HBMEC invasion observed with the CNF1 mutant. The failures to secrete CNF1 and invade HBMEC of the
fdx
mutant were restored to the levels of the parent strain by complementation with
fdx
. These findings demonstrate for the first time that ferredoxin is involved in secretion of CNF1 across the inner membrane in meningitis-causing
E. coli
K1.
Growth-Inhibitory Antibodies Are Not Necessary for Protective Immunity to Malaria Infection
Authors: Murhandarwati E. Elsa Herdiana , Wang Lina , de Silva Harini D. , Ma Charles , Plebanski Magdalena , Black Casilda G. , Coppel Ross L.
Published: November 2009

The absence of a validated surrogate marker for the immune state has complicated the design of a subunit vaccine against asexual stages ofPlasmodium falciparum. In particular, it is not known whether the capacity to induce antibodies that inhibit parasite growthin vitrois an important criterion for selection ofP. falciparumproteins to be assessed in human vaccine trials. We examined this issue in thePlasmodium yoeliirodent malaria model using the 19-kDa C-terminal fragment of merozoite surface protein 1 (MSP119). To examine the relationship between inhibitory antibodies in immunized mice and the immune state, as indicated by resistance to a blood-stage challenge, we used an allelic replacement strategy to generate a transgenicP. falciparumline that expresses MSP119fromP. yoelii. We show that MSP119is functionally conserved across these two divergentPlasmodiumspecies, and replacing PfMSP119with PyMSP119has no detectable effect on parasite growthin vitro. By comparing growth rates of this transgenic line with a matched transgenic line that expresses the endogenous PfMSP119, we developed an assay to measure the specific growth-inhibitory activity directed exclusively to the PyMSP119protein in the sera from vaccinated animals. To validate this assay, sera from rabbits immunized with recombinant PyMSP119were tested and showed specific inhibitory activity in a concentration-dependent manner. In mice that were immunized with recombinant PyMSP119, the levels of PyMSP119-specific inhibitory activity did not correlate with the total antibody levels measured by enzyme-linked immunosorbent assay. Furthermore, they did not correlate with resistance to subsequent blood-stage infection, and some mice with complete protection showed no detectable inhibitory activity in their prechallenge sera. These data indicated that growth-inhibitory activity measuredin vitrowas not a reliable predictor of immune statusin vivo, and the reliance on this criterion to select vaccine candidates for human clinical trials may be misplaced. The transgenic lines further offer useful tools for comparing the efficacy of MSP119-based vaccines that utilize different immunization regimens and antigen formulations.