bluuebunny/crossref_metadata_2025 huggingface dataset:
A new pair of HLA‐C alleles, Cw* 12042 and Cw*1203, differing at the KIR‐related dimorphism of codons 77–80
Authors: Vilches C. , Bunce M. , van Dam M. , de Pablo R.
Published: September 2008

Abstract: A previously unknown HLA‐C variant of the Cw*12 group was identified by PCR‐SSP from genomic DNA of cell NDS‐JD. Molecular cloning and nucleotide sequence analysis permitted the characterization of the complete coding region of this new allele, Cw*12042. The new variant differs from the recently reported Cw*12041 by two silent changes at exons 2 and 3, and from Cw*1203 by coding changes at codons 77 and 80. Cw*1203 (Ser‐Asn) and Cw*12042 (Asn‐Lys) constitute the second known example of HLA‐C alleles only differing at the KIR‐related dimorphism of residues 77–80. The new allele is associated in cell NDS‐JD with the haplotype HLA‐A*2403, Cw*12042, B*51, DRB1*1502, DRB5*0102, DQB1*0601, possibly related from the evolutionary aspect to the ancestral haplotype A*2402, Cw*1202, B*5201, DRB1*1502, DRB5*0102, DQBl*0601.
Analysis of Sir2E in the cellular slime mold Dictyostelium discoideum: Cellular localization, spatial expression and overexpression
Authors: Katayama Takahiro , Yasukawa Hiro
Published: September 2008

It has been reported that Dictyostelium discoideum encodes four silent information regulator 2 (Sir2) proteins (Sir2A–D) showing sequence similarity to human homologues of Sir2 (SIRT1–3). Further screening in a database revealed that D. discoideum encodes an additional Sir2 homologue (Sir2E). The amino acid sequence of Sir2E is not similar to those of SIRTs but is similar to those of proteins encoded by Giardia lamblia, Cryptosporidium hominis and Cryptosporidium parvum. Fluorescence of Sir2E‐green fluorescent protein fusion protein was detected in the D. discoideum nucleus, indicating that Sir2E is a nuclear localizing protein. Reverse transcription–polymerase chain reaction and whole‐mount in situ hybridization analyses showed that D. discoideum expressed sir2E in amoebae in the growth phase and in prestalk cells in the developmental phase. D. discoideum overexpressing sir2E grew faster than the wild type. These results indicate that Sir2E plays important roles both in the growth phase and developmental phase of D. discoideum.
Valosin‐containing protein/p97 interacts with sperm‐activating and sperm‐attracting factor (SAAF) in the ascidian egg and modulates sperm‐attracting activity
Authors: Kondoh Eri , Konno Aru , Inaba Kazuo , Oishi Tohru , Murata Michio , Yoshida Manabu
Published: September 2008

Sperm chemotaxis toward an egg is observed in many animals, and the control of sperm‐attracting activity is thought to play an important role in ensuring fertilization. However, the mechanism underlying the release of a sperm attractant from an egg is still obscure. In this study, we examined the systems involved in the release of sperm‐activating and sperm‐attracting factor (SAAF), which is the sperm attractant of the ascidian Ciona intestinalis. Here, we show that the egg acquires sperm‐attracting activity after germinal vesicle breakdown. Further, since the cytoplasmic extracts of immature oocytes exhibit no sperm‐attracting activity, the SAAF in oocytes may be activated after germinal vesicle breakdown. We found 13 SAAF‐binding proteins in an egg plasma membrane extract and identified five proteins by proteomic analysis: valosin‐containing protein (VCP)/p97, proteasome alpha 2 subunit, MGC97756 protein, proteasome subunit Y, and beta‐tubulin. In particular, the interaction between VCP/p97 and SAAF was confirmed by a pull‐down assay. VCP/p97 is initially localized in the germinal vesicle, and during oocyte maturation, it shifts to the endoplasmic reticulum in the cortical regions. Thus, VCP/p97 is a potential modulator of SAAF release from the egg.
Initial observation of potential factors involved in the specification process of oral‐aboral axis in the sand dollar Scaphechinus mirabilis
Authors: Satoh Kanehide , Kominami Tetsuya
Published: September 2008

To elucidate factors involved in the oral‐aboral axis specification, several observations and experiments were undertaken using the sand dollar Scaphechinus mirabilis. Unlike in Strongylcentrotus purpuratus, localization of mitochondria was not detected in unfertilized eggs. After fertilization, however, the bulk of mitochondria became localized to the opposite side of sperm entry. The first cleavage divided this mitochondrial cluster into daughter blastomeres. On the other hand, a second cleavage produced daughter blastomeres containing quite different amounts of mitochondria. To know whether such mitochondrial localization affects the oral‐aboral axis specification, 4‐cell‐stage embryos were separated along the second cleavage plane. Although both half embryos developed into morphologically normal plutei, some differences, such as the number of pigment cells, were noticed between the siblings. In contrast, cell tracing revealed that the first cleavage separated the oral from the aboral part in most cases, indicating that the unequal distribution of mitochondria is not critical for the oral‐aboral axis specification. Further, stained and non‐stained half embryo fragments were combined. Such combined embryos developed into normal plutei with a single oral‐aboral axis. The plane dividing labeled and non‐labeled parts were incident, oblique or perpendicular to the median plane of the combined embryo, and the appearance frequencies of those labeling patterns were similar to those obtained by cell tracing in intact embryos. Interestingly, the half fragments derived from embryos inseminated earlier showed a tendency to form the oral part. These suggest that several factors as well as the localized cytoplasmic components would be involved in the specification process of oral‐aboral axis.
Effect of different challenge doses after repeated citalopram treatment on extracellular serotonin level in the medial prefrontal cortex: In vivo microdialysis study
Authors: Muraki Ihoko , Inoue Takeshi , Hashimoto Shinji , Izumi Takeshi , Koyama Tsukasa
Published: September 2008

Aims:  In order to elucidate the relevance between the delayed onset of clinical efficacy of selective serotonin re‐uptake inhibitors (SSRI) and extracellular 5‐HT levels in the medial prefrontal cortex, the present study compared the ability of low‐dose (3 mg/kg) and high‐dose (30 mg/kg) citalopram to increase extracellular 5‐HT levels in the medial prefrontal cortex following repeated citalopram treatment using in vivo microdialysis.

Methods:  An SSRI, citalopram, was given 10 mg/kg, s.c. twice daily for 6 days and once on the seventh day in rats. On the eighth day, rats received a single injection of citalopram (3 or 30 mg/kg s.c.), and extracellular 5‐HT levels were assessed in the medial prefrontal cortex of rats using in vivo brain microdialysis.

Results:  There was no significant difference in basal extracellular 5‐HT levels between the repeated citalopram group and the repeated saline group. The low‐challenge dose of citalopram (3 mg/kg) produced significantly greater increases (170–200% at each time point) in the repeated citalopram group than in the repeated saline group (150%). The high‐challenge dose of citalopram (30 mg/kg), however, increased extracellular 5‐HT levels by 200–250% of basal levels in the repeated citalopram group, which was similar to the increases in the repeated saline group.

Conclusions:  Repeated SSRI treatment enhances the effect of low‐dose SSRI on extracellular 5‐HT levels but not that of high‐dose SSRI.
Family needs and related factors in caring for a family member with mental illness: Adopting assertive community treatment in Japan where family caregivers play a large role in community care
Authors: Sono Tamaki , Oshima Iwao , Ito Junichiro
Published: September 2008

Aim:  In Japan the family plays a large role in community care for persons with mental illness; therefore the aim of the present study was to describe the needs of family caregivers related to assertive community treatment (ACT) and to analyze the relationship of these needs to underlying factors.

Methods:  Participants were recruited from the membership of three family associations of persons with mental illness. Of the 224 family members, 152 (67.9%) completed a self‐report questionnaire consisting of the following measures: demographic variables, family life difficulty scale, global burden, general life satisfaction, subjective health status, family rejection scale, quantity of supportive behaviors, and needs for ACT.

Results:  More than 70% of participants reported that service components of ACT would be beneficial, especially in the future. Functions that helped maintain the ordinary routine of family life were significantly correlated with current needs for ACT.

Conclusions:  When a person has chronic mental illness the family has many needs related to ACT. When functions that maintained the ordinary routine of family life were disturbed, the need for ACT support increased. Elderly parents or siblings were also concerned about the future, when caring for the member with mental illness would become more difficult.
Neurotoxic and neuroprotective metabolites of kynurenine in patients with renal cell carcinoma treated with interferon‐α: Course and relationship with psychiatric status
Authors: Van Gool Arthur R. , Verkerk Robert , Fekkes Durk , Bannink Marjolein , Sleijfer Stefan , Kruit Wim H. J. , van der Holt Bronno , Scharpé Simon , Eggermont Alexander M. M. , Stoter Gerrit , Hengeveld Michiel W.
Published: September 2008

Aims:  Immunotherapy with interferon‐α (IFN‐α) is associated with psychiatric side‐effects, including depression. One of the putative pathways underlying these psychiatric side‐effects involves tryptophan (TRP) metabolism. Cytokines including IFN‐α induce the enzyme indoleamine 2,3‐dioxygenase (IDO), which converts TRP to kynurenine (KYN), leading to a shortage of serotonin (5‐HT). In addition, the production of neurotoxic metabolites of KYN such as 3‐hydroxykynurenine and quinolinic acid (QA) might increase and contribute to IFN‐α‐induced psychopathology. In contrast, other catabolites of KYN, such as kynurenic acid (KA), are thought to have neuroprotective properties.

Methods:  In a group of 24 patients treated with standard IFN‐α for metastatic renal cell carcinoma (RCC), combined psychiatric and laboratory assessments were performed at baseline, 4 and 8 weeks, and at 6 months.

Results:  No psychopathology was observed, despite an increase in neurotoxic challenge as reflected in indices for the balance between neurotoxic and neuroprotective metabolites of KYN.

Conclusions:  The present hypothesis that a shift in the balance between neurotoxic and neuroprotective metabolites of KYN underlies the neuropsychiatric side‐effects of IFN‐α‐based immunotherapy, is neither supported nor rejected.
Expression of a putative nitrite reductase and the reversible inhibition of nitrite‐dependent respiration by nitric oxide in Nitrobacter winogradskyi Nb‐255
Authors: Starkenburg Shawn R. , Arp Daniel J. , Bottomley Peter J.
Published: September 2008

The nitrite oxidizing Alphaproteobacterium, Nitrobacter winogradskyi, primarily conserves energy from the oxidation of nitrite (NO2 − ) to nitrate (NO3 − ) through aerobic respiration. Almost 20 years ago, NO‐dependent NADH formation was reported to occur in both aerobic and anaerobic cell suspensions of N. winogradskyi strain ‘agilis’, suggesting that NO oxidation might contribute to energy conservation by Nitrobacter. Recently, the N. winogradskyi Nb‐255 genome was found to contain a gene (Nwin_2648) that encodes a putative copper‐containing nitrite reductase (NirK), which may reduce NO2 −  to NO. In this study, the putative nirK was found to be maximally transcribed under low O2 (between zero and 4% O2) in the presence of NO2 − . Transcription of nirK was not detected under anaerobic conditions in the absence of NO2 −  or in the presence of NO3 −  and pyruvate. Although net production of NO could not be detected from either aerobically grown or anaerobically incubated cells, exogenous NO was consumed by viable cells and concomitantly inhibited NO2 − ‐dependent O2 uptake in a reversible, concentration dependent manner. Both NO2 − ‐dependent O2 uptake and NO consumption were inhibited by 1 mM cyanide suggesting involvement of cytochrome oxidase with NO consumption. Abiotic consumption of NO was measured, yet, both the rates and kinetics of NO transformation in buffer alone, or by heat killed, or cyanide‐treated cells differed from those of viable cells. In light of this new information, a modified model is proposed to explain how NirK and NO manage electron flux in Nitrobacter.
Sediment denitrifier community composition and nirS gene expression investigated with functional gene microarrays
Authors: Bulow Silvia E. , Francis Christopher A. , Jackson George A. , Ward Bess B.
Published: September 2008

A functional gene microarray was used to investigate denitrifier community composition and nitrite reductase (nirS) gene expression in sediments along the estuarine gradient in Chesapeake Bay, USA. The nirS oligonucleotide probe set was designed to represent a sequence database containing 539 Chesapeake Bay clones, as well as sequences from many other environments. Greatest nirS diversity was detected at the freshwater station at the head of the bay and least diversity at the higher salinity station near the mouth of the Bay. The most common OTUs from the sequence database were detected on the array with high signal strength in most samples. One of the most abundant OTUs, CB2‐S‐138, was identified as dominant at the mid‐bay site by both microarray and quantitative PCR assays, but it comprised a much smaller fraction of the assemblage in the north and south bay samples. cDNA (transcribed from total RNA extracts) targets were hybridized to the same array to compare the profiles of community composition at the DNA (relative abundance) and mRNA (gene expression) levels. Only the three dominant denitrifying groups (in terms of relative strength of DNA hybridization signal) were detected at the mRNA level. These results suggest that the most actively denitrifying groups are responsible for most nirS expression as well.
Dynamics of Campylobacter colonization of a natural host, Sturnus vulgaris (European Starling)
Authors: Colles F. M. , McCarthy N. D. , Howe J. C. , Devereux C. L. , Gosler A. G. , Maiden M. C. J.
Published: September 2008

Wild European Starlings (Sturnus vulgaris) shed Campylobacter at high rates, suggesting that they may be a source of human and farm animal infection. A survey of Campylobacter shedding of 957 wild starlings was undertaken by culture of faecal specimens and genetic analysis of the campylobacters isolated: shedding rates were 30.6% for Campylobacter jejuni, 0.6% for C. coli and 6.3% for C. lari. Genotyping by multilocus sequence typing (MLST) and antigen sequence typing established that these bacteria were distinct from poultry or human disease isolates with the ST‐177 and ST‐682 clonal complexes possibly representing starling‐adapted genotypes. There was seasonal variation in both shedding rate and genotypic diversity, both exhibiting a maximum during the late spring/early summer. Host age also affected Campylobacter shedding, which was higher in younger birds, and turnover was rapid with no evidence of cross‐immunity among Campylobacter species or genotypes. In nestlings, C. jejuni shedding was evident from 9 days of age but siblings were not readily co‐infected. The dynamics of Campylobacter infection of starlings differed from that observed in commercial poultry and consequently there was no evidence that wild starlings represent a major source of Campylobacter infections of food animals or humans.
Microbial eukaryotes in the hypersaline anoxic L'Atalante deep‐sea basin
Authors: Alexander Eva , Stock Alexandra , Breiner Hans‐Werner , Behnke Anke , Bunge John , Yakimov Michail M. , Stoeck Thorsten
Published: September 2008

The frontiers of eukaryote life in nature are still unidentified. In this study, we analysed protistan communities in the hypersaline (up to 365 g l−1 NaCl) anoxic L'Atalante deep‐sea basin located in the eastern Mediterranean Sea. Targeting 18S ribosomal RNA retrieved from the basin's lower halocline (3501 m depth) we detected 279 protistan sequences that grouped into 42 unique phylotypes (99% sequence similarity). Statistical analyses revealed that these phylotypes account only for a proportion of the protists inhabiting this harsh environment with as much as 50% missed by this survey. Most phylotypes were affiliated with ciliates (45%), dinoflagellates (21%), choanoflagelates (10%) and uncultured marine alveolates (6%). Sequences from other taxonomic groups like stramenopiles, Polycystinea, Acantharea and Euglenozoa, all of which are typically found in non‐hypersaline deep‐sea systems, are either missing or very rare in our cDNA clone library. Although many DHAB sequences fell within previously identified environmental clades, a large number branched relatively deeply. Phylotype richness, community membership and community structure differ significantly from a deep seawater reference community (3499 m depth). Also, the protistan community in the L'Atalante basin is distinctively different from any previously described hypersaline community. In conclusion, we hypothesize that extreme environments may exert a high selection pressure possibly resulting in the evolution of an exceptional and distinctive assemblage of protists. The deep hypersaline anoxic basins in the Mediterranean Sea provide an ideal platform to test for this hypothesis and are promising targets for the discovery of undescribed protists with unknown physiological capabilities.
Impact of Native Plants on Bird and Butterfly Biodiversity in Suburban Landscapes
Authors: BURGHARDT KARIN T. , TALLAMY DOUGLAS W. , GREGORY SHRIVER W.
Published: September 2008

Abstract:  Managed landscapes in which non‐native ornamental plants are favored over native vegetation now dominate the United States, particularly east of the Mississippi River. We measured how landscaping with native plants affects the avian and lepidopteran communities on 6 pairs of suburban properties in southeastern Pennsylvania. One property in each pair was landscaped entirely with native plants and the other exhibited a more conventional suburban mixture of plants—a native canopy with non‐native groundcover and shrubs. Vegetation sampling confirmed that total plant cover and plant diversity did not differ between treatments, but non‐native plant cover was greater on the conventional sites and native plant cover was greater on the native sites. Several avian (abundance, species richness, biomass, and breeding‐bird abundance) and larval lepidopteran (abundance and species richness) community parameters were measured from June 2006 to August 2006. Native properties supported significantly more caterpillars and caterpillar species and significantly greater bird abundance, diversity, species richness, biomass, and breeding pairs of native species. Of particular importance is that bird species of regional conservation concern were 8 times more abundant and significantly more diverse on native properties. In our study area, native landscaping positively influenced the avian and lepidopteran carrying capacity of suburbia and provided a mechanism for reducing biodiversity losses in human‐dominated landscapes.
Voting Green*
Authors: Coan Travis G. , Holman Mirya R.
Published: September 2008

Objectives. Economics, partisanship, and demographics have all been identified as linked to support for environmental protection. The principal objective of this study is to extend the extant literature by using a larger data set and a variety of methods.

Methods. We use variety of statistical methods to test measures of party strength, demographics, and economics against county‐level data from 29 environmental initiative elections in 13 states.

Results. Democratic partisanship is the most consistent predictor of aggregate support for environmental measures. This trend holds through pooled, individual‐level, and ecological inference analysis. Median family income and income squared are consistently significant, as is education.

Conclusion. Based on these data, we reach three general conclusions. First, while several variables are consistently significant, party strength is the most consistent predictor of pro‐environmental voting across states and initiatives. Second, our analyses suggest that limiting analyses to data from a single state or region may have important implications for statistical inferences. Lastly, a preliminary analysis using methods of ecological inference suggests that the aggregate results are robust to ecological problems.
Evidence of Environmental Justice: A Critical Perspective on the Practice of EJ Research and Lessons for Policy Design*
Authors: Noonan Douglas S.
Published: September 2008

Objective. This article gleans important lessons for environmental justice (EJ) policy from the empirical literature and demonstrates them using EJ analyses of Superfund sites. It constructively critiques the EJ literature and suggests some future directions for designing policy and framing the discourse.

Methods. The research methods of many quantitative EJ studies are reviewed. To demonstrate sensitivity to researchers' choices, logit models are estimated to explain the nationwide distribution of Superfund sites (and deletions from the NPL) using various spatial scales, control variables, and definitions of proximity.

Results. Most empirical EJ studies examine cross‐sectional distributions for aggregated demographic measures, dwelling on the implied counterfactual or causal mechanism briefly, if ever. The EJ analysis for Superfund sites exhibits much sensitivity to modeling choices and to whether environmental conditions or policy impacts are modeled.

Conclusions. The findings highlight the limitations of conventional EJ research designs. Several implications for the design of EJ policy are drawn, emphasizing the importance of clarity about counterfactuals and which sorts of impacts are relevant. Principles for a revised EJ policy framework are proposed.
“I Pay Enough Taxes Already!” Applying Economic Voting Models to Environmental Referendums*
Authors: Bornstein Nicholas , Thalmann Philippe
Published: September 2008

Objectives.Models of economic voting have rarely been applied to referendum votes. We fill this gap by testing citizens' voting behavior on environmental policy in relation to their perception of the business cycle and general orientation toward politics. Thus, the study examines the personal, institutional, and economic determinants of vote choice on 36 environmental bills from 1983 to 2004 in Switzerland.

Methods.We apply a logistic hierarchical model, where individual characteristics on Level 1 are nested within contextual determinants situated on Level 2.Results. We confirm the crucial importance of the individual‐level variables education, political affinity, car ownership, and urbanity. Classifying the electorate into five groups, using open‐ended survey questions about respondents' reasons for approval or dismissal of the bills, allows for finer hypotheses testing. We show that the individuals' positive perception of their personal current economic condition has a positive effect on the likelihood of supporting the proposals. In turn, we prove the negative, constraining effect of deteriorating macroeconomic conditions on approval rates.

Conclusions.By applying economic voting models to referendum analyses we advance the understanding of citizens' vote choice on environmental ballots, we show the role of context, and we propose an original typology of voters' general orientation toward politics.
Exploring Causes of Smart Growth Policy Adoption: Many Challenges Persist*
Authors: Anthony Jerry
Published: September 2008

This article briefly presents the historical evolution of land‐use policies from their origins in the early 20th century to their current form, describes pertinent approaches used in policy adoption and efficacy research, and discusses some of the pitfalls encountered by researchers in this area.
Education and Smart Growth Policies in U.S. Cities: A Response to Lenahan O'Connell*
Authors: Portney Kent E.
Published: September 2008

Objective. This response to Lenahan O'Connell's article “Exploring the Social Roots of Smart Growth Policy Adoption by Cities” examines whether the relationship between education and the adoption of smart growth programs in U.S. cities is reflective of the new political culture and rooted in postmaterial values or, perhaps, just reflective of a slightly different way of thinking about traditional economic development.

Methods. Using data for 45 U.S. cities that have articulated broad policies to try to become more sustainable, this analysis includes a measure of the severity of air pollution as an indicator of the need for smart growth programs.

Results. The measure of need is more strongly related to the pursuit of smart growth than is either education or income.

Conclusions. Since the level of air pollution is frequently understood to make economic growth difficult or impossible, the results suggest that smart growth programs might be just as likely motivated by traditional economic development as by postmaterial values, and there is a need to develop a deeper understanding of the motivates for adopting such programs.
Usefulness of intra‐oral ultrasonography to predict neck metastasis in patients with tongue carcinoma
Authors: Natori T , Koga M , Anegawa E , Nakashima Y , Tetsuka M , Yoh J , Kusukawa J
Published: September 2008

Objective:  To assess tissue characterization relating with neck metastasis of invasive tongue cancer, we investigate the usefulness of intra‐oral ultrasonography (US).

Materials and methods:  The patients with squamous cell carcinoma of the tongue (n = 110) were preoperatively evaluated with intra‐oral US. The US images were compared with histological sections. The histological and ultrasonographic parameters were evaluated for their correlation with neck metastasis.

Results and conclusion:  High‐quality ultrasonic images were obtained, and all lesions over 1 mm thickness by histology were detected. There was a significant correlation (P < 0.0001) between measurements of tumor thickness by US and histology. Univariate analysis showed that the histological parameters influencing neck metastasis were mode of invasion (P = 0.0006), muscular invasion (P < 0.0001), stromal reaction (P = 0.0002), and tumor thickness (P = 0.0004). Of the ultrasonographic parameters, shape of margin (P = 0.019), pattern of margin (P = 0.033), internal echo signal (P = 0.035), and tumor thickness (P < 0.0001) showed a significant correlation with neck metastasis. Ultrasound images of oral tongue cancer reflected the histological structures. Tumors with diffuse invasive mode shows an irregular and unclear tumor margins on US image. Thickness of 8 mm by ultrasound is useful as a cut‐off point of predicting risk of neck metastasis of tongue cancer. Intra‐oral US is a reliable tool in objectively predicting subclinical neck metastasis in tongue cancer.
Ligand binding promotes prion protein aggregation – role of the octapeptide repeats
Authors: Yu Shuiliang , Yin Shaoman , Pham Nancy , Wong Poki , Kang Shin‐Chung , Petersen Robert B. , Li Chaoyang , Sy Man‐Sun
Published: September 2008

Aggregation of the normal cellular prion protein, PrP, is important in the pathogenesis of prion disease. PrP binds glycosaminoglycan (GAG) and divalent cations, such as Cu2+ and Zn2+. Here, we report our findings that GAG and Cu2+ promote the aggregation of recombinant human PrP (rPrP). The normal cellular prion protein has five octapeptide repeats. In the presence of either GAG or Cu2+, mutant rPrPs with eight or ten octapeptide repeats are more aggregation prone, exhibit faster kinetics and form larger aggregates than wild‐type PrP. When the GAG‐binding motif, KKRPK, is deleted the effect of GAG but not that of Cu2+ is abolished. By contrast, when the Cu2+‐binding motif, the octapeptide‐repeat region, is deleted, neither GAG nor Cu2+ is able to promote aggregation. Therefore, the octapeptide‐repeat region is critical in the aggregation of rPrP, irrespective of the promoting ligand. Furthermore, aggregation of rPrP in the presence of GAG is blocked with anti‐PrP mAbs, whereas none of the tested anti‐PrP mAbs block Cu2+‐promoted aggregation. However, a mAb that is specific for an epitope at the N‐terminus enhances aggregation in the presence of either GAG or Cu2+. Therefore, although binding of either GAG or Cu2+ promotes the aggregation of rPrP, their aggregation processes are different, suggesting multiple pathways of rPrP aggregation.
Are Montane Forests Demographic Sinks for Bornean White‐bearded GibbonsHylobates albibarbis?
Authors: Marshall Andrew J.
Published: September 2008

I estimated habitat‐specific population densities for a population of Bornean white‐bearded gibbonsHylobates albibarbisinhabiting seven distinct forest types at Gunung Palung National Park, West Kalimantan, Indonesia. Population densities in montane forests (0.44 individuals/km2) were almost ten times lower than those in the next best habitat (upland granite forest; 4.2 individuals/km2) and far lower than those in lowland forest types. Demographic data on 33 gibbon groups living across the seven forest types showed that reproduction was substantially depressed in montane forests compared to high‐quality lowland habitats. A simple model suggests that montane forests are demographic sinks for gibbons at Gunung Palung. Follow‐up data from observations of montane groups 5 yr after the initial observation period support this result. As high‐quality lowland forests (source habitat for gibbons) are being disproportionately lost in and around Gunung Palung National Park due to illegal logging and conversion to oil palm plantations, an increasing percentage of the remaining forest in the park comprises sink habitat for gibbons. This result has disquieting implications for the long‐term viability of gibbon populations at Gunung Palung. In addition, as montane forests are generally low‐quality habitat for most rainforest vertebrates, and since lowland forests are being lost at alarming rates across the tropics, source‐sink population dynamics similar to those I describe here may characterize populations of other tropical vertebrate species.
Horizontal Accountability in Intergovernmental Organizations
Authors: Grigorescu Alexandru
Published: September 2008

Many intergovernmental organizations (IOs) have recently established offices of internal oversight. Yet scandals such as the one surrounding the Oil-for-Food Program in the United Nations have revealed serious flaws in the design of these institutions, especially their lack of independence from top administrators of the bureaucracies that they are supposed to oversee. This study argues that this is due, in great part, to the initial use of an imperfect domestic model. It shows that, in addition to using a flawed model as a starting point for negotiations, states and IO officials intentionally weakened oversight offices even more. The study argues that member-states need to quickly give such offices increased independence in order to make them more effective and to avoid the continued erosion of the legitimacy of IOs.
Pharmacokinetic and Safety Evaluation of BILR 355, a Second-Generation Nonnucleoside Reverse Transcriptase Inhibitor, in Healthy Volunteers
Authors: Huang Fenglei , Koenen-Bergmann Michael , MacGregor Thomas R. , Ring Arne , Hattox Susan , Robinson Patrick
Published: September 2008

BILR 355 is a second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) under clinical development for the treatment of human immunodeficiency virus infection, particularly in those who harbor virus resistant to the currently available NNRTIs. Two single-center, double-blinded, placebo-controlled, parallel dose-escalation studies were conducted to evaluate the pharmacokinetics and safety of oral BILR 355 administration alone and after coadministration with ritonavir (RTV) at 100 mg. Following a single dose of BILR 355 in oral solution, the mean half life (
t
1/2
) was 2 to 4 h, with peak concentrations occurring at 0.5 to 1 h postadministration. The mean apparent clearance (CL/
F
) ranged from 79.2 to 246 liters/h for administered doses of 12.5 mg to 100 mg. This observed nonlinearity in CL/
F
resulted from the increased bioavailability attributed to a saturated absorption and/or elimination process at higher doses. In contrast, after the coadministration of single doses of 5 mg to 87.5 mg of BILR 355 with RTV, the mean CL/
F
ranged from 5.88 to 8.47 liters/h. Over the dose range (5 to 87.5 mg) studied, systemic BILR 355 exposures were approximately proportional to the doses administered when they were coadministered with RTV. With RTV coadministration, the mean
t
1/2
increased to 10 to 16 h, and the mean time of the maximum concentration in plasma lengthened to 1.5 to 5 h. Compared to the values for BILR 355 given alone, the mean area under the concentration-time curve from time zero to infinity, the maximum concentration in plasma, and the
t
1/2
of BILR 355 achieved after coadministration with RTV increased 15- to 30-fold, 2- to 5-fold, and 3- to 5-fold, respectively. In both studies, BILR 355 appeared to be safe and well tolerated in healthy volunteers when the outcomes in the treated volunteers were compared with those in the placebo group.
Serial Daptomycin Selection Generates Daptomycin-NonsusceptibleStaphylococcus aureusStrains with a Heterogeneous Vancomycin-Intermediate Phenotype
Authors: Camargo Ilana Lopes Baratella da Cunha , Neoh Hui-Min , Cui Longzhu , Hiramatsu Keiichi
Published: September 2008

In order to better understand the mechanism of daptomycin resistance, we generated a daptomycin-nonsusceptible derivative strain, strain 10*3d1 (MIC = 3.0 μg/ml), by in vitro exposure of methicillin-resistantStaphylococcus aureusstrain N315ΔIP (MIC = 0.5 μg/ml) to daptomycin. We also obtained a daptomycin-susceptible phenotypic revertant strain, strain 10*3d1-10 (MIC = 1.0 μg/ml), by passaging 10*3d1 in drug-free medium for 10 days. The resultant triple-isogenic strains were analyzed for their phenotypes and gene expression by microarray analysis. No significant differences in the membrane fluidities of 10*3d1 and 10*3d1-10 compared to the membrane fluidity of N315ΔIP were observed. Resistant strain 10*3d1 had the highest membrane potential, followed by strains 10*3d1-10 and N315ΔIP. The vancomycin and teicoplanin MICs also increased. Teichoic acid genes (tagA,tagG),mprFencoding lysyl-phosphatidylglycerol, andclsencoding cardiolipin synthase were downregulated in 10*3d1 and 10*3d1-10. ThevraFandvraGgenes, which encode ATP binding cassette transporter proteins, were upregulated in 10*3d1. ThevraSRtwo-component regulatory system was upregulated, and electron microscopy revealed that the cell wall of 10*3d1 was significantly thicker than that of the parental strain. Taken together, daptomycin exposure selected a daptomycin-nonsusceptible strain with a phenotype similar to that of heterogeneous vancomycin-intermediateS. aureusand a transcription profile that partially overlapped that of heterogeneous vancomycin-intermediateS. aureus.
Regulatory T Cells Are Locally Induced during Intravaginal Infection of Mice withNeisseria gonorrhoeae
Authors: Imarai Mónica , Candia Enzo , Rodriguez-Tirado Carolina , Tognarelli Javier , Pardo Mirka , Pérez Tomas , Valdés Daniel , Reyes-Cerpa Sebastián , Nelson Pablo , Acuna-Castillo Claudio , Maisey Kevin
Published: September 2008

Neisseria gonorrhoeaeis a gram-negative diplococcus that in human beings produces gonorrhea. Much clinical evidence has led to the conclusion that gonococcus has important mechanisms to evade host immune functions; however, these mechanisms are only now beginning to be elucidated. In this study, we determined that the BALB/c mouse is a good animal model to study gonococcus infection and examined the immune response against the bacteria. We determined that after intravaginal inoculation of mice withNeisseria gonorrhoeae, the bacteria reached and invaded the upper female reproductive tissues and elicited a T-cell-specific immune response associated with a very weak humoral response, altogether resembling gonococcus infection and disease in women. Remarkably, in the draining lymph nodes of the genital tracts of infected mice, we found an increase of regulatory T lymphocytes, namely, transforming growth factor β1-positive CD4+T cells and CD4+CD25+Foxp3+T cells. Altogether, results indicate thatN. gonorrhoeaeinduces regulatory T cells, which might be related to the local survival of the pathogen and the establishment of a chronic asymptomatic infection.
Experimental Malaria Infection Triggers Early Expansion of Natural Killer Cells
Authors: Kim Charles C. , Parikh Sunil , Sun Joseph C. , Myrick Alissa , Lanier Lewis L. , Rosenthal Philip J. , DeRisi Joseph L.
Published: September 2008

In order to gain a better understanding of gene expression during early malaria infection, we conducted microarray analysis of early blood responses in mice infected with erythrocytic-stagePlasmodium chabaudi. Immediately following infection, we observed coordinated and sequential waves of immune responses, with interferon-associated gene transcripts dominating by 16 h postinfection, followed by strong increases in natural killer (NK) cell-associated and major histocompatibility complex class I-related transcripts by 32 h postinfection. We showed by flow cytometry that the observed elevation in NK cell-associated transcripts was the result of a dramatic increase in the proportion of NK cells in the blood during infection. Subsequent microarray analysis of NK cells isolated from the peripheral blood of infected mice revealed a cell proliferation expression signature consistent with the observation that NK cells replicate in response to infection. Early proliferation of NK cells was directly observed in studies with adoptively transferred cells in infected mice. These data indicate that the early response toP. chabaudiinfection of the blood is marked by a primary wave of interferon with a subsequent response by NK cells.
On the selection of samples for multivariate regression analysis: application to near-infrared (NIR) calibration models for the prediction of pulp yield in Eucalyptus nitens
Authors: Mora Christian R. , Schimleck Laurence R.
Published: September 2008

The effects of using reduced calibration sets on the development of near-infrared (NIR) calibration models for the prediction of kraft pulp yield in Eucalyptus nitens (Dean & Maiden) Maiden trees were explored. Three selection techniques based on NIR spectral data (CADEX (computer-aided design of experiments), DUPLEX, and SELECT algorithms) and one selection method based on a measured property (RANKING algorithm) were used for analysis and compared against a model using all data. The effect of using calibration sets of different sizes was also evaluated. All sample-selection methods resulted in models of similar performance compared with the model fitted using all samples. For calibration purposes, RANKING selection resulted in models with the lowest errors of cross-validation, followed by the DUPLEX, CADEX, and SELECT methods. In terms of validation, the SELECT and CADEX methods resulted in lower errors of prediction compared with the DUPLEX and RANKING algorithms. In general, cross-validation and prediction errors decreased as the number of calibration samples increased. These results show that it is possible to obtain adequate NIR calibration models with a reduced number of samples allowing the remaining samples to be used for model validation and that sample selection based on NIR spectral data alone is as successful as selection based on a measured property.
Lakeside riparian forests support diversity of wood fungi in managed boreal forests
Authors: Komonen Atte , Niemi Mari E. , Junninen Kaisa
Published: September 2008

Riparian forests often have a more diverse tree species composition and more woody debris than neighboring upland forests, but little is known about their importance for the conservation of deadwood-dependent species. We studied the forest characteristics and the diversity of wood fungi (poroid Aphyllophorales) in lakeside riparian (flat and sloping topography) and upland boreal forests in eastern Finland. Riparian forests had a higher density of broadleaved trees and broadleaved debris than did upland forests. A total of 48 species of wood fungi were recorded, including eight red-listed or old-growth forest indicator species. Overall, more species and records and greater diversity were observed in the flat riparian sites than in the sloped riparian and upland sites. The mean species richness did not differ significantly among site categories, indicating greater β diversity among the flat riparian sites. Species composition was more similar between the two riparian categories than between the riparian and upland sites. Riparian sites also hosted more fungal species associated with broadleaved trees. The results show that riparian forests support the diversity of wood fungi in managed boreal forests. Diversity of deadwood-dependent organisms can be promoted by leaving wider and completely unharvested riparian buffer zones.
Comparing biomass and nutrient removals of stems and fresh and predried whole trees in thinnings in two Norway spruce experiments
Authors: Stupak Inge , Nordfjell Tomas , Gundersen Per
Published: September 2008

In Denmark, thinning trees used for energy purposes are cut and left to dry in the stand before they are removed as whole trees. This practice causes shedding of needles and reduces nutrient removals for the benefit of long-term site fertility. It is uncertain, however, to what extent needles are shed and actual nutrient loss is affected by this practice. To address this question, we compared biomass and nutrient removals in two Norway spruce ( Picea abies (L.) Karst) experiments in western Denmark. Three contemporary thinning harvest intensities were examined: harvesting of fresh whole trees, predried whole trees, and stems only. The whole trees were chipped individually, and samples were removed to determine moisture and nutrient contents, whereas sample discs were removed from harvested stems. The biomass content of the cut whole trees was estimated to decrease 17% during predrying, whereas nutrient contents decreased 35%–60% for N, P, and K and <32% for Ca and Mg. The biomass content of stems was estimated to be 35%–42% lower than that of fresh whole trees. The corresponding differences in nutrient contents were in the range 84%–89% for N, P, and K and 73%–80% for Ca and Mg. Predrying and technological methods to reduce nutrient removals were compared and discussed.
THE VARIATION FORMULAS FOR THE EQUIVARIANT RAY–SINGER METRIC
Authors: WEISS HARTMUT
Published: September 2008

We give a new and detailed proof of the variation formulas for the equivariant Ray–Singer metric, which are originally due to J. M. Bismut and W. Zhang.
CYCLIC COVERINGS OF ABELIAN VARIETIES AND THE GENERALIZED YANG–MILLS SYSTEM FOR A FIELD WITH GAUGE GROUP SU(2)
Authors: LESFARI A.
Published: September 2008

In this paper, we consider a dynamical system related to the Yang–Mills system for a field with gauge group SU(2). We solve this system in terms of genus two hyperelliptic functions. The corresponding invariant surface defined by the two constants of motion can be completed as a cyclic double cover of an abelian surface (the jacobian of a genus 2 curve) and we show that this system is algebraic completely integrable in the generalized sense. Also we show that this system is part of an algebraic completely integrable system in five unknowns having three constants of motion.
TRANSLATIONS AND DYNAMICS
Authors: TRESGUERRES ROMUALDO
Published: September 2008

We analyze the role played by local translational symmetry in the context of gauge theories of fundamental interactions. Translational connections and fields are introduced, with special attention being paid to their universal coupling to other variables, as well as to their contributions to field equations and to conserved quantities.
CANONICAL CONNECTIONS IN GAUGE-NATURAL FIELD THEORIES
Authors: FERRARIS MARCO , FRANCAVIGLIA MAURO , PALESE MARCELLA , WINTERROTH EKKEHART
Published: September 2008

We investigate canonical aspects concerning the relation between symmetries and conservation laws in gauge-natural field theories. In particular, we find that a canonical spinor connection can be selected by the simple requirement of the global existence of canonical superpotentials for the Lagrangian describing the coupling of gravitational and Fermionic fields. In fact, the naturality of a suitably defined variational Lagragian implies the existence of an associated energy-momentum conserved current. Such a current defines a Hamiltonian form in the corresponding phase space; we show that an associated Hamiltonian connection is canonically defined along the kernel of the generalized gauge-natural Jacobi morphism and uniquely characterizes the canonical spinor connection.
Stochastic formulation of SPICE-type electronic circuit simulation with polynomial chaos
Authors: Strunz Kai , Su Qianli
Published: September 2008

A methodology for efficient tolerance analysis of electronic circuits based on nonsampling stochastic simulation of transients is formulated, implemented, and validated. We model the stochastic behavior of all quantities that are subject to tolerance spectrally with polynomial chaos. A library of stochastic models of linear and nonlinear circuit elements is created. In analogy to the deterministic implementation of the SPICE electronic circuit simulator, the overall stochastic circuit model is obtained using nodal analysis. In the proposed case studies, we analyze the influence of device tolerance on the response of a lowpass filter, the impact of temperature variability on the output of an amplifier, and the effect of changes of the load of a diode bridge on the probability density function of the output voltage. The case studies demonstrate that the novel methodology is computationally faster than the Monte Carlo method and more accurate and flexible than the root-sum-square method. This makes the stochastic circuit simulator, referred to as PolySPICE, a compelling candidate for the tolerance study of reliability-critical electronic circuits.
Metrics-based design selection tool for aspect oriented software development
Authors: Babu Chitra , Vijayalakshmi R.
Published: September 2008

Software metrics provide a means for software practitioners to assess the quality of their software. Ideally, this information should be available earlier in the software development lifecycle, since changes are much more expensive to incorporate in the later stages. Design level metrics offer an elegant way of capturing this information. Research in software design metrics has focused primarily on procedural and object oriented software. However, such metrics are currently not available for Aspect Oriented Software Development (AOSD), which is an emerging paradigm. Aspect Oriented Programming (AOP) is an approach that allows programmers to modularize crosscutting concerns that are scattered across multiple modules. Separation of concerns through aspects has the advantages of increased reliability, adaptability and better reuse. The objective of this paper is to propose suitable metrics for the Aspect Oriented Design (AOD) and to develop a tool that will automatically select a better design based on the proposed metrics. In this paper, class and sequence diagrams are used to represent an AOD. The proposed design level metrics are applied to two alternative designs of an illustrative case study. The tool selects the design that better suits stakeholder requirements, based on logical inferences obtained from these metrics regarding the quality of the Aspect Oriented software.