bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Bayesian Model for Ranking Hazardous Road Sites
Authors: Brijs Tom , Karlis Dimitris , Van den Bossche Filip , Wets Geert 
Published: August 2007

SummaryRoad safety has recently become a major concern in most modern societies. The identification of sites that are more dangerous than others (black spots) can help in better scheduling road safety policies. This paper proposes a methodology for ranking sites according to their level of hazard. The model is innovative in at least two respects. Firstly, it makes use of all relevant information per accident location, including the total number of accidents and the number of fatalities, as well as the number of slight and serious injuries. Secondly, the model includes the use of a cost function to rank the sites with respect to their total expected cost to society. Bayesian estimation for the model via a Markov chain Monte Carlo approach is proposed. Accident data from 519 intersections in Leuven (Belgium) are used to illustrate the methodology proposed. Furthermore, different cost functions are used to show the effect of the proposed method on the use of different costs per type of injury.
Combining Census and Registration Data to Estimate Detailed Elderly Migration Flows in England and Wales
Authors: Raymer James , Abel Guy , Smith Peter W. F. 
Published: August 2007

SummaryA log-linear model is developed to estimate detailed elderly migration flows by combining data from the 2001 UK census and National Health Services patient register. After showing that the census and National Health Service migration flows can be reasonably combined, elderly migration flows between groupings of local authority districts by age, sex and health status for the 2000–2001 and 2003–2004 periods are estimated and then analysed to show how the patterns have changed. By combining registration data with census data, we can provide recent estimates of detailed elderly migration flows, which can be used for improvements in social planning or policy.
Romanticism and Forgery
Authors: Groom Nick 
Published: August 2007

AbstractSeveral literary forgers emerged in the later eighteenth century: notably James Macpherson (Ossian), Thomas Chatterton (Thomas Rowley) and William Henry Ireland (the Shakespeare forger). These cases of literary forgery were highly controversial at the time, and had a lasting impact on the Romantic movement, particularly in the understanding of authenticity, inspiration and the figure of the poet, although by this time plagiarism, hoaxing and impersonation had superseded forgery – most clearly in the cases of Princess Caraboo, Joanna Southcott and the seduction of the Maid of Buttermere. Serious critical attention to both forgers and impostors has dramatically increased in recent years, with feminist, post‐colonial and psychoanalytic readings. Cases of writers of ‘fakelit’ also have serious implications for criticism today.
Cellular Effects of Reversed Amidines on
Trypanosoma cruzi
Authors: Silva C. F. , Meuser M. B. , De Souza E. M. , Meirelles M. N. L. , Stephens C. E. , Som P. , Boykin D. W. , Soeiro M. N. C. 
Published: August 2007

ABSTRACT

Aromatic diamidines represent a class of DNA minor groove-binding ligands that exhibit high levels of antiparasitic activity. Since the chemotherapy for Chagas' disease is still an unsolved problem and previous reports on diamidines and related analogues show that they have high levels of activity against
Trypanosoma cruzi
infection both in vitro and in vivo, our present aim was to evaluate the cellular effects in vitro of three reversed amidines (DB889, DB702, and DB786) and one diguanidine (DB711) against both amastigotes and bloodstream trypomastigotes of
T. cruzi
, the etiological agent of Chagas ' disease. Our data show that the reversed amidines have higher levels of activity than the diguanidine, with the order of trypanocidal activities being as follows: DB889 > DB702 > DB786 > DB711. Transmission electron microscopy analysis showed that the reversed amidines induced many alterations in the nuclear morphology, swelling of the endoplasmic reticulum and Golgi structures, and consistent damage in the mitochondria and kinetoplasts of the parasites. Interestingly, in trypomastigotes treated with the reversed amidine DB889, multiple axoneme structures (flagellar microtubules) were noted. Flow cytometry analysis confirmed that the treated parasites presented an important loss of the mitochondrial membrane potential, as revealed by a decrease in rhodamine 123 fluorescence. Our results show that the reversed amidines have promising activities against the relevant mammalian forms of
T. cruzi
and display high trypanocidal effects at very low doses. This is especially the case for DB889, which merits further in vivo evaluation.
Galanin Message-Associated Peptide Suppresses Growth and the Budded-to-Hyphal-Form Transition ofCandida albicans
Authors: Rauch Isabella , Lundström Linda , Hell Markus , Sperl Wolfgang , Kofler Barbara 
Published: August 2007

ABSTRACTThe expression of the mRNA encoding galanin message-associated peptide (GMAP) in human keratinocytes is upregulated by lipopolysaccharides and exposure toCandida albicans. GMAP has growth-inhibiting activity againstC. albicansand inhibits the budded-to-hyphal-form transition, establishing GMAP as a possible new component of the innate immune system.
The Antifungal Polyketide Ambruticin Targets the HOG Pathway
Authors: Vetcher Leandro , Menzella Hugo G. , Kudo Toshiaki , Motoyama Takayuki , Katz Leonard 
Published: August 2007

ABSTRACT
The polyketide ambruticin is an attractive candidate for drug development as an antifungal agent, but its mechanism of action has not yet been elucidated. Here we present evidence that ambruticin exerts its effect by targeting HOG, the osmotic stress control pathway, through Hik1, a group III histidine kinase.
Genetic Characteristics and Clonal Dissemination of β-Lactamase-Negative Ampicillin-ResistantHaemophilus influenzaeStrains Isolated from the Upper Respiratory Tract of Patients in Japan
Authors: Hotomi Muneki , Fujihara Keiji , Billal Dewan S. , Suzuki Kenji , Nishimura Tadao , Baba Shunkichi , Yamanaka Noboru 
Published: August 2007

ABSTRACTWe evaluated the recent prevalence of antimicrobial-resistantHaemophilus influenzaeisolated from the upper respiratory tracts (URT) of patients in Japan. Mutations in theftsIgene, which encodes penicillin binding protein 3 (PBP3), and the clonal dissemination of the resistant strains were also investigated. A total of 264H. influenzaeisolates were collected from patients with URT infections. According to the criteria of the Clinical and Laboratory Standards Institute for the susceptibility ofH. influenzaeto ampicillin (AMP), the isolates were distributed as follows: 161 (61.0%) susceptible strains (MIC ≤ 1 μg/ml), 37 (14.0%) intermediately resistant strains (MIC = 2 μg/ml), and 66 (25.0%) resistant strains (MIC ≥ 4 μg/ml). According to PCR-based genotyping, 172 (65.1%) of the isolates had mutations in theftsIgene and were negative for the β-lactamase (bla) gene. These 172 isolates were thus defined as genetically β-lactamase-negative ampicillin-resistant (gBLNAR) strains. TheftsImutant group included 98 (37.1%) strains with group I/II mutations in the variable mutated region (group I/II gBLNAR) and 74 (28.0%) strains with group III mutations in the highly mutated region (group III gBLNAR). Eighty-seven (33.0%) of the isolates were genetically β-lactamase-negative ampicillin-susceptible (gBLNAS) strains. The group III gBLNAR strains showed resistance to β-lactams. Only five strains (1.9%) were positive for ablagene encoding TEM-type β-lactamase. The three clusters consisting of 16 strains found among the 61 BLNAR strains (MIC ≥ 4 μg/ml and without theblagene) showed identical or closely related DNA restriction fragment patterns. Those isolates were frequently identified among strains with a MIC to AMP of 16 μg/ml. The current study demonstrates the apparent dissemination and spread of a resistant clone ofH. influenzaeamong medical centers in Japan. The gBLNAR strains show a remarkable prevalence amongH. influenzaeisolates, with the prevalence increasing with time. This fact should be taken into account when treating URT infections.
2,N
6
-Disubstituted Adenosine Analogs with Antitrypanosomal and Antimalarial Activities
Authors: Rodenko Boris , van der Burg Alida M. , Wanner Martin J. , Kaiser Marcel , Brun Reto , Gould Matthew , de Koning Harry P. , Koomen Gerrit-Jan 
Published: August 2007

ABSTRACT

A library of 2,N
6
-disubstituted adenosine analogs was synthesized and the analogs were tested for their antiprotozoal activities. It was found that 2-methoxy and 2-histamino and
N
6
-
m
-iodobenzyl substitutions generally produced analogs with low levels of antiprotozoal activity. The best antiplasmodial activity was achieved with large aromatic substitutions, such as
N
6
-2,2-diphenylethyl and naphthylmethyl, which could indicate a mechanism of action through aromatic stacking with heme in the digestive vacuole of
Plasmodium
spp. The activities against
Trypanosoma cruzi
trypomastigotes and
Leishmania donovani
amastigotes were generally low; but several analogs, particularly those with cyclopentylamino substitutions, displayed potent activities against
Trypanosoma brucei rhodesiense
and
T. b. brucei
bloodstream forms in vitro. The most active were 2-cyclopentylamino-
N
6
-cyclopentyladenosine (compound NA42) and 2-cyclopentylamino-
N
6
-cyclopentyladenine (compound NA134), with the nucleobase an order of magnitude more potent than the nucleoside, at 26 ± 4 nM. It was determined that the mode of action of these purines was trypanostatic, with the compounds becoming trypanocidal only at much higher concentrations. Those 2,N
6
-disubstituted purines tested for their effects on purine transport in
T. b. brucei
displayed at best a moderate affinity for the transporters. It is highly probable that the large hydrophobic substitutions, which bestow high calculated octanol-water coefficient values on the analogs, allow them to diffuse across the membrane. Consistent with this view, the analogs were as effective against a
T. b. brucei
strain lacking the P2 nucleoside transporter as they were against the parental strain. As the analogs were not toxic to human cell lines, the purine analogs are likely to act on a trypanosome-specific target.
A Cysteine Protease Inhibitor Cures Chagas' Disease in an Immunodeficient-Mouse Model of Infection
Authors: Doyle Patricia S. , Zhou Yuan M. , Engel Juan C. , McKerrow James H. 
Published: August 2007

ABSTRACT

Chagas' disease, caused by the parasite
Trypanosoma cruzi
, remains the leading cause of cardiopathy in Latin America with about 12 million people infected. Classic clinical manifestations derive from infection of muscle cells leading to progressive cardiomyopathy, while some patients develop megacolon or megaesophagus. A very aggressive clinical course including fulminant meningoencephalitis has been reported in patients who contract Chagas' disease in the background of immunodeficiency. This includes patients with human immunodeficiency virus infection as well as patients receiving immunosuppressive therapy for organ transplant. Currently, only two drugs are approved for the treatment of Chagas' disease, nifurtimox and benznidazole. Both have significant limitations due to common and serious side effects as well as limited availability. A promising group of new drug leads for Chagas' disease is cysteine protease inhibitors targeting cruzain, the major protease of
T. cruzi
. The inhibitor
N
-methyl-Pip-F-homoF-vinyl sulfonyl phenyl (
N
-methyl-Pip-F-hF-VSφ) is in late-stage preclinical development. Therefore, the question arose as to whether protease inhibitors targeting cruzain would have efficacy in Chagas' disease occurring in the background of immunodeficiency. To address this question, we studied the course of infection in recombinase-deficient (Rag1
−/−
) and normal mice infected with
T. cruzi
. Infections localized to heart and skeletal muscle in untreated normal animals, while untreated Rag1
−/−
mice showed severe infection in all organs and predominantly in liver and spleen. Treatment with the dipeptide
N
-methyl-Pip-F-hF-VSφ rescued immunodeficient animals from lethal Chagas' infection. The majority (60 to 100%) of inhibitor-treated Rag1
−/−
mice had increased survival, negative PCR, and normal tissues by histopathological examination.
Complete Nucleotide Sequence of the pCTX-M3 Plasmid and Its Involvement in Spread of the Extended-Spectrum β-Lactamase GeneblaCTX-M-3
Authors: Gołębiewski M. , Kern-Zdanowicz I. , Zienkiewicz M. , Adamczyk M. , Żyliǹska J. , Baraniak A. , Gniadkowski M. , Bardowski J. , Cegłowski P. 
Published: August 2007

ABSTRACTHere we report the nucleotide sequence of pCTX-M3, a highly conjugative plasmid that is responsible for the extensive spread of the gene coding for the CTX-M-3 extended-spectrum β-lactamase in clinical populations of the familyEnterobacteriaceaein Poland. The plasmid belongs to the IncL/M incompatibility group, is 89,468 bp in size, and carries 103 putative genes. BesidesblaCTX-M-3, it also bears theblaTEM-1,aacC2, andarmAgenes, as well as integronicaadA2,dfrA12, andsul1, which altogether confer resistance to the majority of β-lactams and aminoglycosides and to trimethoprim-sulfamethoxazole. The conjugal transfer genes are organized in two blocks,traandtrb, separated by a spacer sequence where almost all antibiotic resistance genes and multiple mobile genetic elements are located. OnlyblaCTX-M-3, accompanied by an ISEcp1element, is placed separately, in a DNA fragment previously identified as a fragment of theKluyvera ascorbatachromosome. On the basis of sequence analysis, we speculate that pCTX-M3 might have arisen from plasmid pEL60 from plant pathogenErwinia amylovoraby acquiring mobile elements with resistance genes. This suggests that plasmids of environmental bacterial strains could be the source of those plasmids now observed in bacteria pathogenic for humans.
Multiple Antibiotics Exert Delayed Effects against the
Plasmodium falciparum
Apicoplast
Authors: Dahl Erica L. , Rosenthal Philip J. 
Published: August 2007

ABSTRACT

Several classes of antibiotics exert antimalarial activity. The mechanisms of action of antibiotics against malaria parasites have been unclear, and prior studies have led to conflicting results, in part because they studied antibiotics at suprapharmacological concentrations. We examined the antimalarial effects of azithromycin, ciprofloxacin, clindamycin, doxycycline, and rifampin against chloroquine-resistant (W2) and chloroquine-sensitive (3D7)
Plasmodium falciparum
strains. At clinically relevant concentrations, rifampin killed parasites quickly, preventing them from initiating cell division. In contrast, pharmacological concentrations of azithromycin, ciprofloxacin, clindamycin, and doxycycline were relatively inactive against parasites initially but exerted a delayed death effect, in which the progeny of treated parasites failed to complete erythrocytic development. The drugs that caused delayed death did not alter the distribution of apicoplasts into developing progeny. However, the apicoplasts inherited by the progeny of treated parasites were abnormal. The loss of apicoplast function became apparent as the progeny of antibiotic-treated parasites initiated cell division, with the failure of schizonts to fully mature or for erythrocyte rupture to take place. These findings explain the slow antimalarial action of multiple antibiotics.
Artemisinin-Resistant Mutants of
Toxoplasma gondii
Have Altered Calcium Homeostasis
Authors: Nagamune Kisaburo , Moreno Silvia N. J. , Sibley L. David 
Published: August 2007

ABSTRACT

Artemisinin is a plant sesquiterpene lactone that has become an important drug for combating malaria, especially in regions where resistance to other drugs is widespread. While the mechanism of action is debated, artemisinin has been reported to inhibit the sarcoplasmic endoplasmic reticulum Ca
2+
ATPase (SERCA) in the malaria parasite. Artemisinin is also effective against
Toxoplasma
in vitro and in vivo, although it is less potent and, hence, is generally not used therapeutically to treat toxoplasmosis. To explore the mechanism of action, we generated chemically derived mutants of
Toxoplasma gondii
that were resistant to growth inhibition by this compound in vitro. Three artemisinin-resistant (ART
r
) mutant clones that differed in their sensitivities in vitro by three- to fivefold compared with that of the wild-type parasites were obtained. ART
r
mutants were cross-resistant to other derivatives of artemisinin, the most potent of which was artemisone. Resistance was not due to molecular alterations or differences in the expression of SERCA or other putative targets, such as proteins that code for multidrug resistance or translationally controlled tumor protein. ART
r
mutants were resistant to the induction of protein secretion from micronemes, a calcium-dependent process that is triggered by artemisinin. ART
r
mutants were not cross-resistant to secretion induced by thapsigargin but were more sensitive and were unable to regulate cytoslic calcium following treatment with this compound. These studies implicate calcium homeostasis in the mechanism of action of artemisinins against apicomplexan parasites.
Comparative Analysis of IncHI2 Plasmids Carrying
bla
CTX-M-2
or
bla
CTX-M-9
from
Escherichia coli
and
Salmonella enterica
Strains Isolated from Poultry and Humans
Authors: Fernández Aurora García , Cloeckaert Axel , Bertini Alessia , Praud Karine , Doublet Benoît , Weill François-Xavier , Carattoli Alessandra 
Published: August 2007

ABSTRACT

Salmonella enterica bla
CTX-M-2
and
bla
CTX-M-9
plasmid backbones from isolates from Belgium and France were analyzed. The
bla
CTX-M-2-
plasmids from both human and poultry isolates were related to the IncHI2 pAPEC-O1-R plasmid, previously identified in the United States in avian
Escherichia coli
strains; the
bla
CTX-M-9
plasmids were closely related to the IncHI2 R478 plasmid.
Hemolysin and the Multifunctional Autoprocessing RTX Toxin Are Virulence Factors during Intestinal Infection of Mice with
Vibrio cholerae
El Tor O1 Strains
Authors: Olivier Verena , Haines G. Kenneth , Tan Yanping , Satchell Karla J. Fullner 
Published: August 2007

ABSTRACT

The seventh cholera pandemic that started in 1961 was caused by
Vibrio cholerae
O1 strains of the El Tor biotype. These strains produce the pore-forming toxin hemolysin, a characteristic used clinically to distinguish classical and El Tor biotypes. Even though extensive in vitro data on the cytolytic activities of hemolysin exist, the connection of hemolysin to virulence in vivo is not well characterized. To study the contribution of hemolysin and other accessory toxins to pathogenesis, we utilized the model of intestinal infection in adult mice sensitive to the actions of accessory toxins. In this study, we showed that 4- to 6-week-old streptomycin-fed C57BL/6 mice were susceptible to intestinal infection with El Tor strains, which caused rapid death at high doses. Hemolysin had the predominant role in lethality, with a secondary contribution by the multifunctional autoprocessing RTX (MARTX) toxin. Cholera toxin and hemagglutinin/protease did not contribute to lethality in this model. Rapid death was not caused by increased dissemination due to a damaged epithelium since the numbers of CFU recovered from spleens and livers 6 h after infection did not differ between mice inoculated with hemolysin-expressing strains and those infected with non-hemolysin-expressing strains. Although accessory toxins were linked to virulence, a strain defective in the production of accessory toxins was still immunogenic since mice immunized with a multitoxin-deficient strain were protected from a subsequent lethal challenge with the wild type. These data suggest that hemolysin and MARTX toxin contribute to vaccine reactogenicity but that the genes for these toxins can be deleted from vaccine strains without affecting vaccine efficacy.
Six Genes Are Preferentially Transcribed by the Circulating and Sequestered Forms ofPlasmodium falciparumParasites That Infect Pregnant Women
Authors: Francis Susan E. , Malkov Vladislav A. , Oleinikov Andrew V. , Rossnagle Eddie , Wendler Jason P. , Mutabingwa Theonest K. , Fried Michal , Duffy Patrick E. 
Published: August 2007

ABSTRACTIn areas of stable malaria transmission, susceptibility toPlasmodium falciparummalaria increases during first pregnancy. Women become resistant to pregnancy malaria over successive pregnancies as they acquire antibodies against the parasite forms that sequester in the placenta, suggesting that a vaccine is feasible. Placental parasites are antigenically distinct and bind receptors, like chondroitin sulfate A (CSA), that are not commonly bound by other parasites. We used whole-genome-expression analysis to find transcripts that distinguish parasites of pregnant women from other parasites and employed a novel approach to define and adjust for cell cycle timing of parasites. Transcription of six genes was substantially higher in both placental parasites and peripheral parasites from pregnant women, and each gene encodes a protein with a putative export sequence and/or transmembrane domain. This cohort of genes includesvar2csa, a member of the variant PfEMP1 gene family previously implicated in pregnancy malaria, as well as five conserved genes of unknown functions. Women in East Africa acquire antibodies over successive pregnancies against a protein encoded by one of these genes,PFD1140w, and this protein shows seroreactivity similar to that of VAR2CSA domains. These findings suggest that a suite of genes may be important for the genesis of the placental binding phenotype ofP. falciparumand may provide novel targets for therapeutic intervention.
CD4 T-Cell Epitopes Associated with Protective Immunity Induced following Vaccination of Mice with an Ehrlichial Variable Outer Membrane Protein
Authors: Nandi Bisweswar , Hogle Kathryn , Vitko Nicholas , Winslow Gary M. 
Published: August 2007

ABSTRACT

The ehrlichiae express variable outer membrane proteins (OMPs) that play important roles in both pathogenesis and host defense. Previous studies revealed that OMPs are immunodominant B-cell antigens and that passive transfer of anti-OMP antibodies can protect SCID mice from fatal ehrlichial infection. In this study, we used a model of fatal monocytotropic ehrlichiosis caused by
Ehrlichia
bacteria from
Ixodes ovatus
(IOE) to determine whether OMP immunization could generate protective immunity in immunocompetent mice. Immunization of C57BL/6 mice with a purified recombinant OMP expressed by IOE
omp19
generated protection from fatal IOE infection and elicited robust humoral and CD4 T-cell responses. To identify CD4 T-cell epitopes within OMPs, we performed enzyme-linked immunospot analyses for gamma interferon (IFN-γ) production using a panel of overlapping 16-mer peptides from IOE OMP-19. Five immunoreactive peptides comprising residues 30 to 45, 77 to 92, 107 to 122, 197 to 212, and 247 to 264 were identified; the strongest response was generated against OMP-19
107-122
. Most of the peptides are conserved between
E. muris
and
E. chaffeensis
OMP-19, and they elicited IFN-γ production in CD4 T cells from
E. muris
-infected mice, indicating that T-cell epitope cross-reactivity likely contributes to heterologous immunity. Accordingly, CD4 T-cell responses to both OMP-19 and OMP-19
107-122
were of greater magnitude following high-dose IOE challenge of mice that had been immunized by prior infection with
E. muris
. Our studies cumulatively identify B- and T-cell epitopes that are associated with protective homologous and heterologous immunity during ehrlichial infection.