bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virtual Environments and the Acceleration of Experiential Learning
Authors: Wild Chris 
Published: August 2010

Summary Darius et al. (2007) and Nolan & Temple Lang (2007) give examples of virtual environments that can, for specific purposes, substitute for the real world. We are in the early stages of developments that could revolutionize statistics education by making it possible to capture efficiently important aspects of the thinking and practice of professional statisticians previously learned only from long years of experience. The ability of virtual environments to automate processes provides a potent weapon for tackling the tyranny that Time exercises over such modes of learning. We discuss the many new possibilities that are opened up by virtual environments together with cognitive and pedagogical imperatives to be addressed to ensure that environments actually do teach the lessons they were designed to teach. We echo Nolan and Temple Lang's call for the development of environments to be modular and open source. Taking the R‐project as a model, this can lead to a growing repository of building blocks that make the construction of future environments less costly, thus facilitating the realization of more and more ambitious conceptions.
Exopolysaccharides of Lactobacillus rhamnosus GG form a protective shield against innate immune factors in the intestine
Authors: Lebeer Sarah , Claes Ingmar J. J. , Verhoeven Tine L. A. , Vanderleyden Jos , De Keersmaecker Sigrid C. J. 
Published: August 2010

SummaryProbiotic bacteria are administered as live microorganisms to provide a health benefit to the host. Insight into the adaptation factors that promote the survival and persistence of probiotics in the gastrointestinal tract (GIT) is important to understand their performance. In this study, the role of the long galactose‐rich exopolysaccharides (EPS) of the prototypical probiotic strain Lactobacillus rhamnosus GG (LGG) was investigated. In a competition experiment with wild type, the isogenic EPS mutant CMPG5351 exhibited a reduced persistence in the murine GIT, especially in the lower parts of the intestine. This was surprising as our previous in vitro studies had shown an increased adhesion capacity for this EPS mutant. Follow‐up assays indicated that this mutant is more sensitive towards host innate defence molecules, such as the LL‐37 antimicrobial peptide and complement factors. This suggests that EPS forms a protective shield for LGG against these molecules in the GIT. Moreover, culturing LGG wild‐type in subinhibitory concentrations of host defence factors such as LL‐37 resulted in increased production of EPS, indicating that bacterial EPS production is modulated in the host to fine‐tune the balance between adhesion and immune evasion. These observations are of interest in understanding the dynamics of adaptation of probiotics to the host environments.
Interobserver variability for retreatment indications after Ranibizumab loading doses in neovascular age‐related macular degeneration
Authors: Framme Carsten , Panagakis Georgios , Walter Andreas , Gamulescu Maria Andreea , Herrmann Wolfgang , Helbig Horst 
Published: August 2010

Abstract.Purpose:  To assess the interobserver variability (IOV) in indicating retreatment for neovascular Age‐related macular degeneration 4 weeks after three Ranibizumab loading doses using spectral domain OCT (SD‐OCT) as the primary objective diagnostic tool.Material and methods:  Four observers decided for or against 4th Ranibizumab injection in 108 patients by six different rating rounds (RR) based on the SD‐OCT findings after the loading doses. Postoperative OCT images were supplemented consecutively with information from a chart review as the ‘patients subjective estimation of vision (SE)’, the course of best‐corrected visual acuity (BCVA) and the preoperative OCT as well as all information collectively. Agreement rates (AR) and Kappa statistics were calculated.Results:  Based on post‐treatment OCT findings only (RR1), mean reinjection rate of all observers was 37.5%. Adding supplementary information, mean reinjection rate decreased to 20% when all information was available reflecting the ‘real’ situation (RR 6). Interobserver agreement rates varied from 66.7% to 90.7% depending on rating rounds and interobserver pairs. Mean AR and Kappa values (KV) were as following: AR 81.6%, KV 0.61 (RR1: ‘only post‐OP OCT’); AR 76.7%, KV 0.33 (RR2: post‐OP OCT + SE); AR 80.3%, KV 0.45 (RR3: post‐OP OCT + BCVA); AR 80.7%, KV 0.46 (RR4: pre‐ and post‐OP OCT); AR 82.2%, KV 0.49 (RR5: post‐OP OCT + SE + BCVA); and finally AR 83.6%, KV 0.47 (RR6: pre‐ and post‐OP OCT + SE + BCVA). The overall mean agreement rate was 80.9% with a Kappa of 0.47.Conclusion:  IOV for indicating retreatment after three Ranibizumab loading doses reveals only moderate agreement in Kappa statistics, which seems to be too low considering the high costs for retreatments. More concise guidelines based on the post‐treatment OCT scans as the presumably most sensitive and noninvasive objective tool to follow choroidal neovascularization activity by judging the course of sub‐ and intraretinal fluid are necessary.
Distances between thoracic spinous processes in Warmblood foals: A radiographic study
Authors: SINDING M. F. , BERG L. C. 
Published: August 2010

SummaryReason for performing study:The aetiological factors behind impinged or overriding of dorsal spinous processes (‘kissing spine syndrome’, KSS) are not clearly understood. Back conformation, breed, age, training and gender may play important roles in this condition. Radiographic changes vary and abnormalities are seen in many clinically normal horses, but the conclusion of previous studies in mature horses is that interspinous spaces <4 mm are considered too narrow and potentially indicative of KSS.Objectives:To evaluate whether narrowing of the interspinous space was present in a population of normal Warmblood foals.Materials and methods:The mean interspinous space width in the area of T10–L1 was measured on radiographs from 25 Warmblood foals aged 9–88 days.Results:Mean ± s.d. interspinous space width was found to be between 5.9 ± 1.2 and 8.9 ± 2.6 mm with the narrowest space in the area T16–T17 and the widest space in T10–T12. No interspinous spaces were <4 mm wide. Gender and location of the interspinous space significantly affected the width of the distance between the spinous processes.Conclusions and potential relevance:In this study none of the interspinous spaces were <4 mm and therefore none of the foals showed signs of impinged or overriding of dorsal spinous processes known as KSS based on the current definitions. Consequently, in this population, there did not appear to be a congenital narrowing of the interspinous space. However, long‐term follow‐up studies, including detailed information on imposed factors such as training, are needed in order to further elucidate a possible congenital component in the aetiology of KSS.
Report of the Second Havemeyer EHV‐1 Workshop, Steamboat Springs, Colorado, USA, September 2008
Authors: KYDD J. H. , SLATER J. , OSTERRIEDER N. , ANTCZAK D. F. , LUNN D. P. 
Published: August 2010

SummaryThis report summarises the findings of the Second Havemeyer EHV‐1 Workshop, which was held in Steamboat Springs, Colorado, USA in September 2008. A total of 38 delegates, consisting of veterinary clinicians and scientists from academia and industry participated in a series of sessions that focused on equine herpesvirus myeloencephalopathy (EHM). Each session consisted of a review, followed by short presentations on current research topics. The sessions included EHM epidemiology, in vivo and in vitro models for studying EHM, EHV‐1 virulence determinants, real‐time PCR diagnostics, antiviral medications and new vaccination technologies. The report summarises the key advances identified during and since the meeting. Citations are restricted to selected reviews and papers published since the workshop.
The rank of a hypergeometric system
Authors: Berkesch Christine 
Published: August 2010

AbstractThe holonomic rank of the A-hypergeometric system MA(β) is the degree of the toric ideal IA for generic parameters; in general, this is only a lower bound. To the semigroup ring of A we attach the ranking arrangement and use this algebraic invariant and the exceptional arrangement of non-generic parameters to construct a combinatorial formula for the rank jump of MA(β). As consequences, we obtain a refinement of the stratification of the exceptional arrangement by the rank of MA(β) and show that the Zariski closure of each of its strata is a union of translates of linear subspaces of the parameter space. These results hold for generalized A-hypergeometric systems as well, where the semigroup ring of A is replaced by a non-trivial weakly toric module M⊆ℂ[ℤA] . We also provide a direct proof of the main result in [M. Saito, Isomorphism classes of A-hypergeometric systems, Compositio Math. 128 (2001), 323–338] regarding the isomorphism classes of MA (β) .
Subinhibitory Concentrations of Protein Synthesis-Inhibiting Antibiotics Promote Increased Expression of the
agr
Virulence Regulator and Production of Phenol-Soluble Modulin Cytolysins in Community-Associated Methicillin-Resistant
Staphylococcus aureus
Authors: Joo Hwang-Soo , Chan June L. , Cheung Gordon Y. C. , Otto Michael 
Published: August 2010

ABSTRACT

Tetracycline, clindamycin, and other protein synthesis inhibitors at subinhibitory concentrations significantly increased the expression of the pivotal virulence regulator
agr
and production of the
agr
-regulated cytolytic phenol-soluble modulins in the community-associated methicillin-resistant
Staphylococcus aureus
(CA-MRSA) strain USA300. Our results suggest that such protein synthesis inhibitors may exacerbate the progression of CA-MRSA disease when applied at concentrations that are too low or when treating infections caused by strains resistant to those antibiotics.
Population Pharmacokinetics and Pharmacodynamics of Artemether and Lumefantrine during Combination Treatment in Children with Uncomplicated Falciparum Malaria in Tanzania
Authors: Hietala Sofia Friberg , Mårtensson Andreas , Ngasala Billy , Dahlström Sabina , Lindegårdh Niklas , Annerberg Anna , Premji Zul , Färnert Anna , Gil Pedro , Björkman Anders , Ashton Michael 
Published: August 2010

ABSTRACT
The combination of artemether (ARM) and lumefantrine is currently the first-line treatment of uncomplicated falciparum malaria in mainland Tanzania. While the exposure to lumefantrine has been associated with the probability of adequate clinical and parasitological cure, increasing exposure to artemether and the active metabolite dihydroartemisinin (DHA) has been shown to decrease the parasite clearance time. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine in African children with uncomplicated malaria. In addition to drug concentrations and parasitemias from 50 Tanzanian children with falciparum malaria, peripheral parasite densities from 11 asymptomatic children were included in the model of the parasite dynamics. The population pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine were modeled in NONMEM. The distribution of artemether was described by a two-compartment model with a rapid absorption and elimination through metabolism to dihydroartemisinin. Dihydroartemisinin concentrations were adequately illustrated by a one-compartment model. The pharmacokinetics of artemether was time dependent, with typical oral clearance increasing from 2.6 liters/h/kg on day 1 to 10 liters/h/kg on day 3. The pharmacokinetics of lumefantrine was sufficiently described by a one-compartment model with an absorption lag time. The typical value of oral clearance was estimated to 77 ml/h/kg. The proposed semimechanistic model of parasite dynamics, while a rough approximation of the complex interplay between malaria parasite and the human host, adequately described the early effect of ARM and DHA concentrations on the parasite density in malaria patients. However, the poor precision in some parameters illustrates the need for further data to support and refine this model.
TelA Contributes to the Innate Resistance of
Listeria monocytogenes
to Nisin and Other Cell Wall-Acting Antibiotics
Authors: Collins Barry , Joyce Susan , Hill Colin , Cotter Paul D. , Ross R. Paul 
Published: August 2010

ABSTRACT

Nisin is a class I bacteriocin (lantibiotic), which is employed by the food and veterinary industries and exhibits potent activity against numerous pathogens. However, this activity could be further improved through the targeting and inhibition of factors that contribute to innate nisin resistance. Here we describe a novel locus,
lmo1967
, which is required for optimal nisin resistance in
Listeria monocytogenes
. The importance of this locus, which is a homologue of the tellurite resistance gene
telA
, was revealed after the screening of a
mariner
random mutant bank of
L. monocytogenes
for nisin-susceptible mutants. The involvement of
telA
in nisin resistance was confirmed through an analysis of a nonpolar deletion mutant. In addition to being 4-fold-more susceptible to nisin, the Δ
telA
strain was also 8-fold-more susceptible to gallidermin and 2-fold-more susceptible to cefuroxime, cefotaxime, bacitracin, and tellurite. This is the first occasion upon which
telA
has been investigated in a Gram-positive organism and also represents the first example of a link being established between a
telA
gene and resistance to cell envelope-acting antimicrobials.
Genetic and Functional Variability of AmpC-Type β-Lactamases from
Acinetobacter baumannii
Authors: Rodríguez-Martínez José-Manuel , Poirel Laurent , Nordmann Patrice 
Published: August 2010

ABSTRACT

The incidence of naturally occurring AmpC β-lactamases with extended activities toward several cephalosporins was evaluated among 17 ceftazidime (CAZ)-resistant
Acinetobacter baumannii
isolates. Five AmpC β-lactamases (named ADC β-lactamases) were identified, among which those possessing the Val208Ala (inside the omega-loop) or Asn283Ser (helix H-10) substitution conferred higher levels of resistance (4- to 64-fold higher) to CAZ and to cefotaxime in
Escherichia coli
. This study demonstrates that peculiar AmpCs playing a role in resistance to broad-spectrum cephalosporins in
A. baumannii
may be identified.
Activity of the Histone Deacetylase Inhibitor FR235222 on
Toxoplasma gondii
: Inhibition of Stage Conversion of the Parasite Cyst Form and Study of New Derivative Compounds
Authors: Maubon Danièle , Bougdour Alexandre , Wong Yung-Sing , Brenier-Pinchart Marie-Pierre , Curt Aurélie , Hakimi Mohamed-Ali , Pelloux Hervé 
Published: August 2010

ABSTRACT

Bradyzoite-to-tachyzoite conversion plays a role in the pathogenesis of recrudescence of ocular toxoplasmosis and disease in immunocompromised persons. The currently available medicines are ineffective on cysts and fail to prevent reactivation of latent toxoplasmosis. A previous study showed that the histone deacetylase inhibitor FR235222 has a dramatic effect on tachyzoite growth and induces tachyzoite-to-bradyzoite conversion
in vitro
. The present study shows that FR235222 can target
in vitro
-converted cysts and bradyzoites. Moreover, the compound is active on
ex vivo T. gondii
cysts. Free bradyzoites isolated after lysis of the cell wall did not proliferate
in vitro
when the cyst was treated with FR235222. The results imply that this compound is able to cross the
T. gondii
cystic cell wall. Fluorescent labeling shows that the compound impairs the capacity of the bradyzoites to convert without damaging the cyst wall integrity.
In vivo
inoculation of formerly treated cysts fails to infect mice when these cysts were treated with FR235222. We used our structural knowledge of FR235222 and its target,
T. gondii
HDAC3, to synthesize new FR235222 derivative compounds. We identified two new molecules that are highly active against tachyzoites. They harbor a better selectivity index that is more suitable for a future
in vivo
approach. These results identify FR235222 and its derivatives as new lead compounds in the range of therapeutics available for acute and chronic toxoplasmosis.
A Chimeric Protein That Functions as both an Anthrax Dual-Target Antitoxin and a Trivalent Vaccine
Authors: Wu Gaobing , Hong Yuzhi , Guo Aizhen , Feng Chunfang , Cao Sha , Zhang Cheng-Cai , Shi Ruiping , Tan Yadi , Liu Ziduo 
Published: August 2010

ABSTRACT

Effective measures for the prophylaxis and treatment of anthrax are still required for counteracting the threat posed by inhalation anthrax. In this study, we first demonstrated that the chimeric protein LFn-PA, created by fusing the protective antigen (PA)-binding domain of lethal factor (LFn) to PA, retained the functions of the respective molecules. On the basis of this observation, we attempted to develop an antitoxin that targets the binding of lethal factor (LF) and/or edema factor (EF) to PA and the transportation of LF/EF. Therefore, we replaced PA in LFn-PA with a dominant-negative inhibitory PA (DPA), i.e., PA
F427D
. In
in vitro
models of anthrax intoxication, the LFn-DPA chimera showed 3-fold and 2-fold higher potencies than DPA in protecting sensitive cells against anthrax lethal toxin (LeTx) and edema toxin (EdTx), respectively. In animal models, LFn-DPA exhibited strong potency in rescuing mice from lethal challenge with LeTx. We also evaluated the immunogenicity and immunoprotective efficacy of LFn-DPA as an anthrax vaccine candidate. In comparison with recombinant PA, LFn-DPA induced significantly higher levels of the anti-PA immune response. Moreover, LFn-DPA elicited an anti-LF antibody response that could cross-react with EF. Mice immunized with LFn-DPA tolerated a LeTx challenge that was 5 times its 50% lethal dose. Thus, LFn-DPA represents a highly effective trivalent vaccine candidate for both preexposure and postexposure vaccination. Overall, we have developed a novel and dually functional reagent for the prophylaxis and treatment of anthrax.
The Initial 96 Hours of Invasive Pulmonary Aspergillosis: Histopathology, Comparative Kinetics of Galactomannan and (1→3)-β-
d
-Glucan, and Consequences of Delayed Antifungal Therapy
Authors: Hope William W. , Petraitis Vidmantas , Petraitiene Ruta , Aghamolla Tamarra , Bacher John , Walsh Thomas J. 
Published: August 2010

ABSTRACT

Acute invasive pulmonary aspergillosis is a rapidly progressive and frequently lethal infection. Relatively little is known about early events in the pathogenesis and relationship between the cell wall biomarkers galactomannan and (1→3)-β-
d
-glucan. The consequences of delayed antifungal therapy are also poorly defined. A persistently neutropenic rabbit model of invasive pulmonary aspergillosis was used to describe the histopathology of early invasive pulmonary aspergillosis and the kinetics of galactomannan and (1→3)-β-
d
-glucan. The time course of both molecules was mathematically modeled by using a population methodology, and Monte Carlo simulations were performed. The effect of progressive delay in the administration of amphotericin B deoxycholate 1 mg/kg at 24, 48, 72, and 96 h postinoculation on fungal burden, lung weight, pulmonary infarct score, and survival was determined. Histopathology showed phagocytosis of conidia by pulmonary alveolar macrophages at 4 h postinoculation. At 12 to 24 h, there was a progressive focal inflammatory response with conidial germination and hyphal extension. Subsequently, hyphae invaded into the contiguous lung. Galactomannan and (1→3)-β-
d
-glucan had similar trajectories, and both exhibited considerable interindividual variability, which was reflected in Monte Carlo simulations. Concentrations of both molecules began to rise <24 h postinoculation before pulmonary hemorrhagic infarction was present. Delays of 72 and 96 h in the administration of amphotericin B resulted in fungal burdens and lung weights that were indistinguishable from those of controls, respectively. Galactomannan and (1→3)-β-
d
-glucan have similar kinetics and are comparable biomarkers of early invasive pulmonary aspergillosis. Antifungal treatment at ≥48 h postinoculation is associated with suboptimal therapeutic outcomes.
1-
O
-Hexadecyloxypropyl Cidofovir (CMX001) Effectively Inhibits Polyomavirus BK Replication in Primary Human Renal Tubular Epithelial Cells
Authors: Rinaldo Christine Hanssen , Gosert Rainer , Bernhoff Eva , Finstad Solrun , Hirsch Hans H. 
Published: August 2010

ABSTRACT

Antiviral drugs for treating polyomavirus BK (BKV) replication in polyomavirus-associated nephropathy or hemorrhagic cystitis are of considerable clinical interest. Unlike cidofovir, the lipid conjugate 1-
O
-hexadecyloxypropyl cidofovir (CMX001) is orally available and has not caused detectable nephrotoxicity in rodent models or human studies to date. Primary human renal proximal tubular epithelial cells were infected with BKV-Dunlop, and CMX001 was added 2 h postinfection (hpi). The intracellular and extracellular BKV DNA load was determined by quantitative PCR. Viral gene expression was examined by quantitative reverse transcription-PCR, Western blotting, and immunofluorescence microscopy. We also examined host cell viability, proliferation, metabolic activity, and DNA replication. The titration of CMX001 identified 0.31 μM as the 90% effective concentration (EC
90
) for reducing the extracellular BKV load at 72 hpi. BKV large T antigen mRNA and protein expression was unaffected at 24 hpi, but the intracellular BKV genome was reduced by 90% at 48 hpi. Late gene expression was reduced by 70 and 90% at 48 and 72 hpi, respectively. Comparisons of CMX001 and cidofovir EC
90
s from 24 to 96 hpi demonstrated that CMX001 had a more rapid and enduring effect on BKV DNA and infectious progeny at 96 hpi than cidofovir. CMX001 at 0.31 μM had little effect on overall cell metabolism but reduced bromodeoxyuridine incorporation and host cell proliferation by 20 to 30%, while BKV infection increased cell proliferation in both rapidly dividing and near-confluent cultures. We conclude that CMX001 inhibits BKV replication with a longer-lasting effect than cidofovir at 400× lower levels, with fewer side effects on relevant host cells
in vitro
.