bluuebunny/crossref_metadata_2025_split huggingface dataset:
Von Wille‐brand's disease in UK dober‐manns: Possible correlation of a polymorphic DNA marker with disease status
Authors: Holmes N. G. , Shaw S. C. , Dickens H. F. , Coombes L. M. , Ryder E. J. , Littlewood J. D. , Binns M. M. 
Published: April 2008

ABSTRACTNinety‐one dobermanns have been typed for a polymorphic microsatellite DNA marker situated within an intron of the von Willebrand factor gene and the alleles correlated with von Wille‐brand's disease status. Two alleles were identified, one associated only with the normal gene and the other with both normal and disease genes.
Photo‐induced Reactive Oxygen Species Generation by Different Water‐soluble Fullerenes (C60) and Their Cytotoxicity in Human Keratinocytes
Authors: Zhao Baozhong , Bilski Piotr J. , He Yu‐Ying , Feng Li , Chignell Colin F. 
Published: April 2008

AbstractIn this study we report the phototoxicity toward HaCaT keratinocytes that results from the photogeneration of superoxide and singlet oxygen (1O2) by four different “water‐soluble” fullerene (C60) preparations—monomeric (γ‐CyD)2/C60 (γ‐cyclodextrin bicapped C60) and three aggregated forms—THF/nC60 (prepared by solvent exchange from THF solution); Son/nC60 (prepared by sonication of a toluene/water mixture); and γ‐CyD/nC60 (prepared by heating the [γ‐CyD]2/C60 aqueous solution). Our results demonstrate that all four C60 preparations photogenerate 1O2 efficiently. However, the properties of C60‐generated 1O2, including its availability for reactions in solution, are markedly different for the monomeric and aggregated forms. 1O2 produced by monomeric (γ‐CyD)2/C60 is quenchable by NaN3 and its quantum yield in D2O, which is only weakly dependent on oxygen concentration, is as high as C60 in toluene. In contrast, 1O2 generated from aggregated C60 is not quenchable by NaN3, exhibits a solvent‐independent short‐lived lifetime (ca 2.9 μs), is highly sensitive to oxygen concentration while its phosphorescence is redshifted. All these features indicate that 1O2 is sequestered inside the C60 aggregates, which may explain why these preparations were not phototoxic toward HaCaT cells. Electron paramagnetic resonance studies demonstrated the generation of the C60 anion radical (C60•−) when (γ‐CyD)2/C60 was irradiated (λ > 300 nm) in the presence of a reducing agent (NADH); spin trapping experiments (λ > 400 nm) with 5,5‐dimethyl‐1‐pyrroline N‐oxide clearly showed the generation of superoxide resulting from the reaction of C60•− with oxygen. In vitro tests with HaCaT keratinocytes provided evidence that (γ‐CyD)2/C60 phototoxicity is mainly mediated by 1O2 (Type II mechanism) with only a minor contribution from free radicals (Type I mechanism).
Posaconazole against
Candida glabrata
Isolates with Various Susceptibilities to Fluconazole
Authors: Spreghini Elisabetta , Maida Carmelo Massimo , Tomassetti Serena , Orlando Fiorenza , Giannini Daniele , Milici Maria Eleonora , Scalise Giorgio , Barchiesi Francesco 
Published: April 2008

ABSTRACT

We investigated the in vitro activities of posaconazole (POS), fluconazole (FLC), amphotericin B (AMB), and caspofungin (CAS) against four clinical isolates of
Candida glabrata
with various susceptibilities to FLC (FLC MICs ranging from 1.0 to >64 μg/ml). POS MICs ranged from ≤0.03 to 0.5 μg/ml; AMB MICs ranged from 0.25 to 2.0 μg/ml, while CAS MICs ranged from 0.03 to 0.25 μg/ml. When FLC MICs increased, so did POS MICs, although we did not observe any isolate with a POS MIC greater than 0.5 μg/ml. Time-kill experiments showed that POS, FLC, and CAS were fungistatic against all isolates, while AMB at eight times the MIC was fungicidal against three out of four isolates of
C. glabrata
tested. Then, we investigated the activity of POS in an experimental model of disseminated candidiasis using three different isolates of
C. glabrata
: one susceptible to FLC (S; FLC MICs ranging from 1.0 to 4.0 μg/ml; POS MIC of ≤0.03 μg/ml), one susceptible in a dose-dependent manner (SDD; FLC MICs ranging from 32 to 64 μg/ml; POS MICs ranging from 0.125 to 0.25 μg/ml), and another one resistant to FLC (R; FLC MIC of >64 μg/ml; POS MIC of 0.5 μg/ml). FLC significantly reduced the kidney burden of mice infected with the S strain (
P
= 0.0070) but not of those infected with the S-DD and R strains. POS was significantly effective against all three isolates at reducing the kidney fungal burden with respect to the controls (
P
ranging from 0.0003 to 0.029). In conclusion, our data suggest that POS may be a useful option in the management of systemic infections caused by
C. glabrata
. Additionally, the new triazole may be a therapeutic option in those cases where an FLC-resistant isolate is found to retain a relatively low POS MIC.
Population Pharmacokinetics of Rifampin in Pulmonary Tuberculosis Patients, Including a Semimechanistic Model To Describe Variable Absorption
Authors: Wilkins Justin J. , Savic Radojka M. , Karlsson Mats O. , Langdon Grant , McIlleron Helen , Pillai Goonaseelan , Smith Peter J. , Simonsson Ulrika S. H. 
Published: April 2008

ABSTRACT

This article describes the population pharmacokinetics of rifampin in South African pulmonary tuberculosis patients. Three datasets containing 2,913 rifampin plasma concentration-time data points, collected from 261 South African pulmonary tuberculosis patients aged 18 to 72 years and weighing 28.5 to 85.5 kg and receiving regular daily treatment that included administration of rifampin (450 to 600 mg) for at least 10 days, were pooled. A compartmental pharmacokinetic model was developed using nonlinear mixed-effects modeling. Variability in the shape of the absorption curve was described using a flexible transit compartment model, in which a delay in the onset of absorption and a gradually changing absorption rate were modeled as the passage of drug through a chain of hypothetical compartments, ultimately reaching the absorption compartment. A previously described implementation was extended to allow its application to multiple-dosing data. The typical population estimate of oral clearance was 19.2 liters·h
−1
, while the volume of distribution was estimated to be 53.2 liters. Interindividual variability was estimated to be 52.8% for clearance and 43.4% for volume of distribution. Interoccasional variability was estimated for CL/F (22.5%) and mean transit time during absorption (67.9%). The use of single-drug formulations was found to increase both the mean transit time (by 104%) and clearance (by 23.6%) relative to fixed-dose-combination use. A strong correlation between clearance and volume of distribution suggested substantial variability in bioavailability, which could have clinical implications, given the dependence of treatment effectiveness on exposure. The final model successfully described rifampin pharmacokinetics in the population studied and is suitable for simulation in this context.
Multivalent Presentation of Antihantavirus Peptides on Nanoparticles Enhances Infection Blockade
Authors: Hall Pamela R. , Hjelle Brian , Brown David C. , Ye Chunyan , Bondu-Hawkins Virginie , Kilpatrick Kathleen A. , Larson Richard S. 
Published: April 2008

ABSTRACTViral entry into susceptible host cells typically results from multivalent interactions between viral surface proteins and host entry receptors. In the case of Sin Nombre virus (SNV), a New World hantavirus that causes hantavirus cardiopulmonary syndrome, infection involves the interaction between viral membrane surface glycoproteins and the human integrin αvβ3. Currently, there are no therapeutic agents available which specifically target SNV. To address this problem, we used phage display selection of cyclic nonapeptides to identify peptides that bound SNV and specifically prevented SNV infection in vitro. We synthesized cyclic nonapeptides based on peptide sequences of phage demonstrating the strongest inhibition of infection, and in all cases, the isolated peptides were less effective at blocking infection (9.0% to 27.6% inhibition) than were the same peptides presented by phage (74.0% to 82.6% inhibition). Since peptides presented by the phage were pentavalent, we determined whether the identified peptides would show greater inhibition if presented in a multivalent format. We used carboxyl linkages to conjugate selected cyclic peptides to multivalent nanoparticles and tested infection inhibition. Two of the peptides, CLVRNLAWC and CQATTARNC, showed inhibition that was improved over that of the free format when presented on nanoparticles at a 4:1 nanoparticle-to-virus ratio (9.0% to 32.5% and 27.6% to 37.6%, respectively), with CQATTARNC inhibition surpassing 50% when nanoparticles were used at a 20:1 ratio versus virus. These data illustrate that multivalent inhibitors may disrupt polyvalent protein-protein interactions, such as those utilized for viral infection of host cells, and may represent a useful therapeutic approach.
Enhancement of Diagnostic Efficiency by a Gamma Interferon Release Assay for Pulmonary Tuberculosis
Authors: Kanunfre Kelly Aparecida , Leite Olavo Henrique Munhoz , Lopes Max Igor , Litvoc Marcelo , Ferreira Antonio Walter 
Published: April 2008

ABSTRACT
This study was designed to examine the use of the QuantiFERON-TB Gold assay as an aid in the diagnosis of active pulmonary tuberculosis (TB) in Brazilian patients. Using the receiver operating characteristic curve, the cutoff was adjusted to ≥0.20 IU/ml. The sensitivity increased to 86%, with 100% specificity. All TB patients with negative sputum smear microscopy and negative culture results were positive using this test.
The Innate Immune Response toSalmonella entericaSerovar Typhimurium by Macrophages Is Dependent on TREM2-DAP12
Authors: Charles Julia F. , Humphrey Mary Beth , Zhao Xiaodan , Quarles Ellen , Nakamura Mary C. , Aderem Alan , Seaman William E. , Smith Kelly D. 
Published: April 2008

ABSTRACTMacrophage recognition ofSalmonella entericaserovar Typhimurium leads to a cascade of signaling events, including the activation of Src family and Syk kinases and the production of reactive oxygen species (ROS), which are critical for host innate defense during early stages of bacterial infection. ROS production depends on the NADPH oxidase, but little is known about the innate immune receptors and proximal adapters that regulateSalmonella-induced ROS. Herein, we demonstrate that serovar Typhimurium induces ROS through a pathway that requires both triggering receptor expressed on myeloid cells 2 (TREM2) and DAP12. This pathway is highly analogous to the pathways utilized by Fc receptors and integrins to regulate ROS production. Oral infection of mice with serovar Typhimurium demonstrates that the DAP12-dependent pathway regulates cecal colonization during early stages ofSalmonellainfection. Thus, DAP12 is an important regulator ofSalmonella-induced ROS production in macrophages, and TREM2 is essential for linking DAP12 to the innate response to serovar Typhimurium.
Streptococcus pneumoniae
Surface Protein PcpA Elicits Protection against Lung Infection and Fatal Sepsis
Authors: Glover David T. , Hollingshead Susan K. , Briles David E. 
Published: April 2008

ABSTRACT

Previous studies have suggested that pneumococcal choline binding protein A (PcpA) is important for the full virulence of
Streptococcus pneumoniae
, and its amino acid sequence suggests that it may play a role in cellular adherence. PcpA is under the control of a manganese-dependent regulator and is only expressed at low manganese concentrations, similar to those found in the blood and lungs. PcpA expression is repressed under high manganese concentrations, similar to those found in secretions. In this study, we have demonstrated that PcpA elicits statistically significant protection in murine models of pneumonia and sepsis. In the model of pneumonia with each of four challenge strains, statistically fewer
S. pneumoniae
cells were recovered from the lungs of mice immunized with PcpA and alum versus mice immunized with alum only. The immunizations reduced the median CFU by 4- to 400-fold (average of 28-fold). In the model of sepsis using strain TIGR4, PcpA expression resulted in shorter times to become moribund and subcutaneous immunization with PcpA increased survival times of mice infected with wild-type PcpA-expressing pneumococci.
RespiratoryFrancisella tularensisLive Vaccine Strain Infection Induces Th17 Cells and Prostaglandin E2, Which Inhibits Generation of Gamma Interferon-Positive T Cells
Authors: Woolard Matthew D. , Hensley Lucinda L. , Kawula Thomas H. , Frelinger Jeffrey A. 
Published: April 2008

ABSTRACTTwo key routes ofFrancisella tularensisinfection are through the skin and airway. We wished to understand how the route of inoculation influenced the primary acute adaptive immune response. We show that an intranasal inoculation of theF. tularensislive vaccine strain (LVS) with a 1,000-fold-smaller dose than an intradermal dose results in similar growth kinetics and peak bacterial burdens. In spite of similar bacterial burdens, we demonstrate a difference in the quality, magnitude, and kinetics of the primary acute T-cell response depending on the route of inoculation. Further, we show that prostaglandin E2secretion in the lung is responsible for the difference in the gamma interferon (IFN-γ) response. Intradermal inoculation led to a large number of IFN-γ+T cells 7 days after infection in both the spleen and the lung. In contrast, intranasal inoculation induced a lower number of IFN-γ+T cells in the spleen and lung but an increased number of Th17 cells in the lung. Intranasal infection also led to a significant increase of prostaglandin E2(PGE2) in the bronchoalveolar lavage fluid. Inhibition of PGE2production with indomethacin treatment resulted in increased numbers of IFN-γ+T cells and decreased bacteremia in the lungs of intranasally inoculated mice. This research illuminates critical differences in acute adaptive immune responses between inhalational and dermal infection withF. tularensisLVS mediated by the innate immune system and PGE2.
Expression of the
Mycobacterium tuberculosis acr
-Coregulated Genes from the DevR (DosR) Regulon Is Controlled by Multiple Levels of Regulation
Authors: Vasudeva-Rao Hema M. , McDonough Kathleen A. 
Published: April 2008

ABSTRACT

Little is known about how
Mycobacterium tuberculosis
regulates gene expression in response to its host environment, despite its importance as a pathogen. We previously characterized 10

a

cr
-
c
oregulated
g
enes (ACGs), all of which belong to the DevR (DosR) “dormancy” regulon, and identified one to three copies of a conserved 18-bp palindromic DNA motif in the promoter of each ACG family member. In the present study, we used base substitution analyses to assess the importance of individual motif copies and to identify additional regulatory sequences in five ACG promoters. Regulation of
acr
,
acg
, Rv2623,
narK2
, and Rv1738 was examined by using single-copy
M. tuberculosis
promoter-
lacZ
reporter constructs in
Mycobacterium bovis
BCG under conditions of ambient air versus hypoxia, each in shaking versus standing shallow culture conditions. We found that regulation of these ACG promoters is more heterogeneous than expected and is controlled at multiple levels. In addition to the positive regulation previously associated with DevR (DosR) and the 18-bp ACG motif, we identified negative regulation associated with sequences in the 5′ untranslated regions of
acg
and Rv2623 and positive regulation associated with far upstream regulatory regions of
narK2
and Rv1738. The importance of individual ACG motifs varied among the promoters examined, and Rv1738 was exceptional in that its ACG motif copies were associated with negative, rather than positive, regulation under some conditions. Further understanding of this important regulon requires the identification of additional regulators that compete and/or collaborate with DevR (DosR) to regulate its individual gene members.
Genetic Differentiation of
Escherichia coli
O157:H7 Clades Associated with Human Disease by Real-Time PCR
Authors: Riordan James T. , Viswanath Sandeep B. , Manning Shannon D. , Whittam Thomas S. 
Published: April 2008

ABSTRACT

The rapid and accurate identification of
Escherichia coli
O157:H7 strains is central to reducing the impact of outbreaks. A real-time PCR-based approach to differentiating major outbreak lineages of O157 with novel single-nucleotide polymorphisms is described. The utility of this method is in detection of hypervirulent strains in cases of clinical disease.
Cleavage of Group 1 Coronavirus Spike Proteins: How Furin Cleavage Is Traded Off against Heparan Sulfate Binding upon Cell Culture Adaptation
Authors: de Haan C. A. M. , Haijema B. J. , Schellen P. , Schreur P. Wichgers , te Lintelo E. , Vennema H. , Rottier P. J. M. 
Published: April 2008

ABSTRACT
A longstanding enigmatic feature of the group 1 coronaviruses is the uncleaved phenotype of their spike protein, an exceptional property among class I fusion proteins. Here, however, we show that some group 1 coronavirus spike proteins carry a furin enzyme recognition motif and can actually be cleaved, as demonstrated for a feline coronavirus. Interestingly, this feature can be lost during cell culture adaptation by a single mutation in the cleavage motif; this, however, preserves a heparan sulfate binding motif and renders infection by the virus heparan sulfate dependent. We identified a similar cell culture adaptation for the human coronavirus OC43.
Functions of the ORF9-to-ORF12 Gene Cluster in Varicella-Zoster Virus Replication and in the Pathogenesis of Skin Infection
Authors: Che Xibing , Reichelt Mike , Sommer Marvin H. , Rajamani Jaya , Zerboni Leigh , Arvin Ann M. 
Published: April 2008

ABSTRACT
The gene cluster composed of varicella-zoster virus (VZV) open reading frame 9 (ORF9) to ORF12 encodes four putative tegument proteins and is highly conserved in most alphaherpesviruses. In these experiments, the genes within this cluster were deleted from the VZV parent Oka (POKA) individually or in combination, and the consequences for VZV replication were evaluated with cultured cells in vitro and with human skin xenografts in SCID mice in vivo. As has been reported for ORF10, ORF11 and ORF12 were dispensable for VZV replication in melanoma and human embryonic fibroblast cells. In contrast, deletion of ORF9 was incompatible with the recovery of infectious virus. ORF9 localized to the virion tegument and formed complexes with glycoprotein E, which is an essential protein, in VZV-infected cells. Recombinants lacking ORF10 and ORF11 (POKAΔ10/11), ORF11 and ORF12 (POKAΔ11/12), or ORF10, ORF11 and ORF12 (POKAΔ10/11/12) were viable in cultured cells. Their growth kinetics did not differ from those of POKA, and nucleocapsid formation and virion assembly were not disrupted. In addition, these deletion mutants showed no differences compared to POKA in infectivity levels for primary human tonsil T cells. Deletion of ORF12 had no effect on skin infection, whereas replication of POKAΔ11, POKAΔ10/11, and POKAΔ11/12 was severely reduced, and no virus was recovered from skin xenografts inoculated with POKAΔ10/11/12. These results indicate that with the exception of ORF9, the individual genes within the ORF9-to-ORF12 gene cluster are dispensable and can be deleted simultaneously without any apparent effect on VZV replication in vitro but that the ORF10-to-ORF12 cluster is essential for VZV virulence in skin in vivo.
Poliovirus 2A
Pro
Increases Viral mRNA and Polysome Stability Coordinately in Time with Cleavage of eIF4G
Authors: Kempf Brian J. , Barton David J. 
Published: April 2008

ABSTRACT

Poliovirus (PV) 2A protease (2A
Pro
) cleaves eukaryotic initiation factors 4GI and 4GII (eIF4GI and eIF4GII) within virus-infected cells, effectively halting cap-dependent mRNA translation. PV mRNA, which does not possess a 5′ cap, is translated via cap-independent mechanisms within viral protease-modified messenger ribonucleoprotein (mRNP) complexes. In this study, we determined that 2A
Pro
activity was required for viral polysome formation and stability. 2A
Pro
cleaved eIF4GI and eIF4GII as PV polysomes assembled. A 2A
Cys109Ser
(2A
Pro
with a Cys109Ser mutation) protease active site mutation that prevented cleavage of eIF4G coordinately inhibited the de novo formation of viral polysomes, the stability of viral polysomes, and the stability of PV mRNA within polysomes. 2A
Cys109Ser
-associated defects in PV mRNA and polysome stability correlated with defects in PV mRNA translation. 3C
Pro
activity was not required for viral polysome formation or stability. 2A
Pro
-mediated cleavage of eIF4G along with poly(rC) binding protein binding to the 5′ terminus of uncapped PV mRNA appear to be concerted mechanisms that allow PV mRNA to form mRNP complexes that evade cellular mRNA degradation machinery.
Experimental study of reinforced masonry walls subjected to combined axial load and out-of-plane bendingThis article is one of a selection of papers published in this Special Issue on Masonry.
Authors: Liu Y. , Hu K. 
Published: April 2008

Twelve reinforced masonry wall specimens with nominal dimensions of 2400 mm × 800 mm × 150 mm were tested under eccentric compressive loading with varying eccentricity to thickness ratios, e/t, and end eccentricity ratios, e1/e2. Pinned-pinned support conditions resulted in a slenderness ratio of 17.1 for all specimens. Test results showed that the variation of ultimate load, Pu, and effective modulus of rigidity values, EIeff, at failure depended on the type of failure mode, which was influenced by e/t and e1/e2ratios and their interaction. Comparing ultimate loads obtained by test against those calculated using the EIeffvalues from the Canadian standard CSA S304.1-04 and against the ones calculated using the EIeffvalues proposed herein indicates that, while the moment magnifier method used in the current Canadian design standard to account for secondary effects is effective, the standard underestimates EIeffvalues, especially in regions where compression-controlled failure tends to predominate and, thus, leads to a conservative design. However, the use of proposed EIeffvalues in combination with the moment magnifier method provides estimations of ultimate loads in reasonably good agreement with test results.
Enforcing appropriate process execution for exploiting idle resources from outside operating systems
Authors: Abe Yoshihisa , Yamada Hiroshi , Kono Kenji 
Published: April 2008

Idle resources can be exploited not only to run important local tasks such as data replication and virus checking, but also to make contributions to society by participating in open computing projects like SETI@home [2]. When executing background processes to utilize such valuable idle resources, we need to explicitly control them so that the user will not be discouraged from exploiting idle resources by foreground performance degradation. Unfortunately, common priority-based schedulers lack such explicit execution control. In addition, to encourage active use of idle resources, a mechanism for controlling background processes should not require modifications to the underlying operating system or user applications. If such modifications are required, the user may be reluctant to employ the mechanism.
In this paper, we argue that we can reasonably detect resource contention between foreground and background processes and properly control background process execution at the user level. We infer the existence of resource contention from the approximated resource shares of background processes. Our approach takes advantage of dynamically instrumented probes, which are becoming increasingly popular, in estimating the resource shares. Also, it considers different resource types in combination and can handle varied workloads, including multiple background processes.
We show that our system effectively avoids the performance degradation of foreground activities by suspending background processes in an appropriate fashion. Our system keeps the increase in foreground execution time due to background processes below 16.9%, or much lower in most of our experiments. Also, we extend our approach to address undesirable resource allocations to CPU-intensive processes that can occur in multiprocessor environments.