bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Tipranavir-Ritonavir on Pharmacokinetics of Raltegravir
Authors: Hanley William D. , Wenning Larissa A. , Moreau Allison , Kost James T. , Mangin Eric , Shamp Trisha , Stone Julie A. , Gottesdiener Keith M. , Wagner John A. , Iwamoto Marian 
Published: April 2009

ABSTRACT

Raltegravir (RAL) is a novel and potent human immunodeficiency virus type 1 integrase inhibitor that is predominantly metabolized via glucuronidation. The protease inhibitor combination tipranavir (TPV) at 500 mg and ritonavir (RTV) at 200 mg (TPV-RTV) has inhibitory and inductive effects on metabolic enzymes, which includes the potential to induce glucuronosyltransferase. Because RAL may be coadministered with TPV-RTV, there is the potential for the induction of RAL metabolism. Consequently, we assessed the effect of TPV-RTV on the pharmacokinetics of RAL and the safety and tolerability of this combination. Eighteen healthy adults were enrolled in this open-label study. The participants received RAL at 400 mg twice daily for 4 days (period 1) and TPV-RTV twice daily for 7 days (period 2), followed immediately by 400 mg RAL with TPV-RTV twice daily for 4 days (period 3). Under steady-state conditions, the RAL concentration at 12 h (
C
12
) was decreased when RAL was administered with TPV-RTV (geometric mean ratio [GMR], 0.45; 90% confidence interval [CI] 0.31, 0.66;
P
= 0.0021); however, the area under the concentration-time curve from time zero to 12 h (GMR, 0.76; 90% CI, 0.49, 1.19;
P
= 0.2997) and the maximum concentration in serum (GMR, 0.82; 90% CI, 0.46, 1.46;
P
= 0.5506) were not substantially affected. There were no serious adverse experiences or discontinuations due to study drug-related adverse experiences, and RAL coadministered with TPV-RTV was generally well tolerated. Although the RAL
C
12
was decreased with TPV-RTV in this study, favorable efficacy data collected in phase III studies substantiate that TPV-RTV may be coadministered with RAL without dose adjustment.
In Vitro Elution of Daptomycin by a Synthetic Crystallic Semihydrate Form of Calcium Sulfate, Stimulan
Authors: Kanellakopoulou Kyriaki , Panagopoulos Periklis , Giannitsioti Efthymia , Tsaganos Thomas , Carrer Dionyssia-Pinelopi , Efstathopoulos Nicolas , Giamarellos-Bourboulis Evangelos J. 
Published: April 2009

ABSTRACT
A synthetic crystallic semihydrate form of calcium sulfate, Stimulan, was evaluated as a biodegradable carrier for the daily in vitro elution of daptomycin. Daptomycin and Stimulan were admixed at a ratio of 95:5. Elution lasted for 28 days. Eluted concentrations peaked on days 1 and 11, when the mean values were 1,320.1 and 949.2 μg/ml, respectively. The lowest eluted concentration was detected on day 28. These results support the application of the system described in experimental models of osteomyelitis.
Purification of Legiobactin and Importance of This Siderophore in Lung Infection byLegionella pneumophila
Authors: Allard Kimberly A. , Dao Jenny , Sanjeevaiah Prakash , McCoy-Simandle Kessler , Chatfield Christa H. , Crumrine David S. , Castignetti Domenic , Cianciotto Nicholas P. 
Published: April 2009

ABSTRACTWhen cultured in a low-iron medium,Legionella pneumophilasecretes a siderophore (legiobactin) that is both reactive in the chrome azurol S (CAS) assay and capable of stimulating the growth of iron-starved legionellae. Using anion-exchange high-pressure liquid chromatography (HPLC), we purified legiobactin from culture supernatants of a virulent strain ofL. pneumophila. In the process, we detected the ferrated form of legiobactin as well as other CAS-reactive substances. Purified legiobactin had a yellow-gold color and absorbed primarily from 220 nm and below. In accordance, nuclear magnetic resonance spectroscopy revealed that legiobactin lacks aromatic carbons, and among the 13 aliphatics present, there were 3 carbonyls. When examined by HPLC, supernatants fromL. pneumophilamutants inactivated forlbtAandlbtBcompletely lacked legiobactin, indicating that the LbtA and LbtB proteins are absolutely required for siderophore activity. Independently derivedlbtAmutants, but not a complemented derivative, displayed a reduced ability to infect the lungs of A/J mice after intratracheal inoculation, indicating that legiobactin is required for optimal intrapulmonary survival byL. pneumophila. This defect, however, was not evident when thelbtAmutant and its parental strain were coinoculated into the lung, indicating that legiobactin secreted by the wild type can promote growth of the mutant intrans. Legiobactin mutants grew normally in murine lung macrophages and alveolar epithelial cells, suggesting that legiobactin promotes something other than intracellular infection of resident lung cells. Overall, these data represent the first documentation of a role for siderophore expression in the virulence ofL. pneumophila.
Borrelia burgdorferi
RevA Antigen Binds Host Fibronectin
Authors: Brissette Catherine A. , Bykowski Tomasz , Cooley Anne E. , Bowman Amy , Stevenson Brian 
Published: April 2009

ABSTRACT

Borrelia burgdorferi
, the Lyme disease-causing spirochete, can persistently infect its vertebrate hosts for years.
B. burgdorferi
is often found associated with host connective tissue, where it interacts with components of the extracellular matrix, including fibronectin. Some years ago, a borrelial surface protein, named BBK32, was identified as a fibronectin-binding protein. However,
B. burgdorferi
BBK32 mutants are still able to bind fibronectin, indicating that the spirochete possesses additional mechanisms for adherence to fibronectin. We now demonstrate that RevA, an unrelated
B. burgdorferi
outer surface protein, binds mammalian fibronectin in a saturable manner. Site-directed mutagenesis studies identified the amino terminus of the RevA protein as being required for adhesion to fibronectin. RevA bound to the amino-terminal region of fibronectin. RevA binding to fibronectin was not inhibited by salt or heparin, suggesting that adhesin-ligand interactions are primarily nonionic and occur through the non-heparin-binding regions of the fibronectin amino-terminal domains.
revA
genes are widely distributed among Lyme disease spirochetes, and the present studies determined that all RevA alleles tested bound fibronectin. In addition, RevB, a paralogous protein found in a subset of
B. burgdorferi
strains, also bound fibronectin. We also confirmed that RevA is produced during mammalian infection but not during colonization of vector ticks and determined that
revA
transcription is controlled through a mechanism distinct from that of BBK32.
Nonhematopoietic Cells Control the Outcome of Infection with
Listeria monocytogenes
in a Nucleotide Oligomerization Domain 1-Dependent Manner
Authors: Mosa Ahmed , Trumstedt Christian , Eriksson Emma , Soehnlein Oliver , Heuts Frank , Janik Katrin , Klos Andreas , Dittrich-Breiholz Oliver , Kracht Michael , Hidmark Åsa , Wigzell Hans , Rottenberg Martin E. 
Published: April 2009

ABSTRACT

We analyzed the defensive role of the cytosolic innate recognition receptor nucleotide oligomerization domain 1 (NOD1) during infection with
Listeria monocytogenes
. Mice lacking NOD1 showed increased susceptibility to systemic intraperitoneal and intravenous infection with high or low doses of
L. monocytogenes
, as measured by the bacterial load and survival. NOD1 also controlled dissemination of
L. monocytogenes
into the brain. The increased susceptibility to reinfection of NOD1
−/−
mice was not associated with impaired triggering of listeria-specific T cells, and similar levels of costimulatory molecules or activation of dendritic cells was observed. Higher numbers of F480
+
Gr1
+
inflammatory monocytes and lower numbers of F480
−
Gr1
+
neutrophils were recruited into the peritoneum of infected WT mice than into the peritoneum of infected NOD1
−/−
mice. We determined that nonhematopoietic cells accounted for NOD1-mediated resistance to
L. monocytogenes
in bone marrow radiation chimeras. The levels of NOD1 mRNA in fibroblasts and bone marrow-derived macrophages (BMM) were upregulated after infection with
L. monocytogenes
or stimulation with different Toll-like receptor ligands. NOD1
−/−
BMM, astrocytes, and fibroblasts all showed enhanced intracellular growth of
L monocytogenes
compared to WT controls. Gamma interferon-mediated nitric oxide production and inhibition of
L. monocytogenes
growth were hampered in NOD1
−/−
BMM. Thus, NOD1 confers nonhematopoietic cell-mediated resistance to infection with
L. monocytogenes
and controls intracellular bacterial growth in different cell populations in vitro.
OspC-Independent Infection and Dissemination by Host-Adapted
Borrelia burgdorferi
Authors: Tilly Kit , Bestor Aaron , Dulebohn Daniel P. , Rosa Patricia A. 
Published: April 2009

ABSTRACT

Borrelia burgdorferi
OspC is required for the spirochete to establish infection in a mammal by tick transmission or needle inoculation. After a brief essential period, the protein no longer is required and the gene can be shut off. Using a system in which spirochetes contain only an unstable wild-type copy of the
ospC
gene, we can obtain mice persistently infected with bacteria lacking OspC. We implanted pieces of infected mouse skin subcutaneously in naïve mice, using donors carrying wild-type or
ospC
mutant spirochetes, and found that both could infect mice by this method, with similar numbers of wild-type or
ospC
mutant spirochetes disseminated throughout the tissues of recipient mice. Recipient mouse immune responses to tissue transfer-mediated infection with wild-type or
ospC
mutant spirochetes were similar. These experiments demonstrate that mammalian host-adapted spirochetes can infect and disseminate in mice in the absence of OspC, thereby circumventing this hallmark of tick-derived or in vitro-grown spirochetes. We propose a model in which OspC is one of a succession of functionally equivalent, essential proteins that are synthesized at different stages of mammalian infection. In this model, another protein uniquely present on host-adapted spirochetes performs the same essential function initially fulfilled by OspC. The strict temporal control of
B. burgdorferi
outer surface protein gene expression may reflect immunological constraints rather than distinct functions.
Subcellular Localization of theStaphylococcus aureusHeme Iron Transport Components IsdA and IsdB
Authors: Pishchany Gleb , Dickey Susan E. , Skaar Eric P. 
Published: April 2009

ABSTRACTStaphylococcus aureusis a human pathogen that represents a tremendous threat to global public health. An important aspect ofS. aureuspathogenicity is the ability to acquire iron from its host during infection. In vertebrates, iron is sequestered predominantly within heme, the majority of which is bound by hemoglobin. To acquire iron,S. aureusbinds hemoglobin, removes heme, and transports it into the cytoplasm, where heme is degraded. This process is carried out by the iron-regulated surface determinant system (Isd); however, the mechanism by which hemoglobin recognition occurs is not completely understood. Here we report that the surface receptor components of the Isd system, IsdA and IsdB, physically interact with each other and are anchored to a discrete location within the cell wall. This organized localization pattern is dependent upon the iron status of the bacterium. Furthermore, we have found that hemoglobin colocalizes with IsdB at discrete sites within the cell wall. Virulence studies revealed that IsdB is required for the efficient colonization of the heart and that IsdB is differentially expressed within infected organs, suggesting thatS. aureusexperiences various degrees of iron starvation depending on the site of infection. These findings significantly expand our understanding of hemoglobin iron acquisition and demonstrate an orchestrated pattern of regulation and localization for theS. aureusheme iron acquisition system.
Diffusion of American lobster (Homarus americanus) in Northumberland Strait, Canada
Authors: den Heyer Cornelia Elizabeth , Chadwick E. Michael P. , Hutchings Jeffrey A. 
Published: April 2009

We tested the hypothesis that American lobster ( Homarus americanus ) movement can be described as diffusion. In 2001 and 2002, 3689 lobsters, captured by experimental trap and trawl surveys, were tagged and released in Northumberland Strait, Canada. Recaptures (n = 413) were reported by roughly 200 commercial fishermen, up to 3 years after release. Only six lobsters, all females, were recaptured more than once. Recapture rates were marginally higher for males (male 12%, female 10%) and varied with area of release (range: 5%–12%) and the fishing gear used for tagging (trap 12%, trawl 11%). Maximum and mean displacements between release and recapture were 58.3 and 12.3 km, respectively. The positive linear correlation between mean square displacement (MSD) and time between release and recapture provides evidence for diffusion. We calculate a diffusion coefficient (D) of 13 km2·week–1; there was no difference in D between sexes. A power analysis showed that MSD is underestimated at small sample sizes. There were insufficient data to test for differences in D associated with sexual maturity or shell hardness at time of release. During the summer in Northumberland Strait, the lobster population spreads about 20 km. The demographic consequences of seasonal diffusion of lobster warrant study.
Detecting declines in the abundance of a bull trout (Salvelinus confluentus) population: understanding the accuracy, precision, and costs of our efforts
Authors: Al-Chokhachy Robert , Budy Phaedra , Conner Mary 
Published: April 2009

Using empirical field data for bull trout ( Salvelinus confluentus ), we evaluated the trade-off between power and sampling effort–cost using Monte Carlo simulations of commonly collected mark–recapture–resight and count data, and we estimated the power to detect changes in abundance across different time intervals. We also evaluated the effects of monitoring different components of a population and stratification methods on the precision of each method. Our results illustrate substantial variability in the relative precision, cost, and information gained from each approach. While grouping estimates by age or stage class substantially increased the precision of estimates, spatial stratification of sampling units resulted in limited increases in precision. Although mark–resight methods allowed for estimates of abundance versus indices of abundance, our results suggest snorkel surveys may be a more affordable monitoring approach across large spatial scales. Detecting a 25% decline in abundance after 5 years was not possible, regardless of technique (power = 0.80), without high sampling effort (48% of study site). Detecting a 25% decline was possible after 15 years, but still required high sampling efforts. Our results suggest detecting moderate changes in abundance of freshwater salmonids requires considerable resource and temporal commitments and highlight the difficulties of using abundance measures for monitoring bull trout populations.
Factors influencing coastal cutthroat trout (Oncorhynchus clarkii clarkii) seasonal survival rates: a spatially continuous approach within stream networks
Authors: Berger Aaron M. , Gresswell Robert E. 
Published: April 2009

Mark–recapture methods were used to examine watershed-scale survival of coastal cutthroat trout ( Oncorhynchus clarkii clarkii ) from two headwater stream networks. A total of 1725 individuals (≥100 mm, fork length) were individually marked and monitored seasonally over a 3-year period. Differences in survival were compared among spatial (stream segment, subwatershed, and watershed) and temporal (season and year) analytical scales, and the effects of abiotic (discharge, temperature, and cover) and biotic (length, growth, condition, density, movement, and relative fish abundance) factors were evaluated. Seasonal survival was consistently lowest and least variable (years combined) during autumn (16 September – 15 December), and evidence suggested that survival was negatively associated with periods of low stream discharge. In addition, relatively low (–) and high (+) water temperatures, fish length (–), and boulder cover (+) were weakly associated with survival. Seasonal abiotic conditions affected the adult cutthroat trout population in these watersheds, and low-discharge periods (e.g., autumn) were annual survival bottlenecks. Results emphasize the importance of watershed-scale processes to the understanding of population-level survival.
From the editor
Authors: Stafford Tom , Chau Patrick Y.K. 
Published: April 2009

Greetings! Welcome to another fine issue of Data Base for Advances in Information Systems.
In this issue we feature a fine paper by Warkentin, Moore, Bekkering and Johnston on the nature of risk in systems development work. The interesting aspect of this work is the notion that risk factors which may hinder development projects, while frequently viewed by development professionals as existing in discrete categories, may well be more holistic and arise from unique organizational culture aspects idiosyncratic to individual firms. This is a break from traditional views of risk issues in systems development, and is likely to give us much food for thought as we consider development practices in the modern and emergent organizational forms of the information age.
Also in this issue, we provide the last of a sequence of special articles brought from the Chinese chapter of AIS for your consideration. The annual meeting of the Chinese Association produced a number of fine papers, many with a decidedly technical flavor, and we wished to showcase some more of those here, following our last issue, which was dedicated to some of the more managerial papers that evolved from that Chinese Association conference. Herein, you will find some interesting work on emerging algorithms for the exploration of data streams (Wang et al.), the use of sequenced algorithms for applying AI approaches to the selection of virtual firm partners (Zhong et al.) and for the use of innovative algorithms to mine Web site data for purposes of fueling recommendation and personalization systems (Wei et al.). These are quite technical approaches, but very important for the effective management and control of the burgeoning online world of information that we are now inhabiting.
We are grateful to guest editors Guoqing Chen, Yu Chen and Kang Xie for bringing this interesting collection of scholarship from our Chinese Association colleagues to our pages. As part of the Editorial vision that Patrick and I have espoused, we anticipate Data Base will continue to lead in the development and publication of leading edge research, the world over.
To that end, we continue to welcome leading edge research from the four corners of the world at our online submission and review portal, found at http://the-database.org. We look forward to seeing some of your best work in these pages soon!
Special issue series for information systems research in China
Authors: Chen Guoqing , Chen Yu , Xie Kang 
Published: April 2009

The past decades have witnessed enormous changes in China on economic, social, and cultural aspects, which have brought far-reaching impacts on global business and technology development. Since the early 1990s, IT has been transforming Chinese business and society, but the country still faces formidable challenges in developing and using the technology to further modernize itself. IT applications in China were introduced relatively late in technology evolution compared to those in the developed countries, forcing business managers to contend with a lack of experience, know-how, and infrastructure. On the other hand, this late start has also meant that Chinese companies could be able to choose from more advanced technologies, learn from the experience of others, and be less bothered by the problems associated with legacy systems.
Along with the development of IT/IS application and management, information systems research in China has also been accelerating and fusing with global academic streams. Notably, research efforts on both managerial and technical perspectives are flourishing in recent years. In 2005, the China Association for Information Systems (CNAIS) was established as a chapter of AIS serving China, aimed at promoting the exchange of ideas, experiences, and knowledge among scholars and professionals engaged in the development, management, and use of information systems and technology. With the support of CNAIS, this series of special issue papers presents some recent progress in IS research from Chinese scholars.
The papers included in this special issue series, which spans volume 40(1) and 40(2), presents extended versions of work selected, via a standard review process, from the 2007 CNAIS Congress (CNAIS2007) held in November 8-10, 2007, in Kunming, China. CNAIS2007 accepted over 170 refereed papers and featured plenary talks by distinguished scholars such as Michael Myers from the University of Auckland and Dennis Galletta from the University of Pittsburgh. Among the papers selected for this special issue series, four them focus on the management aspect of information systems while three concentrate on technical research, giving rise to two natural groups, respectively.
As the guest editors of this special issue series, we would like to thank all the authors for the contributions and all referees for their kind cooperation and help. We heartily thank Professor Patrick Y.K. Chau, Global Co-Editor of The DATA BASE for Advances in Information Systems, for providing us with the opportunity to edit and publish this issue, as well as for his valuable guidance in the editorial process.
Regulation of the Human Cardiac Mitochondrial Ca2+Uptake by 2 Different Voltage-Gated Ca2+Channels
Authors: Michels Guido , Khan Ismail F. , Endres-Becker Jeannette , Rottlaender Dennis , Herzig Stefan , Ruhparwar Arjang , Wahlers Thorsten , Hoppe Uta C. 
Published: April 2009

Background—Impairment of intracellular Ca2+homeostasis and mitochondrial function has been implicated in the development of cardiomyopathy. Mitochondrial Ca2+uptake is thought to be mediated by the Ca2+uniporter (MCU) and a thus far speculative non-MCU pathway. However, the identity and properties of these pathways are a matter of intense debate, and possible functional alterations in diseased states have remained elusive.Methods and Results—By patch clamping the inner membrane of mitochondria from nonfailing and failing human hearts, we have identified 2 previously unknown Ca2+-selective channels, referred to as mCa1 and mCa2. Both channels are voltage dependent but differ significantly in gating parameters. Compared with mCa2 channels, mCa1 channels exhibit a higher single-channel amplitude, shorter openings, a lower open probability, and 3 to 5 subconductance states. Similar to the MCU, mCa1 is inhibited by 200 nmol/L ruthenium 360, whereas mCa2 is insensitive to 200 nmol/L ruthenium 360 and reduced only by very high concentrations (10 μmol/L). Both mitochondrial Ca2+channels are unaffected by blockers of other possibly Ca2+-conducting mitochondrial pores but were activated by spermine (1 mmol/L). Notably, activity of mCa1 and mCa2 channels is decreased in failing compared with nonfailing heart conditions, making them less effective for Ca2+uptake and likely Ca2+-induced metabolism.Conclusions—Thus, we conclude that the human mitochondrial Ca2+uptake is mediated by these 2 distinct Ca2+channels, which are functionally impaired in heart failure. Current properties reveal that the mCa1 channel underlies the human MCU and that the mCa2 channel is responsible for the ruthenium red–insensitive/low-sensitivity non-MCU–type mitochondrial Ca2+uptake.