bluuebunny/crossref_metadata_2025_split huggingface dataset:
VX-950, a Novel Hepatitis C Virus (HCV) NS3-4A Protease Inhibitor, Exhibits Potent Antiviral Activities in HCV Replicon Cells
Authors: Lin Kai , Perni Robert B. , Kwong Ann D. , Lin Chao 
Published: April 2006

ABSTRACT

The NS3-4A serine protease of hepatitis C virus (HCV) is essential for viral replication and therefore has been one of the most attractive targets for developing specific antiviral agents against HCV. VX-950, a highly selective, reversible, and potent peptidomimetic inhibitor of the HCV NS3-4A protease, is currently in clinical development for the treatment of hepatitis C. In this report, we describe the in vitro characterization of anti-HCV activities of VX-950 in subgenomic HCV replicon cells. Incubation with VX-950 resulted in a time- and dose-dependent reduction of HCV RNA and proteins in replicon cells. Moreover, following a 2-week incubation with VX-950, a reduction in HCV RNA levels of 4.7 log
10
was observed, and this reduction resulted in elimination of HCV RNA from replicon cells, since there was no rebound in replicon RNA after withdrawal of the inhibitor. The combination of VX-950 and alpha interferon was additive to moderately synergistic in reducing HCV RNA in replicon cells with no significant increase in cytotoxicity. The benefit of the combination was sustained over time: a 4-log
10
reduction in HCV RNA level was achieved following a 9-day incubation with VX-950 and alpha interferon at lower concentrations than when either VX-950 or alpha interferon was used alone. The combination of VX-950 and alpha interferon also suppressed the emergence of in vitro resistance mutations against VX-950 in replicon cells.
Nebulized Amphotericin B Combined with Intravenous Amphotericin B in Rats with Severe Invasive Pulmonary Aspergillosis
Authors: Ruijgrok Elisabeth J. , Fens Marcel H. A. M. , Bakker-Woudenberg Irma A. J. M. , van Etten Els W. M. , Vulto Arnold G. 
Published: April 2006

ABSTRACT
Nebulized amphotericin B (AMB) combined with intravenous AMB was studied in persistently leukopenic rats with invasive pulmonary aspergillosis. Pulmonary concentrations of AMB after aerosol treatment were substantially higher than after intravenous liposomal AMB. Nebulized liposomal AMB in addition to intravenous AMB resulted in significantly prolonged survival compared to controls.
Vibrio cholerae
InV117, a Class 1 Integron Harboring
aac(6′)-Ib
and
bla
CTX-M-2
, Is Linked to Transposition Genes
Authors: Soler Bistué Alfonso J. C. , Martín Fernando A. , Petroni Alejandro , Faccone Diego , Galas Marcelo , Tolmasky Marcelo E. , Zorreguieta Angeles 
Published: April 2006

ABSTRACT

A ca. 150-kbp
Vibrio cholerae
O1 biotype El Tor plasmid includes
bla
CTX-M-2
and a variant of
aac(6′)-Ib
within InV117, an orf513-bearing class 1 integron. InV117 is linked to a
tnp1696
module in which IRl carries an insertion of IS
4321
R. The complete structure could be a potential mobile element.
Virucidal Activity of a GT-Rich Oligonucleotide against Herpes Simplex Virus Mediated by Glycoprotein B
Authors: Shogan Benjamin , Kruse Lori , Mulamba Gilbert B. , Hu André , Coen Donald M. 
Published: April 2006

ABSTRACT

We have investigated the antiviral mechanism of a phosphorothioate oligonucleotide, ISIS 5652, which has activity against herpes simplex virus (HSV) in the low micromolar range in plaque reduction assays. We isolated a mutant that is resistant to this compound. Marker rescue and sequencing experiments showed that resistance was due to at least one of three mutations in the
UL27
gene which result in amino acid changes in glycoprotein B (gB). Because gB has a role in attachment and entry of HSV, we tested the effects of ISIS 5652 at these stages of infection. The oligonucleotide potently inhibited attachment of virus to cells at 4°C; however, the resistant mutant did not exhibit resistance at this stage. Moreover, a different oligonucleotide with little activity in plaque reduction assays was as potent as ISIS 5652 in inhibiting attachment. Similarly, ISIS 5652 was able to inhibit entry of preattached virions into cells at 37°C, but the mutant did not exhibit resistance in this assay. The mutant did not attach to or enter cells more quickly than did wild-type virus. Strikingly, incubation of wild-type virus with 1 to 2 μM ISIS 5652 at 37°C led to a time-dependent, irreversible loss of infectivity (virucidal activity). No virucidal activity was detected at 4°C or with an unrelated oligonucleotide at 37°C. The resistant mutant and a marker-rescued derivative containing its
gB
mutations exhibited substantial resistance to this virucidal activity of ISIS 5652. We hypothesize that the GT-rich oligonucleotide induces a conformational change in gB that results in inactivation of infectivity.
Effects of an Opal Termination Codon Preceding the nsP4 Gene Sequence in the O'Nyong-Nyong Virus Genome on
Anopheles gambiae
Infectivity
Authors: Myles Kevin M. , Kelly Cindy L. H. , Ledermann Jeremy P. , Powers Ann M. 
Published: April 2006

ABSTRACT

The genomic RNA of an alphavirus encodes four different nonstructural proteins, nsP1, nsP2, nsP3, and nsP4. The polyprotein P123 is produced when translation terminates at an opal termination codon between nsP3 and nsP4. The polyprotein P1234 is produced when translational readthrough occurs or when the opal termination codon has been replaced by a sense codon in the alphavirus genome. Evolutionary pressures appear to have maintained genomic sequences encoding both a stop codon (opal) and an open reading frame (arginine) as a general feature of the O'nyong-nyong virus (ONNV) genome, indicating that both are required at some point. Alternate replication of ONNVs in both vertebrate and invertebrate hosts may determine predominance of a particular codon at this locus in the viral quasispecies. However, no systematic study has previously tested this hypothesis in whole animals. We report here the results of the first study to investigate in a natural mosquito host the functional significance of the opal stop codon in an alphavirus genome. We used a full-length cDNA clone of ONNV to construct a series of mutants in which the arginine between nsP3 and nsP4 was replaced with an opal, ochre, or amber stop codon. The presence of an opal stop codon upstream of nsP4 nearly doubled (75.5%) the infectivity of ONNV over that of virus possessing a codon for the amino acid arginine at the corresponding position (39.8%). Although the frequency with which the opal virus disseminated from the mosquito midgut did not differ significantly from that of the arginine virus on days 8 and 10, dissemination did began earlier in mosquitoes infected with the opal virus. Although a clear fitness advantage is provided to ONNV by the presence of an opal codon between nsP3 and nsP4 in
Anopheles gambiae
, sequence analysis of ONNV RNA extracted from mosquito bodies and heads indicated codon usage at this position corresponded with that of the virus administered in the blood meal. These results suggest that while selection of ONNV variants is occurring, de novo mutation at the position between nsP3 and nsP4 does not readily occur in the mosquito. Taken together, these results suggest that the primary fitness advantage provided to ONNV by the presence of an opal codon between nsP3 and nsP4 is related to mosquito infectivity.
Measuring Atmospheric Stability with GPS
Authors: de Haan Siebren 
Published: April 2006

AbstractNowcasting of convective systems plays a crucial role in weather forecasting. The strength of convection depends on the (in)stability of the air column. The stability can be detected by radiosonde observations. However, these observations are not frequent (typically 2 times per day) and are expensive to deploy. In this article a method is presented to detect the stability of the atmosphere based on high-frequency global positioning system (GPS) path-delay observations. The convection parameter derived from these observations is the power of the nonisotropic GPS path-delay signal. Comparisons with the convective available potential energy obtained from radiosonde observations show a correlation with the convection parameter obtained from GPS. This result implies that, because of the continuous availability of GPS estimates and the good land coverage, this method of detecting atmospheric stability may be beneficial to forecasters.
Decadal Variability of the Midlatitude Climate System Driven by the Ocean Circulation
Authors: Hogg Andrew Mc C. , Dewar William K. , Killworth Peter D. , Blundell Jeffrey R. 
Published: April 2006

Abstract
A midlatitude coupled ocean–atmosphere model is used to investigate interactions between the atmosphere and the wind-driven ocean circulation. This model uses idealized geometry, yet rich and complicated dynamic flow regimes arise in the ocean due to the explicit simulation of geostrophic turbulence. An interdecadal mode of intrinsic ocean variability is found, and this mode projects onto existing atmospheric modes of variability, thereby controlling the time scale of the atmospheric modes. It is also shown that ocean circulation controls the time scale of the SST response to wind forcing, and that coupled feedback mechanisms thus modify variability of the atmospheric circulation. It is concluded that ocean–atmosphere coupling in the midlatitudes is unlikely to produce new modes of variability but may control the temporal behavior of modes that exist in uncoupled systems.
Hepatocyte growth factor mediates angiopoietin-induced smooth muscle cell recruitment
Authors: Kobayashi Hanako , DeBusk Laura M. , Babichev Yael O. , Dumont Daniel J. , Lin Pengnian Charles 
Published: April 2006

Abstract
Communication between endothelial cells (ECs) and mural cells is critical in vascular maturation. Genetic studies suggest that angiopoietin/Tie2 signaling may play a role in the recruitment of pericytes or smooth muscle cells (SMCs) during vascular maturation. However, the molecular mechanism is unclear. We used microarray technology to analyze genes regulated by angiopoietin-1 (Ang1), an agonist ligand for Tie2, in endothelial cells (ECs). We observed that hepatocyte growth factor (HGF), a mediator of mural cell motility, was up-regulated by Ang1 stimulation. We confirmed this finding by Northern blot and Western blot analyses in cultured vascular endothelial cells. Furthermore, stimulation of ECs with Ang1 increased SMC migration toward endothelial cells in a coculture assay. Addition of a neutralizing anti-HGF antibody inhibited Ang1-induced SMC recruitment, indicating that the induction of SMC migration by Ang1 was caused by the increase of HGF. Interestingly, Ang2, an antagonist ligand of Tie2, inhibited Ang1-induced HGF production and Ang1-induced SMC migration. Finally, we showed that deletion of Tie2 in transgenic mouse reduced HGF production. Collectively, our data reveal a novel mechanism of Ang/Tie2 signaling in regulating vascular maturation and suggest that a delicate balance between Ang1 and Ang2 is critical in this process.
Simultaneous bone marrow and intestine transplantation promotes marrow-derived hematopoietic stem cell engraftment and chimerism
Authors: Nakao Atsunori , Toyokawa Hideyoshi , Kimizuka Kei , Nalesnik Michael A. , Nozaki Isao , Bailey Robert J. , Demetris Anthony J. , Starzl Thomas E. , Murase Noriko 
Published: April 2006

AbstractOrgan allografts have been shown to provide a syngeneic microenvironment for organ-based donor hematopoietic stem cells to maintain long-lasting chimerism after transplantation. We hypothesized that organ allografts would also support engraftment and hematopoiesis of adjunctively infused donor marrow stem cells, syngeneic to organ grafts, in nonmyeloablated recipients. In BN-to-LEW and GFP-to-ACI rat combinations, donor bone marrow (BM) infusion together with small intestine transplantation (SITx) under short-course tacrolimus immunosuppression resulted in persistent macrochimerism (more than 5%) for 150 days. In contrast, after BM infusion or SITx alone, chimerism was temporary and disappeared by day 100. Y-chromosome polymerase chain reaction (PCR) in sex-mismatched male BM plus female intestine or female BM plus male intestine transplantation into female recipients suggested that persistent macrochimerism was derived from infused BM. BM infusion together with lymphoid-depleted intestine grafts also supported macrochimerism development; however, third-party intestine grafts did not. After GFP-positive BM plus wild-type (WT) SITx into ACI, large numbers of GFP-positive leukocytes were found in WT intestine grafts. Isolated cells from WT intestine grafts developed GFP-positive CFU-Cs and propagated multilineage GFP-positive leukocytes when adoptively transferred into lethally irradiated WT recipients. These findings suggest that intestine allograft supports simultaneously infused donor (syngeneic to organ grafts) marrow stem cell engraftment, differentiation, and persistence of chimerism.
Dendritic cells in pathogen recognition and induction of immune responses: a functional genomics approach
Authors: Foti Maria , Granucci Francesca , Pelizzola Mattia , Beretta Ottavio , Ricciardi-Castagnoli Paola 
Published: April 2006

Abstract
At the 38th Annual Meeting of the Society for Leukocyte Biology held in Oxford this year, the biology of dendritic cells (DCs) and macrophages was discussed. In particular, functional genomics approaches were presented to investigate transcriptional changes during microbe and phagocytes interactions. Here, we report functional genomics studies likely to be of interest to the Journal of Leukocyte Biology readers with a particular emphasis on DC biology. DCs are professional antigen-presenting cells, which are essential for the initiation and regulation of natural killer, T, and T rgulatory cell responses. Immature DCs, resident in peripheral sites, are specialized in antigen capture and continually sample soluble and particulate antigens in their local environment. DCs express receptors for cytokines, chemokines, endogenous danger signals, and microbial structures. The interactions between DCs and microorganism are complex, but progress in the past few years has shed light on several aspects of these processes. Infectious disease is the result of an intimate relationship between pathogens and hosts. Thus, understanding the cross-talk between host and pathogen is essential to improve our knowledge of infectious disease. Functional genomics and proteomics applied to DCs and macrophage biology are now providing powerful tools to dissect, at the molecular level, host-pathogen interactions.
Community pharmacists and depression: the pharmacist as intermediary between patient and physician
Authors: Landers M , Blenkinsopp A , Pollock K , Grime J 
Published: April 2006

Abstract

Objectives
To describe community pharmacists' experiences and contributions to the management of mild to moderate depression in primary care and to explore their interactions with patients and physicians.

Method
Qualitative semi-structured interview study with a purposive sample of 20 community pharmacists from a range of backgrounds in one area of England. Pharmacists were asked to describe their involvement in the management of depression from patients' self-diagnosis and self-treatment through to treatment with antidepressants. They were asked to cite examples of the questions that they were asked by patients about depression and its treatment, and about their practice in advising patients with first-time and repeat prescriptions for antidepressants. Attitudes and practice relating to compliance and concordance with antidepressants were explored.

Key findings
Pharmacists were asked a wide range of questions by patients about antidepressants and depression. Often these questions posed ethical dilemmas for the pharmacists by raising topics that crossed inter-professional boundaries. Pharmacists generally saw their role as encouraging patients to take antidepressant treatment and they reported providing technical information, mainly when the first prescription was dispensed. Most pharmacists worked from a “compliance” model although this appeared to conflict sometimes with their own views about the appropriateness of antidepressant treatment. Pharmacists rarely entered into discussion with patients on their feelings about treatment or their intention to take it. Monitoring of compliance to antidepressants was largely seen as the province of the physician and pharmacists appeared to feel unable to undertake this role effectively. Nevertheless 17 of the pharmacists expressed a wish to extend their role in the management of depression.

Conclusions
Pharmacists' accounts showed that patients have unmet needs in relation to the management of depression and treatment with antidepressants. Achieving concordance in the tripartite relationship between patient, GP and pharmacist poses considerable challenges. However, our findings suggest that pharmacists could play a larger role as first-line advisers on depression and its treatment if the identified barriers can be overcome.
Patient receipt of, and preferences for receiving, antidepressant information
Authors: Sleath Betsy , Wurst Keele 
Published: April 2006

Abstract

Objective
The purpose of the study was to examine patient receipt of, and preferences for receiving, antidepressant information.

Method/setting
The study had a cross-sectional design. Eight community pharmacies in central North Carolina participated in the study. Eighty-three English-speaking patients who were picking up antidepressant prescriptions were interviewed by a research assistant. The main outcome measures included: patient receipt of verbal antidepressant information; the number and type of educational messages contained in the written antidepressant leaflets that patients received; the percentage of patients who had a reading level below the reading level of the antidepressant information leaflet; whether patients reported reading the leaflets and how satisfied they were with the leaflets; and how patients preferred to receive antidepressant information.

Key findings
Seventeen per cent of patients did not receive verbal information about how long the medication would take to work from anyone. Only 50 per cent of patients were told what to do if a major side effect occurred. Almost 11 per cent of patients had a reading level below the level of the written pharmacy antidepressant information leaflet. Just over one-third (36 per cent) of patients preferred to receive only written antidepressant information. Less educated patients were significantly more likely to want to receive antidepressant information verbally. Of those patients who preferred to receive verbal antidepressant information or both verbal and written information, 92 per cent chose pharmacists as their first or second choice for providing them with verbal information.

Conclusion
The majority of patients taking antidepressants want to receive verbal information and view pharmacists as an important source of information. Pharmacists have the potential to improve antidepressant adherence if they take the time to educate patients verbally about their medications.
Practice-based pharmaceutical services: a systematic review
Authors: Fish Alison , Watson Margaret C , Bond Christine M 
Published: April 2006

AbstractBackgroundGeneral practice-based pharmaceutical services are increasingly common, ranging from global medication changes (eg, generic switch) to individual patient medication review and educational interventions.AimTo conduct a systematic review of the effectiveness of practice-based pharmaceutical interventions.DesignA systematic review of general practice-based pharmaceutical services.SettingGeneral practice in the UK, Australia, Canada, Scandinavia and the US.Outcome measuresThe effect and cost of practice-based pharmaceutical services.MethodsElectronic databases were searched and pharmaceutical organisations were contacted. Studies fulfilling the review criteria were considered for inclusion. Duplicate independent data screening and abstraction was undertaken. Three indicators were used to assess the quality of included studies: method of random allocation; allocation concealment; and proportion of subjects followed to the end of the study.ResultsA total of 2,707 references were identified: 256 full publications were retrieved and 16 randomised, controlled trials (RCTs) met the inclusion criteria. Included studies assessed either the professional interface (educational outreach and general prescribing advice) or the patient interface (medication review and patient-specific prescribing advice). Three trials included all three quality markers. Most studies were effective in achieving one or more of the desired outcomes from pharmaceutical intervention. Two trials showed no statistically significant differences between the study and control groups post intervention.ConclusionsMany evaluations of practice-based pharmaceutical s***érvices have been published but few meet recognised standards of trial methodology. The results of this review suggest that practice-based pharmaceutical services are effective in achieving desired changes; however, more robust evidence is needed to confirm whether they are effective, efficient and sustainable.
Reaction of Malonaldehyde with Adenosine. Formation of a Novel Adduct Containing a Dioxazatricycloundecene Residue in the Base-pairing Region
Authors: Seto Hiroshi , Seto Takako , Nagakura Koichi , Koike Hiroshi 
Published: April 2006

Abstract
Reaction of malonaldehyde with adenosine at pH 4.5 gave three major adducts including a novel one containing diastereomeric dioxazatricycloundecene residue, formed by addition of three malonaldehyde units.
Aerobic Epoxidation of Olefins Catalyzed by Cobalt(II) Complex Using Propionaldehyde Diethyl Acetal as a Reductant
Authors: Mukaiyama Teruaki , Yorozu Kiyotaka , Takai Toshihiro , Yamada Tohru 
Published: April 2006

Abstract
In the presence of bis(3-methyl-2,4-pentanedionato)cobalt(II) complex catalyst, various trisubstituted olefins are smoothly monooxygenated into the corresponding epoxides in high yields under neutral conditions by the combined use of molecular oxygen and propionaldehyde diethyl acetal.
Porphyrin Synthesis Using Clays. Taking Advantage of Statistical Product Distributions
Authors: Laszlo Pierre , Luchetti Jean 
Published: April 2006

Abstract
Solid acids such as the K10 montmorillonite are useful for preparation of porphyrins from pyrrole condensed with aldehydes. Combining the use of two different aldehydes A and B with unequal, statistical proportions of A and B allows maximization of the relative amount of the desired mixed porphyrin.
Ultrasound-Promoted Synthesis of Arylzinc Compounds Using Zinc Powder and Their Application to Palladium(0)-Catalyzed Synthesis of Multifunctional Biaryls
Authors: Takagi Kentaro 
Published: April 2006

Abstract
Arylzinc compounds containing electron-withdrawing groups such as CO2CH3, CON(CH3)2, CN, Br, Cl, or CF3 at ortho position were prepared readily by the ultrasound-promoted reaction of aryl iodides with zinc powder, which were applied to palladium(0)-catalyzed cross-coupling with aryl halides to afford unsymmetrical and multifunctional biaryls in good yields.
Fe(CO)5/Sulfur-Catalyzed Liquefaction of Yallourn Coal in the Presence of Alcohol and Carbon Monoxide
Authors: Watanabe Yoshihisa , Kawasaki Nori-aki , Yamada Hiro-aki , Wada Kenji , Mitsudo Take-aki 
Published: April 2006

Abstract
Iron/sulfur-catalyzed liquefaction of Yallourn coal using alcohol-carbon monoxide has been investigated. Pentacarbonyliron (Fe(CO)5)/sulfur was found to be an excellent catalyst precursor. In the Fe(CO)5/sulfur catalyzed liquefaction (375 °C-120 min) of Yallourn coal, high conversion (99.5%) was achieved in the presence of ethanol and CO.
Beckmann Rearrangement Catalyzed by the Combined Use of Tetrabutylammonium Perrhenate(VII) and Trifluoromethanesulfonic Acid
Authors: Narasaka Koichi , Kusama Hiroyuki , Yamashita Yuko , Sato Hiroshi 
Published: April 2006

Abstract
Beckmann rearrangement of oximes is catalyzed with tetrabutylammonium perrhenate(VII), trifluoromethanesulfonic acid and hydroxylamine hydrochloride in nitromethane under azeotropic conditions, giving amides in high yield.