bluuebunny/crossref_metadata_2025 huggingface dataset:
A role for the JAK-STAT1 pathway in blocking replication of HSV-1 in dendritic cells and macrophages
Authors: Mott Kevin R , UnderHill David , Wechsler Steven L , Town Terrence , Ghiasi Homayon
Published: May 2009

Background

Macrophages and dendritic cells (DCs) play key roles in host defense against HSV-1 infection. Although macrophages and DCs can be infected by herpes simplex virus type 1 (HSV-1), both cell types are resistant to HSV-1 replication. The aim of our study was to determine factor (s) that are involved in the resistance of DCs and macrophages to productive HSV-1 infection.

Results

We report here that, in contrast to bone marrow-derived DCs and macrophages from wild type mice, DCs and macrophages isolated from signal transducers and activators of transcription-1 deficient (STAT1-/-) mice were susceptible to HSV-1 replication and the production of viral mRNAs and DNA. There were differences in expression of immediate early, early, and late gene transcripts between STAT1+/+and STAT1-/-infected APCs.

Conclusion

These results suggest for the first time that the JAK-STAT1 pathway is involved in blocking replication of HSV-1 in DCs and macrophages.
The effect of exogenous glucagon-like peptide-1 on the glycaemic response to small intestinal nutrient in the critically ill: a randomised double-blind placebo-controlled cross over study
Authors: Deane Adam M , Chapman Marianne J , Fraser Robert JL , Burgstad Carly M , Besanko Laura K , Horowitz Michael
Published: May 2009

Introduction

Hyperglycaemia occurs frequently in the critically ill, affects outcome adversely, and is exacerbated by enteral feeding. Furthermore, treatment with insulin in this group is frequently complicated by hypoglycaemia. In healthy patients and those with type 2 diabetes, exogenous glucagon-like peptide-1 (GLP-1) decreases blood glucose by suppressing glucagon, stimulating insulin and slowing gastric emptying. Because the former effects are glucose-dependent, the use of GLP-1 is not associated with hypoglycaemia. The objective of this study was to establish if exogenous GLP-1 attenuates the glycaemic response to enteral nutrition in patients with critical illness induced hyperglycaemia.

Methods

Seven mechanically ventilated critically ill patients, not previously known to have diabetes, received two intravenous infusions of GLP-1 (1.2 pmol/kg/min) and placebo (4% albumin) over 270 minutes. Infusions were administered on consecutive days in a randomised, double-blind fashion. On both days a mixed nutrient liquid was infused, via a post-pyloric feeding catheter, at a rate of 1.5 kcal/min between 30 and 270 minutes. Blood glucose and plasma GLP-1, insulin and glucagon concentrations were measured.

Results

In all patients, exogenous GLP-1 infusion reduced the overall glycaemic response during enteral nutrient stimulation (AUC30–270 min GLP-1 (2077 ± 144 mmol/l min) vs placebo (2568 ± 208 mmol/l min); P = 0.02) and the peak blood glucose (GLP-1 (10.1 ± 0.7 mmol/l) vs placebo (12.7 ± 1.0 mmol/l); P < 0.01). The insulin/glucose ratio at 270 minutes was increased with GLP-1 infusion (GLP-1 (9.1 ± 2.7) vs. placebo (5.8 ± 1.8); P = 0.02) but there was no difference in absolute insulin concentrations. There was a transient, non-sustained, reduction in plasma glucagon concentrations during GLP-1 infusion (t = 30 minutes GLP-1 (90 ± 12 pmol/ml) vs. placebo (104 ± 10 pmol/ml); P < 0.01).

Conclusions

Acute, exogenous GLP-1 infusion markedly attenuates the glycaemic response to enteral nutrition in the critically ill. These observations suggest that GLP-1 and/or its analogues have the potential to manage hyperglycaemia in the critically ill.

Trial Registration

Australian New Zealand Clinical Trials Registry number: ACTRN12609000093280.
Early signal protein expression profiles in basophils: a population study
Authors: Ishmael Susan , MacGlashan Donald
Published: May 2009

Despite a broad range of functional responses through FceRI, there is limited variation of early signaling elements in basophils.

IgE-mediated histamine release from peripheral blood basophils is highly variable within the general population. Recent studies have shown that the ability of anti-IgE antibody to induce release can be predicted reasonably well by knowing the level of syk expression in the cells. The current study expands a previous survey to include 14 additional early elements known to be involved in activation and deactivation of basophils and showed that with the exception of syk, the variance of expression of 19 other elements (lyn, fyn, csk, cbp/PAG, CIN85, Bob1, c-cbl, SHIP1, SHIP2, p85α, p110δ, btk, PLCγ1, PLCγ2, SHP-1, PTEN, SOS2, CRACM1, and IL-3Rα) was narrow despite a broad range of functional capability in the basophils under study. With syk as the only element with high variance and well-correlated to maximum histamine release and cellular sensitivity, this survey examined the expression levels of two proteins thought to regulate syk expression: Bob1/OCA-B and CIN85. Expression of CIN85 was not correlated to syk expression, but Bob1 expression was negatively correlated to expression of syk and maximum histamine release. However, the expected behavior for this protein should have been as a protector of post-translational syk loss and therefore, positively correlated. Previous studies suggested that post-translational control mechanisms regulated syk expression. However, in this study, steady-state mRNA levels for syk in resting basophils showed a correlation with syk protein expression levels (r=0.593). It is concluded that with the exception of syk expression, the expression of 19 early signaling elements is tightly regulated and that a component of the regulation of syk may be related to control of transcription or processing of syk mRNA.
VASP is a CXCR2-interacting protein that regulates CXCR2-mediated polarization and chemotaxis
Authors: Neel Nicole F. , Barzik Melanie , Raman Dayanidhi , Sobolik-Delmaire Tammy , Sai Jiqing , Ham Amy J. , Mernaugh Raymond L. , Gertler Frank B. , Richmond Ann
Published: May 2009

Chemotaxis regulates the recruitment of leukocytes, which is integral for a number of biological processes and is mediated through the interaction of chemokines with seven transmembrane G-protein-coupled receptors. Several studies have indicated that chemotactic signaling pathways might be activated via G-protein-independent mechanisms, perhaps through novel receptor-interacting proteins. CXCR2 is a major chemokine receptor expressed on neutrophils. We used a proteomics approach to identify unique ligand-dependent CXCR2-interacting proteins in differentiated neutrophil-like HL-60 cells. Using this approach, vasodilator-stimulated phosphoprotein (VASP) was identified as a CXCR2-interacting protein. The interaction between CXCR2 and VASP is direct and enhanced by CXCL8 stimulation, which triggers VASP phosphorylation via PKA- and PKCδ-mediated pathways. The interaction between CXCR2 and VASP requires free F-actin barbed ends to recruit VASP to the leading edge. Finally, knockdown of VASP in HL-60 cells results in severely impaired CXCR2-mediated chemotaxis and polarization. These data provide the first demonstration that direct interaction of VASP with CXCR2 is essential for proper CXCR2 function and demonstrate a crucial role for VASP in mediating chemotaxis in leukocytes.
α3β1 integrin in epidermis promotes wound angiogenesis and keratinocyte-to-endothelial-cell crosstalk through the induction of MRP3
Authors: Mitchell Kara , Szekeres Charles , Milano Vincenzo , Svenson Kimberly B. , Nilsen-Hamilton Marit , Kreidberg Jordan A. , DiPersio C. Michael
Published: May 2009

During cutaneous wound healing, epidermal keratinocytes play essential roles in the secretion of factors that promote angiogenesis. However, specific cues in the wound microenvironment that trigger the production of pro-angiogenic factors by keratinocytes, and the cellular receptors that mediate this response, remain unclear. In this study, we exploited a model of conditional integrin knockout to demonstrate impaired wound angiogenesis in mice that lack α3β1 integrin in epidermis. In addition, we used genetic and shRNA approaches to determine that α3β1-integrin deficiency in keratinocytes leads to reduced mRNA and protein expression of the pro-angiogenic factor mitogen-regulated protein 3 (MRP3; also known as PRL2C4), and to demonstrate that this regulation provides a mechanism of keratinocyte-to-endothelial-cell crosstalk that promotes endothelial-cell migration. Finally, we showed that the impaired wound angiogenesis in epidermis-specific α3-integrin-knockout mice is correlated with reduced expression of MRP3 in wounded epidermis. These findings identify a novel role for α3β1 integrin in promoting wound angiogenesis through a mechanism of crosstalk from epidermal to endothelial cells, and they implicate MRP3 in this integrin-dependent crosstalk. Such a mechanism represents a novel paradigm for integrin-mediated regulation of wound angiogenesis that extends beyond traditional roles for integrins in cell adhesion and migration.
Omi is a mammalian heat-shock protein that selectively binds and detoxifies oligomeric amyloid-β
Authors: Liu Meng-Lu , Liu Ming-Jie , Shen Yan-Fei , Ryu Hoon , Kim Hyeon-Jin , Klupsch Kristina , Downward Julian , Hong Seong-Tshool
Published: May 2009

The cellular generation of toxic metabolites and subsequent detoxification failure can cause the uncontrolled accumulation of these metabolites in cells, leading to cellular dysfunction. Amyloid-β protein (Aβ), a normal metabolite of neurons, tends to form toxic oligomeric structures that cause neurodegeneration. It is unclear how healthy neurons control the levels of intracellular oligomeric Aβ in order to avoid neurodegeneration. Using immunochemical and biochemical studies, we show that the Aβ-binding serine protease Omi is a stress-relieving heat-shock protein that protects neurons against neurotoxic oligomeric Aβ. Through its PDZ domain, Omi binds preferentially to neurotoxic oligomeric forms of Aβ rather than non-toxic monomeric forms to detoxify oligomeric Aβ by disaggregation. This specific interaction leads not only to mutual detoxification of the pro-apoptotic activity of Omi and Aβ-induced neurotoxicity, but also to a reduction of neurotoxic-Aβ accumulation. The neuroprotective role of Omi is further supported by its upregulation during normal neurogenesis and neuronal maturation in mice, which could be in response to the increase in the generation of oligomeric Aβ during these processes. These findings provide novel and important insights into the detoxification pathway of intraneuronal oligomeric Aβ in mammals and the protective roles of Omi in neurodegeneration, suggesting a novel therapeutic target in neurodegenerative diseases.
Molecular dissection of the ILK-PINCH-parvin triad reveals a fundamental role for the ILK kinase domain in the late stages of focal-adhesion maturation
Authors: Stanchi Fabio , Grashoff Carsten , Nguemeni Yonga Carine Flore , Grall Dominique , Fässler Reinhard , Van Obberghen-Schilling Ellen
Published: May 2009

Integrin-linked kinase (ILK) and cytoplasmic adaptors of the PINCH and parvin families form a ternary complex, termed IPP, that localizes to integrin adhesions. We show here that deletion of the genes encoding ILK or PINCH1 similarly blocks maturation of focal adhesions to tensin-rich and phosphotyrosine-poor fibrillar adhesions (FBs) by downregulating expression or recruitment of tensin and destabilizing α5β1-integrin–cytoskeleton linkages. As IPP components are interdependent for integrin targeting and protein stability, functional dissection of the complex was achieved by fusing ILK, PINCH, parvin or their individual motifs to the cytoplasmic tail of β3 integrin, normally excluded from FBs. Using this novel gain-of-function approach, we demonstrated that expression of the C-terminal kinase domain of ILK can restore tensin recruitment and prompt focal-adhesion maturation in IPP-null cells. Debilitating mutations in the paxillin- or ATP-binding sites of ILK, together with α-parvin silencing, revealed a determinant role for ILK-parvin association, but not for direct paxillin binding, in this function. We propose a model in which the C-terminal domain of ILK promotes integrin sorting by reinforcing α5β1-integrin–actin linkage and controls force transmission by targeting tensin to maturing adhesions.
Formation of endothelial lumens requires a coordinated PKCϵ-, Src-, Pak- and Raf-kinase-dependent signaling cascade downstream of Cdc42 activation
Authors: Koh Wonshill , Sachidanandam Kamakshi , Stratman Amber N. , Sacharidou Anastasia , Mayo Anne M. , Murphy Eric A. , Cheresh David A. , Davis George E.
Published: May 2009

In this study, we present data showing that Cdc42-dependent lumen formation by endothelial cells (ECs) in three-dimensional (3D) collagen matrices involves coordinated signaling by PKCϵ in conjunction with the Src-family kinases (SFKs) Src and Yes. Activated SFKs interact with Cdc42 in multiprotein signaling complexes that require PKCϵ during this process. Src and Yes are differentially expressed during EC lumen formation and siRNA suppression of either kinase, but not Fyn or Lyn, results in significant inhibition of EC lumen formation. Concurrent with Cdc42 activation, PKCϵ- and SFK-dependent signaling converge to activate p21-activated kinase (Pak)2 and Pak4 in steps that are also required for EC lumen formation. Pak2 and Pak4 further activate two Raf kinases, B-Raf and C-Raf, leading to ERK1 and ERK2 (ERK1/2) activation, which all seem to be necessary for EC lumen formation. This work reveals a multicomponent kinase signaling pathway downstream of integrin-matrix interactions and Cdc42 activation involving PKCϵ, Src, Yes, Pak2, Pak4, B-Raf, C-Raf and ERK1/2 to control EC lumen formation in 3D collagen matrices.
Loss of dioxin-receptor expression accelerates wound healing in vivo by a mechanism involving TGFβ
Authors: Carvajal-Gonzalez Jose M. , Roman Angel Carlos , Cerezo-Guisado M. Isabel , Rico-Leo Eva M. , Martin-Partido Gervasio , Fernandez-Salguero Pedro M.
Published: May 2009

Delayed wound healing caused by inefficient re-epithelialization underlines chronic skin lesions such as those found in diabetes. The dioxin receptor (AhR) modulates cell plasticity and migration and its activation by occupational polycyclic aromatic hydrocarbons (PAHs) results in severe skin lesions such as contact hypersensitivity, dermatitis and chloracne. Using wild-type (Ahr+/+) and AhR-null (Ahr–/–) mouse primary keratinocyte cultures and tissue explants, we show that lack of AhR increases keratinocyte migration and accelerates skin re-epithelialization without affecting cell proliferation or recruitment of inflammatory cells. Wounds in Ahr–/– animals had elevated numbers of fibroblasts and increased collagen content in their granulation tissue. Importantly, Ahr–/– dermal fibroblasts secreted higher levels of active TGFβ that increased keratinocyte migration in culture and that could account for over-activation of the TGFβ pathway and for faster wound healing in the AhR-null neo-epithelium. Consistently, a TGFβ neutralizing antibody decreased keratinocyte migration in culture and halted re-epithelialization in Ahr–/– mice. Moreover, in vivo treatment with an antisense oligonucleotide for AhR increased TGFβ signaling and improved re-epithelialization in wounds of wild-type mice. These data indicate that AhR is relevant for wound repair and suggest that AhR downmodulation might be a potential new tool for the treatment of chronic, surgical or accidental wounds.
Electrochemical Oxidation Properties of Tetrakis(tert-butyl)phthalocyaninatozinc(II) in Non-Aqueous Media: A Reinvestigation into the Effects of Stacking, Axial Coordination, and Solvent
Authors: Morisue Mitsuhiko , Kameyama Kazuya , Kobuke Yoshiaki
Published: May 2009

The electrochemical oxidation properties of tetrakis(tert-butyl)phthalocyaninatozinc, Zn(t-Bu4Pc), has been reinvestigated for the first systematic exploration in comparison with the authentic properties of porphyrin. The experimental conditions for the oxidation properties of the monomeric Zn(t-Bu4Pc) species were optimized in CH2Cl2 as a non-coordinating solvent to exclude the effect of axial coordination, although most of the previous studies employed coordinating solvents to overcome poor solubility. Employing dilute conditions with 0.1 M tetra-n-butylammonium hexafluorophosphate (n-Bu4N·PF6) as a supporting electrolyte, the effect of axial ligand and solvent on the oxidation behaviors of Zn(t-Bu4Pc) were newly analyzed. The effects of axial coordination on the oxidation properties of Zn(t-Bu4Pc) are discussed from the views of the kinetic process in the charge-compensating step, the structural deformation by axial coordination, and the σ-donation from the axial ligand to the d-orbital of the central zinc. Coordination of axial ligand and polar solvent results in an unusual positive shift of the oxidation potential of Zn(t-Bu4Pc). We propose a ligand dissociation mechanism for the oxidation processes of Zn(t-Bu4Pc) as a rational explanation for the experimental observations. The relevance of the electrochemical properties is supported by spectroscopic characterization.
A Facile Preparation of (4-Aminophenyl)(3-guaiazulenyl)methylium Hexafluorophosphate: Comparative Studies on Spectroscopic, Chemical, and Electrochemical Properties of Monocarbenium Ion and p-Benzoquinodimethane Monoiminium Ion Compounds
Authors: Takekuma Shin-ichi , Ijibata Naohiko , Minematsu Toshie , Takekuma Hideko
Published: May 2009

Reaction of guaiazulene with 4-aminobenzaldehyde in CH3OH in the presence of hexafluorophosphoric acid at 25 °C for 2 h gives the title compound, with an equiv of HPF6, in 56% yield. Interestingly, a solution of the obtained new monocarbenium ion compound, forming a protonated amino group (4-H3N+PF6−), in CH3CN is allowed to stand at room temperature for 48 h, gradually converting to a new 4-(3-guaiazulenyl)methylene-2,5-cyclohexadiene-1-iminium hexafluorophosphate, completely. Furthermore, reductions of the above two products with NaBH4 in a mixed solvent of EtOH and CH3CN afford 4-amino-1-(3-guaiazulenylmethyl)benzene, selectively. Comparative studies on spectroscopic, chemical, and electrochemical properties of the monocarbenium ion compound with those of the 4-methylene-2,5-cyclohexadiene-1-iminium ion compound, are reported.
Mechanism of Isomerization and Acid-Induced Transformations of 3′-Hydroxy-4,4′-dimethoxy-3′-methyl-3-oxo-7,7′-bis(piperidinocarbonyloxy)-2,2′-spirobi[2H,2′H,3H,3′H-benzo[b]thiophene]. Unusual Equilibrium between the Spiro and 3-Hydroxybenzothiophene Systems
Authors: Konieczny Marek T , Sowinski Pawel
Published: May 2009

Mechanistic investigations show that two diastereoisomers of 3′-hydroxy-4,4′-dimethoxy-3′-methyl-3-oxo-7,7′-bis(piperidinocarbonyloxy)-2,2′-spirobi[2H,2′H,3H,3′H-benzo[b]thiophene] (1) equilibrate via an open ring compound: a 3-hydroxybenzothiophene derivative. The result indicates that the spiro form is more stable than the related, aromatic benzothiophene. Acid-catalyzed transformations of 1 are also reported.
Photochemical Reactions in Nanoscopic Organic Domains Generated from Oriented Crystals with Polymers: Nanocrystalline Mosaics as a New Family of Host Materials
Authors: Oaki Yuya , Imai Hiroaki
Published: May 2009

Oriented architectures are formed on nanocrystals with incorporation of organic polymers through a biomimetic route. The composites of potassium sulfate and potassium hydrogen phthalate/poly(acrylic acid) exhibit a mosaic structure consisting of organic polymers and ca. 20 nm nanocrystals. These nanocrystalline mosaics have organic domains originating from organic polymers in nanoscopic scale and serve as a host material for the incorporation and photochemical reaction of organic molecules. Photoisomerization of azobenzene and photodimerization of coumarin are successfully demonstrated in the composite materials, indicating that the nanocrystalline mosaic has potential as a new family of host material.
Catalytic Behavior of Bis(imino)pyridineiron(II) Complex Supported on Clay Minerals during Slurry Polymerization of Ethylene
Authors: Hiyama Yuto , Kawada Yusuke , Ishihama Yoshiyuki , Sakuragi Tsutomu , Ohshima Masa-aki , Kurokawa Hideki , Miura Hiroshi
Published: May 2009

Supported catalysts prepared by an impregnation method using the bis(imino)pyridineiron(II) complex and clay minerals (montmorillonite, fluorotetrasilicic mica, and saponite) were used for ethylene polymerization. The activities of the montmorillonite- and saponite-based catalysts were much higher than that of the mica-based one.
Geochemistry of Rare Earth Elements in Coal—A Case Study from Chongqing, Southwestern China
Authors: Li Dahua , Tang Yuegang , Deng Tao , Chen Kun , Liu Dong
Published: May 2009

The contents and distribution patterns of rare earth elements (REEs) in coals of different geological periods from Chongqing were studied. The results show that the REE content in coals from Chongqing is 165 μg/g, much higher than that of the common Chinese coals, US coals, and the worldwide coals. The concentration of LREE is much higher than that of the heavy ones. However, the ratio of LREEs to HREEs is only 5.11, much lower than that of the ordinary coals from China. There are two types, A and B, of distribution pattern of rare earth elements in coal. The main distribution pattern is A. The distribution pattern of rare earth elements in Sinian and Cambrian stone coals and Early Permian coals is B, and it is dominated by A and followed by B of the Late Permian and Late Triassic coals. In addition, sequential chemical extraction experiments indicated that silicate association dominates the modes of occurrence of REEs in coals from Chongqing.
Optimal Distribution of Economic Value along the LNG Chain from Government and Investor Perspectives
Authors: Furlonge Haydn I.
Published: May 2009

The LNG industry has been experiencing significant changes in recent years in terms of price volatility, market growth, supply increases and infrastructure expansion. To support these developments, LNG pricing models, ownership structures and commercial arrangements have been evolving. Given these dynamics, a study of the distribution of returns along the LNG chain is critical to the key parties involved, namely private investors and host government. This paper takes a holistic approach by developing an integrated economic model of upstream, midstream and downstream segments of the LNG chain. An optimization framework which provides for reliable investment decision-making is used for finding the optimal netback pricing parameters, subject to appropriate bounds being placed for instance on the minimal acceptable rates of return. A hypothetical case study with typical parameters is used to demonstrate the approach. The optimal distribution of value as well as the commercial arrangement from a government perspective is found to be significantly different from that of the investor. A simple multiobjective approach is used to identify compromise solution sets. Ownership by a state-owned energy company was also investigated in terms of optimal distribution of returns, capital allocation and commercial arrangement.
Understanding Willingness-to-Pay Formation of Repeat Bidders in Sequential Online Auctions
Authors: Goes Paulo B. , Karuga Gilbert G. , Tripathi Arvind K.
Published: May 2009

A growing number of vendors are using a sequence of online auctions to sell large inventories of identical items. Although bidding strategies and bidder behavior in single auctions have been extensively studied, limited research exists on bidding in sequential auctions. We seek to explain how bidders in such an environment learn from the information, and form and update their willingness to pay (WTP). Using a large data set from an online auction retailer, we analyze the evolution of the bidders' WTP as well as the effect of auction design on bidders' WTP in sequential auctions. We see our study in the context of a longitudinal field experiment, in which we were able to track actions of repeat bidders over an extended period of time. Our results show that bidders' WTP in sequential auctions can be explained from their demand characteristics, their participation experience in previous auctions, outcomes in previous auctions, and auction design parameters. We also observe, characterize, and measure what we call a modified demand reduction effect exhibited across different auctions, over time, by multiunit demand bidders. Our findings are important to enable better auction mechanism design, and more sophisticated bidding tools that explore the rich information environment of sequential auctions.
Research Note—Toward a Causal Interpretation from Observational Data: A New Bayesian Networks Method for Structural Models with Latent Variables
Authors: Zheng Zhiqiang (Eric) , Pavlou Paul A.
Published: May 2009

Because a fundamental attribute of a good theory is causality, the information systems (IS) literature has strived to infer causality from empirical data, typically seeking causal interpretations from longitudinal, experimental, and panel data that include time precedence. However, such data are not always obtainable and observational (cross-sectional, nonexperimental) data are often the only data available. To infer causality from observational data that are common in empirical IS research, this study develops a new data analysis method that integrates the Bayesian networks (BN) and structural equation modeling (SEM) literatures.

Similar to SEM techniques (e.g., LISREL and PLS), the proposed Bayesian networks for latent variables (BN-LV) method tests both the measurement model and the structural model. The method operates in two stages: First, it inductively identifies the most likely LVs from measurement items without prespecifying a measurement model. Second, it compares all the possible structural models among the identified LVs in an exploratory (automated) fashion and it discovers the most likely causal structure. By exploring the causal structural model that is not restricted to linear relationships, BN-LV contributes to the empirical IS literature by overcoming three SEM limitations (Lee, B., A. Barua, A. B. Whinston. 1997. Discovery and representation of causal relationships in MIS research: A methodological framework. MIS Quart. 21(1) 109–136)—lack of causality inference, restrictive model structure, and lack of nonlinearities. Moreover, BN-LV extends the BN literature by (1) overcoming the problem of latent variable identification using observed (raw) measurement items as the only inputs, and (2) enabling the use of ordinal and discrete (Likert-type) data, which are commonly used in empirical IS studies.

The BN-LV method is first illustrated and tested with actual empirical data to demonstrate how it can help reconcile competing hypotheses in terms of the direction of causality in a structural model. Second, we conduct a comprehensive simulation study to demonstrate the effectiveness of BN-LV compared to existing techniques in the SEM and BN literatures. The advantages of BN-LV in terms of measurement model construction and structural model discovery are discussed.
Iclaprim, a Novel Diaminopyrimidine for the Treatment of Resistant Gram-Positive Infections
Authors: Sincak Carrie A , Schmidt Justin M
Published: May 2009

Objective

To review the pharmacology, microbiology, in vitro susceptibility, pharmacokinetics, clinical trial data, safety, and tolerability of iclaprim, a novel dihydrofolate reductase (DHFR) inhibitor.

Data Sources

A MEDLINE search was conducted from 1966 through December 2008. Additional sources included abstracts from meetings of the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 2001 to 2008 and information available from the manufacturer's Web site.

Study Selection And Data Extraction

In vitro and clinical studies, in addition to Phase 1, 2, and 3 clinical trials, were included.

Data Synthesis

Iclaprim, a novel diaminopyrimidine and DHFR antagonist, has a mechanism of action similar to that of trimethoprim. It has in vitro activity mainly against gram-positive organisms, including resistant Staphylococcus aureus. In Phase 2 and 3 clinical trials, oral and intravenous administration of iclaprim was effective and well tolerated for the treatment of complicated skin and skin structure infections (cSSSI). Trials are currently ongoing for the treatment of ventilator-associated and healthcare-associated pneumonia.

Conclusions

Iclaprim is a promising antimicrobial agent for the treatment of gram-positive organisms, including resistant S. aureus and trimethoprim-, macrolide-, fluoroquinolone-, and glycopeptide-resistant strains. Additionally, in vitro activity similar to that of trimethoprim has been observed against gram-negative and atypical organisms.
Successful Salvage Treatment of Scedosporium apiospermum Keratitis with Topical Voriconazole After Failure of Natamycin
Authors: Al-Badriyeh Daoud , Leung Lok , Davies Geoffrey E , Stewart Kay , Kong David
Published: May 2009

Objective

To report successful management of Scedosporium apiospermum (previously known as Monosporium apiospermum) keratitis with topical voriconazole as monotherapy.

Case Summary

A 54-year-old previously well woman presented to the emergency department with a painful, injected right eye. There was no history of trauma or use of contact lenses. On examination, the right eye was estimated to have visual acuity of hand movement. Slit lamp examination detected a 2.5 × 3.5 mm dense, central corneal infiltrate with overlying epithelial defect. The eye had mild corneal edema with anterior chamber inflammation. Microbiology testing revealed S. apiospermum as the primary pathogen. Hourly administration of topical natamycin 5% resulted in initial improvement in visual acuity to 20/50, with reduction in the size of the central infiltrate. However, 1 month later, the eye infection relapsed, with recurrence of epithelial defect (3.1 × 3.1 mm) and decline in visual acuity to 20/100. Antifungal therapy was switched to topical voriconazole 1%, administered every 2 hours. Vision improved to 20/30 within 5 days, and the central defect had completely re-epithelialized within 1 week.

Discussion

Treatment of S. apiospermum keratitis remains inadequate. A high natamycin minimum inhibitory concentration is necessary to treat S. apiospermum infection, which may explain the persistence of central infiltration despite ongoing therapy. The combined use of topical and oral voriconazole for the treatment of S. apiospermum keratitis has been reported. However, this is the first report of a successful clinical experience using topical voriconazole without oral therapy to manage S. apiospermum keratitis. This eliminates some disadvantages associated with oral voriconazole such as high cost, potential significant toxicity, and drug interactions.

Conclusions

The voriconazole 1% eye drop used alone is a promising, cost-effective, safe option for managing fungal keratitis, even that caused by S. apiospermum. It may have a larger role to play than simply that of adjunctive therapy.
Ultrastructural Analysis of Nanogold-labeled Endocytic Compartments of Yeast Saccharomyces cerevisiae Using a Cryosectioning Procedure
Authors: Griffith Janice , Reggiori Fulvio
Published: May 2009

Yeast Saccharomyces cerevisiae has been a valuable model organism for the study of the endosomal system of eukaryotic cells. Morphological analyses, however, have been limited because of the lack of specific protein markers and of procedures that lead to a satisfactory ultrastructural resolution. We have recently developed an immunoelectron microscopy (IEM) protocol adapted from the Tokuyasu method to prepare cryosections from mildly fixed yeast. This novel approach allows excellent cell preservation and a unique resolution of the yeast morphology. Here, we present a protocol that combines this procedure with the specific labeling of the various endosomal compartments with positively charged Nanogold. In particular, we show that this new protocol generates excellent results when applied for the examination of early and late endosomes, and of mutants with an endosomal trafficking defect. Importantly, this method is compatible with immunogold labeling of protein markers, and it is consequently appropriate for localization studies of both resident and cargo proteins. This new IEM protocol will be a valuable tool for the large community of scientists using yeast as a model system to investigate the membrane transport and the biogenesis of the endosomal system.
Localization of mRNAs and Proteins in Methyl Methacrylate-embedded Tissues
Authors: Torgersen Jacob S. , Takle Harald , Andersen Øivind
Published: May 2009

Precise localization of proteins and mRNA in histological sections is necessary for evaluating spatial gene expression patterns. Here we report sensitive detection of the gene products in fish tissues by immunohistochemistry (IHC) and in situ hybridization (ISH) assays on sections of whole specimens and vertebra embedded in methyl methacrylate (MMA) resin. This plastic resin favors easy preparation of various specimen types and enables preparation of large sections with well-preserved cell morphology. IHC analysis of the muscle regulatory factor MyoD in transverse sections of juvenile cod revealed MyoD-positive cells in the dorsolateral parts of the adaxial muscle. ISH revealed less spatially restricted signals of the bone morphogenic protein bmp4 in muscle and brain. To assess the applicability of ISH on sections of bony tissue, col1a1 and col2a1 expression was investigated in non-decalcified vertebra sections of Atlantic salmon. The former was identified in both chondrocytes and osteoblasts, whereas the latter was mostly evident in chondrocytes. We conclude that MMA resin offers easy preparation of large and problematic tissues and the possibility of carrying out both IHC and ISH analyses using standard protocols.
Molecular Detection of a Novel Human Influenza (H1N1) of Pandemic Potential by Conventional and Real-Time Quantitative RT-PCR Assays
Authors: Poon Leo L M , Chan K H , Smith G J , Leung C S W , Guan Y , Yuen K Y , Peiris J S M
Published: May 2009

Background: Influenza A viruses are medically important viral pathogens that cause significant mortality and morbidity throughout the world. The recent emergence of a novel human influenza A virus (H1N1) poses a serious health threat. Molecular tests for rapid detection of this virus are urgently needed.

Methods: We developed a conventional 1-step RT-PCR assay and a 1-step quantitative real-time RT-PCR assay to detect the novel H1N1 virus, but not the seasonal H1N1 viruses. We also developed an additional real-time RT-PCR that can discriminate the novel H1N1 from other swine and human H1 subtype viruses.

Results: All of the assays had detection limits for the positive control in the range of 1.0 × 10−4 to 2.0 × 10−3 of the median tissue culture infective dose. Assay specificities were high, and for the conventional and real-time assays, all negative control samples were negative, including 7 human seasonal H1N1 viruses, 1 human H2N2 virus, 2 human seasonal H3N2 viruses, 1 human H5N1 virus, 7 avian influenza viruses (HA subtypes 4, 5, 7, 8, 9, and 10), and 48 nasopharyngeal aspirates (NPAs) from patients with noninfluenza respiratory diseases; for the assay that discriminates the novel H1N1 from other swine and human H1 subtype viruses, all negative controls were also negative, including 20 control NPAs, 2 seasonal human H1N1 viruses, 2 seasonal human H3N2 viruses, and 2 human H5N1 viruses.

Conclusions: These assays appear useful for the rapid diagnosis of cases with the novel H1N1 virus, thereby allowing better pandemic preparedness.
Planned versus Actual Betting in Sequential Gambles
Authors: Andrade Eduardo B. , Iyer Ganesh
Published: May 2009

Anecdotal evidence indicates that in a gambling environment, consumers may end up betting more than they had initially planned. The authors assess this phenomenon in a series of three experiments, in which people are exposed to sequential and fair gambles in a two-stage process (planned and actual bets). The results show that in the planning phase, people behave conservatively, betting on average less after an anticipated loss and the same amount after an anticipated gain. However, after experiencing an actual loss in the first gamble, people bet in a subsequent gamble significantly more than they had initially planned, whereas on average, there were no observable differences from the plan after an actual gain. The reason for such asymmetry is due in part to people's tendency to underestimate, at the planning phase of the gamble, the impact of negative emotions in betting decisions during the actual phase of the gamble.
Fear and Loving in Las Vegas: Evolution, Emotion, and Persuasion
Authors: Griskevicius Vladas , Goldstein Noah J. , Mortensen Chad R. , Sundie Jill M. , Cialdini Robert B. , Kenrick Douglas T.
Published: May 2009

How do arousal-inducing contexts, such as frightening or romantic television programs, influence the effectiveness of basic persuasion heuristics? Three theoretical models make different predictions: (1) A general arousal model predicts that arousal should increase the effectiveness of heuristics, (2) an affective valence model predicts that effectiveness should depend on whether the context elicits positive or negative affect, and (3) an evolutionary model predicts that persuasiveness should depend on both the specific emotion elicited and the content of the particular heuristic. Three experiments examine how fear-inducing versus romantic contexts influence the effectiveness of two widely used heuristics—social proof (e.g., “most popular”) and scarcity (e.g., “limited edition”). The results support the predictions from an evolutionary model, showing that fear can lead scarcity appeals to be counterpersuasive and that romantic desire can lead social proof appeals to be counterpersuasive. The findings highlight how an evolutionary theoretical approach can lead to novel theoretical and practical marketing insights.
Assortment Size and Option Attractiveness in Consumer Choice among Retailers
Authors: Chernev Alexander , Hamilton Ryan
Published: May 2009

An important decision that retailers make involves selecting the number of items constituting their assortments. A key issue in making these decisions is the role of assortment size in determining consumers’ choice of a retailer. The authors address this issue by investigating how consumer choice among retailers offering various-sized assortments is influenced by the attractiveness of the options constituting these assortments. The data show that consumer preference for retailers offering larger assortments tends to decrease as the attractiveness of the options in their assortments increases and can even lead to a reversal of preferences in favor of retailers offering smaller assortments. This research further presents evidence that the relationship between assortment size and option attractiveness is concave, such that the marginal impact of assortment size on choice decreases as the attractiveness of the options increases. Data from eight empirical studies offer converging evidence in support of the theoretical predictions.
Differences in Perspective and the Influence of Charitable Appeals: When Imagining Oneself as the Victim is not Beneficial
Authors: Hung Iris W. , Wyer Robert S.
Published: May 2009

Advertisements often stimulate consumers to imagine themselves in a situation in which they would personally benefit from using the product being advertised. However, when an advertisement is intended to induce consumers to benefit someone else (e.g., to donate money for relief of disaster victims), stimulating them to imagine themselves in the situation confronting the beneficiary can sometimes conflict with the image they form of themselves as a potential helper. This conflict in imagined perspective can decrease the advertisement's effectiveness. Five studies confirm this hypothesis. When participants took the perspective of the beneficiary at the time they read an appeal for help, characteristics of the appeal that increased the ease with which they could imagine the situation from this perspective (e.g., a picture of the victim) had a positive effect on both their urge to help and the amount of money they donated. However, when they had an a priori disposition to take the perspective of a potential donor at the time they read the appeal, these same characteristics decreased the appeal's effectiveness.
Breakthrough into action
Authors: Scollon Ron , Scollon Suzie Wong
Published: May 2009

We take as axiomatic from Hymes's work that the linguistic structures of oral narrative should be construed not as abstract and ideal but as artifacts of the human mind in action in society, and that the indissoluble tension between structure and creativity should be moved by analysts in the direction of social justice. The problem we faced in an extended set of action projects aimed at reducing discrimination against Alaska Natives was that problems framed for our attention were often misleading though on the surface clear-cut and reasonable. We began by viewing narrative as a work of social interaction between storyteller and audience in which taboos often dictate indirect statement, and gradually learned to see action as the active punch line. We began to breakthrough into action—acting ourselves in order to learn how people act, what they know and value, how they structure their worlds—using a strategy we now call “nexus analysis.” Taking narrative as the discursive doppelganger of action, we trained educators and medics to perceive and pursue indigenous hunting strategies of carefully surrounding rather than going directly to quarry. We worked through abduction by moving from action to action, becoming directly engaged in processes of social change.
The place of narrative in human affairs: the implications of Hymes's Amerindian work for understanding text and talk
Authors: Collins James
Published: May 2009

Throughout his long career, Dell Hymes studied and wrote about American Indian languages and cultures, and this work has enduring significance for how we think about relations between text and talk. In providing an account of that significance, the article focuses on Hymes's writing about American Indians and narrative, exploring the close interrelations among the two, then discussing his specific contributions to ethnopoetic theory, illustrating these with reference to a Tolowa (Athabaskan) narrative. Because he trenchantly critiqued received assumptions about the relation between speaking and writing, Hymes's ethnopoetic work has implications for ongoing debates about literacy and society, which is discussed at length. I conclude that his narrative scholarship raises but ultimately leaves unsettled fundamental questions about the relation between text and context.
Hymes's linguistics and ethnography in education
Authors: Hornberger Nancy H.
Published: May 2009

Education is one of the arenas in which Hymes has brought his scholarship and politics of advocacy to bear in the world, perhaps most visibly through his University of Pennsylvania Graduate School of Education deanship (1975–1987), but also through the scope and depth of his writings on linguistics and ethnography in education. Language inequality is an enduring theme of Hymes's work, in relation not only to Native American ethnopoetics, narrative analysis, and linguistic socialization, but also to educational linguistics and ethnography in education. Hymes proposed a vision and a set of ways of doing educational linguistics and ethnography in education—from ethnographic monitoring and ethnography of communication to ethnopoetics of oral narrative and ethnography of language policy—that have inspired and informed researchers for a generation and more.
Dell Hymes's visions of enquiry
Authors: Rampton Ben
Published: May 2009

This commentary initially addresses Hymes's uncompromising scrutiny of the institutions of research, ceaselessly setting them alongside the people and processes that academics study. Turning then to the articles in this collection, it links this critical reflexivity to ethnopoetics as a project in the recovery of voices encrypted in the scholarly record, and it notes continuing tensions in the pursuit of equality and rigor. Last, it describes Hymes as a kind of “virtual mentor” for linguistic ethnography outside the United States. In a context where the boundaries between disciplines are often treated lightly, Hymes provides both a map of central currents in contemporary thought and a set of motives and tools for the exploration of local sites—he articulates a view of “social reality as practical activity” that antedates Bourdieu's praxis and Giddens's structuration and pioneers a framework for describing this empirically. In addition, when disciplinary conventions are relativized, and/or practical relevance looms large, there is a route back to first principles in the unflinching mutual interrogation between linguistics and ethnography that runs throughout his work.
Esther in der Interpretation der Kirchenväter: Königin, Vorbild der Tapferkeit oder Typus der Kirche?
Authors: Siquans Agnethe
Published: May 2009

This article deals with the interpretation and use of the book of Esther in patristic texts. A special focus lies on the person of Queen Esther herself. She is described and estimated very differently in different texts. Very often she is praised for her courage und the salvation of her people (sometimes together with Judith). Other texts focus on her prayer and her fast which give her the strength to save her people with God's help. So Esther is an example of Christian life. Especially the plurality of perspectives in the patristic texts can be interesting for modern biblical scholarship.
Origine militare e fiscale dell'hospitalitas. L'esempio dell'Epistula 62 (19) inviata da Ambrogio a Vigilio di Trento
Authors: D'Andrea Claudia Tavolieri
Published: May 2009

The article focuses upon the hospitalitas as it is presupposed in the letter of Ambrose to the new installed bishop Vigil of Trent and looks for the historical background, especially given in the laws of the Emperor collected in Codex Theodosianus VII (De metatis). This leads to a detailed image of the ancient territory of Trent and the special strategic importance of the city and other places nearby. A comparison with the informations about Antiochia and the places where public activities of welfare for the benefit of the society were gathered shows how intensively the classic traditions were still alive in the more and more Christianized atmosphere of the 4th century.
La lettre 177,16-18 de saint Augustin, écho atténué à un conflit d'exégèse patristique au temps de la controverse pélagienne?
Authors: Dalmon Laurence
Published: May 2009

Epistula 177 (written in autumn 416 AD73) was sent to the Roman bishop Innocent 1st to convince him of condemning pelagian heresy. Epistula 177,16-18, which are devoted to the topic of impeccantia, show signs of a exegetical duel which then opposed Augustine and Pelagius concerning an excerpt from the ambrosial commentary of Saint Luke's (Ambrosius, Expositio euangelii secundum Lucam I 17). The contemporary writings of both opponents quite reflect the topicality and vehemence of this debate, which is incidentally mentioned in an excursus, in Epistula 177. Why such a discretion? We shall work upon a personal translation of the text mentioned above. After refocusing the debate on impeccantia, in the broader context of the pelagian controversy, we shall study the issues of the dispute around the ambrosial authority; we shall then try to understand why the signatories of Epistula 177 thought appropriate of toning down this conflict of interpretation in a letter to Rome.