bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building community partnerships: case studies of Community Advisory Boards at research sites in Peru, Zimbabwe, and Thailand
Authors: Morin Stephen F , Morfit Simon , Maiorana Andre , Aramrattana Apinun , Goicochea Pedro , Mutsambi John Michael , Robbins Jonathan Leserman , Richards T Anne 
Published: March 2008

Background Differences in resources, knowledge, and infrastructure between countries initiating and countries hosting HIV prevention research trials frequently yield ethical dilemmas. Community Advisory Boards (CABs) have emerged as one strategy for establishing partnerships between researchers and host communities to promote community consultation in socially sensitive research. Purpose To understand the evolution of CABs and community partnerships at international research sites conducting HIV prevention trials. Methods Three research sites of the HIV Prevention Trials Network (HPTN) were selected to include geographical representation and diverse populations at risk for HIV/AIDS — in Lima, Peru; Chitungwiza, Zimbabwe; and Chiang Mai, Thailand. Data collection included review of secondary data, including academic publications and site-specific progress reports; observations at the research sites; face-to-face interviews with CAB members, research staff, and other key informants; and focus groups with study participants. Rapid assessment techniques were used for data analysis. Results Two of the three CABs developed new strategies for community representation in response to new studies. All three CABs expanded their original function and became advocates for broader community interests beyond HIV prevention. The participation and input of community representatives, in response to critical incidents that occurred at the sites over the past five years, helped to solidify partnerships between researchers and communities. Limitations Rapid Assessment is an exploratory methodology designed to provide an understanding of a situation based on the integration of multiple data sources, collected within a short period of time, without a formal examination of transcribed and coded data. Case studies, as a method, are meant to draw out what can be learned from a single case but are not, in the scientific sense, generalizable. Conclusions In developing countries, CABs can be dynamic entities that enhance the HIV research process, assist in responding to issues involving research ethics, and prepare communities for HIV research. Clinical Trials 2008; 5: 147—156. http://ctj.sagepub.com
Exhaled nitric oxide, systemic inflammation, and the spirometric response to inhaled fluticasone propionate in severe chronic obstructive pulmonary disease: A prospective study
Authors: Kunisaki Ken M. , Rice Kathryn L. , Janoff Edward N. , Rector Thomas S. , Niewoehner Dennis E. 
Published: March 2008

Background: A subset of patients with chronic obstructive pulmonary disease (COPD) may respond more favorably to inhaled corticosteroids (ICS), but no simple method is currently utilized to predict the presence or absence of ICS responses in patients with COPD. We evaluated the ability of exhaled nitric oxide (FENO) and serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], and interleukin-8 [IL-8]) to independently predict spirometric responses to ICS in patients with COPD. Methods: Among 60 ex-smokers with severe COPD (mean FEV1 1.07 L, 36% of predicted), we conducted a single-arm, open-label study. Participants spent four weeks free of any ICS, followed by four weeks of ICS use (fluticasone propionate 500 mcg twice daily). FENO, CRP, IL-6, IL-8, and pre-bronchodilator spirometry were measured immediately before and after the four weeks of ICS use. Results: Baseline FENO, CRP, IL-6, and IL-8 showed no correlations to FEV1 responses to ICS. ICS responders (increase in FEV1 ≥ 200 mL after four weeks of ICS) did have significantly higher baseline FENO levels compared with non-responders (46.5 parts per billion [ppb] vs. 25 ppb, p = 0 .028). The receiver operating characteristic curve for FENO to discriminate responders from non-responders had an area under curve of 0.72. Baseline serum inflammatory markers did not differ between responders and non-responders. Conclusion: In ex-smokers with severe COPD, a measure of local pulmonary inflammation, FENO, may be more closely associated with FEV1 responses to four weeks of ICS than are standard markers of systemic inflammation, serum CRP, IL-6, and IL-8
Iron depletion limits intracellular bacterial growth in macrophages
Authors: Paradkar Prasad N. , De Domenico Ivana , Durchfort Nina , Zohn Irene , Kaplan Jerry , Ward Diane McVey 
Published: March 2008

AbstractMany intracellular pathogens infect macrophages and these pathogens require iron for growth. Here we demonstrate in vitro that the intracellular growth of Chlamydia psittaci, trachomatis, and Legionella pneumophila is regulated by the levels of intracellular iron. Macrophages that express cell surface ferroportin, the only known cellular iron exporter, limit the intracellular growth of these bacteria. Hepcidin is an antimicrobial peptide secreted by the liver in response to inflammation. Hepcidin binds to ferroportin mediating its internalization and degradation. Addition of hepcidin to infected macrophages enhanced the intracellular growth of these pathogens. Macrophages from flatiron mice, a strain heterozygous for a loss-of-function ferroportin mutation, showed enhanced intracellular bacterial growth independent of the presence of exogenous hepcidin. Macrophages, from wild-type or flatiron mice, incubated with the oral iron chelator deferriprone or desferasirox showed reduced intracellular bacterial growth suggesting that these chelators might be therapeutic in chronic intracellular bacterial infections.
Development of patatin knockdown potato tubers using RNA interference (RNAi) technology, for the production of human-therapeutic glycoproteins
Authors: Kim Yoon-Sik , Lee Yong-Hwa , Kim Hyun-Soon , Kim Mi-Sun , Hahn Kyu-Woong , Ko Jeong-Heon , Joung Hyouk , Jeon Jae-Heung 
Published: April 2008

Abstract

Background
Patatins encoded by a multi-gene family are one of the major storage glycoproteins in potato tubers. Potato tubers have recently emerged as bioreactors for the production of human therapeutic glycoproteins (vaccines). Increasing the yield of recombinant proteins, targeting the produced proteins to specific cellular compartments, and diminishing expensive protein purification steps are important research goals in plant biotechnology. In the present study, potato patatins were eliminated almost completely via RNA interference (RNAi) technology to develop potato tubers as a more efficient protein expression system. The gene silencing effect of patatins in the transgenic potato plants was examined at individual isoform levels.

Results
Based upon the sequence similarity within the multi-gene family of patatins, a highly conserved target sequence (635 nts) of patatin gene pat3-k1 [GenBank accession no. DQ114421] in potato plants (Solanum tuberosum L.) was amplified for the construction of a patatin-specific hairpin RNAi (hpRNAi) vector. The CaMV 35S promoter-driven patatin hpRNAi vector was transformed into the potato cultivar Desiree by Agrobacterium-mediated transformation. Ten transgenic potato lines bearing patatin hpRNA were generated. The effects of RNA interference were characterized at both the protein and mRNA levels using 1D and 2D SDS/PAGE and quantitative real-time RT-PCR analysis. Dependent upon the patatin hpRNAi line, patatins decreased by approximately 99% at both the protein and mRNA levels. However, the phenotype (e.g. the number and size of potato tuber, average tuber weight, growth pattern, etc.) of hpRNAi lines was not distinguishable from wild-type potato plants under both in vitro and ex vitro growth conditions. During glycoprotein purification, patatin-knockdown potato tubers allowed rapid purification of other potato glycoproteins with less contamination of patatins.

Conclusion
Patatin-specific hpRNAi effectively suppressed the expression of a majority of patatin variants in potato tubers via the specific degradation of individual mRNAs of the patatin multi-gene family. More importantly, patatin-knockdown potato tubers appear to be an ideal host for the production of human therapeutic glycoproteins, because they eventually allow fast, easy purification of recombinant proteins, with less contamination from potato glycoprotein patatins.
Killing cancer cells by targeted drug-carrying phage nanomedicines
Authors: Bar Hagit , Yacoby Iftach , Benhar Itai 
Published: April 2008

Abstract

Background
Systemic administration of chemotherapeutic agents, in addition to its anti-tumor benefits, results in indiscriminate drug distribution and severe toxicity. This shortcoming may be overcome by targeted drug-carrying platforms that ferry the drug to the tumor site while limiting exposure to non-target tissues and organs.

Results
We present a new form of targeted anti-cancer therapy in the form of targeted drug-carrying phage nanoparticles. Our approach is based on genetically-modified and chemically manipulated filamentous bacteriophages. The genetic manipulation endows the phages with the ability to display a host-specificity-conferring ligand. The phages are loaded with a large payload of a cytotoxic drug by chemical conjugation. In the presented examples we used anti ErbB2 and anti ERGR antibodies as targeting moieties, the drug hygromycin conjugated to the phages by a covalent amide bond, or the drug doxorubicin conjugated to genetically-engineered cathepsin-B sites on the phage coat. We show that targeting of phage nanomedicines via specific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release, resulting in growth inhibition of the target cells in vitro with a potentiation factor of >1000 over the corresponding free drugs.

Conclusion
The results of the proof-of concept study presented here reveal important features regarding the potential of filamentous phages to serve as drug-delivery platform, on the affect of drug solubility or hydrophobicity on the target specificity of the platform and on the effect of drug release mechanism on the potency of the platform. These results define targeted drug-carrying filamentous phage nanoparticles as a unique type of antibody-drug conjugates.
Inhibition of corneal inflammation by liposomal delivery of short-chain, C-6 ceramide
Authors: Sun Yan , Fox Todd , Adhikary Gautam , Kester Mark , Pearlman Eric 
Published: March 2008

AbstractCeramide is recognized as an antiproliferative and proapoptotic sphingolipid metabolite; however, the role of ceramide in inflammation is not well understood. To determine the role of C6-ceramide in regulating inflammatory responses, human corneal epithelial cells were treated with C6-ceramide in 80 nm diameter nanoliposome bilayer formulation (Lip-C6) prior to stimulation with UV-killed Staphylococcus aureus. Lip-C6 (5 μM) inhibited the phosphorylation of proinflammatory and proapoptotic MAP kinases JNK and p38 and production of neutrophil chemotactic cytokines CXCL1, CXCL5, and CXCL8. Lip-C6 also blocked CXC chemokine production by human and murine neutrophils. To determine the effect of Lip-C6 in vivo, a murine model of corneal inflammation was used in which LPS or S. aureus added to the abraded corneal surface induces neutrophil infiltration to the corneal stroma, resulting in increased corneal haze. Mice were treated topically with 2 nMoles (811 ng) Lip-C6 or with control liposomes prior to, or following, LPS or S. aureus stimulation. We found that corneal inflammation was significantly inhibited by Lip-C6 but not control liposomes given prior to, or following, activation by LPS or S. aureus. Furthermore, Lip-C6 did not induce apoptosis of corneal epithelial cells in vitro or in vivo, nor did it inhibit corneal wound healing. Together, these findings demonstrate a novel, anti-inflammatory, nontoxic, therapeutic role for liposomally delivered short-chain ceramide.
Unravelling Referral Paths Relating to the Dental Care of Children: A Study in Liverpool
Authors: Harris Rebecca V , Pender Susan M , Merry Alison , Leo Anthony 
Published: April 2008

Objective To describe primary care referral networks relating to children's dental care and the main influences on referral decisions taken by dentists working in a primary care setting. Design A postal questionnaire to all 130 general dental practitioners (GDPs) in contract with Primary Care Trusts (PCTs), and 24 Community Dental Service (CDS) dentists in Liverpool. Outcome measures Characteristics of patient groups and factors influencing the choice of referral pathway of children referred from primary dental care. Results There were good responses rates (110 [85%] GDPs and 22 [92%] CDS dentists). The two main reasons why GDPs referred children to hospitals were (a) for treatment under general anaesthetic (GA) or relative analgesia (RA) and (b) for restorative care of dentally anxious children. GDPs also referred anxious children requiring simple restorative care and/or RA to the CDS. Only eight GDPs (7%) cited a lack of experience as a reason for referral of dentally anxious children for simple restorative care, compared to 53 (48%) who cited a lack of RA facilities, and 25 (23%) who cited financial considerations. Conclusions GDPs refer children to both hospital services and the CDS, and identify a lack of RA facilities and economic pressures as key reasons for referral.
A General Notion of Realizability
Authors: Birkedal Lars 
Published: April 2008

AbstractWe present a general notion of realizability encompassing both standard Kleene style realizability over partial combinatory algebras and Kleene style realizability over more general structures, including all partial cartesian closed categories. We show how the general notion of realizability can be used to get models of dependent predicate logic, thus obtaining as a corollary (the known result) that the category Equ of equilogical spaces models dependent predicate logic. Moreover, we characterize when the general notion of realizability gives rise to a topos, i.e., a model of impredicative intuitionistic higher-order logic.
Corporate Reporting on the Internet
Authors: Ashbaugh Hollis , Johnstone Karla M. , Warfield Terry D. 
Published: March 2008

In this paper, we examine firms' use of the Internet to enhance the relevance of their financial reporting. We define a firm as practicing Internet Financial Reporting (IFR) when it provides in its web site either (1) a comprehensive set of financial statements (including footnotes and the auditors' report), (2) a link to its annual report elsewhere on the Internet or (3) a link to the U.S. Security and Exchange Commission's (SEC) Electronic Data Gathering, Analysis and Retrieval (EDGAR) system. While 70 percent of the firms in our sample engage in IFR, we find substantial variation in the quality of firms' IFR practices. Specifically, the variations in quality pertain to the timeliness and therefore, the usefulness of firms' financial reporting on the Internet. We find that some firms provide more timely financial disclosures via the Internet (e.g., monthly sales) while other firms report outdated financial data (e.g., two-year old annual reports). We also observe that the usefulness of firms' financial reporting on the Internet depends on how easy it is to access that data, the amount of data disclosed and/or whether users can download or analyze the data.
To substantiate firms' incentives for engaging in IFR, we sent surveys to firms with web sites in our sample and asked them to report their perceived costs and benefits related to establishing an Internet presence. Firms responded to our questions about why they established an Internet presence by indicating that they perceive their web sites to be an important vehicle to disseminate information to shareholders. After documenting how and why firms use the Internet to voluntarily disclose financial information, we develop the implications of such practices for consumers who demand financial information, firms that supply financial data, auditors and market regulators.
An Exploratory Analysis of the 1989 Accounting Firm Megamergers
Authors: Ivancevich Susan H. , Zardkoohi Asghar 
Published: March 2008

The 1989 “megamergers” (creating Ernst & Young and Deloitte & Touche), as well as recent merger activity within the accounting profession, have attracted widespread attention from regulators. Given the magnitude of such mergers, and the regulatory interest generated by them, it becomes increasingly important to understand the impact that such mergers have within the public accounting market.
This study is a descriptive exploratory investigation into the effects of the 1989 mergers. Data for the firms involved in the mergers were compared to data for competitor firms not involved in the mergers (direct rivals) to help to control for the effect of market forces. The post-merger period was characterized by a slight decline in market share for the merged firms compared to their direct rivals, a decline in audit price for both groups, and a decrease in factor costs for the merged firms relative to their direct rivals.
The results of data analysis are consistent with the premise that 1989 megamergers predominantly resulted in increased efficiencies within the audit market that were then passed through to end-users in the form of lower prices. Further study is needed to determine whether these efficiencies within the audit market were offset by market power influences in nonaudit services.
Application of the Business Risk Audit Model: A Field Study
Authors: Eilifsen Aasmund , Knechel W. Robert , Wallage Philip 
Published: March 2008

After confronting unprecedented challenges in the last decade, accounting firms have undertaken extensive effort to improve the basic financial statement audit and to expand external assurance beyond the traditional audit. The re-examination of audit methods has produced a new emphasis on assessing business and process risks in the conduct of an audit. This paper describes the fundamental changes in the audit process and examines their impact in an actual engagement. We first identify outcomes that we expect to observe in an audit based on the business risk model and then study an actual engagement to gather preliminary evidence about our expectations.
The engagement used in this study is the 1997 audit of the Czech bank Cˇeskoslovenska´ Obchodni´ Banka (CˇSOB). Important observations about the new audit process included changes to the audit team structure, changes in administration and timing of the engagement, changes in the risks addressed during the audit and the evidence gathered, increased assurance to the client, and increased opportunities for value-added services. Although the generalization of results from a field study is constrained, this study identifies expectations and effects that can be examined in future larger sample studies.
Stock Option Expense: The Sword of Damocles Revealed
Authors: Botosan Christine A. , Plumlee Marlene A. 
Published: March 2008

Statement of Financial Accounting Standards (SFAS) No. 123 is one of the most controversial accounting standards ever issued by the Financial Accounting Standards Board (FASB 1995) (SFAS No. 123, para. 376). More than five years have passed since SFAS No. 123 first required firms to either recognize or disclose stock option expense based on the fair value of options granted. In light of the fractious debate surrounding its passage and ongoing differences of opinion regarding the usefulness of stock option expense data, this paper reports how the standard impacts firm performance.
This study examines the effect of stock option expense on the diluted earnings per share and return on assets of 100 firms identified by Fortune magazine as “America's Fastest-Growing Companies.” We find that stock option expense has a material impact on the performance measures for a majority of our sample firms. Moreover, our analysis predicts stock option expense will grow over the next several years, potentially doubling in magnitude during that time. We also document some noncompliance with the disclosure requirements of SFAS No. 123, finding that 12 percent of the sample firms provided incomplete information during the most recent year examined.
Managing Pro Forma Stock Option Expense under SFAS No. 123
Authors: Balsam Steven , Mozes Haim A. , Newman Harry A. 
Published: March 2008

We investigate whether footnote disclosures under Statement of Financial Accounting Standards (SFAS) No. 123 are managed in 1996, the first year that the disclosure was required. The 1996 phase-in of SFAS No. 123 provided firms with a unique opportunity to manipulate the pro forma disclosure in the initial years. SFAS No. 123 allows firms discretion in estimating the value of their stock option grants and in allocating that value across accounting periods. Although we find little evidence that firms manage the estimated value of their option grants, we find that firm-specific incentives affect how that value is allocated. Specifically, firms that provide high levels of either CEO compensation or stock option compensation relative to performance allocate a smaller proportion of the options' value to the 1996 pro forma expense, apparently to reduce criticism of that compensation. Small firms and firms that recently went public also allocate a smaller proportion of option value to the 1996 pro forma expense, apparently to increase perceptions of their profitability.
We conjecture that firms were less likely to manage the value of the options granted than the allocation of that value in 1996 because the parameter estimates underlying the reported option value must be disclosed in the footnote, whereas the inputs to the allocation computation are not disclosed.
These results, which suggest that firms manipulated pro forma stock option expense when their estimate choices cannot be observed, have implications for both standard setters and financial statement users. In particular, the FASB's current deliberations on the transition from footnote disclosure to income statement recognition for stock options should consider additional disclosures to minimize unobservable choices. More generally, the FASB may reduce potential manipulation by requiring expanded disclosures about the choices used in computing both pro forma and reported numbers.