bluuebunny/crossref_metadata_2025 huggingface dataset:
Light Delivery over Extended Time Periods Enhances the Effectiveness of Photodynamic Therapy
Authors: Seshadri Mukund , Bellnier David A. , Vaughan Lurine A. , Spernyak Joseph A. , Mazurchuk Richard , Foster Thomas H. , Henderson Barbara W.
Published: May 2008

Purpose: The rate of energy delivery is a principal factor determining the biological consequences of photodynamic therapy (PDT). In contrast to conventional high-irradiance treatments, recent preclinical and clinical studies have focused on low-irradiance schemes. The objective of this study was to investigate the relationship between irradiance, photosensitizer dose, and PDT dose with regard to treatment outcome and tumor oxygenation in a rat tumor model.

Experimental Design: Using the photosensitizer HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide), a wide range of PDT doses that included clinically relevant photosensitizer concentrations was evaluated. Magnetic resonance imaging and oxygen tension measurements were done along with the Evans blue exclusion assay to assess vascular response, oxygenation status, and tumor necrosis.

Results: In contrast to high-incident laser power (150 mW), low-power regimens (7 mW) yielded effective tumor destruction. This was largely independent of PDT dose (drug-light product), with up to 30-fold differences in photosensitizer dose and 15-fold differences in drug-light product. For all drug-light products, the duration of light treatment positively influenced tumor response. Regimens using treatment times of 120 to 240 min showed marked reduction in signal intensity in T2-weighted magnetic resonance images at both low (0.1 mg/kg) and high (3 mg/kg) drug doses compared with short-duration (6-11 min) regimens. Significantly greater reductions in pO2 were observed with extended exposures, which persisted after completion of treatment.

Conclusions: These results confirm the benefit of prolonged light exposure, identify vascular response as a major contributor, and suggest that duration of light treatment (time) may be an important new treatment variable.
Synergistic Growth Inhibition by 9-cis-Retinoic Acid Plus Trastuzumab in Human Hepatocellular Carcinoma Cells
Authors: Tatebe Hideharu , Shimizu Masahito , Shirakami Yohei , Tsurumi Hisashi , Moriwaki Hisataka
Published: May 2008

Purpose: A malfunction of retinoid X receptor-α (RXRα) due to phosphorylation by the Ras/mitogen-activated protein kinase signaling pathway is associated with the development of hepatocellular carcinoma (HCC). The humanized anti-HER2 monoclonal antibody trastuzumab inhibits the activation of HER2 and its multiple downstream signaling pathways, including the Ras/mitogen-activated protein kinase pathway. In this study, the effects of phosphorylation of RXRα on the ability of RXRα ligand 9-cis-retinoic acid (9cRA) and trastuzumab to inhibit growth of HCC cells was examined.

Experimental Design: The effects of a combination of 9cRA plus trastuzumab on the inhibition of cell growth in HLF human HCC cells which express constitutive activation of HER2 protein were examined.

Results: The combination of 9cRA plus trastuzumab synergistically inhibited the growth of HLF cells without affecting the growth of Hc normal human hepatocytes. Combined treatment with these agents acted synergistically to induce apoptosis in HLF cells. The treatment of HLF cells with trastuzumab alone inhibited the phosphorylation of HER2, RXRα, ERK, Akt, and Stat3 proteins and these effects were enhanced when the cells were cotreated with 9cRA. Reporter assays indicated that the combination of 9cRA plus trastuzumab markedly increased both the retinoic acid responsive element and retinoid X responsive element promoter activities in HLF cells.

Conclusion: 9cRA and trastuzumab cooperatively inhibit the activation of HER2 and its downstream signaling pathways, subsequently inhibiting the phosphorylation of RXRα and the growth of HCC cells. This combination might therefore be effective for the chemoprevention and chemotherapy of HCC.
Prognostic Value of the Molecular Detection of Circulating Tumor Cells Using a Multimarker Reverse Transcription-PCR Assay for Cytokeratin 19, Mammaglobin A, and HER2 in Early Breast Cancer
Authors: Ignatiadis Michail , Kallergi Galatea , Ntoulia Maria , Perraki Maria , Apostolaki Stella , Kafousi Maria , Chlouverakis Grigorios , Stathopoulos Efstathios , Lianidou Evi , Georgoulias Vassilis , Mavroudis Dimitris
Published: May 2008

Purpose: To investigate the prognostic value of the molecular detection of circulating tumor cells (CTCs) using three markers [cytokeratin 19 (CK19), mammaglobin A (MGB1), and HER2] in early breast cancer.

Experimental Design: CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells were detected using real-time (CK19) and nested (MGB1 and HER2) reverse transcription-PCR in the peripheral blood of 175 women with stage I to III breast cancer before the initiation of adjuvant chemotherapy. The detection of CTCs was correlated with clinical outcome. In 10 patients, immunofluorescence staining experiments were done to investigate the coexpression of cytokeratin, MGB1, and HER2 in CTCs.

Results: CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells were detected in 41.1%, 8%, and 28.6% of the 175 patients, respectively. Patients had one of the following molecular profiles: CK19mRNA+/MGB1mRNA+/HER2mRNA+ (n = 8), CK19mRNA+/MGB1mRNA+/HER2mRNA− (n = 1), CK19mRNA+/MGB1mRNA−/HER2mRNA+ (n = 42), CK19mRNA+/MGB1mRNA−/HER2mRNA− (n = 21), CK19mRNA−/MGB1mRNA+/HER2mRNA− (n = 5), and CK19mRNA−/MGB1mRNA−/HER2mRNA− (n = 98). Double-immunofluorescence experiments confirmed the following CTC phenotypes: CK+/MGB1+, CK+/MGB1−, CK−/MGB1+, CK+/HER2+, CK+/HER2−, MGB1+/HER2−, and MGB1+/HER2+. In univariate analysis, the detection of CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells was associated with shorter disease-free survival (DFS; P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the detection of CK19mRNA+ and MGB1mRNA+ cells was associated with worse overall survival (P = 0.044 and 0.034, respectively). In multivariate analysis, estrogen receptor–negative tumors and the detection of CK19mRNA+ and MGB1mRNA+ cells were independently associated with worse DFS.

Conclusion: The detection of peripheral blood CK19mRNA+ and MGB1mRNA+ cells before adjuvant chemotherapy predicts poor DFS in women with early breast cancer.
PTOV1 Expression Predicts Prostate Cancer in Men with Isolated High-Grade Prostatic Intraepithelial Neoplasia in Needle Biopsy
Authors: Morote Juan , Fernández Sara , Alaña Lide , Iglesias Carmela , Planas Jacques , Reventós Jaume , Ramón y Cajal Santiago , Paciucci Rosanna , de Torres Inés M.
Published: May 2008

Purpose: To analyze the expression of PTOV1 in high-grade prostatic intraepithelial neoplasia (HG-PIN) and to explore its usefulness to predict prostate cancer in patients with isolated HG-PIN in needle biopsy (prostate needle biopsy).

Experimental Design: PTOV1 expression in HG-PIN lesions from 140 patients was analyzed by immunohistochemistry in a semiquantitative manner (Histo-score). HG-PIN derived from 79 radical prostatectomies for prostate cancer and from 11 cistoprostatectomies for bladder cancer without prostate cancer were used as positive and negative controls, respectively. Fifty patients with HG-PIN without concomitant cancer at their first prostate needle biopsy were chosen as the study group. Patients were followed by a mean of 2.5 repeated prostate needle biopsies (1-5), during a mean period of 12.4 months (1-39).

Results: PTOV1 expression in HG-PIN from radical prostatectomies showed a significantly higher Histo-score (162.6) compared with specimens from cistoprostatectomies (67.0). In the study group, PTOV1 expression was significantly higher in samples with cancer in the follow-up (11 patients, 22%) compared with samples in which cancer was not detected (151.4 versus 94.6). PTOV1 expression was the only independent predictor of cancer in the multivariate analysis and the area under the curve was 0.803 (95% confidence interval, 0.728-0.878). A threshold of 100 for PTOV1 expression provided 90.9% sensitivity, 51.3% specificity, 34.5% positive predictive value, and 95.2% negative predictive value.

Conclusions: PTOV1 is overexpressed in HG-PIN associated with cancer and is a potential marker for studying the carcinogenesis and progression of prostate cancer. Prostate needle biopsy with PTOV1 expression in HG-PIN above a threshold of 100 should be repeated immediately for the likely presence of undiagnosed cancer.
Regional Hypoxia in Glioblastoma Multiforme Quantified with [18F]Fluoromisonidazole Positron Emission Tomography before Radiotherapy: Correlation with Time to Progression and Survival
Authors: Spence Alexander M. , Muzi Mark , Swanson Kristin R. , O'Sullivan Finbarr , Rockhill Jason K. , Rajendran Joseph G. , Adamsen Tom C.H. , Link Jeanne M. , Swanson Paul E. , Yagle Kevin J. , Rostomily Robert C. , Silbergeld Daniel L. , Krohn Kenneth A.
Published: May 2008

Purpose: Hypoxia is associated with resistance to radiotherapy and chemotherapy and activates transcription factors that support cell survival and migration. We measured the volume of hypoxic tumor and the maximum level of hypoxia in glioblastoma multiforme before radiotherapy with [18F]fluoromisonidazole positron emission tomography to assess their impact on time to progression (TTP) or survival.

Experimental Design: Twenty-two patients were studied before biopsy or between resection and starting radiotherapy. Each had a 20-minute emission scan 2 hours after i.v. injection of 7 mCi of [18F]fluoromisonidazole. Venous blood samples taken during imaging were used to create tissue to blood concentration (T/B) ratios. The volume of tumor with T/B values above 1.2 defined the hypoxic volume (HV). Maximum T/B values (T/Bmax) were determined from the pixel with the highest uptake.

Results: Kaplan-Meier plots showed shorter TTP and survival in patients whose tumors contained HVs or tumor T/Bmax ratios greater than the median (P ≤ 0.001). In univariate analyses, greater HV or tumor T/Bmax were associated with shorter TTP or survival (P < 0.002). Multivariate analyses for survival and TTP against the covariates HV (or T/Bmax), magnetic resonance imaging (MRI) T1Gd volume, age, and Karnovsky performance score reached significance only for HV (or T/Bmax; P < 0.03).

Conclusions: The volume and intensity of hypoxia in glioblastoma multiforme before radiotherapy are strongly associated with poorer TTP and survival. This type of imaging could be integrated into new treatment strategies to target hypoxia more aggressively in glioblastoma multiforme and could be applied to assess the treatment outcomes.
A Five-Gene Molecular Grade Index and HOXB13:IL17BR Are Complementary Prognostic Factors in Early Stage Breast Cancer
Authors: Ma Xiao-Jun , Salunga Ranelle , Dahiya Sonika , Wang Wilson , Carney Erin , Durbecq Virginie , Harris Adrian , Goss Paul , Sotiriou Christos , Erlander Mark , Sgroi Dennis
Published: May 2008

Purpose: Histologic tumor grade is a well-established prognostic factor for breast cancer, and tumor grade–associated genes are the common denominator of many prognostic gene signatures. The objectives of this study are as follows: (a) to develop a simple gene expression index for tumor grade (molecular grade index or MGI), and (b) to determine whether MGI and our previously described HOXB13:IL17BR index together provide improved prognostic information.

Experimental Design: From our previously published list of genes whose expression correlates with both tumor grade and tumor stage progression, we selected five cell cycle–related genes to build MGI and evaluated MGI in two publicly available microarray data sets totaling 410 patients. Using two additional cohorts (n = 323), we developed a real-time reverse transcription PCR assay for MGI, validated its prognostic utility, and examined its interaction with HOXB13:IL17BR.

Results: MGI performed consistently as a strong prognostic factor and was comparable with a more complex 97-gene genomic grade index in multiple data sets. In patients treated with endocrine therapy, MGI and HOXB13:IL17BR modified each other's prognostic performance. High MGI was associated with significantly worse outcome only in combination with high HOXB13:IL17BR, and likewise, high HOXB13:IL17BR was significantly associated with poor outcome only in combination with high MGI.

Conclusions: We developed and validated a five-gene reverse transcription PCR assay for MGI suitable for analyzing routine formalin-fixed paraffin-embedded clinical samples. The combination of MGI and HOXB13:IL17BR outperforms either alone and identifies a subgroup (∼30%) of early stage estrogen receptor–positive breast cancer patients with very poor outcome despite endocrine therapy.
MBL2and Hepatitis C Virus Infection among Injection Drug Users
Authors: Brown Elizabeth E , Zhang Mingdong , Zarin-Pass Rebecca , Bernig Toralf , Tseng Fan-Chen , Xiao Nianqing , Yeager Meredith , Edlin Brian R , Chanock Stephen J , O'Brien Thomas R
Published: May 2008

Background

Genetic variations inMBL2that reduce circulating levels and alter functional properties of the mannose binding lectin (MBL) have been associated with many autoimmune and infectious diseases. We examined whetherMBL2variants influence the outcome of hepatitis C virus (HCV) infection.

Methods

Participants were enrolled in the Urban Health Study of San Francisco Bay area injection drug users (IDU) during 1998 through 2000. Study subjects who had a positive test for HCV antibody were eligible for the current study. Participants who were positive for HCV RNA were frequency matched to those who were negative for HCV RNA on the basis of ethnicity and duration of IDU. Genotyping was performed for 15 single nucleotide polymorphisms inMBL2. Statistical analyses of European American and African American participants were conducted separately.

Results

The analysis included 198 study subjects who were positive for HCV antibody, but negative for HCV RNA, and 654 IDUs who were positive for both antibody and virus. There was no significant association between any of the genetic variants that cause MBL deficiency and the presence of HCV RNA. Unexpectedly, theMBL2-289X promoter genotype, which causes MBL deficiency, was over-represented among European Americans who were HCV RNA negative (OR = 1.65, 95% CI 1.05–2.58), although not among the African Americans.

Conclusion

This study found no association between genetic variants that cause MBL deficiency and the presence of HCV RNA. The observation thatMBL2-289X was associated with the absence of HCV RNA in European Americans requires validation.
Ser80Ile mutation and a concurrent Pro25Leu variant of the VHL gene in an extended Hungarian von Hippel-Lindau family
Authors: Patocs Attila , Gergics Peter , Balogh Katalin , Toth Miklos , Fazakas Ferenc , Liko Istvan , Racz Karoly
Published: May 2008

Von Hippel-Lindau disease (VHL) is a rare autosomal dominant disease characterized by development of cystic and tumorous lesions at multiple sites, including the brain, spinal cord, kidneys, adrenals, pancreas, epididymis and eyes. The clinical phenotype results from molecular abnormalities of the VHL tumor suppressor gene, mapped to human chromosome 3p25-26. The VHL gene encodes two functionally active VHL proteins due to the presence of two translational initiation sites separated by 53 codons. The majority of disease-causing mutations have been detected downstream of the second translational initiation site, but there are conflicting data as to whether few mutations located in the first 53 codons, such as the Pro25Leu could have a pathogenic role. In this paper we report a large Hungarian VHL type 2 family consisting of 32 members in whom a disease-causing AGT80AAT (Ser80Ile) c.239G>A, p.Ser80Ile mutation, but not the concurrent CCT25CTT (Pro25Leu) c.74C>T, p.Pro25Leu variant co-segregated with the disease. To our knowledge, the Ser80Ile mutation has not been previously described in VHL type 2 patients with high risk of pheochromocytoma and renal cell cancer. Therefore, this finding represents a novel genotype-phenotype association and VHL kindreds with Ser80Ile mutation will require careful surveillance for pheochromocytoma. We concluded that the Pro25Leu variant is a rare, neutral variant, but the presence such a rare gene variant may make genetic counseling difficult.
Implications of cellobiohydrolase glycosylation for use in biomass conversion
Authors: Jeoh Tina , Michener William , Himmel Michael E , Decker Stephen R , Adney William S
Published: May 2008

The cellulase producing ascomycete, Trichoderma reesei (Hypocrea jecorina), is known to secrete a range of enzymes important for ethanol production from lignocellulosic biomass. It is also widely used for the commercial scale production of industrial enzymes because of its ability to produce high titers of heterologous proteins. During the secretion process, a number of post-translational events can occur, however, that impact protein function and stability. Another ascomycete, Aspergillus niger var. awamori, is also known to produce large quantities of heterologous proteins for industry. In this study, T. reesei Cel7A, a cellobiohydrolase, was expressed in A. niger var. awamori and subjected to detailed biophysical characterization. The purified recombinant enzyme contains six times the amount of N-linked glycan than the enzyme purified from a commercial T. reesei enzyme preparation. The activities of the two enzyme forms were compared using bacterial (microcrystalline) and phosphoric acid swollen (amorphous) cellulose as substrates. This comparison suggested that the increased level of N-glycosylation of the recombinant Cel7A (rCel7A) resulted in reduced activity and increased non-productive binding on cellulose. When treated with the N-glycosidase PNGaseF, the molecular weight of the recombinant enzyme approached that of the commercial enzyme and the activity on cellulose was improved.
Wave propagation in heterogeneous media: Effects of fine-scale heterogeneity
Authors: Delprat-Jannaud Florence , Lailly Patrick
Published: May 2008

We study the multiple scattering effects caused by fine-scale heterogeneity. For this purpose, it is unreasonable to rely on a linearization of the dependency of the wavefield in the parameters that describe the medium. Therefore, the only tools that correctly model wave propagation are based on the numerical solution of the (two-way) wave equation by finite differences or finite elements. A fine grid provides a straightforward approach to account for fine-scale heterogeneity. In this situation, there is no need for high-order schemes. Variational methods allow us to exhibit a numerical scheme that accounts for heterogeneity and that is, by construction, stable, provided a stability condition is fulfilled. This condition is a sufficient-stability condition contrary to the classical necessary-stability conditions. In addition, general mathematical results prove the finite-difference solution is close to the solution of the wave equation when the grid is fine enough. The multiple scattering effects caused by fine-scale heterogeneity are very important. In particular, we observe that imaging the so-computed synthetic data by standard migration techniques (that assume a linearization of the above-mentioned dependency) shows a strongly noise-corrupted image. This illustrates the importance of preprocessing data to remove the effect of multiple scattering. We try to improve the signal-to-noise ratio by removing multiples related to the free surface. Although significant noise reduction is achieved, even more sophisticated preprocessing is required to obtain a clear image of the subsurface.
Field investigation of Love waves in near-surface seismology
Authors: Eslick Robert , Tsoflias Georgios , Steeples Don
Published: May 2008

We examine subsurface conditions and survey parameters suitable for successful exploitation of Love waves in near-surface investigations. Love-wave generation requires the existence of a low shear-velocity surface layer. We examined the minimum thickness of the near-surface layer necessary to generate and record usable Love-wave data sets in the frequency range of [Formula: see text]. We acquired field data on a hillside with flat-lying limestone and shale layers that allowed for the direct testing of varying overburden thicknesses as well as varying acquisition geometry. The resulting seismic records and dispersion images were analyzed, and the Love-wave dispersion relation for two layers was examined analytically. We concluded through theoretical and field data analysis that a minimum thickness of [Formula: see text] of low-velocity material is needed to record usable data in the frequency range of interest in near-surface Love-wave surveys. The results of this study indicate that existing guidelines for Rayleigh-wave data acquisition, such as receiver interval and line length, are also applicable to Love-wave data acquisition.
Conductivity-depth imaging of helicopter-borne TEM data based on a pseudolayer half-space model
Authors: Huang Haoping , Rudd Jonathan
Published: May 2008

Helicopter-borne time-domain electromagnetic (HTEM) systems with a concentric horizontal coil configuration have been used increasingly in mineral exploration. Conductivity-depth imaging (CDI) is a useful tool for mapping the distribution of geologic conductivity and for identifying conductive targets. A CDI algorithm for HTEM systems with a concentric coil configuration is developed based on the pseudolayer half-space model. Primary advantages of this model are immunity to altimeter errors and better resolution of conductive layers than other half-space models. Effective depth is derived empirically from the diffusion depth and apparent thickness of the pseudolayer. A table lookup procedure is established based on the analytic solution of a half-space model to speed up processing. This efficiency makes generation of real-time conductivity-depth images possible. Tests on synthetic data demonstrate that the pseudolayer conductivity-depth-imaging algorithm maps a wider range of conduc-tivities and does a better job of resolving highly conductive layers, compared with that of the homogeneous half-space model. Effective depths are close to true depths in many circumstances. Field examples show stable and geologically meaningful conductivity-depth images.
Internal Control Quality and Audit Pricing under the Sarbanes-Oxley Act
Authors: Hoitash Rani , Hoitash Udi , Bedard Jean C.
Published: May 2008

This paper extends prior research on audit risk adjustment by examining the association of audit pricing with problems in internal control over financial reporting, disclosed under Sections 404 and 302 of the Sarbanes-Oxley Act [SOX]. While studies of auditors' responses to internal control risk provide mixed evidence, it is important to re-examine this issue using data on specific client problems not available prior to SOX. As a baseline, we first establish a strong association of audit fees with internal control problems disclosed in the first year of implementation of Section 404, consistent with prior research (e.g., Raghunandan and Rama 2006). We then address two issues on which prior results are contradictory. In a broadly based sample of accelerated filers, we find that audit pricing for companies with internal control problems varies by problem severity, when severity is measured either as material weaknesses versus significant deficiencies, or by nature of the problem. Also, while audit fees increase during the 404 period, our tests show less relative risk adjustment under Section 404 than under Section 302 in the prior year. Further examining intertemporal effects, we find that companies disclosing internal control problems under Section 302 continue to pay higher fees the following year, even if no problems are disclosed under Section 404. Overall, our findings provide detailed insight into audit risk adjustment during the initial period of SOX implementation.
The Moral Intensity of Reduced Audit Quality Acts
Authors: Coram Paul , Glavovic Alma , Ng Juliana , Woodliff David R.
Published: May 2008

Underlying attributes of reduced audit quality (RAQ) acts are investigated in this research paper. Since RAQ acts may result from ethical judgments, we examine whether they could vary because of differences in moral intensity. Moral intensity was proposed by Jones (1991) in a model that looked at the attributes of the moral issue itself. This study examines whether auditors perceive seven different RAQ acts to differ on three components of Jones' model (social consensus, magnitude of consequences, and probability of effect). Little variation was found on the social consensus dimension showing that auditors think the acts equally wrong. However, significant differences in perceptions about the RAQ acts relating to the probability of effect and the magnitude of consequences were found. The results suggest that RAQ acts differ in terms of their moral intensity, and hence auditors' decisions to undertake RAQ behavior may be issue-contingent. The study provides empirical support for Jones' model by showing, in an audit context, that moral intensity factors vary with the moral issue.
Audit Documentation Methods: A Path Model of Cognitive Processing, Memory, and Performance
Authors: Payne Elizabeth A. , Ramsay Robert J.
Published: May 2008

One result of Public Company Accounting Oversight Board Auditing Standard No. 3 Audit Documentation (AS No. 3) (PCAOB 2004) is that audit firms are using more detailed audit workpapers and fewer summary memos to document their procedures. We explore implications of the choice of these two documentation methods. Specifically, we develop and test a model showing how different forms of documentation affect the cognitive processes auditors use during audit testing, and how differences in cognitive processing affect auditors' memory and two performance measures (error detection and recognition of a potentially fraudulent pattern in the evidence).

The results of path analysis show auditors who prepare detailed workpapers spend more total time on the task, and total time is associated with identifying more errors and better pattern recognition. Auditors who prepare summary memos examine the evidence items a greater number of times, which is associated with better pattern recognition and increased memory. The overall result is that each method enhances cognitive processing differently and the manner of cognitive processing affects performance measures differently. Documentation by summary memos is more efficient and results in better memory of the evidence. Documentation by detailed workpapers results in better error detection for one type of error and permits a self-review of documented evidence by the preparer, which enhances pattern recognition. Finally, documentation by detailed workpapers provides evidence that may potentially enhance pattern recognition at the reviewer level.
Costs to Comply with SOX Section 404
Authors: Krishnan Jagan , Rama Dasaratha , Zhang Yinghong
Published: May 2008

This study examines companies' costs to comply with SOX 404 and identifies factors that are associated with these costs. SOX 404 costs can be classified into three categories: internal labor costs, external consulting and technology expenses, and auditor attestation charges. While prior research has examined audit fees associated with SOX 404, we examine both total costs and auditor attestation costs associated with SOX 404. Based on a sample of companies that voluntarily disclosed SOX 404 cost information during the period from January 2003 to September 2005, we find that the mean (median) total compliance costs for Section 404 is $2.2 ($1.2) million. Regression analyses indicate that the total compliance costs are positively associated with firm size, the presence of material internal control weaknesses, the cost of setting up new computer systems and establishing formal internal control policies, the involvement of large auditors, the appointment of new CEOs, and are negatively associated with firms in regulated industries and firms that raised new financing. Firm size and the incidence of material weaknesses are also the drivers of SOX 404 audit costs, one component of total SOX 404 costs.
Risk Monitoring and Control in Audit Firms: A Research Synthesis
Authors: Bedard Jean C. , Deis Donald R. , Curtis Mary B. , Jenkins J. Gregory
Published: May 2008

This paper summarizes the research literature related to audit firm quality control, with a dual purpose: (1) to provide information on the current state of knowledge with regard to the ways in which audit firms monitor and control firm-level risk; and (2) to identify specific areas in which there is currently insufficient research. We review literature on a number of specific topics under the overall heading of firm-level risk monitoring and control, including: client acceptance/continuance procedures, auditor independence (partner and firm rotation, employing former auditors, nonaudit services, partner compensation), electronic decision aids, consultation units, procedures for communicating weaknesses and taking corrective action, and review of engagement activities (including engagement quality reviews, peer reviews, and regulatory inspections). We conclude with a discussion of research relevant to the issue of whether smaller audit firms should be subject to the same level of quality control regulation as larger firms.
The Influence of Auditor Experience on the Persuasiveness of Information Provided by Management
Authors: Kaplan Steven E. , O'Donnell Edward F. , Arel Barbara M.
Published: May 2008

In this paper, we test whether experience limits auditors' reliance on management-provided information when that information is more favorable than an objective benchmark. In an experiment, we find that experience as an audit senior and the favorableness of management information interact to influence auditor assessments of the reliability of internal controls. While auditors with low levels of experience at the senior rank give assessments that are more favorable, when management's assessment is favorable, high-experience senior auditors' judgments are not influenced by management's assessment. We conclude that as auditors gain experience, they also gain persuasion knowledge, which allows them to deflect management's persuasion attempts.
Audit Committee Member Support for Proposed Audit Adjustments: Pre-SOX versus Post-SOX Judgments
Authors: DeZoort F. Todd , Hermanson Dana R. , Houston Richard W.
Published: May 2008

This study examines differences in audit committee member judgments before the Sarbanes-Oxley Act (“pre-SOX”) versus after the act was passed (“post-SOX”) as well as audit committee member perceptions of the effects of SOX. Based on experimental materials administered to 372 public company audit committee members (131 pre-SOX from DeZoort et al. [2003a] and 241 post-SOX), we find that audit committee support for an auditor-proposed adjustment is significantly higher in the post-SOX period. Additional analyses reveal that the effect of SOX differs between audit committee members who are CPAs versus non-CPAs. Specifically, the greater audit committee member support for the proposed adjustment post-SOX is attributable to members who are CPAs. In general, audit committee members in the post-SOX period feel more responsible for resolving the accounting issue, perceive that audit committee members have greater expertise to evaluate the accounting issue, and also are more concerned with reporting accuracy and a need for conservative financial reporting than those in the pre-SOX period. We also find that post-SOX respondents who support the auditor's proposed adjustment have more favorable views of the benefits of SOX, and they believe more strongly that audit committees in the post-SOX period are more conservative and have more power than they did pre-SOX. We discuss implications and avenues for future research.
One‐Step Ionic‐Liquid‐Assisted Electrochemical Synthesis of Ionic‐Liquid‐Functionalized Graphene Sheets Directly from Graphite
Authors: Liu Na , Luo Fang , Wu Haoxi , Liu Yinghui , Zhang Chao , Chen Ji
Published: May 2008

Graphite, inexpensive and available in large quantities, unfortunately does not readily exfoliate to yield individual graphene sheets. Here a mild, one‐step electrochemical approach for the preparation of ionic‐liquid‐functionalized graphite sheets with the assistance of an ionic liquid and water is presented. These ionic‐liquid‐treated graphite sheets can be exfoliated into functionalized graphene nanosheets that can not only be individuated and homogeneously distributed into polar aprotic solvents, but also need not be further deoxidized. Different types of ionic liquids and different ratios of the ionic liquid to water can influence the properties of the graphene nanosheets. Graphene nanosheet/polystyrene composites synthesized by a liquid‐phase blend route exhibit a percolation threshold of 0.1 vol % for room temperature electrical conductivity, and, at only 4.19 vol %, this composite has a conductivity of 13.84 S m−1, which is 3–15 times that of polystyrene composites filled with single‐walled carbon nanotubes.
Invention and modification of a new tool use behavior: ant‐fishing in trees by a wild chimpanzee (Pan troglodytes verus) at Bossou, Guinea
Authors: Yamamoto Shinya , Yamakoshi Gen , Humle Tatyana , Matsuzawa Tetsuro
Published: May 2008

Wild chimpanzees are known to have a different repertoire of tool use unique to each community. For example, “ant‐dipping” is a tool use behavior known in several chimpanzee communities across Africa targeted at driver ants (Dorylus spp.) on the ground, whereas “ant‐fishing,” which is aimed at carpenter ants (Camponotus spp.) in trees, has primarily been observed among the chimpanzees of Mahale in Tanzania. Although the evidence for differences between field sites is accumulating, we have little knowledge on how these tool use behaviors appear at each site and on how these are modified over time. This study reports two“ant‐fishing” sessions which occurred 2 years apart by a young male chimpanzee at Bossou, Guinea. Ant‐fishing had never been observed before in this community over the past 27 years. During the first session, at the age of 5, he employed wands of similar length when ant‐fishing in trees to those used for ant‐dipping on the ground, which is a customary tool use behavior of this community. Two years later, at the age of 7, his tools for ant‐fishing were shorter and more suitable for capturing carpenter ants. This observation is a rare example of innovation in the wild and does provide insights into problem‐solving and learning processes in chimpanzees. Am. J. Primatol. 70:699–702, 2008. © 2008 Wiley‐Liss, Inc.
Chirale Olefine als Steuerungsliganden in der asymmetrischen Katalyse
Authors: Defieber Christian , Grützmacher Hansjörg , Carreira Erick M.
Published: May 2008

Einen direkten Weg zur Einführung stereogener Zentren bieten metallkatalysierte asymmetrische Prozesse. Aus diesem Grund ist die Entwicklung neuartiger chiraler Liganden, die effizient einen asymmetrischen Verlauf von Reaktionen bewirken können, essenziell in der modernen organischen Synthese. Während eine Vielzahl an chiralen Liganden bekannt ist, die über ein Heteroatom an das Metallzentrum binden, fanden Verbindungen, die über Kohlenstoffatome koordinieren, bisher wenig Beachtung. In dieser Übersicht stellen wir die zunehmende Zahl solcher chiraler, chelatisierender Olefinliganden und ihre Anwendung in metallkatalysierten Umsetzungen vor.
Gasspeicherung in nanoporösen Materialien
Authors: Morris Russell E. , Wheatley Paul S.
Published: May 2008

Die Speicherung von Gasen in Festkörpern gewinnt zunehmend an Bedeutung. Anwendungen und Perspektiven dieser Technologie reichen von der Energiewirtschaft und dem Umweltschutz bis hin zur Biologie und Medizin. Hoch poröse Festkörper wie Zeolithe, Kohlenstoffmaterialien, Polymere und metall‐organische Netzwerke sind mit breit variierbaren chemischen Zusammensetzungen und Strukturen zugänglich. In diesen Architekturen können zahlreiche Gase adsorbiert und gespeichert werden – allen voran Wasserstoff, aber auch Methan, Stickstoffmonoxid und Kohlendioxid. Allerdings ist die Entwicklung von Materialien mit hinreichender Adsorptionskapazität und Lebensdauer, kontrollierbarem Gasfluss und effizienter Wiederbeladung nicht trivial. Das unterschiedliche chemische Verhalten der einzelnen Gase macht es erforderlich, die Eigenschaften des porösen Materials sorgfältig auf die gewünschte Anwendung abzustimmen.
Development of bifunctional photoactivatable benzophenone probes and their application to glycoside substrates
Authors: Qvit Nir , Monderer‐Rothkoff Galya , Ido Ayelet , Shalev Deborah E. , Amster‐Choder Orna , Gilon Chaim
Published: May 2008

Photoaffinity labeling is used to covalently attach ligands to macromolecules to determine their spatial arrangement and structure. Benzophenone (BP) groups are widely used for covalent photoaffinity labeling and for probing protein interactions. We developed bifunctional BP photoactivatable derivatives using three different general chemical approaches. In addition to the photoaffinity reactivity of the BP, these derivatives contain an additional group: A radioactive tracer for biological studies, or an N‐ethylmaleimide group as an additional crosslinker, or a biotin group to be used during purification and characterization of probe–protein complexes using the high‐affinity biotin–avidin interaction. A model series of photoaffinity labeling probes was synthesized based on the arbutin ligand. These compounds can be used as probes to study the arbutin binding site of microbial β‐glucoside transporters by photolabeling residues in its vicinity. The second functionality provides additional options for studying proteins and binding sites. The probes were developed using different methodologies: (i) a diazotation reaction; (ii) protecting group methodology; and (iii) solid‐phase synthesis. These procedures are general and provide a simple and versatile approach for synthesizing bifunctional BP ligands, as demonstrated here on arbutin. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 526–536, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Catheter‐based therapy for acute ischemic stroke: A national unmet need
Authors: DeVries James T. , White Christopher J. , Cunningham Michael C. , Ramee Steven R.
Published: May 2008

Early reperfusion therapy for acute stroke, similar to acute myocardial infarction, has the best opportunity to reduce morbidity and mortality. Treatment options include intravenous (IV) thrombolysis therapy and/or catheter‐based therapy (CBT). Catheter‐based therapies include local intra‐arterial thrombolysis, mechanical thrombectomy, and angioplasty techniques. Intravenous thrombolysis is limited to the first three hours after symptom onset, which excludes many patients with disabling stroke deficits. Catheter‐based therapy is effective up to seven hours after onset, but availability is limited by the lack of neurointerventionalists available around the clock to provide this care. To increase the number of providers for acute stroke reperfusion therapy, we have formed a multidisciplinary team to take advantage of cardiologists' carotid stent placement experience to provide continuous coverage for emergency reperfusion therapy. We present two cases of acute stroke treated with CBT by interventional cardiologists. © 2008 Wiley‐Liss, Inc.
Carotid artery stent placement is safe in the very elderly (≥80 years)
Authors: Velez Carlos A. , White Christopher J. , Reilly John P. , Jenkins J. Stephen , Collins Tyrone J. , Grise Mark A. , McMullan Paul W. , Ramee Stephen R.
Published: May 2008

Background: Carotid artery stent (CAS) placement is an alternative to carotid endarterectomy (CEA) for stroke prevention. Clinical adoption of CAS depends on its safety and efficacy compared to CEA. There are conflicting reports in the literature regarding the safety of CAS in the elderly. To address these safety concerns, we report our single‐center 13‐year CAS experience in very elderly (≥80 years of age) patients. Methods: Between 1994 and 2007, 816 CAS procedures were performed at the Ochsner Clinic Foundation. Very elderly patients, those ≥80 years of age, accounted for 126 (15%) of all CAS procedures. Independent neurologic examination was performed before and after the CAS procedure. Results: The average patient age was 82.9 ± 2.9 years. Almost one‐half (44%) were women and 40% were symptomatic from their carotid stenoses. One‐third of the elderly patients met anatomic criteria for high surgical risk as their indication for CAS. The procedural success rate was 100% with embolic protection devices used in 50%. The 30‐day major adverse coronary or cerebral events (MACCE) rate was 2.7% (n = 3) with all events occurring in the symptomatic patient group [death = 0.9% (n = 1), myocardial infarction = 0%, major (disabling) stroke = 0.9% (n = 1), and minor stroke = 0.9% (n = 1)]. Conclusion: Elderly patients, ≥80 years of age, may undergo successful CAS with a very low adverse event rate as determined by an independent neurological examination. We believe that careful case selection and experienced operators were keys to our success. © 2008 Wiley‐Liss, Inc.
ChemInform Abstract: Nanoscaling Laws of Magnetic Nanoparticles and Their Applicabilities in Biomedical Sciences
Authors: Jun Young‐Wook , Seo Jung‐Wook , Cheon Jinwoo
Published: May 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Surface preparation of AlN substrates
Authors: Chen X. F. , Siche D. , Albrecht M. , Hartmann C. , Wollweber J. , Xu X. G.
Published: May 2008

The Al‐polar surfaces of AlN wafers cut from physical vapor transport grown crystals were lapped and polished. Polishing procedures were developed to produce surfaces for epitaxial growth. The surface scratches and subsurface damage caused by mechanical polishing were removed by a final chemical mechanical polishing (CMP) process, which yielded a perfect surface ready for epitaxial growth. After CMP the average root mean square surface roughness on a 5 µm × 5 µm area was 0.1 nm. Characterization of the polished surfaces by electron back scatter diffraction and cathodoluminescence showed no subsurface damage. The difference of orientation dependent material removal rate during CMP went up with the increase of the misorientation from (0001) surface. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Kinetics of histone H2AX phosphorylation and Chk2 activation in A549 cells treated with topotecan and mitoxantrone in relation to the cell cycle phase
Authors: Zhao Hong , Traganos Frank , Darzynkiewicz Zbigniew
Published: May 2008

The DNA topoisomerase I (topo1) inhibitor topotecan (TPT) and topo2 inhibitors doxorubicin, etoposide and mitoxantrone (MXT) are widely used antitumor drugs. They stabilize otherwise transient (“cleavable”) complexes of topo1 or topo2 with DNA, respectively. Collisions of DNA replication forks (during replication) or progressing RNA polymerase molecules (during transcription) with these complexes convert them into double‐strand DNA breaks (DSBs). Formation of DSBs triggers activation of ATM and phosphorylation of histone H2AX, the markers that have been used to correlate DNA damage with cell cycle phase or induction of apoptosis. In the present study we explored a relationship between H2AX phosphorylation and activation of checkpoint kinase 2 (Chk2) in human lung carcinoma A549 cells treated with TPT or with MXT. Activation of Chk2 was detected immunocytochemically using a phospho‐specific (Thr68) Ab and measuring Chk2‐Thr68Pimmunofluorescence (IF), concurrently with DNA content, by laser scanning cytometry. In the untreated cells, activated Chk2 was present predominantly in centrosomes. Upon treatment with TPT or MTX, the activated Chk2 presented itself in form of either minute or large IF foci in the cell's nucleoplasm. H2AX phosphorylation whether induced by TPT or MXT was rapid, with the maximal rate occurring during the initial 2 h and peaking at 2 h of treatment. TPT or MXT induced Chk2 activation occurred at a distinctly slower pace, peaking at 4 h. While TPT‐induced H2AX phosphorylation and Chk2 activation were maximal in S‐phase cells, Chk2 activation was also much pronounced in G2M cells; the least affected by TPT were G1 cells. MTX‐induced H2AX phosphorylation was maximal in G1 cells while Chk2 activation was maximal in G2M and minimal in G1 cells. The pattern of cell‐cycle phase specific response to TPT or MXT by H2AX phosphorylation and Chk2 activation was different when measured either as integrated or maximal pixel of γH2AX or Chk2‐Thr68P IF, the former reflecting total IF per nucleus the latter stressing the punctate (foci) character of expression of these phospho‐modified proteins. © 2008 International Society for Advancement of Cytometry
An Unusual Cause of Young Hypertension
Authors: Sivakumar K. G. , Fernando Edwin M. , Jayakumar M.
Published: May 2008

A 16‐year‐old male was evaluated for hypertension. On clinical examination, he had features suggestive of type 1 neurofibromatosis (NF1). Further, he had feeble pulse over both lower limbs, with arterial bruit over the abdomen. A magnetic resonance angiogram revealed constriction of the abdominal aorta with bilateral renal artery stenosis. This type of vascular lesion in NF1 is a rare entity. It may be progressive and requires timely intervention to control hypertension and prevent ischemic nephropathy.
When emotions of others affect decisions in public good dilemmas: An instrumental view
Authors: Wubben Maarten J. J. , De Cremer David , van Dijk Eric
Published: May 2008

The present research examines whether the emotional display (i.e. anger vs. guilt) of another group member affects people's decision‐making in a public good dilemma. In two experiments we investigated whether the expressed emotion is particularly informative when communicated by a group member who is highly instrumental in reaching the provision point. A first experiment demonstrated that participants were more likely to exit the group when anger as opposed to guilt was communicated, but especially when the group member displaying the emotion was able to contribute many endowments to the public good. Expected justice (based on past inferences) in the group mediated this effect, suggesting that communicated anger signals more than guilt that the group will not set out to achieve fairness. In agreement with this, a second experiment showed that when it was not possible to exit the group, participants preferred to install a democratic leader more when a wealthy group member communicated anger as opposed to guilt. Additionally, this study provided experimental evidence that a communicated emotion is only used for subsequent decision‐making when more explicit information (i.e. a promise to contribute) is absent. Copyright © 2008 John Wiley & Sons, Ltd.