bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced nigrostriatal neuron-specific, long-term expression by using neural-specific promoters in combination with targeted gene transfer by modified helper virus-free HSV-1 vector particles
Authors: Cao Haiyan , Zhang Guo-rong , Wang Xiaodan , Kong Lingxin , Geller Alfred I 
Published: April 2008

Abstract

Background
Direct gene transfer into neurons has potential for developing gene therapy treatments for specific neurological conditions, and for elucidating neuronal physiology. Due to the complex cellular composition of specific brain areas, neuronal type-specific recombinant gene expression is required for many potential applications of neuronal gene transfer. One approach is to target gene transfer to a specific type of neuron. We developed modified Herpes Simplex Virus (HSV-1) particles that contain chimeric glycoprotein C (gC) – glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) proteins. HSV-1 vector particles containing either gC – GDNF or gC – BDNF target gene transfer to nigrostriatal neurons, which contain specific receptors for GDNF or BDNF. A second approach to achieve neuronal type-specific expression is to use a cell type-specific promoter, and we have used the tyrosine hydroxylase (TH) promoter to restrict expression to catecholaminergic neurons or a modified neurofilament heavy gene promoter to restrict expression to neurons, and both of these promoters support long-term expression from HSV-1 vectors. To both improve nigrostriatal-neuron specific expression, and to establish that targeted gene transfer can be followed by long-term expression, we performed targeted gene transfer with vectors that support long-term, neuronal-specific expression.

Results
Helper virus-free HSV-1 vector packaging was performed using either gC – GDNF or gC – BDNF and vectors that contain either the TH promoter or the modified neurofilament heavy gene promoter. Vector stocks were injected into the midbrain proximal to the substantia nigra, and the rats were sacrificed at either 4 days or 1 month after gene transfer. Immunofluorescent costaining was performed to detect both recombinant gene products and nigrostriatal neurons. The combination of targeted gene transfer with neuronal-specific promoters improved nigrostriatal neuron-specific expression (83 to 93%) compared to either approach alone, and supported long-term (1 month) expression at levels similar to those observed using untargeted gene transfer.

Conclusion
Targeted gene transfer can be used in combination with neuronal-specific promoters to achieve a high level of nigrostriatal neuron-specific expression. Targeted gene transfer can be followed by long-term expression. Nigrostriatal neuron-specific expression may be useful for specific gene therapy approaches to Parkinson's disease or for genetic analyses of nigrostriatal neuron physiology.
Haplotype analysis of TP53 polymorphisms, Arg72Pro and Ins16, in BRCA1 and BRCA2 mutation carriers of French Canadian descent
Authors: Cavallone Luca , Arcand Suzanna L , Maugard Christine , Ghadirian Parviz , Mes-Masson Anne-Marie , Provencher Diane , Tonin Patricia N 
Published: April 2008

Abstract

Background
The TP53 polymorphisms Arg72Pro (Ex4+199 G>C) and Ins16 (IVS3+24 ins16) have been proposed to modify risk of breast cancer associated with germline BRCA1 and BRCA2 mutations. Allele frequencies of these polymorphisms were investigated to determine if they modify risk in BRCA mutation carriers in breast cancer cases drawn from French Canadian cancer families, a population shown to exhibit strong founder effects.

Methods
The frequencies of the TP53 alleles, genotypes and haplotypes of 157 index breast cancer cases comprised of 42 BRCA1 mutation carriers, 57 BRCA2 mutation carriers, and 58 BRCA mutation-negative cases, where each case was drawn from independently ascertained families were compared. The effect of TP53 variants on the age of diagnosis was also investigated for these groups. The TP53 polymorphisms were also investigated in 112 women of French Canadian descent with no personal history of cancer.

Results
The BRCA mutation-positive groups had the highest frequency of homozygous carriers of the 72Pro allele compared with mutation-negative group. The TP53 polymorphisms exhibited linkage disequilibrium (p < 0.001), where the 72Arg and Ins16minus alleles occurred in strong disequilibrium. The highest frequency of carriers of Ins16minus-72Arg haplotype occurred in the BRCA mutation-negative groups. The BRCA1 mutation carriers homozygous for the 72Pro allele had the youngest ages of diagnosis of breast cancer. However none of these observations were statistically significant. In contrast, the BRCA2 mutation carriers homozygous for the 72Pro allele had a significantly older age of diagnosis of breast cancer (p = 0.018). Moreover, in this group, the mean age of diagnosis of breast cancer in carriers of the Ins16minus-72Arg haplotype was significantly younger than that of the individuals who did not this carry this haplotype (p = 0.009).

Conclusion
We observed no significant association of breast cancer risk with TP53 genetic variants based on BRCA1/2 mutation carrier status. Although the small sample size did not permit analysis of all possible haplotypes, we observed that BRCA2 mutation carriers harboring the Ins16minus-72Arg haplotype had a significantly younger mean age of diagnosis of breast cancer. These observations suggest that investigations in a larger French Canadian sample are warranted to further elucidate the effects of TP53 variants on age of diagnosis of breast cancer among BRCA1 and BRCA2 mutation carriers.
Occurrence of cancer at multiple sites: Towards distinguishing multigenesis from metastasis
Authors: Zhang Wei-Kang , Zhang Chun , Zhang Jing J , Liu Shi V 
Published: April 2008

AbstractBackgroundOccurrence of tumors at multiple sites is a hallmark of malignant cancers and contributes to the high mortality of cancers. The formation of multi-site cancers (MSCs) has conventionally been regarded as a result of hematogenous metastasis. However, some MSCs may appear as unusual in the sense of vascular dissemination pattern and therefore be explained by alternative metastasis models or even by non-metastatic independent formation mechanisms.ResultsThrough literature review and incorporation of recent advance in understanding aging and development, we identified two alternative mechanisms for the independent formation of MSCs: 1) formation of separate tumors from cancer-initiating cells (CICs) mutated at an early stage of development and then diverging as to their physical locations upon further development, 2) formation of separate tumors from different CICs that contain mutations in some convergent ways. Either of these processes does not require long-distance migration and/or vascular dissemination of cancer cells from a primary site to a secondary site. Thus, we classify the formation of these MSCs from indigenous CICs (iCICs) into a new mechanistic category of tumor formation – multigenesis.ConclusionA multigenesis view on multi-site cancer (MSCs) may offer explanations for some "unusual metastasis" and has important implications for designing expanded strategies for the diagnosis and treatment of cancers.ReviewersThis article was reviewed by Carlo C. Maley nominated by Laura F. Landweber and Razvan T. Radulescu nominated by David R. Kaplan. For the full reviews, please go to the Reviewers' comments section.
Lysophospholipid metabolism facilitates Toll-like receptor 4 membrane translocation to regulate the inflammatory response
Authors: Jackson Simon K , Abate Wondwossen , Parton Joan , Jones Simon , Harwood John L 
Published: April 2008

AbstractSepsis, an overwhelming inflammatory response to infection, is a major cause of morbidity and mortality worldwide and has no specific therapy. Phospholipid metabolites, such as lysophospholipids, have been shown to regulate inflammatory responses in sepsis, although their mechanism of action is not well understood. The phospholipid-metabolizing enzymes, lysophospholipid acyltransferases, control membrane phospholipid composition, function, and the inflammatory responses of innate immune cells. Here, we show that lysophosphatidylcholine acyltransferase (LPCAT) regulates inflammatory responses to LPS and other microbial stimuli. Specific inhibition of LPCAT down-regulated inflammatory cytokine production in monocytes and epithelial cells by preventing translocation of TLR4 into membrane lipid raft domains. Our observations demonstrate a new regulatory mechanism that facilitates the innate immune responses to microbial molecular patterns and provide a basis for the anti-inflammatory activity observed in many phospholipid metabolites. This provides the possibility of the development of new classes of anti-inflammatory and antisepsis agents.
Introduction to a Forum on “Bargaining for Absolutism”
Authors: Salvucci Richard J. 
Published: April 2008

Abstract
Cliometrics, the union of history and economics, has impressive successes to its credit. But it also displays a worrisome disregard for historical nuance, sometimes to the point of caricature. “Bargaining for Absolutism” by Alejandra Irigoin and Regina Grafe looks at this question from the standpoint of Douglass North’s work on institutions and particularly, Spanish fiscal institutions in the Americas. The result is an effective critique of the notion of early modern Spain as a centralized monarchy.
Selective Oxidation of Benzyl Alcohol by Heteropolytungstate as Reaction-Controlled Phase-Transfer Catalyst with Hydrogen Peroxide
Authors: Weng Zhihuan , Wang Jinyan , Zhang Shouhai , Jian Xigao 
Published: April 2008

Abstract
The catalytic oxidation of benzyl alcohol to benzaldehyde was studied using heteropolytungstates as reaction-controlled phase-transfer catalysts with 35% aqueous H2O2 as oxidant. Under optimal conditions, 95.0% conversion of benzyl alcohol based on H2O2 and over 99% selectivity of benzaldehyde was obtained with [C7H7N(CH3)3]9PW9O34 as catalyst. In this system, once the H2O2 was consumed, the catalyst could be recovered from the system easily as a solid deposit. The catalysts were characterized by FT-IR, 31P NMR, XRD, and TGA, and the results indicated that the insoluble catalyst [C7H7N(CH3)3]9PW9O34 formed a soluble active species [C7H7N(CH3)3]3[(PO4){WO(O2)2}4] under the action of H2O2; the structure of the fresh catalyst was maintained well after the reaction. The results of catalyst recycling showed that this catalyst exhibits good stability. The effects of various reaction factors, such as solvent and the amount of H2O2 used, were studied.
Optimale Ablaufplanung für zyklische Prozesse mit Pooling-Ressourcen (Optimal Scheduling of Cyclic Processes with Pooling-Resources)
Authors: Mayer Eckart , Wulff Kai , Horst Christoph , Raisch Jörg 
Published: April 2008

Dieser Beitrag behandelt die zeitoptimale Ablaufplanung für zyklische Prozesse mit Pooling-Ressourcen. Wir stellen einen Ansatz vor, mit dem eine große Klasse zyklischer Ablaufplanungsprobleme modelliert werden kann. Wir zeigen, wie das resultierende Modell durch Reduktion der Freiheitsgrade und Reparametrierung vereinfacht werden kann, ohne die optimale Lösung auszuschließen. Durch eine geeignete Transformation wird das reduzierte Problem auf ein lineares gemischt-ganzzahliges Optimierungsproblem abgebildet, das mit etablierten Verfahren effizient gelöst werden kann. Pooling-Ressourcen, d. h. Ressourcen, die bei jeder Aktivierung eine vorgegebene Anzahl von Werkstücken/Proben verarbeiten müssen, lassen sich ebenfalls in den vorgestellten Ansatz integrieren.
The topic of this contribution is the time-optimal scheduling of cyclic processes with pooling resources. We present a modelling framework that captures a large class of cyclic scheduling problems. We show how the resulting model can be considerably simplified without cutting the optimal solution. This involves a reduction and a reparametrisation of the degrees of freedom. The reduced model can be transformed into a linear mixed-integer program (MILP), for which a globally optimal solution can be efficiently computed using standard algorithms and tools. We also show how pooling resources can be treated in our framework. Pooling resources have a capacity greater than one and must, at each activation, be loaded to capacity.
Impact of metformin and rosiglitazone treatment on glucose transporter 4 mRNA expression in women with polycystic ovary syndrome.
Authors: Jensterle Mojca , Janez Andrej , Mlinar Barbara , Marc Janja , Prezelj Janez , Pfeifer Marija 
Published: April 2008

ObjectiveThe insulin-resistant state of the polycystic ovary syndrome (PCOS) was found to be associated with a decreased glucose transporter GLUT4 expression in the insulin target tissues. This study was performed to explore whether the well-known clinical, hormonal and metabolic efficacy of metformin or rosiglitazone treatment is reflected in the modulation of adipocyte GLUT4 mRNA expression in patients with PCOS.MethodsWe enrolled 35 women with PCOS. They received either metformin or rosiglitazone for 6 months. A history, blood samples for the measurement of androgens and s.c. adipose tissue samples were taken at baseline and end point. Quantification of GLUT4 mRNA expression in adipose tissue was performed using real-time quantitative PCR. Homeostasis model assessment (HOMAIR) score calculation was applied as a measure for insulin resistance (IR).ResultsGLUT4 mRNA expression in adipose tissue increased significantly in both groups (P<0.001). The increase was more pronounced in the rosiglitazone group (P=0.040). There was a statistically significant improvement of HOMAIRin both groups (P=0.008). After treatment, frequencies of menstrual bleeding were significantly higher (P<0.001) and serum total testosterone levels significantly lower in both groups (P=0.001).ConclusionsA 6-month therapy with insulin sensitizers resulted in marked improvement in adipose tissue GLUT4 mRNA expression in PCOS patients, rosiglitazone being more effective when compared with metformin. The augmentation of the insulin signal transduction was accompanied by a significant improvement of HOMAIR, menstrual pattern and androgen profile.
Black Oil Empirical PVT Correlations Screening for the Niger Delta Crude
Authors: Ikiensikimama Sunday Sunday , Madu John , Dipeolu Lanre 
Published: April 2008

Abstract
Reservoir fluid physical property values constitute an integral part of the data required for comprehensive study of the reservoir and for optimal design of oil recovery and production schemes. More specifically, Pressure-Volume-Temperature (PVT) data corresponding to the reservoir fluid are needed to validate the well test property and to provide meaningful interpretation. In the absence of laboratory measured PVT data, property correlations are used for property estimation as well as for material balance calculations ranging from simple estimations to detailed reservoir performance studies. In addition, estimation of reservoir reserves and the design of the best depletion strategy are feasible only when realistic and reasonably accurate values of the reservoir fluid property are available.
This work screens several empirical PVT correlations for their applicability to the Niger Delta crude. The data used was obtained from conventional PVT reports that derive the various fluid properties through differential liberation process from different oil fields in the Niger Delta. A total of 237 reports were gathered for this study. Full spectrum of oil properties was evaluated. The analysis was done for the following oil properties: oil FVF, pressure, solution GOR, oil compressibility, and oil viscosity, all investigated at bubblepoint. Also same properties were studied for undersaturated oil. Other properties investigated are total oil FVF, viscosity below bubblepoint and dead oil viscosity. For all the correlations, both quantitative – statistical calculations and qualitative – performance (cross plots) plots, analyses were done. Finally, different correlations are recommended for different properties with accuracies for the Niger Delta – black oil.
Discretionary Reporting of Stock Options by IPO Firms
Authors: Beams Joseph D. , Amoruso Anthony J. , Richardson Frederick M. 
Published: April 2008

The revision of SFAS No. 123 (SFAS No. 123R, FASB 2004) requires companies to recognize the fair value of employee stock options. In addition, nonpublic companies will no longer be permitted to assume stock price volatility of zero when calculating the fair value of their stock options. This study finds that the zero volatility assumption allowed under the original version of SFAS No. 123 (FASB 1995) resulted in an average estimated fair value of options that was $1.06 (40 percent) less than the fair value calculated using a peer group volatility estimate for firms undergoing an initial public offering (IPO). However, IPO firms that estimated their volatility underreported option values by an even larger magnitude than the group using the zero volatility assumption. Perhaps these firms reported a downward-biased estimate of volatility to inhibit analysts from computing option values using more reasonable volatility estimates.
Contrary to the findings for public companies, we find that a large percentage of sample firms issued in-the-money options prior to going public. Following the IPO, only a small portion of firms issued in-the-money options. The concerns regarding recognizing option expense may be less important than the benefits of granting in-the-money options for IPO firms.
Industry Specialization by Auditors
Authors: Hogan Chris E. , Jeter Debra C. 
Published: April 2008

Dramatic changes in recent years in the audit market suggest the timeliness of an investigation of trends in auditor concentration and an extension of prior research (e.g., Danos and Eichenseher 1982). In recent press, large audit firms have claimed that specialization is a goal of increasing importance. Peat Marwick, for example, has restructured along industry lines, claiming to be recruiting professionals for national teams of multidisciplinary experts organized to “focus on the same industry to serve clients optimally.” On the other hand, litigation concerns might prompt auditors to diversify their risks by diversifying their clientele.
In this study, we examine trends in industry specialization from 1976 to 1993 and the industry factors which may affect specialization; whether market share increases are greater for audit firms classified as specialists; and whether the nation's largest audit firms have increased their market share in the industries which they have identified as their focus industries. We find evidence that concentration levels have increased over this period, consistent with the claims of the large audit firms. We find that auditor concentration levels are higher in regulated industries, in more concentrated industries and in industries experiencing rapid growth, but lower in industries with a high risk of litigation. Levels of concentration have increased over time in nonregulated industries providing evidence that scale economies or superior efficiencies of heavy-involvement auditors are not limited to regulated industries but extend to nonregulated industries as well. We also find that for the audit firms classified as market leaders at the beginning of the year, market share has increased over time, whereas market share has declined for firms with a smaller share at the beginning of the year. This suggests that there are returns to investing in specialization.
Auditor Resignations and the Market for Audit Services
Authors: Raghunandan K. , Rama D. V. 
Published: April 2008

This paper examines the market for audit services when the incumbent auditor of an SEC registrant has resigned from the engagement. While many previous studies of auditor changes have examined auditor dismissals by the client, only a few studies have specifically focused on auditor resignations. Auditor resignations constitute a unique setting because they may indicate increased likelihood of possible future losses to the new auditor, and provide an opportunity to test the demand-and-supply side incentives in the market for audit services.
Results from analyses of 156 auditor resignations and a control sample of 375 auditor dismissals indicate that Big 6 firms were less likely to serve as the successor auditor when the predecessor has resigned, after controlling for three other factors identified as proxies for litigation risk to the auditor (client's financial stress, industry membership and proportion of total assets in receivables and inventory). The effects were especially pronounced for the subset of resignees in financial stress. These results support suggestions that the implications of auditor resignations are different from auditor dismissals, and provide supporting evidence for the suggestions that supply-side incentives should be considered in examining the market for audit services.
The Role of Problem Representation Shifts in Auditor Decision Processes in Analytical Procedures
Authors: Bierstaker James L. , Bedard Jean C. , Biggs Stanley F. 
Published: April 2008

In audit analytical procedures, research has shown that auditors have difficulty proposing possible explanations for financial statement discrepancies (Bedard and Biggs 1991a). One source of this difficulty is that auditors may represent analytical procedures problems incorrectly; that is, their mental image of the problem does not contain the underlying cause of the discrepancies. Because shifting initial representations of problems is difficult, auditor decision processes are affected. The purpose of this study is to investigate how problem representation shifts can lead auditors to better insight into possible explanations of discrepancies, and thus improve auditor decision processes in analytical procedures. To accomplish this purpose, verbal protocol data from Bedard and Biggs (1991a) were used to develop a series of problem representations and prompts for the analytical procedures task used in that study. The prompts were given to activate relevant knowledge structures in memory and encourage successive shifts toward the correct representation. Think-aloud verbal protocols were collected from 12 senior auditors with three to five years' experience to provide evidence of problem representation shifts and decision processes.
The results indicate that: (1) all subjects initially formulated an unproductive problem representation; (2) only one subject shifted to a productive problem representation and solved the case without prompts; and (3) even with prompts two subjects were unable to solve the case. These findings suggest that shifting to a productive problem representation was critical in achieving effective decision processes and identifying the seeded error in this analytical procedures task. Auditors who developed a thorough understanding of the financial relationships in the case prior to proposing potential solutions were better able to shift problem representations and solve the case. In addition, two processes related to an explanation inherited from client management, “wheel spinning” and truncated hypothesis generation, inhibited problem representation shifts.