bluuebunny/crossref_metadata_2025 huggingface dataset:
A temporal comparison of AltaVista Web searching
Authors: Jansen Bernard J. , Spink Amanda , Pedersen Jan
Published: February 2005

Major Web search engines, such as AltaVista, are essential tools in the quest to locate online information. This article reports research that used transaction log analysis to examine the characteristics and changes in AltaVista Web searching that occurred from 1998 to 2002. The research questions we examined are (1) What are the changes in AltaVista Web searching from 1998 to 2002? (2) What are the current characteristics of AltaVista searching, including the duration and frequency of search sessions? (3) What changes in the information needs of AltaVista users occurred between 1998 and 2002? The results of our research show (1) a move toward more interactivity with increases in session and query length, (2) with 70% of session durations at 5 minutes or less, the frequency of interaction is increasing, but it is happening very quickly, and (3) a broadening range of Web searchers' information needs, with the most frequent terms accounting for less than 1% of total term usage. We discuss the implications of these findings for the development of Web search engines.
Clearing up “implicit knowledge”: Implications for Knowledge Management, information science, psychology, and social epistemology
Authors: Day Ronald E.
Published: February 2005

“Implicit knowledge” and “tacit knowledge” in Knowledge Management (KM) are important, often synonymous, terms. In KM they often refer to private or personal knowledge that needs to be made public. The original reference of “tacit knowledge” is to the work of the late scientist and philosopher, Michael Polanyi (Polanyi, 1969), but there is substantial evidence that the KM discourse has poorly understood Polanyi's term. Two theoretical problems in Knowledge Management's notion of “implicit knowledge,” which undermine empirical work in this area, are examined. The first problem involves understanding the term “knowledge” according to a folk‐psychology of mental representation to model expression. The second is epistemological and social: understanding Polanyi's term, tacit knowing as a psychological concept instead of as an epistemological problem, in general, and one of social epistemology and of the epistemology of the sciences, in particular. Further, exploring Polanyi's notion of tacit knowing in more detail yields important insights into the role of knowledge in science, including empirical work in information science. This article has two parts: first, there is a discussion of the folk‐psychology model of representation and the need to replace this with a more expressionist model. In the second part, Polanyi's concept of tacit knowledge in relation to the role of analogical thought in expertise is examined. The works of philosophers, particularly Harré and Wittgenstein, are brought to bear on these problems. Conceptual methods play several roles in information science that cannot satisfactorily be performed empirically at all or alone. Among these roles, such methods may examine historical issues, they may critically engage foundational assumptions, and they may deploy new concepts. In this article the last two roles are examined.
Rheological characterization and dissolution kinetics of fibrin gels crosslinked by a microbial transglutaminase
Authors: Sun Yan , Giraudier Olivier , Garde Véronique Larreta
Published: February 2005

Various fibrin gels were prepared with a microbial transglutaminase under miscellaneous conditions. The gels were characterized through their rheological properties. The influence of fibronectin addition and that of covalent bonding on the viscoelastic characteristics were evaluated. Gel elasticity is proportional to fibrinogen concentration but shows a nonlinear dependence on transglutaminase concentration. Additional crosslink of fibronectin in fibrin gels has no effect on the rheological character of the matrix. Dissolution kinetics in concentrated urea solutions evidences the role of covalent bonds on gel stability. The rheological properties and gel stability are discussed in relation with the enzyme‐catalyzed covalent bonding. The microbial enzyme reactions are compared to those of FXIII and tissue transglutaminases. © 2005 Wiley Periodicals, Inc. Biopolymers, 2005
The structure of “unstructured” regions in peptides and proteins: Role of the polyproline II helix in protein folding and recognition*
Authors: Rath Arianna , Davidson Alan R. , Deber Charles M.
Published: February 2005

Classical descriptions of the three‐dimensional shapes of proteins usually invoke three main structures: α‐helix, β‐sheet, and β‐turn. More recently, the polyproline II (PPII) structure has been implicated in diverse biological activities including signal transduction, transcription, cell motility, and immune response. Concurrently, evidence is accumulating that PPII structure has a significant role in the unfolded states of proteins. In this article, we connect the structural properties of PPII helices to their roles in protein recognition and protein unfolded states. The properties unique to the PPII conformation are linked to the exploitation of this structure for the molecular recognition of proteins, using peptide ligands of the Src homology 3 (SH3) domain as an example. The evidence supporting a role for PPII conformation in protein‐unfolded states is also presented in the context of the forces that may stabilize the PPII conformation in unfolded polypeptides. © Wiley Periodicals Inc. Biopolymers (Pept Sci), 2005
Artificial diiron proteins: From structure to function
Authors: Calhoun Jennifer R. , Nastri Flavia , Maglio Ornella , Pavone Vincenzo , Lombardi Angela , DeGrado William F.
Published: February 2005

De novo protein design provides an attractive approach for the construction of models to probe the features required for the function of complex metalloproteins. These minimal models contain the essential elements believed necessary for activity of the protein. In this article, we summarize the design, structure determination, and functional properties of a family of artificial diiron proteins. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005
Ring‐Opening Protonolysis of Sila[1]ferrocenophanes as a Route to Stabilized Silylium Ions
Authors: Bourke Sara C. , MacLachlan Mark J. , Lough Alan J. , Manners Ian
Published: February 2005

The ring‐opening reactions of a series of sila[1]ferrocenophanes with protic acids of anions with various degrees of noncoordinating character have been explored. Ferrocenyl‐substituted silyl triflates FcSiMe2OTf (5 a) and Fc3SiOTf (5 b) (Fc=(η5‐C5H4)Fe(η5‐C5H5)) were synthesized by means of HOTf‐induced ring‐opening protonolysis of strained sila[1]ferrocenophanes fcSiMe2 (3 a) and fcSiFc2 (3 b) (fc=(η5‐C5H4)2Fe). Reaction of 3 a and 3 b with HBF4 yielded fluorosubstituted ferrocenylsilanes FcSiMe2F (6 a) and Fc3SiF (6 b) and suggested the intermediacy of a highly reactive silylium ion capable of abstracting F− from the [BF4]− ion. Generation of the solvated silylium ions [FcSiMe2⋅THF]+ (7a+), [Fc3Si⋅THF]+ (7b+) and [FcSiiPr2⋅OEt2]+ (7c+) at low temperatures, by reaction of the corresponding sila[1]ferrocenophanes (3 a, 3 b, and fcSiiPr2 (3 c), respectively) with H(OEt2)(S)TFPB (S=Et2O or THF; TFPB=tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate) was monitored by using low‐temperature 1H, 13C, and 29Si NMR spectroscopy. In situ reaction of 7a+, 7b+, and 7c+ with excess pyridine generated [FcSiMe2⋅py]+ (8a+), [Fc3Si⋅py]+ (8b+), and [FcSiiPr2⋅py]+ (8c+), respectively, as observed by 1H, 13C, and 29Si NMR spectroscopy. A preparative‐scale reaction of 3 b with H(OEt2)(THF)TFPB at −60 °C and subsequent addition of excess pyridine gave isolable red crystals of 8b‐[TFPB]⋅CHCl3, which were characterized by 1H and 29Si NMR spectroscopy as well as by single‐crystal X‐ray diffraction.
The expression of Bcl‐2 family proteins differs between nonsmall cell lung carcinoma subtypes
Authors: Berrieman Helen K. , Smith Laura , O'Kane Sara L. , Campbell Anne , Lind Michael J. , Cawkwell Lynn
Published: February 2005

BACKGROUND

Proteins of the Bcl‐2 family play a key role in the control of apoptosis and carry out both proapoptotic and antiapoptotic functions. However, with the exception of Bcl‐2 itself, little is known about the expression of these potentially critical proteins in nonsmall cell lung carcinoma.

METHODS

Immunohistochemistry was used to study the expression of Bcl‐2 and 6 other Bcl‐2 family proteins in a pilot series of 41 archival nonsmall cell lung carcinoma specimens (19 adenocarcinomas and 22 squamous cell carcinomas).

RESULTS

Overexpression of the apoptosis inhibitors Bcl‐2 and Bcl‐XL was observed in 10 of 41 samples (24%) and in 11 of 41 samples (27%), respectively. Loss of expression of proapoptotic proteins was observed as follows: Bak, 24 of 41 samples (59%); Bad, 21 of 41 samples (51%); Bid, 20 of 41 samples (49%); Bax, 14 of 41 samples (34%); and Bim/Bod, 2 of 41 samples (5%). Statistically significant differences in expression between adenocarcinoma samples and squamous cell carcinoma samples were observed for Bcl‐XL (overexpression in 11 of 19 adenocarcinomas [58%] vs. 0 of 22 squamous cell carcinomas [0%]; P < 0.001) and for Bad (loss of expression in 5 of 19 adenocarcinomas [26%] vs. 16 of 22 squamous cell carcinomas [73%]; P = 0.004).

CONCLUSIONS

Although this was only a pilot study, the results revealed significant differences in the expression of apoptosis‐related proteins both between individual samples of nonsmall cell lung carcinoma and between the two main histologic subtypes. Such differences may play a role in the development of lung tumors; and, if it is found that these differences are of clinical importance, then it may be required to regard nonsmall cell lung carcinoma subtypes as separate entities rather than as one disease. Cancer 2005. © 2005 American Cancer Society.
Employment pathways in a large cohort of adult cancer survivors
Authors: Short Pamela Farley , Vasey Joseph J. , Tunceli Kaan
Published: February 2005

BACKGROUND

Employment and work‐related disability were investigated in a cohort of adult cancer survivors who were working when they were diagnosed from 1997 to 1999 with a variety of cancers. Employment from the time of diagnosis through the early years of survivorship was studied, self‐reported effects of cancer survival on disability and employment were quantified, and risk factors associated with cancer‐related disability and withdrawal from employment were identified.

METHODS

One thousand four hundred thirty‐three cancer survivors were interviewed by telephone from 1 year to nearly 5 years after diagnosis. They were asked retrospectively about employment from the time of diagnosis to follow‐up and about work‐related disability at follow‐up. They also were asked whether disabilities or reasons for quitting work were cancer‐related. Return to work and quitting work were projected over time in a life‐table analysis. Risk factors were identified from logit analyses.

RESULTS

One of five survivors reported cancer‐related disabilities at follow‐up. Half of those with disabilities were working. A projected 13% of all survivors had quit working for cancer‐related reasons within 4 years of diagnosis. More than half of survivors quit working after the first year, when three‐quarters of those who stopped for treatment returned to work. Survivors of central nervous system, head and neck, and Stage IV blood and lymph malignancies had the highest adjusted risk of disability or quitting work.

CONCLUSIONS

Cancer survival sometimes has long‐term effects on employment and the ability to work. Employment outcomes can be improved with innovations in treatment and with clinical and supportive services aimed at better management of symptoms, rehabilitation, and accommodation of disabilities. Cancer 2005. © 2005 American Cancer Society.
Quantitative changes in calretinin immunostaining in the cochlear nuclei after unilateral cochlear removal in young ferrets
Authors: Fuentes‐Santamaria Verónica , Alvarado Juan Carlos , Taylor Anna R. , Brunso‐Bechtold Judy K. , Henkel Craig K.
Published: February 2005

Neurons of the cochlear nuclei receive axosomatic endings from primary afferent fibers from the cochlea and have projections that diverge to form parallel ascending auditory pathways. These cells are characterized by neurochemical phenotypes such as levels of calretinin. To test whether or not early deafferentation results in changes in calretinin immunostaining in the cochlear nucleus, unilateral cochlear ablations were performed in ferrets soon after hearing onset (postnatal day [P]30–P40). Two months later, changes in calretinin immunostaining as well as cell size, volume, and synaptophysin immunostaining were assessed in the anteroventral (AVCN), posteroventral (PVCN), and dorsal cochlear nucleus (DCN). A decrease in calretinin immunostaining was evident ipsilaterally within the AVCN and PVCN but not in the DCN. Further analysis revealed a decrease both in the calretinin‐immunostained neuropil and in the calretinin‐immunostained area within AVCN and PVCN neurons. These declines were accompanied by significant ipsilateral decreases in volume as well as neuron area in the AVCN and PVCN compared with the contralateral cochlear nucleus and unoperated animals, but not compared with the DCN. In addition, there was a significant contralateral increase in calretinin‐immunostained area within AVCN and PVCN neurons compared with control animals. Finally, a decrease in area of synaptophysin immunostaining in both the ipsilateral AVCN and PVCN without changes in the number of boutons was found. The present data demonstrate that unilateral cochlear ablation leads to 1) decreased immunostaining of the neuropil in the AVCN and PVCN ipsilaterally, 2) decreased calretinin immunostaining within AVCN and PVCN neurons ipsilaterally, 3) synaptogenesis in the AVCN and PVCN ipsilaterally, and 4) increased calretinin immunostaining within AVCN and PVCN neurons contralaterally. J. Comp. Neurol. 483:458–475, 2005. © 2005 Wiley‐Liss, Inc.
Hodological characterization of the septum in anuran amphibians: II. Efferent connections
Authors: Endepols Heike , Roden Katja , Walkowiak Wolfgang
Published: February 2005

The efferent connections of the septum of the gray treefrog Hyla versicolor were studied by combining anterograde and retrograde tracing with biotin ethylendiamine (Neurobiotin). The lateral septal complex projects mainly to the medial pallium, limbic regions (e.g., amygdala and nucleus accumbens), and hypothalamic areas but also to sensory nuclei in the diencephalon and midbrain. The central septal complex strongly innervates the medial pallium, limbic, and hypothalamic areas but also specific sensory (including olfactory) regions. The medial septal complex sends major projections to all olfactory nuclei and a weaker projection to the hypothalamus. Our results indicate that all septal nuclei may modify the animal's internal state via efferents to limbic and hypothalamic areas. Via projections to the medial pallium, lateral and central septal complexes may be involved in learning processes as well. Because of their connections to specific sensory areas, all septal areas are in a position to influence sensory processing. Furthermore, our data suggest that both the postolfactory eminence and the bed nucleus of the pallial commissure are not part of the septal complex, rather, the postolfactory eminence seems to be comparable to the mammalian primary olfactory cortex, whereas the bed nucleus may be analogous to the mammalian subfornical organ. J. Comp. Neurol. 483:437–457, 2005. © 2005 Wiley‐Liss, Inc.
Performance engineering in data Grids
Authors: Laure Erwin , Stockinger Heinz , Stockinger Kurt
Published: February 2005

The vision of Grid computing is to facilitate worldwide resource sharing among distributed collaborations. With the help of numerous national and international Grid projects, this vision is becoming reality and Grid systems are attracting an ever increasing user base. However, Grids are still quite complex software systems whose efficient use is a difficult and error‐prone task. In this paper we present performance engineering techniques that aim to facilitate an efficient use of Grid systems, in particular systems that deal with the management of large‐scale data sets in the tera‐ and petabyte range (also referred to as data Grids). These techniques are applicable at different layers of a Grid architecture and we discuss the tools required at each of these layers to implement them. Having discussed important performance engineering techniques, we investigate how major Grid projects deal with performance issues particularly related to data Grids and how they implement the techniques presented. Copyright © 2005 John Wiley & Sons, Ltd.
Self adaptivity in Grid computing
Authors: Vadhiyar Sathish S. , Dongarra Jack J.
Published: February 2005

Optimizing a given software system to exploit the features of the underlying system has been an area of research for many years. Recently, a number of self‐adapting software systems have been designed and developed for various computing environments. In this paper, we discuss the design and implementation of a software system that dynamically adjusts the parallelism of applications executing on computational Grids in accordance with the changing load characteristics of the underlying resources. The migration framework implemented by our software system is aimed at performance‐oriented Grid systems and implements tightly coupled policies for both suspension and migration of executing applications. The suspension and migration policies consider both the load changes on systems as well as the remaining execution times of the applications thereby taking into account both system load and application characteristics. The main goal of our migration framework is to improve the response times for individual applications. We also present some results that demonstrate the usefulness of our migration framework. Published in 2005 by John Wiley & Sons, Ltd.
The role of performance engineering techniques in the context of the Grid
Authors: Hey A. J. G. , Papay J. , Surridge M.
Published: February 2005

Performance engineering can be described as a collection of techniques and methodologies whose aim is to provide reliable prediction, measurement and validation of the performance of applications on a variety of computing platforms. This paper reviews techniques for performance estimation and performance engineering developed at the University of Southampton and presents application case studies in task scheduling for engineering meta‐applications, and capacity engineering for a financial transaction processing system. These show that it is important to describe performance in terms of a resource model, and that the choice of models may have to trade accuracy for utility in addressing the operational issues. We then present work from the on‐going EU funded Grid project GRIA, and show how lessons learned from the earlier work have been applied to support a viable business model for Grid service delivery to a specified quality of service level. The key in this case is to accept the limitations of performance estimation methods, and design business models that take these limitations into account rather than attempting to provide hard guarantees over performance. We conclude by identifying some of the key lessons learned in the course of our work over many years and suggest possible directions for future investigations. Copyright © 2005 John Wiley & Sons, Ltd.
Distributed computing in practice: the Condor experience
Authors: Thain Douglas , Tannenbaum Todd , Livny Miron
Published: February 2005

Since 1984, the Condor project has enabled ordinary users to do extraordinary computing. Today, the project continues to explore the social and technical problems of cooperative computing on scales ranging from the desktop to the world‐wide computational Grid. In this paper, we provide the history and philosophy of the Condor project and describe how it has interacted with other projects and evolved along with the field of distributed computing. We outline the core components of the Condor system and describe how the technology of computing must correspond to social structures. Throughout, we reflect on the lessons of experience and chart the course travelled by research ideas as they grow into production systems. Copyright © 2005 John Wiley & Sons, Ltd.
The design and implementation of Grid database services in OGSA‐DAI
Authors: Antonioletti Mario , Atkinson Malcolm , Baxter Rob , Borley Andrew , Chue Hong Neil P. , Collins Brian , Hardman Neil , Hume Alastair C. , Knox Alan , Jackson Mike , Krause Amy , Laws Simon , Magowan James , Paton Norman W. , Pearson Dave , Sugden Tom , Watson Paul , Westhead Martin
Published: February 2005

Initially, Grid technologies were principally associated with supercomputer centres and large‐scale scientific applications in physics and astronomy. They are now increasingly seen as being relevant to many areas of e‐Science and e‐Business. The emergence of the Open Grid Services Architecture (OGSA), to complement the ongoing activity on Web Services standards, promises to provide a service‐based platform that can meet the needs of both business and scientific applications. Early Grid applications focused principally on the storage, replication and movement of file‐based data. Now the need for the full integration of database technologies with Grid middleware is widely recognized. Not only do many Grid applications already use databases for managing metadata, but increasingly many are associated with large databases of domain‐specific information (e.g. biological or astronomical data). This paper describes the design and implementation of OGSA‐DAI, a service‐based architecture for database access over the Grid. The approach involves the design of Grid Data Services that allow consumers to discover the properties of structured data stores and to access their contents. The initial focus has been on support for access to Relational and XML data, but the overall architecture has been designed to be extensible to accommodate different storage paradigms. The paper describes and motivates the design decisions that have been taken, and illustrates how the approach supports a range of application scenarios. The OGSA‐DAI software is freely available fromhttp://www.ogsadai.org.uk. Copyright © 2005 John Wiley & Sons, Ltd.
Hyperlog—A flexible log‐like transform for negative, zero, and positive valued data
Authors: Bagwell C. Bruce
Published: February 2005

Background

The remarkable success of cytometry over the past 30 years is largely due to its uncanny ability to display populations that vastly differ in numbers and fluorescence intensities on one scale. The log transform implemented in hardware as a log amplifier or in software normalizes signals or channels so that these populations appear as clearly discernible peaks. With the advent of multiple fluorescence cytometry, spectral crossover compensation of these signals has been necessary to properly interpret the data. Unfortunately, because compensation is a subtractive process, it can produce negative and zero valued data. The log transform is undefined for these values and, as a result, forces computer algorithms to truncate these values, creating a few problems for cytometrists. Data truncation biases displays making properly compensated data appear undercompensated; thus, enticing many operators to overcompensate their data. Also, events truncated into the first histogram channel are not normally visible with typical two‐dimensional graphic displays, thus hiding a large number of events and obscuring the true proportionality of negative distributions. In addition, the log transform creates unequal binning that can dramatically distort negative population distributions.

Methods and Results

The HyperLog transform is a log‐like transform that admits negative, zero, and positive values. The transform is a hybrid type of transform specifically designed for compensated data. One of its parameters allows it to smoothly transition from a logarithmic to linear type of transform that is ideal for compensated data.

Conclusions

The HyperLog transform is easily implemented in computer systems and results in display systems that present compensated data in an unbiased manner. © 2005 Wiley‐Liss, Inc.
Preoperative sequential chemotherapy in locally advanced squamous cell carcinoma of the head and neck
Authors: Faivre Sandrine , Marti Adina , Rixe Olivier , Janot François , Julieron Morbize , Gatineau Michel , Temam Stéphane , Armand Jean‐Pierre , Domenge Christian , Luboinski Bernard , Raymond Eric
Published: February 2005

Background.

Induction chemotherapy may contribute to decreased local and distant recurrences in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) resectable for cure.

Methods.

Patients with previously untreated locally advanced stage III–IV (N0–2, M0) SCCHN received a dose‐dense sequential regimen combining cisplatin/5‐fluorouracil followed by bleomycin/methotrexate/hydroxyurea. Induction chemotherapy was followed by locoregional surgery and/or radiation therapy.

Results.

Among 37 patients, 23 (62%) had T4 primary tumors. Grade 3 to 4 asymptomatic hematologic toxicity occurred in less than 15% of patients. Nonhematologic toxicities were limited to grade 1 to 2 in less than 20% of patients. In the overall cohort (intent‐to‐treat; n = 35), 24 (68.5%) of 35 patients had objective clinical responses, including nine complete responses (25.7%). Fifty‐seven percent of patients were free of disease at 2.5 years.

Conclusions.

Sequential induction chemotherapy is feasible and active in patients with locally advanced head and neck cancers and may further include recent compounds such as taxanes. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005
Prospective validation of the Martínez‐Gimeno Clinicopathologic Scoring System (MGSS) for evaluating risk of cervical lymph node metastases of squamous cell carcinoma of the oral cavity
Authors: Martínez‐Gimeno Carlos , Molinero Antonio Perera , Castro Victoria , Sastre Maria Julia Muñoz , Castro Emilio Espejo , Aguirre‐Jaime Armando
Published: February 2005

Background.

The prediction of neck metastasis from oral squamous cell carcinoma is an unresolved issue. The Martínez‐Gimeno Scoring System (MGSS) is an index designed as a predictive aid that may be implemented after analysis of the tumor resection.

Methods.

A double‐blind cohort study was designed and carried out in a tertiary hospital. Seventy‐nine consecutive patients diagnosed with squamous cell carcinoma of the oral cavity requiring local resection and neck dissections were included. After tumor resection, the MGSS was applied, and patients were then classified into one of four groups on the basis of the MGSS score: group I, 7 to 12 points; group II, 13 to 16 points; group III, 17 to 20 points; and group IV, 21 to 30 points. After this, pathologic analysis of the neck specimen was performed to detect metastasis. The results, histopathologic analysis of the neck specimens, and previously tabulated MGSS scores were then compared, and on the basis of their results an estimation of the predictive validity of MGSS of neck metastases was obtained. A correlational analysis was performed, comparing metastases to a set of predictive factors, including the MGSS score. A logistic binary regression model that used metastases as the dependent variable was adjusted in an attempt to estimate odd ratios for these factors.

Results.

Twenty‐six cases displayed metastases. The metastatic nodes measured from 0.5 to 7 cm and were smaller than 1.5 cm in 46% of the cases. The rates of metastases in the four groups were as follows: group 1, 0%; group II, 21%; group III, 50%; and group IV, 67%. MGSS had a sensitivity of 100% (95% confidence interval [CI], 98% to 100%) for predicting metastases from oral squamous cell carcinoma, a specificity of 55% (95% CI, 44% to 66%), an overall efficiency of 73% (95% CI, 63% to 83%), a positive predictive value of 59% (95% CI, 48% to 70%), and a negative predictive value of 100% (95% CI, 98% to 100%). The correlation between various predictive factors and the presence of metastases showed a value of r = .87 (p = .001) with the MGSS score. No correlation was found between the MGSS score and the size of the metastatic lymph node. In the logistic regression model, the MGSS score displayed an odds ratio of 3.5 (95% CI, 1.9–6.3; p = .00001) for the presence of metastases in patients with squamous cell carcinoma of the oral cavity.

Conclusion.

The MGSS is a useful index for the prediction of neck node metastases that is applied at the start of the analysis of the tumor resection in patients with squamous cell carcinoma of the oral cavity. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005
Dynamic MR lymphangiography and carbon dye for sentinel lymph node detection: A solution for sentinel lymph node biopsy in mucosal head and neck cancer
Authors: Nason Richard W. , Torchia Mark G. , Morales Carmen M. , Thliveris James
Published: February 2005

Background.

The practical application of sentinel lymph node biopsy in squamous cell carcinoma of the head and neck is restricted by the time sensitivity of blue dye and lack of spatial resolution and nonspecific node enhancement with radiocolloid. This study evaluates the use of magnetic resonance (MR) lymphangiography and carbon dye labeling to circumvent these limitations.

Methods.

Gadomer/carbon dye mixture was injected into the tongue and stifle of adult swine (n = 4). MR lymphatic mapping was followed by intraoperative mapping with isosulfan blue dye. Sentinel lymph node biopsy and completion node dissection were performed 60 minutes after injection in four nodal basins and at 7 days after injection in eight.

Results.

The technique was successful in all 12 nodal basins. The sentinel lymph nodes were stained black at the time of the immediate and delayed dissections.

Conclusions.

MR lymphangiography provides temporal and anatomic localization of the sentinel lymph node with a single investigation. Carbon dye is a sensitive and persistent visual marker of MRI‐targeted sentinel lymph nodes. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005
Prolactin inhibits apoptosis of ovarian carcinoma cells induced by serum starvation or cisplatin treatment
Authors: Asai‐Sato Mikiko , Nagashima Yoji , Miyagi Etsuko , Sato Ken , Ohta Ichiro , Vonderhaar Barbara K. , Hirahara Fumiki
Published: February 2005

Prolactin, a peptide hormone essential for the development and function of reproductive organs, is involved in development of breast, prostate and colorectal cancers. However, the role of prolactin on the carcinogenesis of ovarian carcinomas is unclear. In this study, we show that mRNA of prolactin receptor is expressed in 5 out of 9 ovarian carcinoma cell lines, 15 out of 17 cases of surgical samples and all of normal ovarian surface epithelium, while prolactin transcript is detected only in 1 ovarian carcinoma cell line and in 1 of the surgical samples. For the prolactin receptor‐positive ovarian carcinoma cells, exogenous prolactin did not affect the proliferation but markedly inhibited apoptosis. Therefore, actual cell growth was enhanced by prolactin in a dose‐dependent manner. The blocking of prolactin receptor by antibody severely impaired the antiapoptotic and growth‐promoting effects of prolactin. Interestingly, the cisplatin‐induced cell death of the prolactin receptor‐positive cells was significantly inhibited by pretreatment with prolactin. These findings indicate a responsiveness of ovarian carcinomas to prolactin and suggest that the prolactin/prolactin receptor system may be a new therapeutic target of ovarian carcinomas. © 2005 Wiley‐Liss, Inc.
Novel mechanism of hybrid liposomes‐induced apoptosis in human tumor cells
Authors: Matsumoto Yoko , Iwamoto Yasunori , Matsushita Taku , Ueoka Ryuichi
Published: February 2005

Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of these liposomes, such as size, membrane fluidity, phase transition temperature and hydrophobicity can be controlled by changing the composition. Hybrid liposomes composed of dimyristoylphosphatidylcholine and polyoxyethylene (10) dodecyl ether were found to inhibit the growth of human promyelocytic leukemia (HL‐60) cells without using any drugs. Induction of apoptosis by hybrid liposomes in HL‐60 cells was verified on the basis of fluorescence microscopy and flow cytometry analysis, after fusion and accumulation of hybrid liposomes, which was revealed on the basis of microphysiometer. We elucidated the pathways of apoptosis induced by the hybrid liposomes. That is, hybrid liposomes fused and accumulated in tumor cell membranes, and the apoptosis signal first passed through mitochondria, caspase‐9 and caspase‐3, second through Fas, caspase‐8, caspase‐3 and then reached the nucleus. Hybrid liposomes themselves can induce apoptosis in human tumor cells along with high inhibitory effects on the growth of tumor cells. © 2005 Wiley‐Liss, Inc.
DNA repair gene XPC genotypes/haplotypes and risk of lung cancer in a Chinese population
Authors: Hu Zhibin , Wang Yonggang , Wang Xinru , Liang Gang , Miao Xiaoping , Xu Yaochu , Tan Wen , Wei Qingyi , Lin Dongxin , Shen Hongbing
Published: February 2005

DNA repair is central to normal cellular functions, and polymorphisms of DNA repair genes may cause variation in DNA repair capacity in the general population. Newly identified polymorphisms of xeroderma pigmentosum group C (XPC), one of the nucleotide excision repair genes, were shown to contribute to genetic susceptibility to cancer. In this study, we hypothesized that 2 exonic variants C499T and A939C and their haplotypes in XPC are associated with lung cancer risk. To test this hypothesis, we performed a case‐control study of 320 histologically confirmed lung cancer patients and 322 age and sex frequency‐matched cancer‐free controls in a Chinese population. Multivariate logistic regression analyses revealed that the risks [adjusted odds ratios (ORs) and 95% confidence intervals (CIs)] associated with the XPC variant genotypes were 1.57 (95% CI = 1.13–2.19) for 499CT/TT and 1.21 (95% CI = 0.87–1.69) for 939AC/CC compared with the 499CC and 939AA wild‐type homozygotes, respectively. Individuals with both putative risk genotypes (499CT/TT and 939AC/CC) had a greater risk of lung cancer (adjusted OR = 2.37; 95% CI = 1.33–4.21) compared with individuals with both wild‐type genotypes (499CC and 939AA). When we performed the haplotype analysis and assumed the XPC 499T and 939C as risk alleles, the adjusted ORs increased as the number of variants in the haplotype genotypes increased (ptrend < 0.001). In the stratified analysis, the greatest risk was found in smokers having the combined variant genotypes (adjusted OR = 7.36; 95% CI = 3.19–17.00) compared with nonsmokers having both wild‐type genotypes and in smokers with 2 or 3 haplotype variants (adjusted OR = 7.27; 95% CI = 3.37–15.68) compared with nonsmokers having 0 haplotype variant. These findings indicate that XPC exonic variants may contribute to the risk of lung cancer in the Chinese population, and these variant genotypes may modulate the risk of lung cancer associated with smoking. © 2005 Wiley‐Liss, Inc.
Transcription factor AP‐2γ, a novel marker of gonocytes and seminomatous germ cell tumors
Authors: Pauls Katharina , Jäger Richard , Weber Susanne , Wardelmann Eva , Koch Arend , Büttner Reinhard , Schorle Hubert
Published: February 2005

Most germ cell tumors (GCTs) arise from intratubular germ cell neoplasias (IGCNUs, also referred to as carcinoma in situ), which are thought to originate from a transformed fetal germ cell, the gonocyte. However, the nature of the molecular pathways involved in IGCNU formation remains elusive. Therefore, identification of novel oncofetal markers is an important prerequisite to further our understanding of the etiology of this tumor entity. In the present study, we show that in humans AP‐2γ is expressed in gonocytes at weeks 12–37 of gestation, indicating a role of this transcription factor in fetal germ cell development. AP‐2γ and c‐KIT, a known target of AP‐2 transcription factors, were coexpressed in gonocytes, making a direct regulation possible. With increasing differentiation of fetal testis, gradual downregulation of AP‐2γ from the 12th to 37th week of gestation was observed. Furthermore, AP‐2γ was expressed abundantly in 25/25 IGCNUs, 52/53 testicular seminomas, 10/10 metastatic seminomas, 9/9 extragonadal seminomas and 5/5 dysgerminomas. In embryonal carcinomas and choriocarcinomas, focal staining only was observed. Spermatocytic seminomas, teratomas and yolk sac tumors as well as normal adult testis and various control tissues were negative for AP‐2γ. The expression pattern of AP‐2γ, like that of other oncofetal markers, supports the model of a gonocytal origin of IGCNUs and germ cell tumors. Finally, our results provide the basis for applying AP‐2γ immunohistochemistry to the detection of GCT, a tumor entity with a steadily growing incidence in the male population worldwide. © 2005 Wiley‐Liss, Inc.
Tumor‐induced antibodies resemble the response to tissue damage
Authors: Preiss Susanne , Kammertoens Thomas , Lampert Christoph , Willimsky Gerald , Blankenstein Thomas
Published: February 2005

Tumor‐associated antibodies are frequently detected in cancer patients. To ask whether the recognized antigens are rejection antigens, we screened a cDNA expression library of the mouse TS/A tumor with TS/A‐immune serum and isolated 8 IgG‐reactive clones, representing self‐antigens that were expressed in normal tissues and other tumor lines. Three of the antigens had previously been identified in the human system by this cloning strategy. None of the antigens revealed to be a rejection antigen in normal mice demonstrated by an otherwise effective plasmid immunization. For one of the identified antigens, α‐catenin, it is shown that the induction of IgG antibodies by protein immunization does not correlate with tumor rejection. For another antigen, vimentin, it is shown that vimentin‐deficient but not vimentin‐competent mice reject vimentin‐expressing tumors indicating T ‐cell tolerance despite the fact that tumor cell immunization induces antivimentin IgG antibodies. Tissue damage induced by adenovirus infection induced an antibody response similar to tumor cell immunization, exemplified with 2 of the antigens. We conclude that the tumor‐induced antibodies mirror tissue damage and that the antibody‐inducing antigens can serve as rejection antigens if they are recognized as foreign. © 2005 Wiley‐Liss, Inc.
Birth characteristics and adult cancer incidence: Swedish cohort of over 11,000 men and women
Authors: McCormack Valerie A. , dos Santos Silva Isabel , Koupil Ilona , Leon David A. , Lithell Hans O.
Published: February 2005

Associations between larger size at birth and increased rates of adult cancer have been proposed but few empirical studies have examined this hypothesis. We investigated overall and site‐specific cancer incidence in relation to birth characteristics in a Swedish population‐based cohort of 11,166 singletons born in 1915–1929 for whom we have detailed obstetric data and who were alive in 1960. A total of 2,685 first primary cancers were registered during follow‐up from 1960 to 2001. A standard deviation (SD) increase in birth weight for gestational age (GA) was associated with (sex‐adjusted) increases of 13% (95% CI = 0.03–0.23) in the rates of digestive cancers and of 17% (95% CI = 0.01–0.35) in the rates of lymphatic cancers. Women who had higher birth weights also had increased rates of breast cancer under age 50 years (by 39% per SD increase; 95% CI = 0.09–0.79), but reduced rates (by 24%; 95% CI = 0.07–0.38) of endometrial (corpus uteri) cancer at all ages. There was no evidence of associations with other cancer sites. For overall cancer incidence, men had an 8% increased risk at all ages per SD increase in birth weight for GA while women only had an increased risk under age 50 years (mainly driven by the association with breast cancer). These findings provide evidence of a modest association of birth size and adult cancer risk, resulting from positive associations with a few cancer sites and a possible inverse association with endometrial cancer. © 2005 Wiley‐Liss, Inc.
RASSF1A is not appropriate as an early detection marker or a prognostic marker for non‐small cell lung cancer
Authors: Choi Naeyun , Son Dae‐Soon , Song Inseung , Lee Hye‐Sook , Lim Yoo‐Sung , Song Min Sup , Lim Dae‐Sik , Lee Jinseon , Kim Hojoong , Kim Jhingook
Published: February 2005

Aberrant methylation of several tumor suppressor genes often occurs during the pathogenesis of lung cancer. RASSF1A is one of the tumor suppressor genes, and it is frequently inactivated by hypermethylation of its promoter region in a variety of human cancers, including lung cancer. It has recently been suggested that RASSF1A methylation was frequently observed in poorly differentiated tumors, and that it was correlated with adverse survival in lung adenocarcinoma (Tomizawa Y, et al., Clin Cancer Res 2002;8:2362–8). In this study, we investigated the pathogenetic and clinicopathologic significance of RASSF1A methylation for the development and/or progression of non small cell lung cancer (NSCLC). We examined 116 cases of NSCLC for the methylation status of RASSF1A. Methylation‐specific analysis demonstrated that 40.5% (47 of 116) of the cases were methylated at the CpG sites in the promoter. Methylation of RASSF1A was associated with cellular differentiation (p = 0.0244) and it was related to survival (p = 0.0276). However, there was no association between RASSF1A methylation and the individual clinicopathologic features: TNM stage (p > 0.1), recurrence (p > 0.1), lymphatic permeation (p > 0.1) and smoking duration time (p > 0.1). Furthermore, we analyzed RASSF1A's probability as a prognostic marker by using stepwise Cox proportional hazard regression testing. As a result, the stage proved to be the most important factor (p = 0.0089), more than any other factors such as age, gender, cell type, methylation status, differentiation, smoking duration time, tumor size and lymph node permeation. There was no other significant factor other than stage and age. These results show that epigenetic inactivation of RASSF1A cannot be a prognostic marker of NSCLC. © 2005 Wiley‐Liss, Inc.
Retracted: Additive antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), and the nonsteroidal antiandrogen, bicalutamide (Casodex), in prostate cancer cells in vitro
Authors: Festuccia Claudio , Gravina Giovanni Luca , Angelucci Adriano , Millimaggi Danilo , Muzi Paola , Vicentini Carlo , Bologna Mauro
Published: February 2005

Progression from an androgen‐dependent to an androgen‐independent state often occurs in patients with prostate cancer (PCa) who undergo hormonal therapy. We have investigated whether inhibition of the epidermal growth factor receptor (EGFR) signaling pathway affects the antitumor effect of a nonsteroidal antiandrogen. Gefitinib (Iressa), an EGFR tyrosine kinase inhibitor, and bicalutamide (Casodex), a nonsteroidal antiandrogen [androgen receptor (AR) antagonist], were administered alone and in combination to AR‐positive human PCa cell lines. FACS analysis showed lower EGFR expression levels on AR‐positive cells (LNCaP, CWR22, CWR22R 2152 and AR‐transfected DU145 cell lines) compared with AR‐negative cells (DU145, PC3 and TSU‐Pr1). Moreover, in AR‐transfected DU145 cells, chronic treatment with bicalutamide increased EGFR expression to levels similar to androgen‐independent DU145 cells. All AR‐positive PCa cell lines were sensitive to gefitinib (IC50 = 0.1–0.6 μM), whereas higher concentrations of bicalutamide were needed to reduce AR‐positive PCa cell line proliferation (IC50 = 0.8–2.0 μM). Low doses of gefitinib increased the antitumor effects of bicalutamide by strongly reducing the IC50 of bicalutamide (approximately 10‐fold). Similarly, bicalutamide increased the antiproliferative effects of gefitinib by reducing the IC50 of gefitinib (approximately 5‐fold). Taken together, our data suggest that in androgen‐dependent cell lines, addition of gefitinib in combination with bicalutamide results in concurrent dual inhibition of AR and EGFR/HER2 pathways. This causes a significant delay in the onset of EGFR‐driven androgen independence. © 2005 Wiley‐Liss, Inc.
Evaluation of an immunochemical fecal occult blood test with automated reading in screening for colorectal cancer in a general average‐risk population
Authors: Launoy Guy D. , Bertrand Hughes J. , Berchi Celia , Talbourdet Vincent Y. , Guizard Anne Valérie N. , Bouvier Véronique M. , Caces Emile R.
Published: February 2005

Colorectal cancer screening is a high public health priority in all industrialized countries. However, the low sensitivity of the common guaiac screening test (HemoccultII) makes practitioners and public health decision makers reluctant to set up a national screening program. In recent years, immunochemical tests based on the use of a specific antibody have been found to be more sensitive than the HemoccultII test. However, for screening purposes, any gain in sensitivity is of interest only if specificity and positive predictive value are satisfactory. Our aim was to assess the performance of an immunochemical test with an automated reading technique (Magstream 1000) for different hemoglobin content cut‐off points. The study was carried out in the general population aged 50–74 years in the geographic area of Cotentin (Normandy, France). From 1 January 2001 to 31 December 2002, 7,421 one‐time screening tests (Magstream) were administered by general practitioners and occupational physicians to patients at the end of regular consultations. Colonoscopy was proposed to the 434 people with a positive test. All cancers occurring in the study population between 1 January 2001 and 31 December 2003 were collected by general practitioners, gastroenterologists and the local registry. At the usual positivity threshold (20 ng hemoglobin/ml), screening sensitivity and specificity at 2 years of follow‐up with 95% CIs were, respectively, 0.85 (0.72–0.98) and 0.94 (0.94–0.95). If the hemoglobin content cut‐off point had been set at 50 ng/ml instead of the usual cut‐off, positivity would have been 3.1% and positive predictive value for a cancer or a large adenoma would have been 0.49, with sensitivity of 0.68–0.83 and specificity of 0.97. Our results suggest that use of an immunochemical test with an automated reading technique could improve the prospects for mass‐screening for colorectal cancer since it offers a promising alternative to guaiac tests. © 2005 Wiley‐Liss, Inc.
Hourglasses and Hamilton cycles in 4‐connected claw‐free graphs
Authors: Kaiser Tomáš , Li MingChu , Ryjáček Zdeněk , Xiong Liming
Published: February 2005

We show that if G is a 4‐connected claw‐free graph in which every induced hourglass subgraph S contains two non‐adjacent vertices with a common neighbor outside S, then G is hamiltonian. This extends the fact that 4‐connected claw‐free, hourglass‐free graphs are hamiltonian, thus proving a broader special case of a conjecture by Matthews and Sumner. © 2005 Wiley Periodicals, Inc. J Graph Theory 48: 267–276, 2005