bluuebunny/crossref_metadata_2025 huggingface dataset:
Lip impressions: a new method for monitoring morphological changes in orofacial granulomatosis
Authors: Chiandussi S , Tappuni AR , Watson TF , White A , Escudier MP , Sanderson JD , Challacombe SJ
Published: July 2006

Aim:  To develop and evaluate an objective method for assessing lip size and treatment‐related morphological changes in orofacial granulomatosis (OFG) patients.

Materials and methods:  Patients with swollen lips because of OFG (n = 21) were enrolled. A light‐body polyvinylsiloxane material was used to take lip impressions before and after treatment (n = 10), or during treatment (n = 11). Plaster models were cast from the impressions and the lips were measured using callipers. The intra‐examiner and inter‐examiner reproducibility of the technique were assessed.

Results:  OFG patients had significantly larger lips than controls (P < 0.0001). The coefficient of variation on repeated measurements of the same impression was 1.6% and for duplicate impressions was 2.6%. Significant reduction in lip size was shown in all 10 patients after diet restriction (P < 0.002). Seven of 11 patients whose impressions were taken at least 3 months after the initiation of cinnamon‐ and benzoate‐free diet also showed reduction in lip size during follow up (P < 0.002).

Conclusions:  Serial lip impressions appear to be reliable for routine quantification of morphological changes of the lips in OFG patients. We present a new reproducible and sensitive method for assessing changes in lip size in response to treatment in OFG.
Moors, Race, and the Study of English Renaissance Literature: A Brief Retrospective
Authors: Floyd‐Wilson Mary
Published: July 2006

In thirty years the study of race in early modern literature has moved from the margins of scholarship to occupy its now central role in the analysis of English Renaissance culture. Narrow typological interpretations of blackness dominated Renaissance racial studies in the past. Feminist criticism in the late 80s opened up the field in its examination of how gender and class inform constructions of racial differences – both black and white. In the past fifteen years, scholars have recognized the necessity of tracing the emergence of racial differences in a wider range of disciplines and contexts, including scientific discourse, geography, religious identity, and trade relations.
Concepts in the care and welfare of captive elephants
Authors: VEASEY J.
Published: July 2006

Zoos are duty bound to maintain a high standard of welfare for all animals for which they are responsible. For elephants, this represents a greater challenge than for many other species; their sheer size, sophisticated social life, high level of intelligence and large behavioural repertoire, combined with their origins in tropical and subtropical climates mean that replicating the physical, social and environmental requirements needed for a high standard of welfare in captivity is a significant challenge. This is compounded by the difficulties in measuring welfare generally, and specifically for animals such as elephants within zoo environments. Evidence does exist relating to the longevity, reproductive success and the health status of captive elephants which suggests that their management is not at as high a standard as it is for many other species kept in zoos, and that elephant welfare is likely to be compromised as a result. It is suggested that for as long as elephants remain in captivity that their management should be based around the requirements of the animals themselves taking into account an understanding of their biology and behavioural ecology. Given the difficulties in measuring welfare, it is suggested that those responsible for elephant management should not rely on proof of suffering prior to making adjustments to their programmes, but in the first instance consider the likely physical and behavioural needs of the elephant. As a minimum, facilities should provide for those behaviours and contingencies which are biologically significant in terms of survival and reproduction in the wild, which take up a significant proportion of an elephant's time in the wild and are not necessarily triggered by external stimuli alone. It is suggested that a high standard of captive elephant welfare is theoretically attainable and that significant improvements in welfare are likely to be achieved by addressing inadequacies in the physical environment which predispose captive elephants to trauma and by providing for appropriate social and foraging opportunities.
Feeding Asian and African elephants Elephas maximus and Loxodonta africana in captivity
Authors: HATT J.‐M. , CLAUSS M.
Published: July 2006

Considering the low rate of reproduction in Asian elephants Elephas maximus and African elephants Loxodonta africana in captivity, and the critical status of the size of the captive population, nutrition plays an important role in the captive management of elephants. This paper highlights two major reviews of the subject but emphasizes those aspects of the feeding regime that seem of particular importance and practical relevance. Obesity and colic are of major concern and offering good‐quality hay as a staple diet item over an extended period of the day is the most important recognized prophylactic measure against these conditions. Fruits, cereals, bread or pelleted feeds are not recommended owing to their high financial cost and contribution to obesity, respectively. The use of pelleted compound feeds may only be warranted to address mineral or vitamin deficiencies in the hay supplied to elephants.
Reproduction of Bali starlings Leucopsar rothschildi at Durrell Wildlife Conservation Trust, Jersey
Authors: WILLIAMS T. M. , FEISTNER A. T. C.
Published: July 2006

The Critically Endangered Bali starling Leucopsar rothschildi is the only endemic avian species on the island of Bali, Indonesia. In 1998 the wild population comprised c. 25 birds, of which only eight to ten were wild born. An international captive‐breeding programme to restore a viable and self‐sustaining population in Bali was established in 1987. In order to understand better the reproductive activity of Bali starlings at the Durrell Wildlife Conservation Trust, Jersey, small cameras were placed inside the nestboxes of six pairs. Details of egg production and egg turning were recorded for 16 clutches, and incubation data were recorded for 14 clutches. Mean clutch size was 2·8±0·20 SE eggs. Females incubated eggs significantly more than ♂♂ (median 143‐6 hours vs 46·8 hours, ♀vs♂). During the day (0500–2100 hours) eggs were turned every c. 13 minutes. At night eggs were incubated by ♀♀ while ♂♂ roosted in the nestbox. The median duration of incubation was 15·5 ± 0·24 SE days. Behaviour of parents and chicks during hatch and rearing was recorded for seven broods. Hatching success was 68% and for each pair the mean brood size was two chicks. Females carried out significantly more brooding (t= 7·08, df=6, P<0·001), preening (t= 2·94, df=6, P= 0·025) and manipulation (t= 2·50, df=6, P= 0·046) of chicks than ♂♂. Males provided significantly more feeds (62%) than ♀♀ (38%) (t= 4.035, df=6, P= 0·006). Only five birds survived > 30 days, of which three were parent‐reared and two hand‐reared. All parents assisted chicks during hatching. Synchronous hatching was recorded for 45% of chicks. Nutritional requirements of chicks were higher during the first 9 days post‐hatch. Chick survival was compromised by parents feather plucking the chicks.
Developing models for mother–infant behaviour in Black rhinoceros and Reticulated giraffe Diceros bicornis michaeli and Giraffa camelopardalis reticulata at Brookfield Zoo, Illinois
Authors: GREENE T. V. , MANNE S. P. , REITER L. M.
Published: July 2006

For over a decade the behaviours of mothers and newborn calves of Black rhinoceros Diceros bicornis michaeli and Reticulated giraffe Giraffa camelopardalis reticulata have been observed at Brookfield Zoo during the critical first few weeks post‐partum. Consistent patterns were seen for individuals within species, allowing models of time budgets, including ranges of variability surrounding each behaviour, to be developed. Once the model is created any data collected for neonates can be compared to the mean values in the model so infant development and the adequacy of maternal care can be assessed quantitatively.
A Dielectric Polymer with High Electric Energy Density and Fast Discharge Speed
Authors: Chu Baojin , Zhou Xin , Ren Kailiang , Neese Bret , Lin Minren , Wang Qing , Bauer F. , Zhang Q. M.
Published: July 2006

Dielectric polymers with high dipole density have the potential to achieve very high energy density, which is required in many modern electronics and electric systems. We demonstrate that a very high energy density with fast discharge speed and low loss can be obtained in defect-modified poly(vinylidene fluoride) polymers. This is achieved by combining nonpolar and polar molecular structural changes of the polymer with the proper dielectric constants, to avoid the electric displacement saturation at electric fields well below the breakdown field. The results indicate that a very high dielectric constant may not be desirable to reach a very high energy density.
Mode Locking of Electron Spin Coherences in Singly Charged Quantum Dots
Authors: Greilich A. , Yakovlev D. R. , Shabaev A. , Efros Al. L. , Yugova I. A. , Oulton R. , Stavarache V. , Reuter D. , Wieck A. , Bayer M.
Published: July 2006

The fast dephasing of electron spins in an ensemble of quantum dots is detrimental for applications in quantum information processing. We show here that dephasing can be overcome by using a periodic train of light pulses to synchronize the phases of the precessing spins, and we demonstrate this effect in an ensemble of singly charged (In,Ga)As/GaAs quantum dots. This mode locking leads to constructive interference of contributions to Faraday rotation and presents potential applications based on robust quantum coherence within an ensemble of dots.
Aneuploidy and Isochromosome Formation in Drug-Resistant
Candida albicans
Authors: Selmecki Anna , Forche Anja , Berman Judith
Published: July 2006

Resistance to the limited number of available antifungal drugs is a serious problem in the treatment of
Candida albicans
. We found that aneuploidy in general and a specific segmental aneuploidy, consisting of an isochromosome composed of the two left arms of chromosome 5, were associated with azole resistance. The isochromosome forms around a single centromere flanked by an inverted repeat and was found as an independent chromosome or fused at the telomere to a full-length homolog of chromosome 5. Increases and decreases in drug resistance were strongly associated with gain and loss of this isochromosome, which bears genes expressing the enzyme in the ergosterol pathway targeted by azole drugs, efflux pumps, and a transcription factor that positively regulates a subset of efflux pump genes.
Chemoselective Hydrogenation of Nitro Compounds with Supported Gold Catalysts
Authors: Corma Avelino , Serna Pedro
Published: July 2006

The selective reduction of a nitro group when other reducible functions are present is a difficult process that often requires stoichiometric amounts of reducing agents or, if H
2
is used, the addition of soluble metals. Gold nanoparticles supported on TiO
2
or Fe
2
O
3
catalyzed the chemoselective hydrogenation of functionalized nitroarenes with H
2
under mild reaction conditions that avoided the accumulation of hydroxylamines and their potential exothermic decomposition. These chemoselective hydrogenation gold catalysts also provide a previously unknown route for the synthesis of the industrially relevant cyclohexanone oxime from 1-nitro-1-cyclohexene.
Nutritional aspects of women strength athletes
Authors: Volek J S , Forsythe C E , Kraemer W J
Published: July 2006

Strength training elicits sports related and health benefits for both men and women. Although sexual dimorphism is observed in exercise metabolism, there is little information outlining the specific nutritional needs of women strength athletes. Many women athletes restrict energy intake, specifically fat consumption, in order to modify body composition, but this nutritional practice is often counter-productive. Compared to men, women appear to be less reliant on glycogen during exercise and less responsive to carbohydrate mediated glycogen synthesis during recovery. Female strength athletes may require more protein than their sedentary and endurance training counterparts to attain positive nitrogen balance and promote protein synthesis. Therefore, women strength athletes should put less emphasis on a very high carbohydrate intake and more emphasis on quality protein and fat consumption in the context of energy balance to enhance adaptations to training and improve general health. Attention to timing of nutrient ingestion, macronutrient quality, and dietary supplementation (for example, creatine) are briefly discussed as important components of a nutritionally adequate and effective strength training diet for women.
A MULTITHREADED SQL SERVICE
Authors: CÉRIN CHRISTOPHE , GAUDIOT JEAN-LUC , KOSKAS MICHEL
Published: July 2006

In this paper, we describe in detail a novel SQL service based on radix tree data structures and we show how to multithread the service in order to execute it on distributed platforms. The SQL service is currently developed in the context of SMP platforms but should be deployed in the future on grid platforms. The development of the SQL service is part of the Grid Explorer project. The project (French part) aims at building a grid emulator to study the behavior of grids. One need in the project is for a database software to store experimental conditions and to analyze traces of execution (for instance, to find in "real time" frequent episodes for the CPU load metric in order to predict the future state of the grid). We plan to use our SQL service on an SMP platform for this purpose.
Roles of phospholipase A2 isoforms in swelling- and melittin-induced arachidonic acid release and taurine efflux in NIH3T3 fibroblasts
Authors: Pedersen Stine F. , Poulsen Kristian A. , Lambert Ian H.
Published: July 2006

Osmotic swelling of NIH3T3 mouse fibroblasts activates a bromoenol lactone (BEL)-sensitive taurine efflux, pointing to the involvement of a Ca2+-independent phospholipase A2 (iPLA2) (Lambert IH. J Membr Biol 192: 19–32, 2003). We report that taurine efflux from NIH3T3 cells was not only increased by cell swelling but also decreased by cell shrinkage. Arachidonic acid release to the cell exterior was similarly decreased by shrinkage yet not detectably increased by swelling. NIH3T3 cells were found to express cytosolic calcium-dependent cPLA2-IVA, cPLA2-IVB, cPLA2-IVC, iPLA2-VIA, iPLA2-VIB, and secretory sPLA2-V. Arachidonic acid release from swollen cells was partially inhibited by BEL and by the sPLA2-inhibitor manoalide. Cell swelling elicited BEL-sensitive arachidonic acid release from the nucleus, to which iPLA2-VIA localized. Exposure to the bee venom peptide melittin, to increase PLA2 substrate availability, potentiated arachidonic acid release and osmolyte efflux in a volume-sensitive, 5-lipoxygenase-dependent, cyclooxygenase-independent manner. Melittin-induced arachidonic acid release was inhibited by manoalide and slightly but significantly by BEL. A BEL-sensitive, melittin-induced PLA2 activity was also detected in lysates devoid of sPLA2, indicating that both sPLA2 and iPLA2 contribute to arachidonic acid release in vivo. Swelling-induced taurine efflux was inhibited potently by BEL and partially by manoalide, whereas the reverse was true for melittin-induced taurine efflux. It is suggested that in NIH3T3 cells, swelling-induced taurine efflux is dependent at least in part on arachidonic acid release by iPLA2 and possibly also by sPLA2, whereas melittin-induced taurine efflux is dependent on arachidonic acid release by sPLA2 and, to a lesser extent, iPLA2.
Effects of “priming” exercise on pulmonary O2 uptake and muscle deoxygenation kinetics during heavy-intensity cycle exercise in the supine and upright positions
Authors: Jones Andrew M. , Berger Nicolas J. A. , Wilkerson Daryl P. , Roberts Claire L.
Published: July 2006

We hypothesized that the performance of prior heavy exercise would speed the phase 2 oxygen consumption (V̇o2) kinetics during subsequent heavy exercise in the supine position (where perfusion pressure might limit muscle O2 supply) but not in the upright position. Eight healthy men (mean ± SD age 24 ± 7 yr; body mass 75.0 ± 5.8 kg) completed a double-step test protocol involving two bouts of 6 min of heavy cycle exercise, separated by a 10-min recovery period, on two occasions in each of the upright and supine positions. Pulmonary O2 uptake was measured breath by breath and muscle oxygenation was assessed using near-infrared spectroscopy (NIRS). The NIRS data indicated that the performance of prior exercise resulted in hyperemia in both body positions. In the upright position, prior exercise had no significant effect on the time constant (τ) of the V̇o2 response in phase 2 ( bout 1: 29 ± 10 vs. bout 2: 28 ± 4 s; P = 0.91) but reduced the amplitude of the V̇o2 slow component ( bout 1: 0.45 ± 0.16 vs. bout 2: 0.22 ± 0.14 l/min; P = 0.006) during subsequent heavy exercise. In contrast, in the supine position, prior exercise resulted in a significant reduction in the phase 2 τ ( bout 1: 38 ± 18 vs. bout 2: 24 ± 9 s; P = 0.03) but did not alter the amplitude of the V̇o2 slow component ( bout 1: 0.40 ± 0.29 vs. bout 2: 0.41 ± 0.20 l/min; P = 0.86). These results suggest that the performance of prior heavy exercise enables a speeding of phase 2 V̇o2 kinetics during heavy exercise in the supine position, presumably by negating an O2 delivery limitation that was extant in the control condition, but not during upright exercise, where muscle O2 supply was probably not limiting.
Activation of GIRK Channels by Muscarinic Receptors and Group II Metabotropic Glutamate Receptors Suppresses Golgi Cell Activity in the Cochlear Nucleus of Mice
Authors: Irie Tomohiko , Fukui Iwao , Ohmori Harunori
Published: July 2006

Granule cells and parallel fiber circuits in the dorsal cochlear nucleus (DCN) play a role in integration of multimodal sensory with auditory inputs. The activity of granule cells is regulated through inhibitory connections made by Golgi cells. Golgi cells in turn probably receive parallel fiber inputs and regulate activity of the DCN. We have investigated the electrophysiological properties of Golgi cells using the whole cell patch-clamp method in slices made from transgenic mice that express green fluorescent protein driven by the promotor of metabotropic glutamate receptor subtype 2. Stimulation of auditory nerve fibers (ANFs) and of parallel fibers evoked glutamatergic excitatory postsynaptic currents (EPSC) through AMPA receptors. The strengths and latencies of these inputs differed, however. ANF stimulation evoked EPSCs after 4.7 ± 0.4 ms, whereas parallel fiber stimulation evoked EPSCs after 1.4 ± 0.2 ms that were on average 2.5 times as large. The multiple peaks and prolonged activity suggest the presence of polysynaptic connections between ANFs and Golgi cells. Agonists for group II metabotropic glutamate receptors (mGluRs) and for muscarinic receptors induced membrane hyperpolarization and suppressed the firing of Golgi cells by activating G-protein-coupled inward rectifier K+ (GIRK) channels. These results strongly suggest that Golgi cells were regulated through the combined activities of glutamatergic and cholinergic synapses, which presumably regulated the temporal firing patterns of granule cells and through them the activity of principal cells of the DCN.
Unexpected Abundance of HLA Class II Presented Peptides in Primary Renal Cell Carcinomas
Authors: Dengjel Jörn , Nastke Maria-Dorothea , Gouttefangeas Cécile , Gitsioudis Gitsios , Schoor Oliver , Altenberend Florian , Müller Margret , Krämer Björn , Missiou Anna , Sauter Martina , Hennenlotter Jörg , Wernet Dorothee , Stenzl Arnulf , Rammensee Hans-Georg , Klingel Karin , Stevanović Stefan
Published: July 2006

Purpose: To elicit a long-lasting antitumor immune response, CD8+ and CD4+ T cells should be activated. We attempted to isolate HLA-DR–presented peptides directly from dissected solid tumors, in particular from renal cell carcinoma, to identify MHC class II ligands from tumor-associated antigens (TAA) for their use in peptide-based immunotherapy.

Experimental Design: Tumor specimens were analyzed by immunohistochemical staining for their HLA class II expression. HLA class II peptides were subsequently isolated and identified by mass spectrometry. Gene expression analysis was done to detect genes overexpressed in tumor tissue. Peptides from identified TAAs were used to induce peptide-specific CD4+ T-cell responses in healthy donors and in tumor patients.

Results: In the absence of inflammation, expression of MHC class II molecules is mainly restricted to cells of the immune system. To our surprise, we were able to isolate and characterize hundreds of class II peptides directly from primary dissected solid tumors, especially from renal cell carcinomas, and from colorectal carcinomas and transitional cell carcinomas. Infiltrating leukocytes expressed MHC class II molecules and tumor cells, very likely under the influence of IFNγ. Our list of identified peptides contains ligands from several TAAs, including insulin-like growth factor binding protein 3 and matrix metalloproteinase 7. The latter bound promiscuously to HLA-DR molecules and were able to elicit CD4+ T-cell responses.

Conclusions: Thus, our direct approach will rapidly expand the limited number of T-helper epitopes from TAAs for their use in clinical vaccination protocols.
MUC4 Is a Novel Prognostic Factor of Extrahepatic Bile Duct Carcinoma
Authors: Tamada Shugo , Shibahara Hiroaki , Higashi Michiyo , Goto Masamichi , Batra Surinder K. , Imai Kohzoh , Yonezawa Suguru
Published: July 2006

Purpose: Many of the patients with extrahepatic bile duct carcinoma (EHBDC) show a poor outcome. We have reported that MUC4 is a novel prognostic factor of pancreatic adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to evaluate the prognostic significance of MUC4 expression in EHBDC.

Experimental Design: We examined the expression profile of MUC4 in EHBDC tissues from 70 patients using immunohistochemistry. MUC4 is a membrane mucin like MUC1. In addition, MUC4 is an intramembrane ligand for receptor tyrosine kinase ErbB2 and is related with regulation of p27. We compared the MUC4 expression with MUC1, ErbB2, or p27 expression in EHBDC.

Results: MUC4 was expressed in 36 of the 70 patients with EHBDC. There was no significant correlation between the MUC4 expression and MUC1, ErbB2, or p27 expression. The survival of 19 patients with high MUC4 expression (≥20% of carcinoma cells stained) was significantly worse than that of the 51 patients with low MUC4 expression (under 20% of carcinoma cells stained; P = 0.0072). The univariate analysis showed that high MUC4 expression (P = 0.0072), high MUC1 expression (P = 0.0092), histologic grading (P = 0.0029), surgical margin involvement (P = 0.0137), and nodal metastasis (P = 0.0036) were statistically significant risk factors. The backward stepwise multivariate analysis showed that high MUC4 expression (P = 0.0195) and surgical margin involvement (P = 0.0358) were statistically significant independent risk factors.

Conclusions: MUC4 expression in EHBDC is a new independent factor for poor prognosis and predicts the outcome of patients with EHBDC.
Targeted Therapies in Combination with Chemotherapy in Non–Small Cell Lung Cancer
Authors: Johnson David H.
Published: July 2006

With rare exceptions, attempts to combine so-called targeted agents with standard cytotoxic chemotherapy in advanced non–small cell lung cancer have yielded disappointing results. The reasons underlying these spectacular failures are not always fully understood, but certainly the lack of careful patient selection is a major contributing factor. In addition, recent preclinical and clinical studies indicate that antagonism may exist between the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy primarily in tumor cells with wild-type EGFR. By contrast, tumor cells harboring somatic mutations in EGFR experience massive apoptosis when exposed to the EGFR tyrosine kinase inhibitors. Therefore, in theory, mutant tumor cells should exhibit enhanced cell kill when treated with concomitant chemotherapy and EGFR tyrosine kinase inhibitors akin to what is observed with chemotherapy and trastuzumab in breast cancer. Clinical data from the recently completed TRIBUTE trial support the latter possibility. Ideally, future studies of EGFR tyrosine kinase inhibitors and other targeted drugs will use careful patient selection criteria based on well-characterized and validated predictive markers. However, in the absence of such biomarkers, clinical judgment, common sense, and innovative clinical trial design are necessary to avoid undue delay in drug development.
The Evolving Role of Cetuximab in Non–Small Cell Lung Cancer
Authors: Lilenbaum Rogerio C.
Published: July 2006

Cetuximab is a monoclonal antibody directed against the ligand binding site in the extracellular domain of the epidermal growth factor receptor (EGFR). Cetuximab is currently approved for the treatment of patients with refractory colorectal cancer. In locally advanced head and neck carcinoma, cetuximab in combination with radiotherapy significantly improved survival compared with radiotherapy alone, and this treatment awaits Food and Drug Administration approval. In previously treated non–small cell lung cancer, single-agent cetuximab produced an objective response in 3 of 66 eligible patients and a median survival of 8.1 months. Treatment was well tolerated, with skin rash as the principal toxicity. The vast majority of patients (60 of 66) expressed EGFR by immunohistochemistry but no correlation existed between response and EGFR mutations. Two single-arm phase II trials testing cetuximab in combination with a platinum-based doublet in previously untreated patients showed responses in the range of 26% to 29%, with median survival times of 10 to 11 months. A European phase II randomized trial tested cisplatin/vinorelbine with or without cetuximab as first-line therapy in 86 patients with advanced non–small-cell lung cancer. Overall efficacy was slightly superior in the cetuximab arm and a phase III trial is currently ongoing to definitively determine the role of cetuximab in this setting.
Her2-Targeted Therapies in Non–Small Cell Lung Cancer
Authors: Swanton Charles , Futreal Andy , Eisen Tim
Published: July 2006

Sensitivity to Her2-directed therapies is complex and involves expression not only of Her2 but also of other epidermal growth factor receptor (EGFR) family members, their ligands, and molecules that influence pathway activity, such as insulin-like growth factor-1 receptor, PTEN, and p27. The EGFR experience has taught us that responses can easily be diluted in an unselected cohort of patients. To date, trials of Her2-targeted therapies, such as trastuzumab, have been insufficiently powered to determine whether patients with non–small cell lung cancer (NSCLC) with Her2 gene amplification (rather than overexpression by immunohistochemistry) may benefit from these agents. It is unclear whether agents targeting Her2 might prove successful in future clinical trials in a highly selected patient cohort, either with Her2 amplification or Her2 gene mutations. The frequency of Her2 mutations in NSCLC may be too low to justify a prospective clinical trial in this patient group. The frequency of Her2 amplification (2-23%) in NSCLC and the widespread availability of Her2 fluorescence in situ hybridization analysis may justify a final study of trastuzumab monotherapy in this patient population. The role played by Her2 as the obligate heterodimerization partner for the other EGFR family members renders Her2 an attractive target irrespective of receptor overexpression. The most promising Her2-targeted strategy will likely prove to be combinatorial approaches using an EGFR tyrosine kinase inhibitor together with Her2 dimerization inhibitors.
Epidermal Growth Factor Receptor Kinase Domain Mutations in Esophageal and Pancreatic Adenocarcinomas
Authors: Kwak Eunice L. , Jankowski Janusz , Thayer Sarah P. , Lauwers Gregory Y. , Brannigan Brian W. , Harris Patricia L. , Okimoto Ross A. , Haserlat Sara M. , Driscoll David R. , Ferry David , Muir Beth , Settleman Jeff , Fuchs Charles S. , Kulke Matthew H. , Ryan David P. , Clark Jeff W. , Sgroi Dennis C. , Haber Daniel A. , Bell Daphne W.
Published: July 2006

Purpose: Specific activating mutations within the epidermal growth factor receptor (EGFR) identify a subset of non–small cell lung cancers with dramatic sensitivity to the specific tyrosine kinase inhibitors (TKI), gefitinib and erlotinib. Despite the abundant expression of EGFR protein in a broad range of epithelial cancers, EGFR mutations have not been reported in a substantial fraction of other cancers. Given recent reports of TKI-responsive cases of esophageal and pancreatic cancer, this study was designed to determine the prevalence of EGFR mutations in these gastrointestinal cancers.

Experimental Design: We sequenced exons 18 to 21 of EGFR from 21 cases of Barrett's esophagus, 5 cases of high-grade esophageal dysplasia, 17 cases of esophageal adenocarcinoma, and 55 cases of pancreatic adenocarcinoma. Subsets of esophageal (n = 7) and pancreatic cancer cases (n = 5) were obtained from patients who were subsequently treated with gefitinib or erlotinib-capecitabine, respectively.

Results: Mutations of EGFR were identified in two esophageal cancers (11.7%), three cases of Barrett's esophagus (14.2%), and two pancreatic cancers (3.6%). The mutations consisted of the recurrent missense L858R and in-frame deletion delE746-A750, previously characterized as activating EGFR mutations in non–small cell lung cancer. We also identified the TKI drug resistance–associated EGFR T790M mutation in an untreated case of Barrett's esophagus and the corresponding adenocarcinoma.

Conclusion: The presence of activating mutations within EGFR in both esophageal and pancreatic adenocarcinomas defines a previously unrecognized subset of gastrointestinal tumors in which EGFR signaling may play an important biological role. EGFR mutations in premalignant lesions of Barrett's esophagus also point to these as an early event in transformation of the esophageal epithelium. The role of genotype-directed TKI therapy should be tested in prospective clinical trials.
Inverse Effects of Mucin on Survival of Matched Hereditary Nonpolyposis Colorectal Cancer and Sporadic Colorectal Cancer Patients
Authors: You Jeng-Fu , Hsieh Ling-Ling , Changchien Chung Rong , Chen Jinn-Shiun , Chen Jim-Ray , Chiang Jy-Ming , Yeh Chien Yuh , Hsieh Pao-Shiu , Fan Chung-Wei , Liu Chun-Ting , Tang Reiping
Published: July 2006

Purpose: To compare survival and histologic features of hereditary nonpolyposis colorectal cancer (HNPCC; Lynch syndrome) cases to well-matched sporadic colon cancers from the same patient population.

Experimental Design: Between January 1995 and March 2002, a total of 5,138 consecutive patients underwent resection of primary colorectal adenocarcinoma in a single institution. According to the Amsterdam criteria, 56 HNPCC patients were matched to 147 sporadic colorectal cancer (SCRC) with no family history of cancer and with the same gender, tumor location, and age within 3 years. Immunohistochemical analyses were done for MUC1, MUC2, MUC3, and MUC5AC.

Results: The HNPCC group had a marginally significantly better long-term outcome than the SCRC group (P = 0.058). The trend disappeared after adjustment by tumor-node-metastasis stage in a Cox model (P = 0.774). We noted a difference of >50% in the 5-year cancer-specific survival rates of HNPCC- and SCRC-mucinous groups (92% versus 31%, P = 0.0003). Interaction between mucin and HNPCC and its effects on survival were further confirmed by comparing the Cox models with and without interaction terms (hazard ratio, 0.1; P = 0.034 with adjusting stage). Patients with tumors showing dual expression of mucin and MUC1, which appeared in 11% of those with HNPCC and 50% of those with SCRC, had a lower 5-year cancer-specific survival rate than patients without (30% versus 60%; P = 0.004 by log-rank test; P = 0.039 with adjustment for tumor-node-metastasis stage).

Conclusions: These results suggest that mucin has an inverse effect on survival in patients with HNPCC and SCRC, which might be partly explained by a lower prevalence of MUC1 expression in the mucinous HNPCC group than in the SCRC groups.
c-Met Ectodomain Shedding Rate Correlates with Malignant Potential
Authors: Athauda Gagani , Giubellino Alessio , Coleman Jonathan A. , Horak Christine , Steeg Patricia S. , Lee Ming-Jung , Trepel Jane , Wimberly Jennifer , Sun Jan , Coxon Angela , Burgess Teresa L. , Bottaro Donald P.
Published: July 2006

Purpose: Many proteins are proteolytically released from the cell surface by a process known as ectodomain shedding. Shedding occurs under normal physiologic conditions and can be increased in certain pathologies. Among the many receptors for which ectodomain shedding has been shown is c-Met, the hepatocyte growth factor (HGF) receptor tyrosine kinase. HGF stimulates mitogenesis, motogenesis, and morphogenesis in a variety of cellular targets during development, homeostasis, and tissue regeneration. Inappropriate HGF signaling resulting in unregulated cell proliferation, motility, and invasion occurs in several human malignancies. This can occur through paracrine signaling, autocrine loop formation, receptor mutation, gene amplification, or gene rearrangement, accompanied frequently with overexpression of ligand and/or receptor proteins. We hypothesized that c-Met overexpression in cancer might result in increased ectodomain shedding, and that its measure could be a useful biomarker of tumor progression.

Experimental Design: We developed a sensitive electrochemiluminescent immunoassay to quantitate c-Met protein in cell lysates, culture supernatants, and biological samples.

Results: A survey of cultured cell models of oncogenic transformation revealed significant direct correlations (P < 0.001, t test or ANOVA) between malignant potential and the rate of c-Met ectodomain shedding that was independent of steady-state receptor expression level. Moreover, weekly plasma and urine samples from mice harboring s.c. human tumor xenografts (n = 4 per group) displayed soluble human c-Met levels that were measurable before tumors became palpable and that correlated directly with tumor volume (R2 > 0.92, linear regression).

Conclusions: For a variety of human cancers, c-Met ectodomain shedding may provide a reliable and practical indicator of malignant potential and overall tumor burden.
The International Regimes Database: Designing and Using a Sophisticated Tool for Institutional Analysis
Authors: Young Oran R. , Zürn Michael
Published: July 2006

This article presents the International Regimes Database (IRD), an analytical tool designed to (i) move regime analysis from its current emphasis on the use of discrete case studies to the use of a relational database encompassing comparable data on a large number of cases and (ii) facilitate quantitative as well as qualitative analyses of hypotheses dealing with international regimes. The article describes the architecture of this database, introduces some preliminary findings relating to compliance, decision rules, and programmatic activities, and discusses methodological issues pertaining to the use of the database on the part of other scholars. It provides a short and easily accessible introduction to the book-length treatment of the IRD contained in: Helmut Breitmeier, Oran R. Young, and Michael Zürn, Analyzing International Environmental Regimes, Cambridge, MA: MIT Press, 2006.
Comparing Fixed Effects and Covariance Structure Estimators for Panel Data
Authors: Ejrnæs Mette , Holm Anders
Published: July 2006

In this article, the authors compare the traditional econometric fixed effect estimator with the maximum likelihood estimator implied by covariance structure models for panel data. Their findings are that the maximum like lipoid estimator is remarkably robust to certain types of misspecifications (e.g., deviation from the assumption of an underlying normal distribution). However, with other types of misspecification, the fixed estimator is pre ferable. Furthermore, the authors suggest that the Hausman specification test may be used as a test of the consistency of the maximum likelihood estimator.
Modeling Partially Incomplete Marital Satisfaction Data
Authors: Jansen Ivy , Van den Troost Ann , Molenberghs Geert , Vermulst Ad A. , Gerris Jan R. M.
Published: July 2006

The authors analyze data on marital satisfaction, obtained from couples at two distinct moments in time (1990, 1995). The data are of a bivariate longitudinal type. Moreover, some couples provide incomplete records only, usually because the 1995 follow-up interview has not taken place. The authors propose a hierarchical modeling strategy that takes all these features into account and is more generally valid than a classical complete case or single imputation-based strategy.
Matching Estimators of Causal Effects
Authors: Morgan Stephen L. , Harding David J.
Published: July 2006

As the counterfactual model of causality has increased in popularity, sociologists have returned to matching as a research methodology. In this article, advances over the past two decades in matching estimators are explained, and the practical limitations of matching techniques are emphasized. The authors introduce matching methods by focusing first on ideal scenarios in which stratification and weighting procedures warrant causal inference. Then, they discuss how matching is often undertaken in practice, offering an overview of the most prominent data analysis routines. With four hypothetical examples, they demonstrate how the assumptions behind matching estimators often break down in practice. Even so, the authors argue that matching techniques can be used effectively to strengthen the prosecution of causal questions in sociology.
Supervised feature extraction algorithm based on improved polynomial entropy
Authors: Ding Shifei , Shi Zhongzhi
Published: July 2006

Based on information entropy theory, a novel feature extraction algorithm based on improved polynomial entropy (IPE) is set up. Firstly, the concepts and their properties of information entropy and cross entropy (CE) are analysed and studied. On this foundation, we prove that symmetrical cross entropy (SCE) proposed here based on CE satisfies three axioms of the distance, i.e. nonnegativity, symmetry and triangle inequation. So SCE is a kind of distance measure, which can be used to measure the degree of variation between two random variables. Secondly, for convenience, we propose a new concept of improved polynomial entropy (IPE) based on polynomial entropy (PE), and explain that IPE is equivalent to SCE. Thirdly, we make IPE separability criterion of the classes for feature extraction, and design a novel feature extraction algorithm based on IPE. Fianlly, the experimental results demonstrate that the algorithm proposed here is valid and reliable, and it provides a new research approach for feature extraction, data mining and pattern recognition.
Search goal revision in models of information retrieval
Authors: Hider Philip
Published: July 2006

Research indicates that considerable amounts of search goal revision can take place during user-system interaction. Following a review of the treatment of this phenomenon in various models of information retrieval, an alternative model is proposed which attempts to explain search goal redefinition more fully, by distinguishing between goal change due to new information gained and goal change due to old knowledge remembered. In the case of the latter, it is postulated that external stimuli, contained for example in system feedback, raise the user’s nonconscious knowledge to consciousness, providing the user with a better understanding of their information want and goal. The new model is described as an instance of a more general model of information acquisition, embracing a spectrum of information behaviour, from purposeful query-based searching to incidental encountering.
‘Our desires are ungovernable’
Authors: Halsey Mark , Young Alison
Published: July 2006

Our aim in this article is to contribute to the body of research on graffiti by considering some of the hitherto hidden aspects of graffiti culture. Drawing on detailed interviews with graffiti writers, we examine four main themes: motivations for graffiti writing; thresholds dividing ‘art’ from ‘vandalism’; writers’ reactions to ‘blank’ surfaces; and graffiti’s relation to other types of crime. We orient our discussion towards the affective dimensions of the activity in the hope that the words of writers become a visible and productive presence in urban (and academic) space.
Brazilian National Culture, Organizational Culture and Cultural Agreement
Authors: de Hilal Adriana V. Garibaldi
Published: July 2006

The present study looks into the organizational culture of a Brazilian company, concentrating on its main Brazilian branches as well as on its European, Latin American, Central American, North American and Asian branches, making a total sample of 36 cities and 1742 respondents. Results indicate the influence of national culture on organizational culture, as the dimensions found clearly reflect the ambiguity and double-edged ethic characteristic of Brazilian culture. This study also shows the importance of hierarchy, and of relational networks, which stresses the relevance of the cultural element in organizational structure and functioning. In brief, understanding the double-edged ethic that governs Brazilian culture helps us understand apparently different, ambiguous or even contradictory behaviors reflected in the organizational culture practices of a Brazilian company with international operations. Moreover, there is little empirical research that directly deals with what combination of factors makes individuals agree or disagree over their cultural viewpoints. Consequently, we consider that this study attempts to deal with that issue as the cultural clusters were obtained using a multivariate approach, using demographic variables and the identified organizational dimensions. Thus results suggest the organizational context may increase or reduce the probability of nationality affecting the cultural agreement of group members.
Conceptualizing and Measuring Gunas
Authors: Bhal Kanika T. , Debnath Nivedita
Published: July 2006

Researchers in the field of cross cultural research have highlighted the need to study one culture in depth particularly to understand the complex causes of behaviors those managers in a culture manifest. This article reports the conceptualization and measurement of the Indian personality construct of Gunas; a possible predictor of ethics of Indian managers. The Indian scripture The Gita identifies three personality constructs, collectively referred to as Gunas, that are considered relevant for understanding ethical behavior. The article reports the development of a scale to measure three Gunas– Illumination, Passion and Dullness, through a four-step process. In the first step, construct definitions and items of the three Gunas are generated. The second, third and fourth steps report empirical studies conducted on different samples to assess the factor stability, reliability, discriminant validity, and other validities of the scale. The scale is used to predict spirituality, ethical frameworks and acts of software piracy in organizations. Implications for cross cultural research as well as practice are discussed.
Efflux pump genes of the resistance-nodulation-division family in Burkholderia cenocepacia genome
Authors: Guglierame Paola , Pasca Maria Rosalia , De Rossi Edda , Buroni Silvia , Arrigo Patrizio , Manina Giulia , Riccardi Giovanna
Published: July 2006

Background

Burkholderia cenocepacia is recognized as opportunistic pathogen that can cause lung infections in cystic fibrosis patients. A hallmark of B. cenocepacia infections is the inability to eradicate the organism because of multiple intrinsic antibiotic resistance. As Resistance-Nodulation-Division (RND) efflux systems are responsible for much of the intrinsic multidrug resistance in Gram-negative bacteria, this study aims to identify RND genes in the B. cenocepacia genome and start to investigate their involvement into antimicrobial resistance.

Results

Genome analysis and homology searches revealed 14 open reading frames encoding putative drug efflux pumps belonging to RND family in B. cenocepacia J2315 strain.

By reverse transcription (RT)-PCR analysis, it was found that orf3, orf9, orf11, and orf13 were expressed at detectable levels, while orf10 appeared to be weakly expressed in B. cenocepacia. Futhermore, orf3 was strongly induced by chloramphenicol. The orf2 conferred resistance to fluoroquinolones, tetraphenylphosphonium, streptomycin, and ethidium bromide when cloned and expressed in Escherichia coli KAM3, a strain lacking the multidrug efflux pump AcrAB. The orf2-overexpressing E. coli also accumulate low concentrations of ethidium bromide, which was restored to wild type level in the presence of CCCP, an energy uncoupler altering the energy of the drug efflux pump.

Conclusion

The 14 RND pumps gene we have identified in the genome of B. cenocepacia suggest that active efflux could be a major mechanism underlying antimicrobial resistance in this microorganism. We have characterized the ORF2 pump, one of these 14 potential RND efflux systems. Its overexpression in E. coli conferred resistance to several antibiotics and to ethidium bromide but it remains to be determined if this pump play a significant role in the antimicrobial intrinsic resistance of B. cenocepacia. The characterization of antibiotic efflux pumps in B. cenocepacia is an obligatory step prior to the design of specific, potent bacterial inhibitors for the improved control of infectious diseases. Consequently, the topic deserves to be further investigated and future studies will involve systematic investigation on the function and expression of each of the RND efflux pump homologs.
Promotion of oogenesis and embryogenesis in theC. elegansgonad by EFL-1/DPL-1 (E2F) does not require LIN-35 (pRB)
Authors: Chi Woo , Reinke Valerie
Published: July 2006

In Caenorhabditis elegans, EFL-1 (E2F), DPL-1 (DP) and LIN-35(pRb) act coordinately in somatic tissues to inhibit ectopic cell division,probably by repressing the expression of target genes. EFL-1, DPL-1 and LIN-35 are also present in the germline, but do not always act together. Strong loss-of-function mutations in either efl-1 or dpl-1 cause defects in oogenesis that result in sterility, while lin-35 mutants are fertile with reduced broods. Microarray-based expression profiling of dissected gonads from efl-1, dpl-1 and lin-35 mutants reveals that EFL-1 and DPL-1 promote expression of an extensively overlapping set of target genes, consistent with the expectation that these two proteins function as a heterodimer. Regulatory regions upstream of many of these target genes have a canonical E2F-binding site, suggesting that their regulation by EFL-1/DPL-1 is direct. Many EFL-1/DPL-1 responsive genes encode proteins required for oogenesis and early embryogenesis, rather than cell cycle components. By contrast, LIN-35 appears to function primarily as a repressor of gene expression in the germline, and the genes that it acts on are for the most part distinct from those regulated by EFL-1 and/or DPL-1. Thus, in vivo, C. elegans E2F directly promotes oogenesis and embryogenesis through the activation of a tissue-specific transcriptional program that does not require LIN-35.