bluuebunny/crossref_metadata_2025_split huggingface dataset:
TH‐D‐BRD‐05: Replacement for Generalized Equivalent Dose in Phenomenological NTCP Models
Authors: Fatyga M , Williamson J 
Published: April 2010

Purpose: phenomenological normal tissue complications probability (NTCP) models use generalized equivalent uniform dose (gEUD) as a summary measure which converts an inhomogeneous dose distribution into an “equivalent” uniform dose. We have investigated adapting gEUD models to brachytherapy dose distributions which are characterized by small focal hotspots. We have found that small hotspots dominate the behavior of gEUD measure. As it is unlikely that clinical NTCP values are determined to this extent by small focal hotspots, we have developed an alternative to gEUD‐based dose‐volume histogram reduction for adapting the phenomenological NTCP models to combined external‐beam and brachytherapy treatments. Our revised metric allows for local saturation in biological effectiveness in volume‐limited high‐dose regions. Materials & Methods: Three summary measures were computed on rectal DVHs. The gBEUD is an equivalent of gEUD, but with the physical dose replaced by biologically equivalent dose (BED). The tESD and vESD measures compute ESD index (equivalent uniform dose leading to the same cell survival fraction as the inhomogeneous dose distribution) on high BED portions of rectal DVHs. The tESD measure uses common BED threshold for all DVHs, which becomes an adjustable parameter of the measure. The vESD measure uses common fraction of the rectal volume as an adjustable parameter, and thus computes a BED threshold for each DVH. Properties of the three measures are compared. A database of 9 prostate patients with 7‐field IMRT boost plans and HDR brachytherapy boost plans delivering biologically equivalent D98 doses were used for the study. Results: For 6 of the 9 patients the gBEUD increased by approximately 100% due to doses confined to volumes <1% of the organ volume. The gEUD/gBEUD measures could be replaced by ESD based metrics, which explicitly incorporate saturation of biological effectiveness of high doses.Acknowledgments: Supported by NIH Grant P01 CA11602.
Engineering Cyanobacteria To Synthesize and Export Hydrophilic Products
Authors: Niederholtmeyer Henrike , Wolfstädter Bernd T. , Savage David F. , Silver Pamela A. , Way Jeffrey C. 
Published: April 2010

ABSTRACTMetabolic engineering of cyanobacteria has the advantage that sunlight and CO2are the sole source of energy and carbon for these organisms. However, as photoautotrophs, cyanobacteria generally lack transporters to move hydrophilic primary metabolites across membranes. To address whether cyanobacteria could be engineered to produce and secrete organic primary metabolites,Synechococcus elongatusPCC7942 was engineered to express genes encoding an invertase and a glucose facilitator, which mediated secretion of glucose and fructose. Similarly, expression of lactate dehydrogenase- and lactate transporter-encoding genes allowed lactate accumulation in the extracellular medium. Expression of the relevant transporter was essential for secretion. Production of these molecules was further improved by expression of additional heterologous enzymes. Sugars secreted by the engineered cyanobacteria could be used to supportEscherichia coligrowth in the absence of additional nutrient sources. These results indicate that cyanobacteria can be engineered to produce and secrete high-value hydrophilic products.
Broad-Host-Range Plasmids for Red Fluorescent Protein Labeling of Gram-Negative Bacteria for Use in the Zebrafish Model System
Authors: Singer John T. , Phennicie Ryan T. , Sullivan Matthew J. , Porter Laura A. , Shaffer Valerie J. , Kim Carol H. 
Published: April 2010

ABSTRACT

To observe real-time interactions between green fluorescent protein-labeled immune cells and invading bacteria in the zebrafish (
Danio rerio
), a series of plasmids was constructed for the red fluorescent protein (RFP) labeling of a variety of fish and human pathogens. The aim of this study was to create a collection of plasmids that would express RFP pigments both constitutively and under
tac
promoter regulation and that would be nontoxic and broadly transmissible to a variety of Gram-negative bacteria. DNA fragments encoding the RFP dimeric (d), monomeric (m), and tandem dimeric (td) derivatives d-Tomato, td-Tomato, m-Orange, and m-Cherry were cloned into the IncQ-based vector pMMB66EH in
Escherichia coli.
Plasmids were mobilized into recipient strains by conjugal mating. Pigment production was inducible in
Escherichia coli
,
Pseudomonas aeruginosa
,
Edwardsiella tarda
, and
Vibrio
(
Listonella
)
anguillarum
strains by isopropyl-β-
d
-thiogalactopyranoside (IPTG) treatment. A spontaneous mutant exconjugant of
P. aeruginosa
PA14 was isolated that expressed td-Tomato constitutively. Complementation analysis revealed that the constitutive phenotype likely was due to a mutation in
lacI
q
carried on pMMB66EH. DNA sequence analysis confirmed the presence of five transitions, four transversions, and a 2-bp addition within a 14-bp region of
lacI.
Vector DNA was purified from this constitutive mutant, and structural DNA sequences for RFP pigments were cloned into the constitutive vector. Exconjugants of
P. aeruginosa
,
E. tarda
, and
V. anguillarum
expressed all pigments in an IPTG-independent fashion. Results from zebrafish infectivity studies indicate that RFP-labeled pathogens will be useful for the study of real-time interactions between host cells of the innate immune system and the infecting pathogen.
Genetic and Expression Analysis of HER-2 and EGFR Genes in Salivary Duct Carcinoma: Empirical and Therapeutic Significance
Authors: Williams Michelle D. , Roberts Dianna B. , Kies Merrill S. , Mao Li , Weber Randal S. , El-Naggar Adel K. 
Published: April 2010

Abstract
Purpose: Salivary duct carcinoma overexpresses epidermal growth factor receptor (EGFR) and HER-2, although the underlying mechanisms remain undefined. Because of the potential utilization of these markers as treatment targets, we evaluated protein and gene status by several techniques to determine complementary value.
Experimental Design: A tissue microarray of 66 salivary duct carcinomas was used for immunohistochemical analysis of HER-2 and EGFR expression (semiquantitatively evaluated into a three-tiered system), and fluorescence in situ hybridization for gene copy number, and chromosomes 7 and 17 ploidy status. Sequencing of exons 18, 19, and 21 of the EGFR gene for mutations was carried out.
Result: For EGFR, 46 (69.7%) of the 66 tumors showed some form of EGFR expression (17 at 3+, 17 at 2+, 12 at 1+) but none gene amplification. Five (9.4%) of 53 tumors showed mutations in exon 18 (n = 3) and exon 19 (n = 2). Polysomy of chromosome 7 (average &gt;2.5 copies/cell) was detected in 15 (25.0%) of 60 tumors (6 at 3+, 5 at 2+, 2 at 1+, 2 at 0+ expression) and correlated with poor 3-year survival (P = 0.015). For HER-2, 17 (25.8%) of 66 tumors expressed HER-2 (10 at 3+, 3 at 2+, 4 at 1+). Eight tumors showed HER-2 gene amplification (6 at 3+, 1 at 1+, 1 at 0+ protein expression). Chromosome 17 polysomy was found in 8 (15.7%) of 51 tumors; two had HER-2 expression (3+, 1+).
Conclusion: Our study shows that salivary duct carcinomas (a) harbor EGFR gene mutations in a subset of tumors that may guide therapy, (b) pursue an aggressive clinical course in cases with chromosome 7 polysomy and high EGFR expression, and (c) with HER-2 gene amplification and protein high expression, may be selected for targeted therapy. Clin Cancer Res; 16(8); 2266–74. ©2010 AACR.
Nuclear Localization of Signal Transducer and Activator of Transcription 3 in Head and Neck Squamous Cell Carcinoma Is Associated with a Better Prognosis
Authors: Pectasides Eirini , Egloff Ann-Marie , Sasaki Clarence , Kountourakis Panteleimon , Burtness Barbara , Fountzilas George , Dafni Urania , Zaramboukas Thomas , Rampias Theodoros , Rimm David , Grandis Jennifer , Psyrri Amanda 
Published: April 2010

AbstractPurpose: A high frequency of head and neck squamous cell cancers (HNSCC) contain constitutively activated signal transducer and activator of transcription 3 (STAT3). To further elucidate the prognostic role of STAT3 in HNSCC, the expression pattern of STAT3 was correlated with outcome in two independent data sets.Experimental Design: STAT3 protein expression analysis was done on a test cohort of 102 patients with HNSCC recruited between 1992 and 2005. Automated quantitative analysis was used to assess STAT3 protein expression. We evaluated associations with clinicopathologic parameters and survival prognosis. Associations were validated in a second, independent cohort of 58 patients with confirmed HNSCC enrolled in the Early Detection Research Network–sponsored study who underwent surgical resection with curative intent at the University of Pittsburgh Medical Center between 2000 and 2004.Results: STAT3 displayed mixed nuclear and cytoplasmic staining. Survival analysis showed that high nuclear STAT3 expression (top tertile versus the rest) was associated with longer progression-free survival (n = 70, mean survival of 88.9 versus 46.7 months, P = 0.012 for the first cohort; n = 37, mean survival of 60.3 versus 33.0 months, P = 0.009 for the second cohort). After best model selection in the multivariable analysis context, only STAT3 was significant, revealing a lower risk of progression and death for patients with high nuclear STAT3-expressing tumors (hazard ratio, 0.28; 95% confidence interval, 0.10-0.82; P = 0.019; and hazard ratio, 0.23; 95% confidence interval, 0.07-0.76; P = 0.016, respectively).Conclusions: Our results indicate that high nuclear STAT3 expression levels by automated quantitative analysis are associated with favorable outcome in HNSCC. Clin Cancer Res; 16(8); 2427–34. ©2010 AACR.
Aprataxin Tumor Levels Predict Response of Colorectal Cancer Patients to Irinotecan-based Treatment
Authors: Dopeso Higinio , Mateo-Lozano Silvia , Elez Elena , Landolfi Stefania , Ramos Pascual Francisco Javier , Hernández-Losa Javier , Mazzolini Rocco , Rodrigues Paulo , Bazzocco Sarah , Carreras Maria Josep , Espín Eloy , Armengol Manel , Wilson Andrew J. , Mariadason John M. , Ramon y Cajal Santiago , Tabernero Josep , Schwartz Simo , Arango Diego 
Published: April 2010

Abstract
Purpose: Irinotecan (CPT11) treatment significantly improves the survival of colorectal cancer patients and is routinely used for the treatment of these patients, alone or in combination with other agents. However, only 20% to 30% of patients show an objective response to irinotecan, and there is great need for new molecular markers capable of identifying the subset of patients who are unlikely to respond.
Experimental Design: Here we used microarray analysis of a panel of 30 colorectal cancer cell lines and immunohistochemistry to identify and validate a new biomarker of response to irinotecan.
Results: A good correlation was observed between irinotecan sensitivity and the expression of aprataxin (APTX), a histidine triad domain superfamily protein involved in DNA repair. Moreover, using an isogenic in vitro system deficient in APTX, we show that aprataxin directly regulates the cellular sensitivity to camptothecin, suggesting that it could be used to predict patient response to irinotecan. We constructed a tissue microarray containing duplicate tumor samples from 135 patients that received irinotecan for the treatment of advanced colorectal cancer. Immunohistochemical assessment of the tumor levels of aprataxin showed a significant association with treatment response and patient survival. Patients with low aprataxin had longer progression-free (9.2 versus 5.5 months; P = 0.03) and overall survival (36.7 versus 19.0 months; P = 0.008) than patients with high tumor aprataxin. No associations were found between coding APTX variants and aprataxin levels or camptothecin sensitivity.
Conclusions: These results show that aprataxin tumor levels can be used to identify patients with low probability of response to irinotecan-based therapy who are ideal candidates to receive treatment with alternative agents in an attempt to improve patient survival. Clin Cancer Res; 16(8); 2375–82. ©2010 AACR.
Potent Preclinical Impact of Metronomic Low-Dose Oral Topotecan Combined with the Antiangiogenic Drug Pazopanib for the Treatment of Ovarian Cancer
Authors: Hashimoto Kae , Man Shan , Xu Ping , Cruz-Munoz William , Tang Terence , Kumar Rakesh , Kerbel Robert S. 
Published: April 2010

Abstract
Low-dose metronomic chemotherapy has shown promising activity in many preclinical and some phase II clinical studies involving various tumor types. To evaluate further the potential therapeutic impact of metronomic chemotherapy for ovarian cancer, we developed a preclinical model of advanced human ovarian cancer and tested various low-dose metronomic chemotherapy regimens alone or in concurrent combination with an antiangiogenic drug, pazopanib. Clones of the SKOV-3 human ovarian carcinoma cell line expressing a secretable β-subunit of human choriogonadotropic (β-hCG) protein and firefly luciferase were generated and evaluated for growth after orthotopic (i.p.) injection into severe combined immunodeficient mice; a highly aggressive clone, SKOV-3-13, was selected for further study. Mice were treated beginning 10 to 14 days after injection of cells when evidence of carcinomatosis-like disease in the peritoneum was established as assessed by imaging analysis. Chemotherapy drugs tested for initial experiments included oral cyclophosphamide, injected irinotecan or paclitaxel alone or in doublet combinations with cyclophosphamide; the results indicated that metronomic cyclophosphamide had no antitumor activity whereas metronomic irinotecan had potent activity. We therefore tested an oral topoisomerase-1 inhibitor, oral topotecan, at optimal biological dose of 1 mg/kg/d. Metronomic oral topotecan showed excellent antitumor activity, the extent of which was significantly enhanced by concurrent pazopanib, which itself had only modest activity, with 100% survival values of the drug combination after six months of continuous therapy. In conclusion, oral topotecan may be an ideal agent to consider for clinical trial assessment of metronomic chemotherapy for ovarian cancer, especially when combined with an antiangiogenic drug targeting the vascular endothelial growth factor pathway, such as pazopanib. Mol Cancer Ther; 9(4); 996–1006. ©2010 AACR.
Protein Kinase G Type Iα Activity in Human Ovarian Cancer Cells Significantly Contributes to Enhanced Src Activation and DNA Synthesis/Cell Proliferation
Authors: Leung Elaine L. , Wong Janica C. , Johlfs Mary G. , Tsang Benjamin K. , Fiscus Ronald R. 
Published: April 2010

Abstract
Previously, we showed that basal activity of nitric oxide (NO)/cyclic GMP (cGMP)/protein kinase G (PKG) signaling pathway protects against spontaneous apoptosis and confers resistance to cisplatin-induced apoptosis in human ovarian cancer cells. The present study determines whether basal PKG kinase activity regulates Src family kinase (SFK) activity and proliferation in these cells. PKG-Iα was identified as predominant isoform in both OV2008 (cisplatin-sensitive, wild-type p53) and A2780cp (cisplatin-resistant, mutated p53) ovarian cancer cells. In both cell lines, ODQ (inhibitor of endogenous NO-induced cGMP biosynthesis), DT-2 (highly specific inhibitor of PKG-Iα kinase activity), and PKG-Iα knockdown (using small interfering RNA) caused concentration-dependent inhibition of DNA synthesis (assessed by bromodeoxyuridine incorporation), indicating an important role of basal cGMP/PKG-Iα kinase activity in promoting cell proliferation. DNA synthesis in OV2008 cells was dependent on SFK activity, determined using highly selective SFK inhibitor, 4-(4′-phenoxyanilino)-6,7-dimethoxyquinazoline (SKI-1). Studies using DT-2 and PKG-Iα small interfering RNA revealed that SFK activity was dependent on PKG-Iα kinase activity. Furthermore, SFK activity contributed to endogenous tyrosine phosphorylation of PKG-Iα in OV2008 and A2780cp cells. In vitro coincubation of recombinant human c-Src and PKG-Iα resulted in c-Src–mediated tyrosine phosphorylation of PKG-Iα and enhanced c-Src autophosphorylation/activation, suggesting that human c-Src directly tyrosine phosphorylates PKG-Iα and the c-Src/PKG-Iα interaction enhances Src kinase activity. Epidermal growth factor–induced stimulation of SFK activity in OV2008 cells increased PKG-Iα kinase activity (indicated by Ser239 phosphorylation of the PKG substrate vasodilator-stimulated phosphoprotein), which was blocked by both SKI-1 and SU6656. The data suggest an important role of Src/PKG-Iα interaction in promoting DNA synthesis/cell proliferation in human ovarian cancer cells. The NO/cGMP/PKG-Iα signaling pathway may provide a novel therapeutic target for disrupting ovarian cancer cell proliferation. Mol Cancer Res; 8(4); 578–91. ©2010 AACR.
Shrine, Images, and Power: The Worship of Former Worthies in Early Nineteenth Century Suzhou
Authors: Han Seunghyun 
Published: April 2010

AbstractIn the 1820s, the literati of Suzhou embarked on a project to build a shrine devoted to the worship of local former worthies and engraved almost six hundred portraits of the latter on the shrine's inner walls. Since the locality already had a paired shrine of eminent officials and local worthies, as had become the case across the empire since the mid-Ming period, why did they need to create a shrine of a similar nature? What was the cultural significance of introducing visual representations of the worthies in the worship? By analyzing the multiple layers of meaning surrounding this shrine-building activity, the present study attempts to illuminate an aspect of the changing state-elite relations in the early nineteenth century. Au cours des années 1820 les lettrés de Suzhou s'engagèrent dans un projet de construction d'un sanctuaire dédié au culte des anciennes personnalités locales éminentes, sur les murs duquel furent gravés les portraits de près de six cents d'entre elles. Dans la mesure, où Suzhou possédait déjà deux sanctuaires, l'un pour les fonctionnaires éminents et l'autre pour les personnalités locales, comme c'était le cas partout dans l'Empire depuis le milieu des Ming, pourquoi fut-il jugé nécessaire d'en créer un autre de même nature? Que signifiait d'un point de vue culturel le fait d'introduire des représentations visuelles des personnalités en question dans les célébrations? En analysant les niveaux de sens multiples qui entourent cette activité de construction, le présent article s'efforce de mettre en lumière un aspect particulier du changement dans les relations entre l'État et les élites au début du xixe siècle.
"Words of Blood and Tears": Petty Urbanites Write Emotion
Authors: Goodman Bryna 
Published: April 2010

AbstractRecent attention to the modern history of emotion in China has traced multiple and shifting discourses. The New Culture Movement that competed with "butterfly fiction" in the first decade of China's new Republic championed an autonomous form of individual personhood that broke with the authoritarian family and arranged marriages, and embraced free love and free choice marriage. In the late 1920s, projects of revolutionary emotional retooling reoriented passion, loyalty, and identity in the direction of the nation. But historians have relatively little source material that illuminates the linkage between changes in elite discourses and the everyday experiences of individual commoners, particularly for the study of emotional expression. The unusual survival of a set of petty-urbanite love letters permits the close textual mapping, in this essay, of the ways in which the broad public circulation in the Republican era of multiple and contradictory discourses of emotion entered into and affected particular commoner lives.
τενκην δ δλως λω: Reading Sappho’s ‘Confession’ (fr. 94) through Penelope
Authors: Larson Stephanie 
Published: April 2010

AbstractScholarship on Sappho’s use of epic models focuses primarily on her incorporation and rewriting of motifs and characters from the Iliadic cycle. This paper rather turns to the Odyssey’s Penelope as exemplar for Sappho fragment 94, also known as Sappho’s ‘Confession’. The author argues that fragment 94 alludes to Penelope and her situation through a series of associative, lexical and narrative points, particularly through the unique adverb δλως and the symbolic image of the soft bed as a locus for desire. At the same time, Sappho can be seen to subvert aspects of Penelope’s fictional story, thereby more poignantly highlighting the focus on separation and change in the poem. Reading Sappho 94 through the Odyssey’s Penelope also supports ascribing the first extant line of the poem to the departing girl and bolsters arguments for a marriage context for the fragment.
Offending the Powerful: Tacitus’ Dialogus de Oratoribus and Safe Criticism
Authors: Strunk Thomas E. 
Published: April 2010

AbstractThis paper argues that the character of Curiatius Maternus in Tacitus’ Dialogus de Oratoribus is consistent throughout the dialogue in his attitude to the imperial regime. Maternus begins the dialogue in outright dissent, while in the second half he appears to be an apologist for the regime. Accepting the ironic reading of Maternus’ concluding speech, this paper asserts that Maternus shifts to figured speech in reaction to M. Aper, who expresses solidarity with the political values and rhetorical style of the delatores, and Vipstanus Messalla, the half-brother of the delator M. Aquilius Regulus. Confronted with such individuals, Maternus recognizes he must change the tenor of his language. Thus, his concluding speech is ironic critique consistent with his earlier dissent.
Bayesian calibration of hydrocarbon reservoir models using an approximate reservoir simulator in the prior specification
Authors: Lødøen Ole Petter , Tjelmeland Håkon 
Published: April 2010

We consider prediction and uncertainty analysis for the ‘history matching’ problem in petroleum reservoir evaluation. Unknown reservoir properties are represented on a fine three dimensional lattice. A ‘reservoir simulator’ takes the reservoir properties as input and gives production properties as output. The history matching problem is to infer the reservoir properties from the observed production history. To run the reservoir simulator on the lattice size of interest is computer intensive, and this severely limits the number of runs possible. We formulate the problem in a Bayesian setting and, following suggestions in the statistical literature, consider the reservoir simulator as an unknown function. To obtain a realistic prior distribution for this function, we propose to combine a coarse lattice (faster) version of the simulator with parameters correcting for bias introduced by the coarser lattice. We simulate from the resulting posterior by Markov chain Monte Carlo (MCMC). We construct an artificial reference reservoir, generate corresponding flow observations, and use our procedure to evaluate the reservoir properties in the resulting posterior distribution. Convergence and mixing are acceptable. The case study demonstrates how the observed production history provides information about both the reservoir properties and the bias correcting parameters included in the prior specification.