bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innate Immune Inflammatory Response against Enteric Bacteria Helicobacter hepaticus Induces Mammary Adenocarcinoma in Mice
Authors: Rao Varada P. , Poutahidis Theofilos , Ge Zhongming , Nambiar Prashant R. , Boussahmain Chakib , Wang Yan Yan , Horwitz Bruce H. , Fox James G. , Erdman Susan E. 
Published: August 2006

Abstract
Inflammation associated with bacterial infections is a risk factor for cancers in humans, yet its role in breast cancer remains poorly understood. We have previously shown that innate immune inflammatory response against intestinal bacteria is sufficient to induce colon cancer. Here we report that infecting Rag2-deficient C57BL/6 ApcMin/+ mice with an intestinal bacterial pathogen, Helicobacter hepaticus, significantly promotes mammary carcinoma in females and enhances intestinal adenoma multiplicity by a tumor necrosis factor α (TNFα)–dependent mechanism. The mammary and intestinal tumor development as well as the increase in proinflammatory mediators is suppressed by adoptive transfer of interleukin 10–competent CD4+CD45RBloCD25+ regulatory (TR) cells. Furthermore, prior exposure of donor mice to H. hepaticus significantly enhances antitumor potency of their TR cells. Interestingly, these microbially experienced TR cells suppress tumorigenesis more effectively in recipient mice irrespective of their tumor etiology. These data suggest that infections with enteric pathogens enhance TR-cell potency and protect against epithelial cancers later in life, potentially explaining paradoxical increases in cancer risk in developed countries having more stringent hygiene practices. The possibility that dysregulated gut microbial infections in humans may lead to cancer in anatomically distant organs, such as breast, highlights the need for novel immune-based strategies in cancer prevention and treatment. (Cancer Res 2006;66(15):7395-400)
A Novel Orally Active Small Molecule Potently Induces G1 Arrest in Primary Myeloma Cells and Prevents Tumor Growth by Specific Inhibition of Cyclin-Dependent Kinase 4/6
Authors: Baughn Linda B. , Di Liberto Maurizio , Wu Kaida , Toogood Peter L. , Louie Tracey , Gottschalk Rachel , Niesvizky Ruben , Cho Hearn , Ely Scott , Moore Malcolm A.S. , Chen-Kiang Selina 
Published: August 2006

Abstract
Cell cycle deregulation is central to the initiation and fatality of multiple myeloma, the second most common hematopoietic cancer, although impaired apoptosis plays a critical role in the accumulation of myeloma cells in the bone marrow. The mechanism for intermittent, unrestrained proliferation of myeloma cells is unknown, but mutually exclusive activation of cyclin-dependent kinase 4 (Cdk4)-cyclin D1 or Cdk6-cyclin D2 precedes proliferation of bone marrow myeloma cells in vivo. Here, we show that by specific inhibition of Cdk4/6, the orally active small-molecule PD 0332991 potently induces G1 arrest in primary bone marrow myeloma cells ex vivo and prevents tumor growth in disseminated human myeloma xenografts. PD 0332991 inhibits Cdk4/6 proportional to the cycling status of the cells independent of cellular transformation and acts in concert with the physiologic Cdk4/6 inhibitor p18INK4c. Inhibition of Cdk4/6 by PD 0332991 is not accompanied by induction of apoptosis. However, when used in combination with a second agent, such as dexamethasone, PD 0332991 markedly enhances the killing of myeloma cells by dexamethasone. PD 0332991, therefore, represents the first promising and specific inhibitor for therapeutic targeting of Cdk4/6 in multiple myeloma and possibly other B-cell cancers. (Cancer Res 2006; 66(15): 7661-7)
PIK3CA Mutations Are an Early Genetic Alteration Associated with FGFR3 Mutations in Superficial Papillary Bladder Tumors
Authors: López-Knowles Elena , Hernández Silvia , Malats Núria , Kogevinas Manolis , Lloreta Josep , Carrato Alfredo , Tardón Adonina , Serra Consol , Real Francisco X. ,   EPICURO Study Group Investigators
Published: August 2006

Abstract
Bladder tumors constitute a very heterogeneous disease. Superficial tumors are characterized by a high prevalence of FGFR3 mutations and chromosome 9 alterations. High-grade and muscle-invasive tumors are characterized by Tp53 mutations and aneuploidy. We have analyzed the sequence of exons 9 and 20 of PIK3CA in a panel of bladder tumors covering the whole spectrum of the disease. DNA from formalin-fixed, paraffin-embedded tumor sections was amplified by PCR and products were sequenced. In an unselected panel of tumors representative of the disease, the PIK3CA mutation prevalence was 13% (11 of 87). Mutations occurred mainly at the previously identified hotspots (codons 542, 545, 1007, and 1047). The distribution according to stage was as follows: papillary urothelial neoplasms of uncertain malignant potential (PUNLMP; 11 of 43, 25.6%), Ta (9 of 57, 16%), T1 (2 of 10, 20%), and muscle-invasive tumors (0 of 20, 0%; P = 0.019). Mutations were associated with low-grade tumors: grade 1 (6 of 27, 22.2%), grade 2 (3 of 23, 13%), and grade 3 (2 of 37, 5.4%; P = 0.047). Overall, PIK3CA mutations were strongly associated with FGFR3 mutations: 18 of 69 (26%) FGFR3mut tumors were PIK3CAmut, versus 4 of 58 (6.9%) FGFR3wt tumors (P = 0.005). Our findings indicate that PIK3CA mutations are a common event that can occur early in bladder carcinogenesis and support the notion that papillary and muscle-invasive tumors arise through different molecular pathways. PIK3CA may constitute a novel diagnostic and prognostic tool, as well as a therapeutic target, in bladder cancer. (Cancer Res 2006; 66(15): 7401-4)
ROS Fusion Tyrosine Kinase Activates a SH2 Domain–Containing Phosphatase-2/Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Signaling Axis to Form Glioblastoma in Mice
Authors: Charest Al , Wilker Erik W. , McLaughlin Margaret E. , Lane Keara , Gowda Ram , Coven Shanie , McMahon Kevin , Kovach Steven , Feng Yun , Yaffe Michael B. , Jacks Tyler , Housman David 
Published: August 2006

Abstract
Glioblastoma multiforme is the most common and lethal form of primary brain cancer. Diagnosis of this advanced glioma has a poor prognosis due to the ineffectiveness of current therapies. Aberrant expression of receptor tyrosine kinases (RTK) in glioblastoma multiformes is suggestive of their role in initiation and maintenance of these tumors of the central nervous system. In fact, ectopic expression of the orphan RTK ROS is a frequent event in human brain cancers, yet the pathologic significance of this expression remains undetermined. Here, we show that a glioblastoma-associated, ligand-independent rearrangement product of ROS (FIG-ROS) cooperates with loss of the tumor suppressor gene locus Ink4a;Arf to produce glioblastomas in the mouse. We show that this FIG-ROS-mediated tumor formation in vivo parallels the activation of the tyrosine phosphatase SH2 domain–containing phosphatase-2 (SHP-2) and a phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling axis in tumors and tumor-derived cell lines. We have established a fully penetrant preclinical model for adult onset of glioblastoma multiforme in keeping with major genetic events observed in the human disease. These findings provide novel and important insights into the role of ROS and SHP-2 function in solid tumor biology and set the stage for preclinical testing of targeted therapeutic approaches. (Cancer Res 2006; 66(15): 7473-81)
Comparable Wages, Inflation, and School Finance Equity
Authors: Taylor Lori L. 
Published: August 2006

A ComparableWage Index (CWI) is an attractive mechanism for measuring geographic variations in the cost of education. A CWImeasures uncontrollable variations in educator pay by observing systematic variations in the earnings of comparable workers who are not educators. Together, the 2000 census and the Occupational Employment Statistics survey support the construction of just such an index. The resulting panel of index values measures wage levels in all parts of the United States from 1997 through 2004 and reveals substantial variation in purchasing power both across school districts and across time. Such inequalities undermine the equity and adequacy goals of school finance formulas. If states were successfully directing additional resources to school districts in high-cost environments, then measured inequality within states should fall when differences in purchasing power are taken into account. Instead, cost adjustment widens the spending gap in all but a handful of states.
Art, Prophecy, and Drama in the Choir of Salisbury Cathedral
Authors: Reeve Matthew 
Published: August 2006

AbstractThe former painted cycle over the vaults of Salisbury Cathedral represents one of the great losses of thirteenth-century English art. This paper focuses on the imagery over the three-bay choir, which features twentyfour Old Testament kings and prophets each holding scrolls with texts prefiguring the Coming of Christ. The content of the cycle derives from a sermon, well known in the Middle Ages, by Pseudo-Augustine: Contra Judaeos, Paganos et Arianos. Yet the most immediate sources lie in twelfth and thirteenth-century extrapolations of the Pseudo-Augustinian sermon in liturgical drama, the so-called Ordo Prophetarum, or prophet plays. This observation leads to a discussion of the relationship of imagery to its liturgical setting. It is argued that the images on the choir vaults were also to be understood allegorically as types of the cathedral canons, who originally sat in the choir stalls below. A reading of the choir as a place of prophecy is located within traditions of liturgical commentary, which allegorize processions through churches as processions through Christian history. This leads to a discussion of the allegorization of the church interior in the Gothic period.
Shadows and Illuminations: Spiritual Journeys to the Dark Side in "Young Goodman Brown" and Eyes Wide Shut
Authors: Neary John 
Published: August 2006

AbstractThe illuminating spiritual journey to wholeness—to "God"—can be fruitfully described as a journey into darkness. Both Christian and Buddhist writers present visions of a trek down into the valley of cares and concerns, or of a "wisdom of no escape" that gently accepts an "interesting, smelly, rich, fertile mess of stuff" to suggest the value of an encounter with darkness. This is related to Paul Tillich's call for a descent to depth, or to Michael Himes's claim that a sacramental imagination sees "what is there" in the wonderful worldly mess rather than rising above it to an ethereal mountaintop. Shadows and illuminations are not separate.Nathaniel Hawthorne's short story "Young Goodman Brown" and Stanley Kubrick's film Eyes Wide Shut are artistic depictions of such a spiritual journey to the dark side. In each case, an initially naive protagonist undergoes a dark adventure that breaks down his naiveté and forces him to confront depth, in Tillich's sense. But each digests his experience differently. The protagonist of Eyes Wide Shut gives up his stubborn certainties for a humble, uncertain, spiritually "silent" openness to the world and to his wife; the protagonist of "Young Goodman Brown," however, returns to his frozen certainties and ends up bitter and despairing. And yet, just as shadows and illuminations cannot be fully dichotomized, perhaps even these different kinds of endings are mutual supplements rather than opposites; perhaps each ending needs to be respected as a variation on the fragile human responses to a spiritual journey.
Measurement of Turbulent Kinetic Energy Dissipation Rate with a Lagrangian Float
Authors: Lien Ren-Chieh , D'Asaro Eric A. 
Published: August 2006

Abstract
This study tests the ability of a neutrally buoyant float to estimate the dissipation rate of turbulent kinetic energy ɛ from its vertical acceleration spectrum using an inertial subrange method. A Lagrangian float was equipped with a SonTek acoustic Doppler velocimeter (ADV), which measured the vector velocity 1 m below the float's center, and a pressure sensor, which measured the float's depth. Measurements were taken in flows where estimates of ɛ varied from 10−8 to 10−3 W kg−1. Previous observational and theoretical studies conclude that the Lagrangian acceleration spectrum is white within the inertial subrange with a level proportional to ɛ. The size of the Lagrangian float introduces a highly reproducible spectral attenuation at high frequencies. Estimates of the dissipation rate of turbulent kinetic energy using float measurements ɛfloat were obtained by fitting the observed spectra to a model spectrum that included the attenuation effect. The ADV velocity measurements were converted to a wavenumber spectrum using a variant of Taylor's hypothesis. The spectrum exhibited the expected −5/3 slope within an inertial subrange. The turbulent kinetic energy dissipation rate ɛADV was computed from the level of this spectrum. These two independent estimates, ɛADV and ɛfloat, were highly correlated. The ratio ɛfloat/ɛADV deviated from one by less than a factor of 2 over the five decades of ɛ measured. This analysis confirms that ɛ can be estimated reliably from Lagrangian float acceleration spectra in turbulent flows. For the meter-sized floats used here, the size of the float and the noise level of the pressure measurements sets a lower limit of ɛfloat &gt; 10−8 W kg−1.
Derivation of the Water Vapor Content from the GNSS Radio Occultations Observations
Authors: Vespe Francesco , Persia Teresa 
Published: August 2006

Abstract
The present work investigates the possibility of retrieving humidity using the bending angle data obtained from radio occultation of GPS signals without additional external information. In particular, with the proposed approach, the dry pressure profiles are obtained by fitting the bending angles of the outer-troposphere layers (from h = h250K up to the stratopause) using the Hopfield dry atmosphere model. The ground pressure and temperature are the parameters of the model to be estimated. In the second step the humidity profiles are extracted by subtracting the contribution resulting from the dry atmosphere from the measured bending angles. Such derivation implies a complex mathematical treatment of the relationship between the bending angle and the refractivity, which is fully explained herein. Furthermore, the method was applied on Challenging Minisatellite Payload (CHAMP) profiles. The CHAMP profiles are achieved by applying heuristic retrieval algorithms based on the canonical transform. The algorithms are applied to minimize the negative refractivity bias that is observed for low-latitude GNSS RO. Thus, the results are shown and discussed in the second part of the paper. Finally, it is widely discussed how the proposed method is able to retrieve refractivity profiles without using the Abel inversion.
One-Lag Estimators for Cross-Polarization Measurements
Authors: Melnikov Valery M. 
Published: August 2006

AbstractEstimators of the linear depolarization ratio (LDR) and cross-polarization correlation coefficients (ρxh) free from noise biases are devised. The estimators are based on the 1-lag correlation functions. The 1-lag estimators can be implemented with radar with simultaneous reception of copolar and cross-polar returns. Absence of noise biases makes the 1-lag estimators useful in eliminating variations of the system gain and in observations of heavy precipitation with enhanced thermal radiation. The 1-lag estimators allow for measurements at lower signal-to-noise ratios than the conventional algorithms.The statistical biases and standard deviations of 1-lag estimates are obtained via the perturbation analysis. It is found that both the 1-lag and conventional estimates of ρxh experience strong statistical biases at ρxh less than 0.3 (i.e., at low canting angles of oblate hydrometeors), and a procedure to correct for this bias is proposed.
Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton
Authors: Kalfa Theodosia A. , Pushkaran Suvarnamala , Mohandas Narla , Hartwig John H. , Fowler Velia M. , Johnson James F. , Joiner Clinton H. , Williams David A. , Zheng Yi 
Published: August 2006

AbstractActin oligomers are a significant structural component of the erythrocyte cytoskeleton. Rac1 and Rac2 GTPases regulate actin structures and have multiple overlapping as well as distinct roles in hematopoietic cells; therefore, we studied their role in red blood cells (RBCs). Conditional gene targeting with a loxP-flanked Rac1 gene allowed Crerecombinase–induced deletion of Rac1 on a Rac2 null genetic background. The Rac1–/–;Rac2–/– mice developed microcytic anemia with a hemoglobin drop of about 20% and significant anisocytosis and poikilocytosis. Reticulocytes increased more than 2-fold. Rac1–/–;Rac2–/– RBCs stained with rhodamine-phalloidin demonstrated F-actin meshwork gaps and aggregates under confocal microscopy. Transmission electron microscopy of the cytoskeleton demonstrated junctional aggregates and pronounced irregularity of the hexagonal spectrin scaffold. Ektacytometry confirmed that these cytoskeletal changes in Rac1–/–;Rac2–/– erythrocytes were associated with significantly decreased cellular deformability. The composition of the cytoskeletal proteins was altered with an increased actin-to-spectrin ratio and increased phosphorylation (Ser724) of adducin, an F-actin capping protein. Actin and phosphorylated adducin of Rac1–/–;Rac2–/– erythrocytes were more easily extractable by Triton X-100, indicating weaker association to the cytoskeleton. Thus, deficiency of Rac1 and Rac2 GTPases in mice alters actin assembly in RBCs and causes microcytic anemia with reticulocytosis, implicating Rac GTPases as dynamic regulators of the erythrocyte cytoskeleton organization.
Apoptotic cell thrombospondin-1 and heparin-binding domain lead to dendritic-cell phagocytic and tolerizing states
Authors: Krispin Alon , Bledi Yaniv , Atallah Mizhir , Trahtemberg Uriel , Verbovetski Inna , Nahari Efrat , Zelig Orly , Linial Michal , Mevorach Dror 
Published: August 2006

AbstractApoptotic cells were shown to induce dendritic cell immune tolerance. We applied a proteomic approach to identify molecules that are secreted from apoptotic monocytes, and thus may mediate engulfment and immune suppression. Supernatants of monocytes undergoing apoptosis were collected and compared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and differentially expressed proteins were identified using tandem mass spectrometry. Thrombospondin-1 (TSP-1) and its cleaved 26-kDa heparin-binding domain (HBD) were identified. We show that TSP-1 is expressed upon induction of monocyte apoptosis in a caspase-dependent pattern and the HBD is cleaved by chymotrypsin-like serine protease. We further show that CD29, CD36, CD47, CD51, and CD91 simultaneously participate in engulfment induction and generation of an immature dendritic cell (iDC) tolerogenic and phagocytic state. We conclude that apoptotic cell TSP-1, and notably its HBD, creates a signalosome in iDCs to improve engulfment and to tolerate engulfed material prior to the interaction with apoptotic cells.
Heat shock protein expression in canine malignant mammary tumours
Authors: Romanucci Mariarita , Marinelli Alessia , Sarli Giuseppe , Salda Leonardo Della 
Published: August 2006

AbstractBackgroundAbnormal levels of Heat Shock Proteins (HSPs) have been observed in many human neoplasms including breast cancer and it has been demonstrated that they have both prognostic and therapeutic implications. In this study, we evaluated immunohistochemical expression of HSPs in normal and neoplastic canine mammary glands and confronted these results with overall survival (OS), in order to understand the role of HSPs in carcinogenesis and to establish their potential prognostic and/or therapeutic value.MethodsImmunohistochemical expression of Hsp27, Hsp72, Hsp73 and Hsp90 was evaluated in 3 normal canine mammary glands and 30 malignant mammary tumours (10in situcarcinomas, 10 invasive carcinomas limited to local structures without identifiable invasion of blood or lymphatic vessels, 10 carcinomas with invasion of blood or lymphatic vessels and/or metastases to regional lymph nodes). A semi-quantitative method was used for the analysis of the results.ResultsWidespread constitutive expression of Hsp73 and Hsp90 was detected in normal tissue, Hsp72 appeared to be focally distributed and Hsp27 showed a negative to rare weak immunostaining. In mammary tumours, a significant increase in Hsp27 (P < 0.01), Hsp72 (P < 0.05) and Hsp90 (P < 0.01) expression was observed as well as a significant reduction in Hsp73 (P < 0.01) immunoreactivity compared to normal mammary gland tissue. Hsp27 demonstrated a strong positivity in infiltrating tumour cells and metaplastic squamous elements of invasive groups. High Hsp27 expression also appeared to be significantly correlated to a shorter OS (P = 0.00087). Intense immunolabelling of Hsp72 and Hsp73 was frequently detected in infiltrative or inflammatory tumour areas. Hsp90 expression was high in all tumours and, like Hsp73, it also showed an intense positivity in lymphatic emboli.ConclusionThese results suggest that Hsp27, Hsp72 and Hsp90 are involved in canine mammary gland carcinogenesis. In addition, Hsp27 appears to be implicated in tumour invasiveness and its high immunodetection in invasive tumours is indicative of a poorer clinical outcome.
Physical activity is related to quality of life in older adults
Authors: Acree Luke S , Longfors Jessica , Fjeldstad Anette S , Fjeldstad Cecilie , Schank Bob , Nickel Kevin J , Montgomery Polly S , Gardner Andrew W 
Published: August 2006

Abstract

Background
Physical activity is associated with health-related quality of life (HRQL) in clinical populations, but less is known whether this relationship exists in older men and women who are healthy. Thus, this study determined if physical activity was related to HRQL in apparently healthy, older subjects.

Methods
Measures were obtained from 112 male and female volunteers (70 ± 8 years, mean ± SD) recruited from media advertisements and flyers around the Norman, Oklahoma area. Data was collected using a medical history questionnaire, HRQL from the Medical Outcomes Survey short form-36 questionnaire, and physical activity level from the Johnson Space Center physical activity scale. Subjects were separated into either a higher physically active group (n = 62) or a lower physically active group (n = 50) according to the physical activity scale.

Results
The HRQL scores in all eight domains were significantly higher (p < 0.05) in the group reporting higher physical activity. Additionally, the more active group had fewer females (44% vs. 72%, p = 0.033), and lower prevalence of hypertension (39% vs. 60%, p = 0.041) than the low active group. After adjusting for gender and hypertension, the more active group had higher values in the following five HRQL domains: physical function (82 ± 20 vs. 68 ± 21, p = 0.029), role-physical (83 ± 34 vs. 61 ± 36, p = 0.022), bodily pain (83 ± 22 vs. 66 ± 23, p = 0.001), vitality (74 ± 15 vs. 59 ± 16, p = 0.001), and social functioning (92 ± 18 vs. 83 ± 19, p = 0.040). General health, role-emotional, and mental health were not significantly different (p > 0.05) between the two groups.

Conclusion
Healthy older adults who regularly participated in physical activity of at least moderate intensity for more than one hour per week had higher HRQL measures in both physical and mental domains than those who were less physically active. Therefore, incorporating more physical activity into the lifestyles of sedentary or slightly active older individuals may improve their HRQL.