bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Mechanisms in the Regulation of Phosphorus Homeostasis
Authors: Berndt Theresa , Kumar Rajiv
Published: February 2009

Phosphorus plays a critical role in diverse biological processes, and, therefore, the regulation of phosphorus balance and homeostasis are critical to the well being of the organism. Changes in environmental, dietary, and serum concentrations of inorganic phosphorus are detected by sensors that elicit changes in cellular function and alter the efficiency by which phosphorus is conserved. Short-term, post-cibal responses that occur independently of hormones previously thought to be important in phosphorus homeostasis may play a larger role than previously appreciated in the regulation of phosphorus homeostasis. Several hormones and regulatory factors such as the vitamin D endocrine system, parathyroid hormone, and the phosphatonins (FGF-23, sFRP-4, MEPE) among others, may play a role only in the long-term regulation of phosphorus homeostasis. In this review, we discuss how organisms sense changes in phosphate concentrations and how changes in hormonal factors result in the conservation or excretion of phosphorus.
Structural and Mössbauer Spectral Studies of Nanosized Aluminum Doped Manganese Zinc Ferrites
Authors: Dhiman R. L. , Taneja S. P. , Reddy V. R.
Published: February 2009

Nanoparticles of aluminum-substituted manganese zinc ferrites,Mn1.05Zn0.05AlxFe1.9−xO4with0.4≤x≤1.0were synthesized by solid-state reaction route and characterized by XRD, TEM, and Mössbauer spectroscopy measurements. The particle size is found to very from 46 to 28 nm with increase of aluminum ions concentration. The unit cell parameter “aO” is found to decrease linearly with aluminum ions concentration due to smaller ionic radius of aluminum. The cation distributions were estimated from X-ray diffraction intensities of various planes. The theoretical lattice parameter, bulk density, porosity, X-ray density, oxygen positional parameter, ionic radii, jump length, as well as bonds and edges lengths of the tetrahedral (A-) and octahedral (B-) sites were determined.Fe57Mössbauer spectra recorded at room temperature were fitted with two sextets corresponding toFe3+ions at tetrahedral (A-) and octahedral (B-) sites. The magnetic hyperfine fields at A- and B-sites show a gradual decrease with increase ofAl3+ion concentration, which has been explained on the basis of supertransferred hyperfine field. The cation distribution obtained from X-ray intensities and Mössbauer data indicates a decrease inFe3+(B)/Fe3+(A)ratio with increasing aluminum concentration thereby suggesting a decrease in ferrimagnetic behavior.
Insulin Receptor Substrate-2 Mediated Insulin-like Growth Factor-I Receptor Overexpression in Pancreatic Adenocarcinoma through Protein Kinase Cδ
Authors: Kwon Junhye , Stephan Susann , Mukhopadhyay Ananya , Muders Michael H. , Dutta Shamit K. , Lau Julie S. , Mukhopadhyay Debabrata
Published: February 2009

Pancreatic adenocarcinoma (PCA) is an almost invariably fatal disease. Recently, it has been shown by several groups as well as ours that insulin-like growth factor-I receptor (IGF-IR) overexpression is related to higher proliferation, survival, angiogenesis, and highly invasive pancreatic tumors. Several studies have been carried out to understand the pathways that lead to growth factor–mediated signaling, but the molecular mechanism of receptor overexpression remains mostly unknown. Treatment with neutralizing antibodies or a specific kinase inhibitor against IGF-IR could block the receptor expression in PCA cells. Furthermore, we also showed that insulin receptor substrate (IRS)-2, but not IRS-1, is involved in regulation of IGF-IR expression, which is most likely not transcriptional control. By blocking mammalian target of rapamycin (mTOR) pathway with rapamycin as well as other biochemical analysis, we defined a unique regulation of IGF-IR expression mediated by protein kinase Cδ (PKCδ) and mTOR pathway. Moreover, we showed that the down-regulation of IGF-IR expression due to IRS-2 small interfering RNA can be compensated by overexpression of dominant-active mutant of PKCδ, suggesting that PKCδ is downstream of IGF-IR/IRS-2 axis. Overall, these findings suggest a novel regulatory role of IRS-2 on the expression of IGF-IR through PKCδ and mTOR in pancreatic cancer cells. [Cancer Res 2009;69(4):1350–7]
Expression of Human Organic Cation Transporter 3 in Kidney Carcinoma Cell Lines Increases Chemosensitivity to Melphalan, Irinotecan, and Vincristine
Authors: Shnitsar Volodymyr , Eckardt Ronny , Gupta Shivangi , Grottker Julia , Müller Gerhard A. , Koepsell Hermann , Burckhardt Gerhard , Hagos Yohannes
Published: February 2009

Renal cell carcinoma (RCC) is usually chemoresistant. This chemoresistance could be overcome if specific cytostatics are applied for which the RCC expresses an uptake transporter. In the present study, we investigated the expression of solute carrier (SLC) transporters in different RCC lines and their ability to interact with chemotherapeutics. We tested five RCC lines for the expression of different SLCs by reverse transcription-PCR and TaqMan real-time PCR. In two of five RCC lines, A498 and 7860, we observed a highly significant expression of SLC22A3 (hOCT3). Uptake of the organic cation [3H]MPP (4-methyl-pyridinium iodide) into these cells and also into hOCT3 stably transfected Chinese hamster ovary (CHO) cells was inhibited by irinotecan, vincristine, and melphalan. The Ki values [determined from Dixon plots] for irinotecan, vincristine, and melphalan were 1.72 ± 0.45 μmol/L, 17 ± 4.81 μmol/L, and 366 ± 51 μmol/L, respectively. Cytotoxic activities of the selected drugs were tested by [3H]thymidine incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays on CHO-hOCT3, A498 (high expression of hOCT3), and ACHN cell lines (low expression of hOCT3). The growth of CHO-hOCT3 was inhibited by 20% more with irinotecan and by 50% more with vincristine compared with nontransfected CHO cells. Melphalan produced 20% to 30% more inhibition in hOCT3-expressing cells compared with nonexpressing control cells. Similar results were obtained for A498 and ACHN cells. Thus, our data support the hypothesis that the sensitivity of tumor cells to chemotherapeutic treatment depends on the expression of transporter proteins mediating specific drug accumulation into target cells. [Cancer Res 2009;69(4):1494–501]
Correlation Analysis between Single-Nucleotide Polymorphism and Expression Arrays in Gliomas Identifies Potentially Relevant Target Genes
Authors: Kotliarov Yuri , Kotliarova Svetlana , Charong Nurdina , Li Aiguo , Walling Jennifer , Aquilanti Elisa , Ahn Susie , Steed Mary Ellen , Su Qin , Center Angela , Zenklusen Jean C. , Fine Howard A.
Published: February 2009

Primary brain tumors are a major cause of cancer mortality in the United States. Therapy for gliomas, the most common type of primary brain tumors, remains suboptimal. The development of improved therapeutics will require greater knowledge of the biology of gliomas at both the genomic and transcriptional levels. We have previously reported whole genome profiling of chromosome copy number alterations (CNA) in gliomas, and now present our findings on how those changes may affect transcription of genes that may be involved in tumor induction and progression. By calculating correlation values of mRNA expression versus DNA copy number average in a moving window around a given RNA probe set, biologically relevant information can be gained that is obscured by the analysis of a single data type. Correlation coefficients ranged from −0.6 to 0.7, highly significant when compared with previous studies. Most correlated genes are located on chromosomes 1, 7, 9, 10, 13, 14, 19, 20, and 22, chromosomes known to have genomic alterations in gliomas. Additionally, we were able to identify CNAs whose gene expression correlation suggests possible epigenetic regulation. This analysis revealed a number of interesting candidates such as CXCL12, PTER, and LRRN6C, among others. The results have been verified using real-time PCR and methylation sequencing assays. These data will further help differentiate genes involved in the induction and/or maintenance of the tumorigenic process from those that are mere passenger mutations, thereby enriching for a population of potentially new therapeutic molecular targets. [Cancer Res 2009;69(4):1596–603]
Suppressor of Cytokine Signaling 3 Promotes Bone Marrow Cells to Differentiate into CD8+ T Lymphocytes in Lung Tissue via Up-Regulating Notch1 Expression
Authors: Zhang Zhuohan , Zeng Bin , Zhang Zhiqian , Jiao Guohui , Li Haijie , Jing Zhizi , Ouyang Jiangbo , Yuan Xin , Chai Limin , Che Yongzhe , Zhang Yuan , Yang Rongcun
Published: February 2009

Suppressor of cytokine signaling 3 (SOCS3) expression in bone marrow cells (BMC) was up-regulated upon exposure to interleukin 6, lipopolysaccharide, or tumor-associated factors. But, how the up-regulated SOCS3 affects differentiation of BMCs is incompletely characterized. Here, we showed that SOCS3 promoted BMCs to intently differentiate into CD8 T cells. Importantly, lung can be as one athymus tissue for the BMCs to differentiate into CD8+ T cells. Notch1 plays a critical role in the differentiation from SOCS3-transfected BMCs to CD8+ T cells. We conclude that the up-regulated SOCS3 in some pathologic conditions, such as tumor and inflammation, might promote BMCs to differentiate into CD8+ T lymphocytes in lung tissue via up-regulating Notch1 expression. This may represent a new mechanism against diseases such as tumor. [Cancer Res 2009;69(4):1578–86]
Effective Immunotherapy against Murine Gliomas Using Type 1 Polarizing Dendritic Cells—Significant Roles of CXCL10
Authors: Fujita Mitsugu , Zhu Xinmei , Ueda Ryo , Sasaki Kotaro , Kohanbash Gary , Kastenhuber Edward R. , McDonald Heather A. , Gibson Gregory A. , Watkins Simon C. , Muthuswamy Ravikumar , Kalinski Pawel , Okada Hideho
Published: February 2009

In an attempt to develop effective vaccines against central nervous system (CNS) tumors, we evaluated the ability of vaccines with standard dendritic cells (DC) versus type 1 polarizing DCs (DC1) to induce glioma-specific type 1 CTLs with CNS tumor-relevant homing properties and the mechanism of their action. C57BL/6 mouse–derived bone marrow cells were cultured with mouse granulocyte/macrophage colony-stimulating factor (GM-CSF) for 6 days, and CD11c+ cells were subsequently cultured with GM-CSF, rmIFN-γ, rmIFN-α, rmIL-4, and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose for 24 hours to generate DC1s. In analogy to their human counterparts, mouse DC1s exhibited surface marker profiles of mature DCs and produced high levels of IL-12 and CXCL10. Importantly for their application as cancer vaccines, such DC1s stably retained their type 1 phenotype even when exposed to type 2–promoting or regulatory T cell (Treg)–promoting environments. Consistently, mouse DC1s induced antigen-specific type 1 CTLs more efficiently than nonpolarized DCs in vitro. DC1s given s.c. migrated into draining lymph nodes, induced antigen-specific CTLs, and suppressed Treg accumulation. In addition, s.c. immunization with DC1s loaded with glioma-associated antigen (GAA)–derived CTL epitope peptides prolonged the survival of CNS GL261 glioma-bearing mice, which was associated with efficient CNS glioma homing of antigen-specific CTLs. Intratumoral injections of GAA peptide-loaded DC1s further enhanced the anti-CNS glioma effects of DC1-based s.c. immunization. Interestingly, the antitumor functions were abrogated with CXCL10−/− mouse–derived DC1s. Collectively, these findings show the anti-CNS glioma effects of DC1-based therapy and a novel role of CXCL10 in the immunologic and therapeutic activity of DC-based cancer vaccines. [Cancer Res 2009;69(4):1587–95]
A High Throughput, Whole Cell Screen for Small Molecule Inhibitors of the Mitotic Spindle Checkpoint Identifies OM137, a Novel Aurora Kinase Inhibitor
Authors: DeMoe Joanna H. , Santaguida Stefano , Daum John R. , Musacchio Andrea , Gorbsky Gary J.
Published: February 2009

In mitosis, the kinetochores of chromosomes that lack full microtubule attachments and/or mechanical tension activate a signaling pathway called the mitotic spindle checkpoint that blocks progression into anaphase and prevents premature segregation of the chromatids until chromosomes become aligned at the metaphase plate. The spindle checkpoint is responsible for arresting cells in mitosis in response to chemotherapeutic spindle poisons such as paclitaxel or vinblastine. Some cancer cells show a weakened checkpoint signaling system that may contribute to chromosome instability in tumors. Because complete absence of the spindle checkpoint leads to catastrophic cell division, we reasoned that drugs targeting the checkpoint might provide a therapeutic window in which the checkpoint would be eliminated in cancer cells but sufficiently preserved in normal cells. We developed an assay to identify lead compounds that inhibit the spindle checkpoint. Most cells respond to microtubule drugs by activating the spindle checkpoint and arresting in mitosis with a rounded morphology. Our assay depended on the ability of checkpoint inhibitor compounds to drive mitotic exit and cause cells to flatten onto the substrate in the continuous presence of microtubule drugs. In this study, we characterize one of the compounds, OM137, as an inhibitor of Aurora kinases. We find that this compound is growth inhibitory to cultured cells when applied at high concentration and potentiates the growth inhibitory effects of subnanomolar concentrations of paclitaxel. [Cancer Res 2009;69(4):1509–16]
Galectin-3 Mediates Nuclear β-Catenin Accumulation and Wnt Signaling in Human Colon Cancer Cells by Regulation of Glycogen Synthase Kinase-3β Activity
Authors: Song Shumei , Mazurek Nachman , Liu Chunming , Sun Yunjie , Ding Qing Qing , Liu Kaifeng , Hung Mien-Chie , Bresalier Robert S.
Published: February 2009

Wnt/β-catenin signaling plays an essential role in colon carcinogenesis. Galectin-3, a β-galactoside–binding protein, has been implicated in Wnt signaling, but the precise mechanisms by which galectin-3 modulates the Wnt pathway are unknown. In the present study, we determined the effects of galectin-3 on the Wnt/β-catenin pathway in colon cancer cells, as well as the mechanisms involved. Galectin-3 levels were manipulated in human colon cancer cells by stable transfection of galectin-3 antisense, short hairpin RNA, or full-length galectin-3 cDNA, and effects on β-catenin levels, subcellular distribution, and Wnt signaling were determined. Galectin-3 levels correlated with β-catenin levels in a variety of colon cancer cell lines. Down-regulation of galectin-3 resulted in decreased β-catenin protein levels but no change in β-catenin mRNA levels, suggesting that galectin-3 modulates β-catenin by another mechanism. Reduction of galectin-3 led to reduced nuclear β-catenin with a concomitant decrease in TCF4 transcriptional activity and expression of its target genes. Conversely, transfection of galectin-3 cDNA into colon cancer cells increased β-catenin expression and TCF4 transcriptional activity. Down-regulation of galectin-3 resulted in AKT and glycogen synthase kinase-3β (GSK-3β) dephosphorylation and increased GSK activity, increasing β-catenin phosphorylation and degradation. Ly294002, an inhibitor of phosphatidylinositol 3-kinase, and dominant-negative AKT, suppressed TCF4 transcriptional activity induced by galectin-3 whereas LiCl, a GSK-3β inhibitor, increased TCF4 activity, mimicking the effects of galectin-3. These results suggest that galectin-3 mediates Wnt signaling, at least in part, by regulating GSK-3β phosphorylation and activity via the phosphatidylinositol 3-kinase/AKT pathway, and, thus, the degradation of β-catenin in colon cancer cells. [Cancer Res 2009;69(4):1343–9]
Integrated Genome-Wide DNA Copy Number and Expression Analysis Identifies Distinct Mechanisms of Primary Chemoresistance in Ovarian Carcinomas
Authors: Etemadmoghadam Dariush , deFazio Anna , Beroukhim Rameen , Mermel Craig , George Joshy , Getz Gad , Tothill Richard , Okamoto Aikou , Raeder Maria B. ,   AOCS Study Group, Harnett Paul , Lade Stephen , Akslen Lars A. , Tinker Anna V. , Locandro Bianca , Alsop Kathryn , Chiew Yoke-Eng , Traficante Nadia , Fereday Sian , Johnson Daryl , Fox Stephen , Sellers William , Urashima Mitsuyoshi , Salvesen Helga B. , Meyerson Matthew , Bowtell David
Published: February 2009

Purpose: A significant number of women with serous ovarian cancer are intrinsically refractory to platinum-based treatment. We analyzed somatic DNA copy number variation and gene expression data to identify key mechanisms associated with primary resistance in advanced-stage serous cancers.

Experimental Design: Genome-wide copy number variation was measured in 118 ovarian tumors using high-resolution oligonucleotide microarrays. A well-defined subset of 85 advanced-stage serous tumors was then used to relate copy number variation to primary resistance to treatment. The discovery-based approach was complemented by quantitative-PCR copy number analysis of 12 candidate genes as independent validation of previously reported associations with clinical outcome. Likely copy number variation targets and tumor molecular subtypes were further characterized by gene expression profiling.

Results: Amplification of 19q12, containing cyclin E (CCNE1), and 20q11.22-q13.12, mapping immediately adjacent to the steroid receptor coactivator NCOA3, was significantly associated with poor response to primary treatment. Other genes previously associated with copy number variation and clinical outcome in ovarian cancer were not associated with primary treatment resistance. Chemoresistant tumors with high CCNE1 copy number and protein expression were associated with increased cellular proliferation but so too was a subset of treatment-responsive patients, suggesting a cell-cycle independent role for CCNE1 in modulating chemoresponse. Patients with a poor clinical outcome without CCNE1 amplification overexpressed genes involved in extracellular matrix deposition.

Conclusions: We have identified two distinct mechanisms of primary treatment failure in serous ovarian cancer, involving CCNE1 amplification and enhanced extracellular matrix deposition. CCNE1 copy number is validated as a dominant marker of patient outcome in ovarian cancer.
Notch1 mediates growth suppression of papillary and follicular thyroid cancer cells by histone deacetylase inhibitors
Authors: Xiao Xueming , Ning Li , Chen Herbert
Published: February 2009

Notch1 is a multifunctional transmembrane receptor that regulates cellular differentiation, development, proliferation, and survival in a variety of contexts. We have previously shown that Notch1 may function as a tumor suppressor and that histone deacetylase (HDAC) inhibitors can induce Notch1 expression in some endocrine cancers. Here, we showed that although there was minimal Notch1 expression in follicular thyroid cancer FTC236 and papillary thyroid cancer DRO cells, transfection of constitutive Notch1 plasmid into these cells led to growth inhibition, down-regulation of cyclin D1, and up-regulation of p21. Treatment of FTC236 cells with HDAC inhibitors valproic acid (1–4 mmol/L) or suberoyl bishydroxamic acid (10–30 μmol/L) induced functional Notch1 protein expression and suppressed cell growth in a dose-dependent manner. Notch1 siRNA interference blocked the antiproliferative effect of HDAC inhibitors. Western blot analysis revealed the reduction of cyclin D1 and the increase of p21 in HDAC inhibitor–treated cells. These results indicate that HDAC inhibitors activate Notch1 signaling in thyroid cancer cells and lead to the suppression of proliferation by cell cycle arrest. Our findings provide the first documentation of the role of Notch1 signaling as a tumor suppressor in DRO and FTC236 cells, suggesting that Notch1 activation may be a potential therapeutic target for papillary and follicular thyroid cancers. [Mol Cancer Ther 2009;8(2):350–6]
Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors
Authors: Forni Claudia , Minuzzo Mario , Virdis Emanuela , Tamborini Elena , Simone Matteo , Tavecchio Michele , Erba Eugenio , Grosso Federica , Gronchi Alessandro , Aman Pierre , Casali Paolo , D'Incalci Maurizio , Pilotti Silvana , Mantovani Roberto
Published: February 2009

Differentiation is a complex set of events that can be blocked by rearrangements of regulatory genes producing fusion proteins with altered properties. In the case of myxoid liposarcoma (MLS) tumors, the causative abnormality is a fusion between the CHOP transcription factor and the FUS or EWS genes. CHOP belongs to and is a negative regulator of the large CAAT/enhancer binding protein family whose α, β,and δ members are master genes of adipogenesis. Recent clinical data indicate a peculiar sensitivity of these tumors to the natural marine compound trabectedin. One hypothesis is that the activity of trabectedin is related to the inactivation of the FUS-CHOP oncogene. We find that trabectedin causes detachment of the FUS-CHOP chimera from targeted promoters. Reverse transcription-PCR and chromatin immunoprecipitation analysis in a MLS line and surgical specimens of MLS patients in vivo show activation of the CAAT/enhancer binding protein–mediated transcriptional program that leads to morphologic changes of terminal adipogenesis. The activity is observed in cells with type 1 but not type 8 fusions. Hence, the drug induces maturation of MLS lipoblasts in vivo by targeting the FUS-CHOP–mediated transcriptional block. These data provide a rationale for the specific activity of trabectedin and open the perspective of combinatorial treatments with drugs acting on lipogenic pathways. [Mol Cancer Ther 2009;8(2):449–57]
Evaluation of Biocompatibility and Cytotoxicity Using Keratinocyte and Fibroblast Cultures
Authors: Wiegand C. , Hipler U.-C.
Published: February 2009

Determination of biocompatibility and cytotoxicity is part of the initial evaluation of medical devices stipulated by ISO standards on biological evaluation of medical devices. Cell culture systems for testing biological reactions to drugs, biomaterials or treatment techniques used in various disciplines have been gaining importance. A wide variety of cell lines are commonly used: cultured fibroblasts from human skin, buccal mucosa, periodontal membrane or embryonic lung; epithelial and HeLa cells; cultures of human keratinocytes and HaCaT cells; different murine cell lines (C3H-L, Balb/c 3T3, L929 and others) as well as murine cells cultured from liver and spleen; T lymphocytes from lymph nodes and macrophages obtained by lavage. All these cells are suitable for the use in biocompatibility tests. Nevertheless, the general opinion is that cytotoxicity tests in vitro will be more convincing when performed with cells that are homologous with the human tissue concerned. In accordance, appropriate cell lines for the use in cytotoxicity and tolerance tests concerning the skin would be human dermal fibroblasts and human epidermal keratinocytes, as they take an active part in the immune response, inflammatory processes and wound healing.
Intrauterine Wachstumsrestriktion und Nierenfunktion – ein Langzeitproblem?
Authors: Dötsch Jörg , Plank Christian
Published: February 2009

Gehäuft ist nach intrauteriner Wachstumsrestriktion (IUGR) ein Auftreten von Nierenfunktionsstörungen im späteren Leben zu beobachten. Hierfür können 2 prinzipielle Entstehungsmodelle beobachtet werden: Einerseits ist nach IUGR eine höhere Prävalenz von Hypertonie und Diabetes mellitus vom Typ 2 belegt – beide Erkrankungen prädisponieren ihrerseits für die Entwicklung einer chronischen Niereninsuffizienz im Erwachsenenalter. Andererseits werden bei einem niedrigen Geburtsgewicht primär renale Veränderungen beobachtet: So ist beispielsweise die Zahl funktionsfähiger Nephrone reduziert. Dies kann langfristig ebenso einen vorzeitigen renalen Funktionsverlust begünstigen. Zudem ist bereits im Kindesalter ein schwererer Verlauf von glomerulären Erkrankungen nach IUGR zu beobachten. So findet sich beim kindlichen nephrotischen Syndrom ein prognostisch ungünstigerer Verlauf und bei der IgA-Nephropathie des Kindes ein höherer Anteil an sklerosierten Glomeruli. Tierexperimentell lässt sich belegen, dass eine erhöhte Entzündungsaktivität und verminderte Regenerationsfähigkeit pathogenetisch zugrunde liegen. Auch zeigt sich, dass nicht nur pränatale, sondern auch postnatale Einflüsse, wie zum Beispiel eine postnatale Hyperalimentation, die Manifestation der renalen Schädigung begünstigen.
The Perception of Prominence Patterns
Authors: Kohler Klaus J.
Published: February 2009

The term ‘stress’ is used to refer to the perceptual salience at certain places in strings of syllables, but it has several different referents: (a) relative syllable salience in an utterance; this is syllable-, not word-oriented; (b) stress in a word; this is part of the lexical phonology; (c) stressing of words in utterances for various aspects of propositional and expressive meaning, often called ‘accent(uation)’. Referents b and c are word- and meaning-oriented. In this article, the terms are more stringently defined. ‘Stress’ is only used to refer to a lexical stress position (referent b), i.e. a syllable in a word that becomes the docking place for various types of ‘accent’ to weight words in utterances (referent c). ‘Stress’ has no physical attributes by itself. ‘Prominence’ refers to the patterns of salience in syllable strings (referent a). The article reports results of an experiment in prominence perception of the logatome baba, in which the physical parameters F0, syllabic duration, and overall acoustic energy were systematically varied across the bisyllable. Sixteen German subjects had to indicate, by pressing buttons of a computerized reaction time device, whether the first or the second syllable was more prominent. F0 was a more powerful cue than the other two. Equal syllable duration on a monotone resulted in more first-syllable judgements, which could be counteracted by a slightly falling F0 contour on the second syllable to reach equal response frequencies for the two syllables. This ties in with Lehiste’s earlier findings that F0 movement increases the perception of duration. Extrapolating from the results, a research programme for prominence perception is developed that will eventually shed new light on the investigation into the nature and manifestation of speech rhythm.
Vascular Leak in a Rat Model of Preeclampsia
Authors: Uddin Mohammad N. , McLean Luciana B. , Hunter Felicia A. , Horvat Darijana , Severson Judson , Tharakan Binu , Childs Ed W. , Puschett Jules B.
Published: February 2009

Background/Aims: Preeclampsia is a hypertensive disorder which develops de novo in women during pregnancy. The urinary excretion of the cardiotonic steroid, marinobufagenin (MBG), is increased prior to the development of hypertension. Preeclamptic patients are volume expanded but much of the excess salt and water appears to be located primarily in the interstitial space. Therefore, ‘capillary leak’ syndrome has been postulated in this disorder. Methods: We evaluated the vascular leakage in normal rats following MBG injection and in a rat model of human preeclampsia. We measured the changes in light intensity comparing that in the intravascular to the extravascular space by assessing ‘leak’ of fluorescein-labeled albumin (FITC-albumin) from mesenteric postcapillary venules. Results: FITC-albumin extravasation continued to increase in a time-dependent fashion after MBG infusion and was significant (p < 0.05) at 60 min of observation when compared to sham rats. We also observed a significant difference in ‘vascular leakage’ in preeclamptic rats compared to control non-pregnant and normal pregnant groups starting at 20 min after the FITC-albumin infusion. Conclusion: We propose that MBG is involved in the production of a ‘vascular leak’ in our rat model of preeclampsia.
Long-Term Use of Low-Molecular-Weight Heparin in Hemodialysis Patients: A 7-Year Experience
Authors: Bernieh B. , Boobes Y. , Al Hakim M.R. , Abouchacra S. , Dastoor H.
Published: February 2009

Background: Low-molecular-weight-heparin (LMWH) is not routinely used as anticoagulant in hemodialysis (HD). The ideal dose and the safety of long-term use are not known. Methods: A prospective three-phase interventional study. Phase 1 involved dose titration, phase 2 safety and efficacy and phase 3 routine practice. Results: During 7 years of the use of the LMWH enoxaparin (EN), 236 patients were treated with a total number of 60,987 HD sessions. The mean dose used during the titration phase was 0.43 ± 0.16 mg/kg/session, which was subsequently reduced in phase 3 to 0.36 ± 0.14 mg/kg/session. The long-term effects of EN on the platelet count and lipid profile were comparable to unfractionated heparin. Conclusion: The long-term use of LMWH (EN) with a reduced dose in HD is practical and safe.
Morning-to-Afternoon Evolution of Marine Stratus Polluted by Underlying Ships: Implications for the Relative Lifetimes of Polluted and Unpolluted Clouds
Authors: Christensen Matthew W. , Coakley James A. , Tahnk William R.
Published: February 2009

Ship tracks appearing in both the morning and afternoon Moderate Resolution Imaging Spectroradiometer (MODIS) imagery for the Pacific Ocean off the west coast of the United States were used to study the morning-to-afternoon evolution of marine stratus polluted by underlying ships and nearby uncontaminated stratus. Analyzed 925-hPa winds were used to predict the afternoon positions of ship tracks found in the morning imagery. Droplet effective radii, visible optical depths, and liquid water amounts were analyzed for morning and afternoon clouds that, based on the low-level winds, were taken to be the same clouds. As found in a previous study by Segrin et al., both morning and afternoon polluted clouds had smaller droplet radii, larger optical depths, and smaller liquid water amounts than the nearby unpolluted clouds. In contrast to the Segrin et al. study, however, the droplet effective radii decreased significantly from morning to afternoon in both the polluted and unpolluted clouds, with the rate of decrease being twice as large for the unpolluted clouds. The larger decrease in the unpolluted clouds is thought to be caused by drizzle, which is probably absent in the polluted clouds. The observations suggest that, with their slower rate of liquid loss, polluted clouds could have longer lifetimes than their unpolluted counterparts. Of interest is that clouds with similar droplet radii but smaller optical depths, and thus smaller droplet number concentrations and liquid water amounts, exhibited higher sensitivities to the effects of elevated particle concentrations and a greater likelihood of appearing in both the morning and afternoon satellite overpasses.
Revisiting the Thermocline Depth in the Equatorial Pacific*
Authors: Yang Haijun , Wang Fuyao
Published: February 2009

The thermocline depth is defined as the depth of the maximum vertical temperature gradient. In the equatorial Pacific, the depth of 20°C isotherm is widely used to represent the thermocline depth. This work proposes that under the circumstance of a significant mean climate shift, it is better to use the original definition of the thermocline depth in studying the long-term changes in mean climate and tropical coupled climate variabilities. For instance, during the transient period of global warming, the tropical thermocline is usually enhanced because the surface layer warms more and faster than the lower layers. The depth of maximum vertical temperature gradient shoals, which is consistent with the enhanced thermocline. However, the 20°C isotherm depth deepens, which suggests a weakened thermocline. This discrepancy exists in both the observations and the future climate simulations of coupled models.
Eddy-Driven Buoyancy Gradients on Eastern Boundaries and Their Role in the Thermocline
Authors: Cessi Paola , Wolfe Christopher L.
Published: February 2009

It is demonstrated that eddy fluxes of buoyancy at the eastern and western boundaries maintain alongshore buoyancy gradients along the coast. Eddy fluxes arise near the eastern and western boundaries because on both coasts buoyancy gradients normal to the boundary are strong. The eddy fluxes are accompanied by mean vertical flows that take place in narrow boundary layers next to the coast where the geostrophic constraint is broken. These ageostrophic cells have a velocity component normal to the coast that balances the geostrophic mean velocity. It is shown that the dynamics in these thin ageostrophic boundary layers can be replaced by effective boundary conditions for the interior flow, relating the eddy flux of buoyancy at the seaward edge of the boundary layers to the buoyancy gradient along the coast. These effective boundary conditions are applied to a model of the thermocline linearized around a mean stratification and a state of rest. The linear model parameterizes the eddy fluxes of buoyancy as isopycnal diffusion. The linear model produces horizontal gradients of buoyancy along the eastern coast on a vertical scale that depends on both the vertical diffusivity and the eddy diffusivity. The buoyancy field of the linear model agrees very well with the mean state of an eddy-resolving computation. Because the east–west difference in buoyancy is related to the zonally integrated meridional velocity, the linear model successfully predicts the meridional overturning circulation.
Combined Effects of Wind, Tide, and Horizontal Density Gradients on Stratification in Estuaries and Coastal Seas
Authors: Burchard Hans
Published: February 2009

The aim of this one-dimensional water column study is to combine modified versions of three characteristic parameters for periodic tidal flow under the influence of a longitudinal buoyancy gradient—the horizontal Richardson number, the inverse Strouhal number, and the inverse Ekman number—into a parameter space study, including constant wind forcing from various directions. It is shown how the underlying dynamical equations can be cast into nondimensional form, depending mainly on these three nondimensional parameters plus the relative wind speed and the wind direction. Idealized model simulations are carried out for the whole realistic range of horizontal Richardson and inverse Strouhal numbers for various latitudes, showing the amplitude of the tidally induced stratification for a wide range of scenarios. It is found that classical threshold values for the horizontal Richardson number, indicating the switch from periodic stratification to permanent stratification, are valid only for special cases, and that this switch also strongly depends on the inverse Strouhal number, the inverse Ekman number, and the wind vector. The transverse residual flow is close to the thermal wind balance for a variety of parameters, and nondimensionalized longitudinal residual flow shows the classical estuarine exchange flow pattern with little variation in the near-bed onshore component. Wind straining is confirmed as an important estuarine and coastal process, enhancing estuarine circulation for offshore (down estuary) winds and vice versa. Agreement with field data from Liverpool Bay is good, including the explanation of a flood tide local maximum of the dissipation rate in the upper half of the water column. An equation for the second time derivative of the potential energy anomaly is derived for quantifying the dynamical processes leading to stratification due to the straining of the horizontal density gradient.
Optimal Noise Filtering for the Ionospheric Correction of GPS Radio Occultation Signals
Authors: Sokolovskiy S. , Schreiner W. , Rocken C. , Hunt D.
Published: February 2009

GPS radio occultation remote sensing of the neutral atmosphere requires ionospheric correction of L1 and L2 signals. The ionosphere-corrected variables derived from radio occultation signals—such as the phase, Doppler, and bending angle—are affected by small-scale ionospheric effects that are not completely eliminated by the ionospheric correction. They are also affected by noise from mainly the L2 signal. This paper introduces a simple method for optimal filtering of the L4 = L1 − L2 signal used to correct the L1 signal, which minimizes the combined effects of both the small-scale ionospheric residual effects and L2 noise on the ionosphere-corrected variables. Statistical comparisons to high-resolution numerical weather models from the European Centre for Medium-Range Weather Forecasts (ECMWF) validate that this increases the accuracy of radio occultation inversions in the stratosphere.
The Retrieval of Land Surface Pressure from MERIS Measurements in the Oxygen A Band
Authors: Lindstrot Rasmus , Preusker Rene , Fischer Jürgen
Published: February 2009

Measurements of the Medium-Resolution Imaging Spectrometer (MERIS) on the Environmental Satellite (Envisat) are used for the retrieval of surface pressure above land and ice surfaces. The algorithm is based on the exploitation of gaseous absorption in the oxygen A band at 762 nm. The strength of absorption is directly related to the average photon pathlength, which in clear-sky cases above bright surfaces is mainly determined by the surface pressure, with minor influences from scattering at aerosols.

Sensitivity studies regarding the influences of aerosol optical thickness and scale height and the temperature profile on the measured radiances are presented. Additionally, the sensitivity of the retrieval to the accuracy of the spectral characterization of MERIS is quantified. The algorithm for the retrieval of surface pressure (SPFUB) is presented and validated against surface pressure maps constructed from ECMWF sea level pressure forecasts in combination with digital elevation model data. The accuracy of SPFUB was found to be within 10 hPa above ice surfaces at Greenland and 15 hPa above desert and mountain scenes in northern Africa and southwest Asia. In a case study above Greenland the accuracy of SPFUB could be enhanced to be better than 3 hPa by spatial averaging over areas of 40 km × 40 km.
Blending Sea Surface Temperatures from Multiple Satellites and In Situ Observations for Coastal Oceans
Authors: Chao Yi , Li Zhijin , Farrara John D. , Hung Peter
Published: February 2009

A two-dimensional variational data assimilation (2DVAR) method for blending sea surface temperature (SST) data from multiple observing platforms is presented. This method produces continuous fields and has the capability of blending multiple satellite and in situ observations. In addition, it allows specification of inhomogeneous and anisotropic background correlations, which are common features of coastal ocean flows. High-resolution (6 km in space and 6 h in time) blended SST fields for August 2003 are produced for a region off the California coast to demonstrate and evaluate the methodology. A comparison of these fields with independent observations showed root-mean-square errors of less than 1°C, comparable to the errors in conventional SST observations. The blended SST fields also clearly reveal the finescale spatial and temporal structures associated with coastal upwelling, demonstrating their utility in the analysis of finescale flows. With the high temporal resolution, the blended SST fields are also used to describe the diurnal cycle. Potential applications of this SST blending methodology in other coastal regions are discussed.
Ensemble-Based Estimates of the Predictability of Wind-Driven Coastal Ocean Flow over Topography
Authors: Kim Sangil , Samelson R. M. , Snyder Chris
Published: February 2009

The predictability of coastal ocean circulation over the central Oregon shelf, a region of strong wind-driven currents and variable topography, is studied using ensembles of 50-day primitive equation ocean model simulations with realistic topography, simplified lateral boundary conditions, and forcing from both idealized and observed wind time series representative of the summer upwelling season. The main focus is on the balance, relevant to practical predictability, between deterministic response to known or well-predicted forcing, uncertainty in initial conditions, and sensitivity to instabilities and topographic interactions. Large ensemble and single-simulation variances are found downstream of topographic features, associated with transitions between along-isobath and cross-isobath flow, which are in turn related both to the time-integrated amplitude of upwelling-favorable wind forcing and to the formation of small-scale eddies. Simulated predictability experiments are conducted and model forecasts are verified by standard statistics including anomaly correlation coefficient, and root-mean-square error. A new variant of relative entropy, the forecast relative entropy, is introduced to quantify the predictive information content in the forecast ensemble, relative to the initial ensemble. The results suggest that, even under conditions of relatively weak wind forcing, the deterministic response is stronger than instability growth over the 3–7-day forecast intervals considered here. Consequently, important elements of the coastal circulation should be accessible to predictive, dynamical forecasts on the nominal 7-day predictability time scale of the atmospheric forcing, provided that sufficiently accurate initializations are available. These results on predictability are consistent with inferences drawn from recent modeling studies of coastal ocean circulation along the central Oregon shelf, and should have general validity for other, similar regions.
Impacts of Soil Heating Condition on Precipitation Simulations in the Weather Research and Forecasting Model
Authors: Fan Xingang
Published: February 2009

Soil temperature is a major variable in land surface models, representing soil energy status, storage, and transfer. It serves as an important factor indicating the underlying surface heating condition for weather and climate forecasts. This study utilizes the Weather Research and Forecasting (WRF) model to study the impacts of changes to the surface heating condition, derived from soil temperature observations, on regional weather simulations. Large cold biases are found in the 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis project (ERA-40) soil temperatures as compared to observations. At the same time, a warm bias is found in the lower boundary assumption adopted by the Noah land surface model. In six heavy rain cases studied herein, observed soil temperatures are used to initialize the land surface model and to provide a lower boundary condition at the bottom of the model soil layer. By analyzing the impacts from the incorporation of observed soil temperatures, the following major conclusions are drawn: 1) A consistent increase in the ground heat flux is found during the day, when the observed soil temperatures are used to correct the cold bias present in ERA-40. Soil temperature changes introduced at the initial time maintain positive values but gradually decrease in magnitude with time. Sensible and latent heat fluxes and the moisture flux experience an increase during the first 6 h. 2) An increase in soil temperature impacts the air temperature through surface exchange, and near-surface moisture through evaporation. During the first two days, an increase in air temperature is seen across the region from the surface up to about 800 hPa (∼1450 m). The maximum near-surface air temperature increase is found to be, averaged over all cases, 0.5 K on the first day and 0.3 K on the second day. 3) The strength of the low-level jet is affected by the changes described above and also by the consequent changes in horizontal gradients of pressure and thermal fields. Thus, the three-dimensional circulation is affected, in addition to changes seen in the humidity and thermal fields and the locations and intensities of precipitating systems. 4) Overall results indicate that the incorporation of observed soil temperatures introduces a persistent soil heating condition that is favorable to convective development and, consequently, improves the simulation of precipitation.
Asymptomatic, Transient Complete Heart Block in a Pediatric Patient with Lyme Disease
Authors: Heckler Alan K. , Shmorhun Daniel
Published: February 2009

Lyme Disease, caused by the spirochete Borrellia burgdorferi, is the most common vector-borne disease in the United States. Clinically, it primarily affects the skin, joints, nervous system, and heart. Lyme carditis occurs in 4%-10% of adults with Lyme disease. Transient variable-level atrioventricular blocks, occurring in 77% of adults with Lyme carditis, are the most common cardiac manifestation. Up to 50% of Lyme carditis patients may develop complete heart block. The incidence of Lyme carditis in the pediatric population is not well established. We present a pediatric patient with a transient asymptomatic complete heart block resulting from Lyme carditis, an under-recognized complication of Lyme disease in the pediatric population.
Decade of Difference (1995—2005)
Authors: Kamler Estelle
Published: February 2009

Background: Massive retirements, increased expectations, and mounting political pressures have resulted in a diminished talent pool for school superintendents. For school boards of the 124 school districts on Long Island, New York, the selection of a superintendent has been further complicated by sky-rocketing taxes and scandals leading to an erosion of trust. To address an increasing number of superintendent vacancies in this region, the majority of local boards hire search consultants. Purpose: This study examines, compares, and assesses the search consultants' process in securing superintendent candidates on Long Island within the social, political, and economic context existing in 1995 and 2005 to determine similarities and differences within the decade. Research Design: For this qualitative case study, search consultants serving Long Island were identified, and in-depth interviews were conducted, tape-recorded, transcribed, and analyzed with coding formulated based on emerging themes. Findings: Long Island boards select predominately retired local superintendents as search consultants and prefer experienced neighboring superintendents to fill vacancies. Consultants rely on outreach for recruitment of candidates, recommend “silent searches,” facilitate school community stakeholders' participation in construction of a candidate's profile, endorse criminal and credit checks, and serve to neutralize negativity toward and/or between board members. Through succession planning, more women are assuming superintendencies; there is no gain for people of color. Conclusions: Mandatory board training targeting effective group decision making and values clarification, use of data, mentoring and advocacy of underrepresentative aspirants, and succession planning appear advisable to attract a broader talent pool and increase diversity in the superintendency.