bluuebunny/crossref_metadata_2025 huggingface dataset:
Graded Exposure Therapy for Long-Standing Disgust-Related Cockroach Avoidance in an Older Male
Authors: Berle David
Published: July 2007

This case study outlines the use of graded in-vivo exposure to reduce an aversion to cockroaches in an older male. Following assessment, seven therapy sessions of in-vivo exposure were conducted where the client was progressively brought into closer and closer contact with cockroaches. A decrease in the client's aversion to cockroaches was apparent at posttreatment and persisted to 5-month follow-up, as evidenced by client reports and decreased behavioral avoidance. The client maintained that his avoidance had been driven by disgust, rather than fear, and the reduction of his avoidance of and aversion to cockroaches indicates that approaches developed for fearful clients may also be effective for clients who do not report fear responses to their avoided stimuli.
The ALA, public libraries and the Great Depression
Authors: Luyt Brendan
Published: July 2007

During the Great Depression of the 1930s, the American Library Association (ALA) became active in an alliance of public administrators, bank executives and teachers defending public spending from powerful populist anti-tax coalitions seeking drastic tax cuts as a solution to economic stagnation. Librarians were encouraged by the ALA to join the fight for 'constructive economy' that would reform and strengthen the role of public institutions. On the surface, this appears to be another example of the cyclical calls for library action that Michael Harris identified as characteristic of the profession's history. But in this case, the threat was real and the campaign produced significant long-term change. Librarians and their institutions became part of a much broader set of social forces that served to re-establish the hegemony of the American state at a time when it was particularly vulnerable to attack. In fact, the ALA's calls for 'constructive economy' foreshadowed and made possible the post-war Fordist compromise between monopoly capital, the state and organized labour. This article examines the role the ALA hoped libraries would play in the campaign against the anti-taxation groups and, using the work of social theorists Antonio Gramsci and Nicos Poulantzas, situates these efforts within the wider political economy of the time.
Nucleolin is a receptor that mediates antiangiogenic and antitumor activity of endostatin
Authors: Shi Hubing , Huang Yujie , Zhou Hao , Song Xiaomin , Yuan Shaopeng , Fu Yan , Luo Yongzhang
Published: July 2007

The exact molecular mechanism of how endostatin inhibits angiogenesis and tumor growth remains uncharacterized. Here, we report that endostatin specifically binds to the cell surface nucleolin with high affinity. Blockage of nucleolin by a neutralizing antibody or knockdown of nucleolin by the RNA interference results in loss of antiendothelial activities of endostatin. Importantly, a neutralizing antinucleolin antibody abrogates the antiangiogenic and antitumor activities of endostatin in vivo. Nucleolin and endostatin are colocalized on the cell surface of endothelial cells of angiogenic blood vessels in the tumor environment. Finally, we found that endostatin is internalized and transported into cell nuclei of endothelial cell via nucleolin. In the nucleus, the phosphorylation of nucleolin, which is critical for cell proliferation, can be inhibited by endostatin. Our studies demonstrate that nucleolin is a novel functional receptor for endostatin, and mediates the antiangiogenic and antitumor activities of endostatin. These findings also provide mechanistic insights of how endostatin specifically inhibits proliferating endothelial cell growth and angiogenesis.
The molecular signature of MDS stem cells supports a stem-cell origin of 5q− myelodysplastic syndromes
Authors: Nilsson Lars , Edén Patrik , Olsson Eleonor , Månsson Robert , Åstrand-Grundström Ingbritt , Strömbeck Bodil , Theilgaard-Mönch Kim , Anderson Kristina , Hast Robert , Hellström-Lindberg Eva , Samuelsson Jan , Bergh Gösta , Nerlov Claus , Johansson Bertil , Sigvardsson Mikael , Borg Åke , Jacobsen Sten Eirik W.
Published: July 2007

Global gene expression profiling of highly purified 5q-deleted CD34+CD38−Thy1+ cells in 5q− myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34+CD38−Thy1+ hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cells. Expression of BMI1, encoding a critical regulator of self-renewal, was up-regulated in 5q− stem cells. Whereas multiple previous MDS genetic screens failed to identify altered expression of the gene encoding the myeloid transcription factor CEBPA, stage-specific and extensive down-regulation of CEBPA was specifically observed in MDS progenitors. These studies establish the importance of molecular characterization of distinct stages of cancer stem and progenitor cells to enhance the resolution of stage-specific dysregulated gene expression.
Requirement of α and β subunit transmembrane helix separation for integrin outside-in signaling
Authors: Zhu Jieqing , Carman Christopher V. , Kim Minsoo , Shimaoka Motomu , Springer Timothy A. , Luo Bing-Hao
Published: July 2007

Adhesion to extracellular ligands through integrins regulates cell shape, migration, growth, and survival. How integrins transmit signals in the outside-to-in direction remains unknown. Whereas in resting integrins the α and β subunit transmembrane domains are associated, ligand binding promotes dissociation and separation of these domains. Here we address whether such separation is required for outside-in signaling. By introduction of an intersubunit disulfide bond, we generated mutant integrin αIIbβ3 with blocked transmembrane separation that binds ligand, mediates adhesion, adopts an extended conformation after ligand binding, and forms antibody-induced macroclusters on the cell surface similarly to wild type. However, the mutant integrin exhibits a profound defect in adhesion-induced outside-in signaling as measured by cell spreading, actin stress-fiber and focal adhesion formation, and focal adhesion kinase activation. This defect was rescued by reduction of the disulfide bond. Our results demonstrate that the separation of transmembrane domains is required for integrin outside-in signal transduction.
Molecular evolution of the reactive oxygen-generating NADPH oxidase (Nox/Duox) family of enzymes
Authors: Kawahara Tsukasa , Quinn Mark T , Lambeth J David
Published: July 2007

Background

NADPH-oxidases (Nox) and the related Dual oxidases (Duox) play varied biological and pathological roles via regulated generation of reactive oxygen species (ROS). Members of the Nox/Duox family have been identified in a wide variety of organisms, including mammals, nematodes, fruit fly, green plants, fungi, and slime molds; however, little is known about the molecular evolutionary history of these enzymes.

Results

We assembled and analyzed the deduced amino acid sequences of 101 Nox/Duox orthologs from 25 species, including vertebrates, urochordates, echinoderms, insects, nematodes, fungi, slime mold amoeba, alga and plants. In contrast to ROS defense enzymes, such as superoxide dismutase and catalase that are present in prokaryotes, ROS-generating Nox/Duox orthologs only appeared later in evolution. Molecular taxonomy revealed seven distinct subfamilies of Noxes and Duoxes. The calcium-regulated orthologs representing 4 subfamilies diverged early and are the most widely distributed in biology. Subunit-regulated Noxes represent a second major subdivision, and appeared first in fungi and amoeba. Nox5 was lost in rodents, and Nox3, which functions in the inner ear in gravity perception, emerged the most recently, corresponding to full-time adaptation of vertebrates to land. The sea urchinStrongylocentrotus purpuratuspossesses the earliest Nox2 co-ortholog of vertebrate Nox1, 2, and 3, while Nox4 first appeared somewhat later in urochordates. Comparison of evolutionary substitution rates demonstrates that Nox2, the regulatory subunits p47phoxand p67phox, and Duox are more stringently conserved in vertebrates than other Noxes and Nox regulatory subunits. Amino acid sequence comparisons identified key catalytic or regulatory regions, as 68 residues were highly conserved among all Nox/Duox orthologs, and 14 of these were identical with those mutated in Nox2 in variants of X-linked chronic granulomatous disease. In addition to canonical motifs, the B-loop, TM6-FAD, VXGPFG-motif, and extreme C-terminal regions were identified as important for Nox activity, as verified by mutational analysis. The presence of these non-canonical, but highly conserved regions suggests that all Nox/Duox may possess a common biological function remained in a long history of Nox/Duox evolution.

Conclusion

This report provides the first comprehensive analysis of the evolution and conserved functions of Nox and Duox family members, including identification of conserved amino acid residues. These results provide a guide for future structure-function studies and for understanding the evolution of biological functions of these enzymes.
Trichostatin A effects on gene expression in the protozoan parasite Entamoeba histolytica
Authors: Ehrenkaufer Gretchen M , Eichinger Daniel J , Singh Upinder
Published: July 2007

Background

Histone modification regulates chromatin structure and influences gene expression associated with diverse biological functions including cellular differentiation, cancer, maintenance of genome architecture, and pathogen virulence. InEntamoeba, a deep-branching eukaryote, short chain fatty acids (SCFA) affect histone acetylation and parasite development. Additionally, a number of active histone modifying enzymes have been identified in the parasite genome. However, the overall extent of gene regulation tied to histone acetylation is not known.

Results

In order to identify the genome-wide effects of histone acetylation in regulatingE. histolyticagene expression, we used whole-genome expression profiling of parasites treated with SCFA and Trichostatin A (TSA). Despite significant changes in histone acetylation patterns, exposure of parasites to SCFA resulted in minimal transcriptional changes (11 out of 9,435 genes transcriptionally regulated). In contrast, exposure to TSA, a more specific inhibitor of histone deacetylases, significantly affected transcription of 163 genes (122 genes upregulated and 41 genes downregulated). Genes modulated by TSA were not regulated by treatment with 5-Azacytidine, an inhibitor of DNA-methyltransferase, indicating that inE. histolyticathe crosstalk between DNA methylation and histone modification is not substantial. However, the set of genes regulated by TSA overlapped substantially with genes regulated during parasite development: 73/122 genes upregulated by TSA exposure were upregulated inE. histolyticacysts (p-value = 6 × 10-53) and 15/41 genes downregulated by TSA exposure were downregulated inE. histolyticacysts (p-value = 3 × 10-7).

Conclusion

This work represents the first genome-wide analysis of histone acetylation and its effects on gene expression inE. histolytica. The data indicate that SCFAs, despite their ability to influence histone acetylation, have minimal effects on gene transcription in cultured parasites. In contrast, the effect of TSA onE. histolyticagene expression is more substantial and includes genes involved in the encystation pathway. These observations will allow further dissection of the effects of histone acetylation and the genetic pathways regulating stage conversion in this pathogenic parasite.
Sialyl Lewis x expression in canine malignant mammary tumours: correlation with clinicopathological features and E-Cadherin expression
Authors: Pinho Salomé S , Matos Augusto JF , Lopes Célia , Marcos Nuno T , Carvalheira Júlio , Reis Celso A , Gärtner Fátima
Published: July 2007

Background

Sialyl Lewis x (sLex) antigen is a carbohydrate antigen that is considered not only a marker for cancer but also implicated functionally in the malignant behaviour of cancer cells. Overexpression of sLex is associated with enhanced progression and metastases of many types of cancer including those of the mammary gland. Canine mammary tumours can invade and give rise to metastases via either lymphatic or blood vessels.

E-Cadherin is specifically involved in epithelial cell-to-cell adhesion. In cancer, E-Cadherin underexpression is one of the alterations that characterizes the invasive phenotype and is considered an invasion/tumour suppressor gene. Partial or complete loss of E-Cadherin expression correlates with poor prognosis in canine malignant mammary cancer.

The aim of this study was to analyse the sLex expression in canine malignant mammary tumours and to evaluate if the presence of sLex correlates with the expression of E-Cadherin and with clinicopathological features.

Methods

Fifty-three cases of canine mammary carcinomas were analysed immunohistochemically using monoclonal antibodies against sLex (IgM) and E-Cadherin (IgG). The clinicopathological data were then assessed to determine whether there was a correlation with sLex tumour expression. Double labelled immunofluorescence staining was performed to analyse the combined expression of sLex and E-Cadherin.

Results

sLex expression was consistently demonstrated in all cases of canine mammary carcinomas with different levels of expression. We found a significant relationship between the levels of sLex expression and the presence of lymph node metastases. We also demonstrated that when E-Cadherin expression was increased sLex was reduced and vice-versa. The combined analysis of both adhesion molecules revealed an inverse relationship.

Conclusion

In the present study we demonstrate the importance of sLex in the malignant phenotype of canine malignant mammary tumours. Our results support the use of sLex as a prognostic tumour marker in canine mammary carcinomas. Furthermore, we showed that sLex and E-Cadherin expression were inversely correlated. Future studies are warranted to clarify the molecular mechanism underlying the relation between sLex and E-Cadherin in canine mammary carcinoma cells which represents an important comparative model to woman breast cancer.
Realm of PD-(D/E)XK nuclease superfamily revisited: detection of novel families with modified transitive meta profile searches
Authors: Knizewski Lukasz , Kinch Lisa N , Grishin Nick V , Rychlewski Leszek , Ginalski Krzysztof
Published: July 2007

Background

PD-(D/E)XK nucleases constitute a large and highly diverse superfamily of enzymes that display little sequence similarity despite retaining a common core fold and a few critical active site residues. This makes identification of new PD-(D/E)XK nuclease families a challenging task as they usually escape detection with standard sequence-based methods. We developed a modified transitive meta profile search approach and to consider the structural diversity of PD-(D/E)XK nuclease fold more thoroughly we analyzed also lower than threshold Meta-BASIC hits to select potentially correct predictions placed among unreliable or incorrect ones.

Results

Application of a modified transitive Meta-BASIC searches on updated PFAM families and PDB structures resulted in detection of five new PD-(D/E)XK nuclease families encompassing hundreds of so far uncharacterized and poorly annotated proteins. These include four families catalogued in PFAM database as domains of unknown function (DUF506, DUF524, DUF1626 and DUF1703) and YhgA-like family of putative transposases. Three of these families represent extremely distant homologs (DUF506, DUF524, and YhgA-like), while two are newly defined in updated database (DUF1626 and DUF1703). In addition, we also confidently identified an extended AAA-ATPase domain in the N-terminal region of DUF1703 family proteins.

Conclusion

Obtained results suggest that detailed analysis of below threshold Meta-BASIC hits may push limits further for distant homology detection in the 'midnight zone' of homology. All identified families conserve the core evolutionary fold, secondary structure and hydrophobic patterns common to existing PD-(D/E)XK nucleases and maintain critical active site motifs that contribute to nucleic acid cleavage. Further experimental investigations should address the predicted activity and clarify potential substrates providing further insight into detailed biological role of these newly detected nucleases.
Expression and function of junctional adhesion molecule-C in human and experimental arthritis
Authors: Palmer Gaby , Busso Nathalie , Aurrand-Lions Michel , Talabot-Ayer Dominique , Chobaz-Péclat Véronique , Zimmerli Claudia , Hammel Philippe , Imhof Beat A , Gabay Cem
Published: July 2007

Junctional adhesion molecule-C (JAM-C) is an adhesion molecule involved in transendothelial migration of leukocytes. In this study, we examined JAM-C expression in the synovium and investigated the role of this molecule in two experimental mouse models of arthritis. JAM-C expression was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry. The effects of a monoclonal anti-JAM-C antibody were assessed in antigen-induced arthritis (AIA) and K/BxN serum transfer-induced arthritis. JAM-C was expressed by synovial fibroblasts in the lining layer and associated with vessels in the sublining layer in human and mouse arthritic synovial tissue. In human tissue, JAM-C expression was increased in rheumatoid arthritis (RA) as compared to osteoarthritis synovial samples (12.7 ± 1.3 arbitrary units in RA versus 3.3 ± 1.1 in OA; p < 0.05). Treatment of mice with a monoclonal anti-JAM-C antibody decreased the severity of AIA. Neutrophil infiltration into inflamed joints was selectively reduced as compared to T-lymphocyte and macrophage infiltration (0.8 ± 0.3 arbitrary units in anti-JAM-C-treated versus 2.3 ± 0.6 in isotype-matched control antibody-treated mice; p < 0.05). Circulating levels of the acute-phase protein serum amyloid A as well as antigen-specific and concanavalin A-induced spleen T-cell responses were significantly decreased in anti-JAM-C antibody-treated mice. In the serum transfer-induced arthritis model, treatment with the anti-JAM-C antibody delayed the onset of arthritis. JAM-C is highly expressed by synovial fibroblasts in RA. Treatment of mice with an anti-JAM-C antibody significantly reduced the severity of AIA and delayed the onset of serum transfer-induced arthritis, suggesting a role for JAM-C in the pathogenesis of arthritis.
Whole-genome analysis of mRNA decay in Plasmodium falciparumreveals a global lengthening of mRNA half-life during the intra-erythrocytic development cycle
Authors: Shock Jennifer L , Fischer Kael F , DeRisi Joseph L
Published: July 2007

Background:

The rate of mRNA decay is an essential element of post-transcriptional regulation in all organisms. Previously, studies in several organisms found that the specific half-life of each mRNA is precisely related to its physiologic role, and plays an important role in determining levels of gene expression.

Results:

We used a genome-wide approach to characterize mRNA decay in Plasmodium falciparum. We found that, globally, rates of mRNA decay increase dramatically during the asexual intra-erythrocytic developmental cycle. During the ring stage of the cycle, the average mRNA half-life was 9.5 min, but this was extended to an average of 65 min during the late schizont stage of development. Thus, a major determinant of mRNA decay rate appears to be linked to the stage of intra-erythrocytic development. Furthermore, we found specific variations in decay patterns superimposed upon the dominant trend of progressive half-life lengthening. These variations in decay pattern were frequently enriched for genes with specific cellular functions or processes.

Conclusion:

Elucidation of Plasmodium mRNA decay rates provides a key element for deciphering mechanisms of genetic control in this parasite, by complementing and extending previous mRNA abundance studies. Our results indicate that progressive stage-dependent decreases in mRNA decay rate function are a major determinant of mRNA accumulation during the schizont stage of intra-erythrocytic development. This type of genome-wide change in mRNA decay rate has not been observed in any other organism to date, and indicates that post-transcriptional regulation may be the dominant mechanism of gene regulation in P. falciparum.
Polyclonal B cell activation in infections: infectious agents’ devilry or defense mechanism of the host?
Authors: Montes Carolina L , Acosta-Rodríguez Eva V , Merino Maria Cecilia , Bermejo Daniela A , Gruppi Adriana
Published: July 2007

Polyclonal B cell activation is not a peculiar characteristic to a particular infection, as many viruses, bacteria, and parasites induce a strong polyclonal B cell response resulting in hyper-γ-globulinemia. Here, we discuss the different roles proposed for polyclonal B cell activation, which can be crucial for early host defense against rapidly dividing microorganisms by contributing antibodies specific for a spectrum of conserved structures present in the pathogens. In addition, polyclonal B cell activation can be responsible for maintenance of memory B cell responses because of the continuous, unrestricted stimulation of memory B cells whose antibody production may be sustained in the absence of the antigens binding-specific BCR. Conversely, polyclonal activation can be triggered by microorganisms to avoid the host-specific, immune response by activating B cell clones, which produce nonmicroorganism-specific antibodies. Finally, some reports suggest a deleterious role for polyclonal activation, arguing that it could potentially turn on anti-self-responses and lead to autoimmune manifestations during chronic infections.
3D ray tracing using a modified shortest-path method
Authors: Bai Chao-ying , Greenhalgh Stewart , Zhou Bing
Published: July 2007

We present an accurate 3D ray-tracing algorithm based on a modified (more flexible and economical) shortest-path method (SPM). Unlike the regular SPM in the 3D case, which uses only primary nodes at the corners of each cell and whose accuracy depends on actual cell size, the new method can work with much larger cell sizes by introducing secondary nodes along all bounding surfaces of the cell. This increases the ray angular coverage and permits detailed specification of the velocity field. The modified SPM simultaneously calculates first-arrival times and gradually locates the related raypaths on all grid nodes as the wave field evolves. Its advantages over the regular SPM are its ability to handle high-contrast velocity models more easily, lower memory requirements and less CPU time, and the capability to calculate a relatively large 3D model without losing accuracy. The maximum relative error bound in the computed traveltimes of the modified SPM is established for a uniform velocity field, which may be considered an upper error bound for the whole model in real problems. The modified method in this study is compared with the regular SPM theoretically and on two specific velocity models. The Marmousi model is used to further test the performance of the new approach for both accuracy and flexibility in a complex velocity field. The study shows that the modified SPM is preferable to regular SPM for real 3D problems.
On the orientation and absolute phase of marine CSEM receivers
Authors: Mittet Rune , Aakervik Odd Marius , Jensen Hans Roger , Ellingsrud Svein , Stovas Alexey
Published: July 2007

Receiver orientation can be recovered from electric and/or magnetic data if it is not directly measured. A receiver dropped on the seabed will end up with an arbitrary orientation, which means that the recorded electric and magnetic x- and y-components will point in arbitrary directions. We demonstrate how both electric and magnetic data can be used to rotate the field data to a coordinate system where the x-direction points in the inline or towline direction or 180° with respect to this direction. The amplitudes of electric and magnetic marine CSEM data are highly offset dependent so we introduce a median filtering approach to handle this problem. An inspection of the electric and/or magnetic phase after normalization with the source-current phase can resolve the remaining problem of the [Formula: see text] spatial rotation. The result is electric and magnetic data where the x-component points in the positive towline direction. We analyze the case of lost temporal synchronization between receivers and the transmitter and show that the proper absolute phase can be recovered approximately by producing precalculated tables for zero or minimum offset of the electric and/or magnetic phase. These tables depend on the frequency, the transmitter length, the water conductivity, and the distance between the receiver and the midpoint of the transmitter. These four quantities are measured during a marine CSEM survey. The method requires electric and/or magnetic data that are not saturated at short offsets. The magnetic zero or minimum offset phase shows less variation with these four parameters than the electric zero or minimum offset phase. Hence, if magnetic data are available, they are preferable to electric data for this type of processing.
Apparent-density mapping using entropic regularization
Authors: Silva João B. C. , Oliveira Francisco S. , Barbosa Valéria C. F. , Campos Velho Haroldo F.
Published: July 2007

We present a new apparent-density mapping method on the horizontal plane that combines the minimization of the first-order entropy with the maximization of the zeroth-order entropy of the estimated density contrasts. The interpretation model consists of a grid of vertical, juxtaposed prisms in both horizontal directions. We assume that the top and the bottom of the gravity sources are flat and horizontal and estimate the prisms’ density contrasts. The minimization of the first-order entropy favors solutions presenting sharp borders, and the maximization of the zeroth-order entropy prevents the tendency of the source estimate to become a single prism. Thus, a judicious combination of both constraints may lead to solutions characterized by regions with virtually constant estimated density contrasts separated by sharp discontinuities. We apply our method to synthetic data from simulated intrusive bodies in sediments that present flat and horizontal tops. By comparing our results with those obtained with the smoothness constraint, we show that both methods produce good and equivalent locations of the sources’ central positions. However, the entropic regularization delineates the boundaries of the bodies with greater resolution, even in the case of 100-m-wide bodies separated by a distance as small as [Formula: see text]. Both the proposed and the global smoothness constraints are applied to real anomalies from the eastern Alps and from the Matsitama intrusive complex, northeastern Botswana. In the first case, the entropic regularization delineates two sources, with a horizontal and nearly flat top being consistent with the known geologic information. In the second case, both constraints produce virtually the same estimate, indicating, in agreement with results of synthetic tests, that the tops of the sources are neither flat nor horizontal.
Applying compactness constraints to differential traveltime tomography
Authors: Ajo-Franklin Jonathan B. , Minsley Burke J. , Daley Thomas M.
Published: July 2007

Tomographic imaging problems are typically ill-posed and often require the use of regularization techniques to guarantee a stable solution. Minimization of a weighted norm of model length is one commonly used secondary constraint. Tikhonov methods exploit low-order differential operators to select for solutions that are small, flat, or smooth in one or more dimensions. This class of regularizing functionals may not always be appropriate, particularly in cases where the anomaly being imaged is generated by a nonsmooth spatial process. Time-lapse imaging of flow-induced velocity anomalies is one such case; flow features are often characterized by spatial compactness or connectivity. By performing inversions on differenced arrival time data, the properties of the time-lapse feature can be directly constrained. We develop a differential traveltime tomography algorithm whichselects for compact solutions, i.e., models with a minimum area of support, through application of model-space iteratively reweighted least squares. Our technique is an adaptation of minimum support regularization methods previously explored within the potential theory community. We compare our inversion algorithm to the results obtained by traditional Tikhonov regularization for two simple synthetic models: one including several sharp localized anomalies and a second with smoother features. We use a more complicated synthetic test case based on multiphase flow results to illustrate the efficacy of compactness constraints for contaminant infiltration imaging. We apply the algorithm to a [Formula: see text]-sequestration-monitoring data set acquired at the Frio pilot site. We observe that in cases where the assumption of a localized anomaly is correct, the addition of compactness constraints improves image quality by reducing tomographic artifacts and spatial smearing of target features.
Inversion of P-wave VSP data for local anisotropy: Theory and case study
Authors: Grechka Vladimir , Mateeva Albena
Published: July 2007

We discuss, improve, and apply the slowness-polarization method for estimating local anisotropy from VSP data. Although the idea of fitting a given anisotropic model to the apparent slownesses measured along a well and polarization vectors recorded by three-component downhole geophones is hardly new, we extend the area of applicability of the technique and make the anisotropic inversion more robust by eliminating the most operationally difficult and noisy portion of the data, the shear waves. We show that the shear-wave velocity is actually unnecessary for fitting the slowness-of-polarization dependence of P-wave VSP data. For the most common geometry of a vertical borehole in a vertically transversely isotropic subsurface, such data are governed by the P-wave vertical velocity [Formula: see text] and two quantities, [Formula: see text] and [Formula: see text], that describe the influence of anisotropy. These quantities depend on conventional anisotropic coefficients [Formula: see text] and [Formula: see text] and absorb the S-wave velocity. We apply the developed theory to a 2D walkaway VSP acquired over a subsalt prospect in the Gulf of Mexico. Our data set contains geophones placed both inside the salt and beneath it, allowing us to estimate the anisotropy of different rock formations. We find the salt to be nearly isotropic in the examined [Formula: see text] [Formula: see text] depth interval. In contrast, the sediments below the salt exhibit substantial anisotropy. While the physical origins of subsalt anisotropy are still to be fully understood, we observe a clear correlation between lithology and the values of [Formula: see text] and [Formula: see text]: both anisotropic coefficients are greater in shales and smaller in the sandier portion of the well.
Management of Metastatic Cervical Cancer: Review of the Literature
Authors: Long Harry J.
Published: July 2007

This article reviews the English-language literature concerning chemotherapy for advanced, recurrent, or metastatic cervix carcinoma. Specifically, it reviews the available literature for active single agents, doublets, triplets, and multiple drug combination chemotherapy. Until recently, single-agent cisplatin was the drug of choice in metastatic cervix cancer. Various doublets, triplets, and quartlets have been reported to have higher objective response rates than single-agent cisplatin when compared in phase III clinical trials. Some have demonstrated improvements in progression-free survival, but only topotecan plus cisplatin has demonstrated an improvement in overall survival. This benefit is most apparent in patients who have a long disease-free interval from primary therapy and who have not received prior cisplatin as a radiosensitizer.
Management of Borderline Ovarian Neoplasms
Authors: Cadron Isabelle , Leunen Karin , Van Gorp Toon , Amant Frederic , Neven Patrick , Vergote Ignace
Published: July 2007

Over the last decades, the management of borderline ovarian tumors (BOTs) has changed from radical surgery to more conservative therapy as a result of the need for fertility-sparing surgery and the increasing use of laparoscopy. The question is whether this is good clinical practice from an oncologic point of view. Here, recent literature regarding management of borderline ovarian neoplasms is reviewed, and oncologic concerns are discussed with emphasis on the mode of surgery and the possibility of fertility-sparing surgery and its consequences. Proper staging is defined as an exploration of the entire abdominal cavity with peritoneal washings, infracolic omentectomy, and multiple peritoneal biopsies as the cornerstone of a successful treatment, and this is only possible through a midline incision. For stage I disease, conservative surgery consisting of unilateral salpingo-oophorectomy or cystectomy in case of bilateral ovarian involvement or when the disease develops in the only remaining ovary is a valuable alternative in a number of young patients who want to preserve their fertility. Patients with advanced-stage disease or who are finished childbearing are treated with radical surgery consisting of peritoneal washings, total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, complete peritoneal resection of macroscopic lesions, or multiple peritoneal biopsies; in case of mucinous BOTs, patients also are treated with an appendectomy.
Multimodality Therapy for Locally Advanced Cervical Carcinoma: State of the Art and Future Directions
Authors: Monk Bradley J. , Tewari Krishnansu S. , Koh Wui-Jin
Published: July 2007

Globally, cervical cancer is the second most common cause of cancer-related mortality among women causing approximately 234,000 deaths annually among developing countries and killing 40,000 in developed nations. Most of these deaths occur in women with bulky or locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stages IIB through IVA, when lesions are not amenable to high cure rates with surgery or radiation (RT). The standard prescription for RT used to treat locally advanced cervical cancer has been dictated by common practice and patterns of care studies. In contrast, the addition of concomitant chemotherapy to RT has been studied in a number of randomized prospective trials, which are discussed in detail. When added to RT, cisplatin reduces the relative risk of death from cervical carcinoma by approximately 50% by decreasing local/pelvic failure and distant metastases. In 1999, weekly intravenous cisplatin at 40 mg/m2for 6 weeks in combination with RT was established as a new standard for the treatment of locally advanced cervical carcinoma. More recently, this recommendation has been expanded to include women with FIGO stage IB2 lesions as well as those with bulky stage IIA cancers. This monograph reviews the state of the art in treating locally advanced cervical cancer with combined chemotherapy and RT and discusses clinical and pathologic prognostic factors that impact cure. Quality of life during and after multimodality therapy is considered as well as ongoing clinical trials and future directions.
Immunologic Approaches to Ovarian Cancer Treatment
Authors: Sabbatini Paul , Odunsi Kunle
Published: July 2007

The clinical course of ovarian cancer is often marked by periods of relapse and remission until chemotherapy resistance develops. Patients in remission with minimal disease burdens are ideally suited for the evaluation of immune-based strategies. The role of immune surveillance in improving outcome has been supported by the correlation of increased survival with the presence or absence of tumor-infiltrating lymphocytes in a given patient. Major obstacles to the development of successful immune strategies include the identification of tumor-restricted immunogenic targets, generation of a sufficient immune response to cause tumor rejection, and approaches to overcome evasion of immune attack. As optimal strategies are being developed, many questions remain. Some of the questions are as follows: What is the best antigen form (eg, peptides, proteins, or tumor lysates)? What are the appropriate adjuvants? Are monovalent or multivalent vaccines likely to be more effective? What is the optimal frequency and duration of vaccination? How should antigen-specific responses be monitored? How should the anticancer response be maintained? In this review, we will explore representative examples of immune strategies under investigation for patients with ovarian carcinoma that illustrate many of these issues. We will review ongoing phase III studies for patients in first clinical remission. Basic principles generic to all these immunotherapeutic approaches will be discussed in the hopes of yielding the most promising results as the field continues to evolve.
Role of Surgery in Ovarian Carcinoma
Authors: Fader Amanda Nickles , Rose Peter G.
Published: July 2007

Surgery plays a critical role in the optimal management of all stages of ovarian carcinoma. In apparent early-stage ovarian cancer, a comprehensive surgical evaluation allows stratification of patients into low- and high-risk categories. Low-risk patients may be candidates for fertility-sparing surgery and can safely avoid chemotherapy and be observed. Treatment of patients with high-risk early- or advanced-stage ovarian cancer usually requires a combined modality approach. Although it is well known that epithelial ovarian cancer is moderately chemosensitive, what distinguishes it most from other metastatic solid tumors is that surgical cytoreduction of tumor volume is highly correlated with prolongation of patient survival. Procedures such as radical pelvic surgery, bowel resection, and aggressive upper abdominal surgery are commonly required to achieve optimal cytoreduction. Women who develop recurrent disease may be eligible for a secondary cytoreductive surgery or may require a surgical intervention to palliate disease-related symptoms. For women at high risk of ovarian cancer, prophylactic bilateral salpingo-oophorectomy significantly reduces the incidence of this disease. The purpose of this article is to provide a comprehensive review of the surgical management of ovarian carcinoma. The roles of primary, interval, and secondary cytoreductive surgeries; second-look procedures; and palliative surgery are reviewed. The indications for fertility-sparing and minimally invasive surgery as well as the current guidelines for prophylactic surgery in high-risk mutation carriers are also discussed.
Orphanin FQ: Evidence for a Role in the Control of the Reproductive Neuroendocrine System
Authors: Foradori Chad D. , Amstalden Marcel , Coolen Lique M. , Singh Sushma R. , McManus Christine J. , Handa Robert J. , Goodman Robert L. , Lehman Michael N.
Published: July 2007

Orphanin FQ (OFQ), also known as nociceptin, is a member of the endogenous opioid peptide family that has been functionally implicated in the control of pain, anxiety, circadian rhythms, and neuroendocrine function. In the reproductive system, endogenous opioid peptides are involved in the steroid feedback control of GnRH pulses and the induction of the GnRH surge. The distribution of OFQ in the preoptic area and hypothalamus overlaps with GnRH, and in vitro evidence suggests that OFQ can inhibit GnRH secretion from hypothalamic fragments. Using the sheep as a model, we examined the potential anatomical colocalization between OFQ and GnRH using dual-label immunocytochemistry. Confocal microscopy revealed that approximately 93% of GnRH neurons, evenly distributed across brain regions, were also immunoreactive for OFQ. In addition, almost all GnRH fibers and terminals in the external zone of the median eminence, the site of neurosecretory release of GnRH, also colocalized OFQ. This high degree of colocalization suggested that OFQ might be functionally important in controlling reproductive endocrine events. We tested this possibility by examining the effects of intracerebroventricular administration of [Arg14, Lys15] OFQ, an agonist to the OFQ receptor, on pulsatile LH secretion. The agonist inhibited LH pulse frequency in both luteal phase and ovariectomized ewes and suppressed pulse amplitude in the latter. The results provide in vivo evidence supporting a role for OFQ in the control of GnRH secretion and raise the possibility that it acts as part of an ultrashort, autocrine feedback loop controlling GnRH pulses.
The Immunophilin Ligands Cyclosporin A and FK506 Suppress Prostate Cancer Cell Growth by Androgen Receptor-Dependent and -Independent Mechanisms
Authors: Periyasamy Sumudra , Warrier Manya , Tillekeratne Manoranjani P. M. , Shou Weinian , Sanchez Edwin R.
Published: July 2007

The androgen receptor (AR) contributes to growth of prostate cancer even under conditions of androgen ablation. Thus, new strategies to target AR activity are needed. The AR interacts with the immunophilin FK506-binding protein 52 (FKBP52), and studies in the FKBP52 knockout mouse have shown that this protein is essential to AR activity in the prostate. Therefore, we tested whether the immunophilin ligand FK506 affected AR activity in prostate cancer cell lines. We also tested the hypothesis that the AR interacts with another immunophilin, cyclophilin 40 (Cyp40), and is regulated by its cognate ligand cyclosporin A (CsA). We show that levels of FKBP52, FKBP51, Cyp40, and a related co-chaperone PP5 were much higher in prostate cancer cells lines [(LNCaP), PC-3, and DU145] compared with primary prostate cells, and that the AR of LNCaP cells can interact with Cyp40. In the absence of androgen, CsA caused inhibition of cell growth in the AR-positive LNCaP and AR-negative PC-3 and DU145 cell lines. Interestingly, FK506 only inhibited LNCaP cells, suggesting a dependence on the AR for this effect. Both CsA and FK506 inhibited growth without inducing apoptosis. In LNCaP cells, CsA completely blocked androgen-stimulated growth, whereas FK506 was partially effective. Further studies in LNCaP cells revealed that CsA and FK506 were able to block or attenuate several stages of AR signaling, including hormone binding, nuclear translocation, and activity at several AR-responsive reporter and endogenous genes. These findings provide the first evidence that CsA and FK506 can negatively modulate proliferation of prostate cells in vitro. Immunophilins may now serve as new targets to disrupt AR-mediated prostate cancer growth.
Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) as a Growth Hormone (GH)-Releasing Factor in Grass Carp: II. Solution Structure of a Brain-Specific PACAP by Nuclear Magnetic Resonance Spectroscopy and Functional Studies on GH Release and Gene Expression
Authors: Sze Kong Hung , Zhou Hong , Yang Yinhua , He Mulan , Jiang Yonghua , Wong Anderson O. L.
Published: July 2007

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been proposed to be the ancestral GHRH. Recently, using grass carp as a model for modern-day bony fish, we demonstrated that PACAP nerve fibers are present in close proximity to carp somatotrophs, and mammalian PACAPs can induce GH secretion in carp pituitary cells. To further examine the role of PACAP as a GH-releasing factor in fish, the structural identity of grass carp PACAP was established by molecular cloning. The newly cloned PACAP was found to be a single-copy gene and expressed in the brain but not other tissues. The mature peptides of PACAP, namely PACAP27 and PACAP38, were synthesized. As revealed by nuclear magnetic resonance spectroscopies, carp PACAP38 is composed of a flexible N terminal from His1 to Ile5, an extended central helix from Phe6 to Val26, and a short helical tail in the C terminal from Arg29 to Arg34. The C-terminal helix is located after a hinge region at Leu27 to Gly28 and is absent in the solution structures of PACAP27. The two forms of PACAPs were effective in elevating GH release and GH transcript expression in grass carp pituitary cells. These stimulatory effects occurred with parallel rises in cAMP and Ca2+ entry via voltage-sensitive Ca2+ channels in carp somatotrophs. The present study represents the first report for solution structures of nonmammalian PACAPs and provides evidence that a brain-specific isoform of PACAP in fish can stimulate GH synthesis and release at the pituitary level, presumably by activating the appropriate postreceptor signaling mechanisms.
Hypoxia Stabilizes Type 2 Deiodinase Activity in Rat Astrocytes
Authors: Lamirand Audrey , Mercier Gilles , Ramaugé Martine , Pierre Michel , Courtin Françoise
Published: July 2007

T4 activation into T3 is catalyzed by type 2 deiodinase (D2) in the brain. The rapid induction of D2 in astrocytes by transient brain ischemia has prompted us to explore the effects of hypoxia on D2 in cultures of astrocytes. Hypoxia (2.5% O2) of cultured astrocytes increased D2 activity, alone or in association with agents stimulating the cAMP pathway. Hypoxia had no effect on D2 mRNA accumulation. Cycloheximide did not block the effect of hypoxia on D2 activity and D2 half-life was enhanced under hypoxia demonstrating a posttranslational action of hypoxia. Furthermore, the D2 activity increase by hypoxia was not additive with the increase promoted by the proteasome inhibitor carbobenzoxy-l-leucyl-l-leucyl-l-leucinal (MG132). This strongly suggests that hypoxia leads to stabilization of D2 by slowing its degradation by the proteasome pathway. Hypoxia, in contrast to MG132, did not block the T4-induced D2 inactivation. A contribution of prolyl hydroxylase to the hypoxia effects on D2 was also suggested on the basis of increased D2 activity after addition of different prolyl hydroxylase inhibitors (cobalt chloride, desferrioxamine, dimethyloxalylglycine, dimethylsuccinate). Specific inhibitors of ERK, p38 MAPK, or phosphatidylinositol 3-kinase pathways were without any effect on hypoxia-increased D2 activity, eliminating their role in the effects of hypoxia. Interestingly, diphenyleneiodonium, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase inhibited the hypoxia-increased D2 indicating a role for some reactive oxygen species in the mechanism of D2 increase. Further studies are required to clarify the precise molecular mechanisms involved in the D2 stabilization by hypoxia.
A component-based approach to the design and implementation of assembly automation system
Authors: Lee S M , Harrison R , West A A , Ong M H
Published: July 2007

This paper describes the application of a novel component-based approach to the design and implementation of an assembly automation system in the automotive production domain. The assembly automation system is composed of autonomous mechatronic units known here as components. The component encapsulates automation hardware, software, control services, and specific automation knowledge and can be integrated into the desired automation system as a common reusable building block without the need to know its low-level implementation details. The component-based concept is outlined and the implementation of a component-based assembly automation system is described in this paper.