bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Frequency Pycnocline Variability in the Northeast Pacific
Authors: Capotondi Antonietta , Alexander Michael A. , Deser Clara , Miller Arthur J.
Published: September 2005

The output from an ocean general circulation model (OGCM) driven by observed surface forcing is used in conjunction with simpler dynamical models to examine the physical mechanisms responsible for interannual to interdecadal pycnocline variability in the northeast Pacific Ocean during 1958–97, a period that includes the 1976–77 climate shift. After 1977 the pycnocline deepened in a broad band along the coast and shoaled in the central part of the Gulf of Alaska. The changes in pycnocline depth diagnosed from the model are in agreement with the pycnocline depth changes observed at two ocean stations in different areas of the Gulf of Alaska. A simple Ekman pumping model with linear damping explains a large fraction of pycnocline variability in the OGCM. The fit of the simple model to the OGCM is maximized in the central part of the Gulf of Alaska, where the pycnocline variability produced by the simple model can account for ∼70%–90% of the pycnocline depth variance in the OGCM. Evidence of westward-propagating Rossby waves is found in the OGCM, but they are not the dominant signal. On the contrary, large-scale pycnocline depth anomalies have primarily a standing character, thus explaining the success of the local Ekman pumping model. The agreement between the Ekman pumping model and OGCM deteriorates in a large band along the coast, where propagating disturbances within the pycnocline, due to either mean flow advection or boundary waves, appear to play an important role in pycnocline variability. Coastal propagation of pycnocline depth anomalies is especially relevant in the western part of the Gulf of Alaska, where local Ekman pumping-induced changes are anticorrelated with the OGCM pycnocline depth variations. The pycnocline depth changes associated with the 1976–77 climate regime shift do not seem to be consistent with Sverdrup dynamics, raising questions about the nature of the adjustment of the Alaska Gyre to low-frequency wind stress variability.
Observations of Inertial Wave Events near the Continental Slope off Goban Spur
Authors: van Aken Hendrik M. , Maas Leo R. M. , van Haren Hans
Published: September 2005

Near-inertial waves were observed during the Ocean Margin Exchange (OMEX-I) experiments with current meters over the continental slope near Goban Spur. The strongest inertial motion was observed in the bottom layer, about 50 m above the 1000-m isobath. There the waves were slightly (1.7%) superinertial and the bottom slope appeared to be critical for the near-inertial peak frequency, allowing the velocity vector to follow the sloping bottom. The vertical velocity component of this motion was responsible for the near-inertial spectral peak in the temperature spectrum, which was also observed in the bottom layer. Evidence was found supporting the speculative hypothesis that high-energy near-inertial wave events were produced during geostrophic adjustment in the variable deep eastern-boundary current over the slope near Goban Spur.
Community Energy: A Social Architecture for an Alternative Energy Future
Authors: Hoffman Steven M. , High-Pippert Angela
Published: September 2005

Community energy based on a mix of distributed technologies offers a serious alternative to the current energy system. The nature of community energy and the role that such initiatives might play in the general fabric of civic life is not, however, well understood. Community energy initiatives might involve only those citizens who prefer to be actively and continuously involved in intense, democratic debate. A more robust conceptualization of community energy might, on the other hand, be guided by Benjamin Barber’s notion of “strong democracy,” in which community energy initiatives would draw upon a much broader citizen base, involving people from many walks of life and from quarters not generally presumed to be part of a sustained democratic process. The history of community energy is explored and a number of case studies are presented to illustrate the problems, prospects, and limitations of a socially and technologically decentralized energy system.
Commitments to Academic Biliteracy
Authors: Gentil Guillaume
Published: September 2005

This article examines the appropriation of academic biliteracy by three French-speaking students at an English-medium university in the Canadian province of Québec. Drawing on Hornberger’s continua model of biliteracy, Bourdieu’s critical social theory, and philosophical hermeneutics, the author conceptualizes individual biliterate development as a subjective and intersubjective evaluative response to social contexts of possibilities for biliteracy. Case study data were collected during 2 ½ years and included autobiographical and text-based interviews, inventories and analyses of academic writing in English and French, classroom-based observations, field notes, and documentation of the legal, historical, institutional, and demographic contexts. Analyses of the participants’ negotiations and trajectories of bilingual academic writing development reveal the challenges and resources of bilingual writers to uphold their commitment to academic biliteracy within English-dominant institutional and disciplinary contexts. Implications for the advancement of multilingual academic literacies are drawn.
Use of interleukin 7 receptor-α knockout donor cells demonstrates the lymphoid independence of dendritic cells
Authors: Takeuchi Satoshi , Katz Stephen I.
Published: September 2005

The precise lineage of dendritic cells (DCs), including skin Langerhans cells (LCs), is unclear. Interleukin 7 (IL-7) and its receptor (IL-7Rα) are known to mediate lymphopoiesis, and IL-7 is also known to be essential for the generation of DCs from lymphoid-committed precursors in vitro. Thus, to determine the developmental lymphoid (or IL-7Rα) dependency of various DCs and to examine the importance of IL-7/IL-7Rα for DC development in vivo, we used IL-7Rα knockout (KO) donor cells to reconstitute DCs/LCs in sublethally irradiated recipients and compared the results to those obtained using wild-type (WT) donor cells. We found that lymphoid lineage cells (except natural killer [NK] cells), including thymocytes, were less efficiently reconstituted by IL-7Rα KO donor cells, whereas myeloid lineage cells and DCs/LCs were equally well reconstituted by both the IL-7Rα KO and WT donor cells. Overall, we conclude that IL-7Rα is not required for the development of DCs/LC in vivo.
Deletion of the selection cassette, but not cis-acting elements, in targeted Flk1-lacZ allele reveals Flk1 expression in multipotent mesodermal progenitors
Authors: Ema Masatsugu , Takahashi Satoru , Rossant Janet
Published: September 2005

Flk1, the gene encoding the vascular endothelial growth factor receptor 2 (VEGFR-2), is a well-known marker for vascular and hematopoietic progenitors and is indispensable for normal hematopoiesis and vasculogenesis. Here we show that Flk1 expression in the early mouse embryo marks a broad spectrum of mesodermal progenitors exiting the primitive streak as well as later mesodermal cell types including some cardiomyocytes, portions of the somites, and all extraembryonic mesoderm cells. These findings made use of an Flk1-lacZ knock-in allele in which the neomycin selection cassette was removed, which resulted in full replication of the endogenous expression of Flk1. Targeted deletion of a region in intron 1 that has been proposed to direct endothelial expression produced no alteration in either endothelial or broader mesodermal expression of the Flk1-lacZ allele. Examination of lacZ expression in homozygotes for the Flk1lacZ neo-out allele revealed that lacZ-expressing mesodermal cells persisted in nonvascular regions. Thus, Flk1 expression marks progenitors with broad mesodermal potential but is not absolutely required for the development of all mesodermal lineages in which it is expressed.
The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status
Authors: Pérez-Galán Patricia , Roué Gaël , Villamor Neus , Montserrat Emili , Campo Elias , Colomer Dolors
Published: September 2005

Mantle-cell lymphoma (MCL) is a mature B-cell lymphoma with an aggressive course and generally poor prognosis. Conventional chemotherapy has little efficacy. Bortezomib is a novel, reversible, and highly specific proteasome inhibitor that appears as a new hope for MCL treatment. We have analyzed the in vitro sensitivity to bortezomib in 4 MCL cell lines and in primary tumor cells from 10 MCL patients. Bortezomib induced phosphatidylserine exposure, mitochondrial depolarization, ROS generation, Bax and Bak conformational changes, and caspase activation. In addition, ROS scavengers, but not pancaspase inhibitors, blocked all apoptosis hallmarks. Protein and mRNA-expression analysis, revealed marked up-regulation of the BH3-only protein Noxa, between 4 to 6 hours after bortezomib addition, independent of p53 status. However, this up-regulation was faster and higher in cells with functional p53. Noxa RNA interference markedly decreased sensitivity to bortezomib, pointing to this protein as a key mediator between proteasome inhibition and mitochondrial depolarization in MCL cells. Noxa interacts with the antiapoptotic protein Mcl-1 and promotes Bak release from Mcl-1, suggesting that up-regulation of Noxa might counteract Mcl-1 accumulation after bortezomib treatment. These findings should be useful to extend the therapeutic strategies in MCL patients and to improve their prognosis.
The principal eosinophil peroxidase product, HOSCN, is a uniquely potent phagocyte oxidant inducer of endothelial cell tissue factor activity: a potential mechanism for thrombosis in eosinophilic inflammatory states
Authors: Wang Jian-Guo , Mahmud Shawn A. , Thompson Jacob A. , Geng Jian-Guo , Key Nigel S. , Slungaard Arne
Published: September 2005

In vivo, bromide (Br–), nitrite (NO2–), and thiocyanate (SCN–) compete for oxidation by eosinophil peroxidase (EPO) and H2O2, yielding, respectively, HOBr, NO2·, and HOSCN. We have recently shown that SCN– is the strongly preferred substrate for EPO in vivo and that HOSCN, in contrast with other EPO-generated oxidants and HOCl, is a relatively weak, cell-permeant, sulfhydryl (SH)–reactive oxidant. We here show that HOSCN is a uniquely potent (up to 100-fold) phagocyte oxidant inducer of tissue factor (TF) activity in human umbilical vein endothelial cells (HUVECs). This induction is attributable to transcriptional up-regulation of TF gene expression dependent upon both activation of the p65/c-Rel TF-κB transcription factor and activity of the ERK1/2 kinase pathway upstream of Egr-1 and was markedly further enhanced in the presence of wortmannin, an inhibitor of the PI3 kinase/Akt pathway. HOSCN also markedly activates the proinflammatory p65/p50 NF-κB pathway. Based on these findings we hypothesize that HOSCN generated by adherent and infiltrating eosinophils may provoke the development of a prothrombotic and proinflammatory endothelial/endocardial phenotype that promotes the pronounced thrombotic diathesis characteristic of the hypereosinophilic syndrome.
Ocular adnexal lymphoma: a clinicopathologic study of a large cohort of patients with no evidence for an association with Chlamydia psittaci
Authors: Rosado Manuel F. , Byrne Gerald E. , Ding Feying , Fields Kenneth A. , Ruiz Phillip , Dubovy Sander R. , Walker Gale R. , Markoe Arnold , Lossos Izidore S.
Published: September 2005

Non-Hodgkin lymphomas are among the most common primary tumors occurring in the ocular adnexa. Herein, we present a 14-year single-institution experience in 62 patients with primary ocular adnexal lymphomas (OALs). Association with Chlamydia psittaci infection is examined in 57 tumor specimens.

Extranodal marginal zone lymphoma (EMZL) was the most frequent histologic subtype (89%). The majority of patients with EMZL (84%) presented with stage E-extranodal (IE), however only 16% had an advanced stage. All stage IE patients were treated with local radiotherapy, whereas patients with disseminated disease received systemic therapy with or without local irradiation. All but 1 patient with EMZL achieved complete remission (CR). During a median follow-up of 52 months (range, 3-153 months), the estimated 5-year overall survival (OS) and freedom from progression (FFP) were 96% and 79%, respectively. During the follow-up, 22% of patients relapsed, mainly in extranodal sites, and 4% transformed to diffuse large B-cell lymphoma. None of the patients exhibited local orbital failure in the radiation field. None of the OAL specimens harbored C psittaci DNA.

Our study demonstrates that EMZLs, accounting for the majority of primary OALs, are characterized by an indolent natural history with frequent, continuous extranodal relapses. In South Florida, OALs are not associated with C psittaci infections.
PKCϵ controls protection against TRAIL in erythroid progenitors
Authors: Mirandola Prisco , Gobbi Giuliana , Ponti Cristina , Sponzilli Ivonne , Cocco Lucio , Vitale Marco
Published: September 2005

Apoptosis plays a central role in the regulation of the size of the hematopoietic stem cell pool as well as in the processes of cell differentiation along the various hematopoietic lineages. TRAIL is a member of the TNF family of cytokines with a known apoptogenic role against a variety of malignant cells and an emerging role in the modulation of normal hematopoiesis. Here we worked on the hypothesis that PKCϵ could act as a switch of the cellular response to TRAIL during erythropoiesis. We demonstrate that EPO-induced erythroid CD34 cells are insensitive to the apoptogenic effect of TRAIL at day 0 due to the lack of specific receptor expression. From day 3 onward, erythroid cells express surface death receptors and become sensitive to TRAIL up to day 7/8 when, notwithstanding death-receptor expression, the EPO-driven up-regulation of PKCϵ intracellular levels renders differentiating erythroid cells resistant to TRAIL likely via Bcl-2 up-regulation. Our conclusion is that in human CD34 cells, EPO promotes a series of events that, being finely regulated in their kinetics, restricts the sensitivity of these cells to TRAIL to a specific period of time, which therefore represents the “TRAIL window” for the negative regulation of erythroid-cell numbers.
Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice
Authors: Kranjc Simona , Cemazar Maja , Grosel Alenka , Sentjurc Marjeta , Sersa Gregor
Published: September 2005

Background

Bleomycin is poorly permeant but potent cytotoxic and radiosensitizing drug. The aim of the study was to evaluate whether a physical drug delivery system – electroporation can increase radiosensitising effect of bleomycin in vitro and in vivo.

Methods

LPB sarcoma cells and tumors were treated either with bleomycin, electroporation or ionizing radiation, and combination of these treatments. In vitro, response to different treatments was determined by colony forming assay, while in vivo, treatment effectiveness was determined by local tumor control (TCD50). Time dependence of partial oxygen pressure in LPB tumors after application of electric pulses was measured by electron paramagnetic oxyimetry.

Results

Electroporation of cells in vitro increased radiosensitising effect of bleomycin for 1.5 times, in vivo radiation response of tumors was enhanced by 1.9 fold compared to response of tumors that were irradiated only. Neither treatment of tumors with bleomycin nor application of electric pulses only, affected radiation response of tumors. Application of electric pulses to the tumors induced profound but transient reduction of tumor oxygenation. Although tumor oxygenation after electroporation partially restored at the time of irradiation, it was still reduced at the level of radiobiologically relevant hypoxia.

Conclusion

Our study shows that application of electric pulses to cells and tumors increases radiosensitising effect of bleomycin. Furthermore, our results demonstrate that the radiobiologically relevant hypoxia induced by electroporation of tumors did not counteract the pronounced radiosensitising effect of electrochemotherapy with bleomycin.
Survey of oxaliplatin-associated neurotoxicity using an interview-based questionnaire in patients with metastatic colorectal cancer
Authors: Leonard Gregory D , Wright Maurice A , Quinn Mary G , Fioravanti Suzanne , Harold Nancy , Schuler Barbara , Thomas Rebecca R , Grem Jean L
Published: September 2005

Background

New chemotherapy regimens for patients with colorectal cancer have improved survival, but at the cost of clinical toxicity. Oxaliplatin, an agent used in first-line therapy for metastatic colorectal cancer, causes acute and chronic neurotoxicity. This study was performed to carefully assess the incidence, type and duration of oxaliplatin neurotoxicity.

Methods

A detailed questionnaire was completed after each chemotherapy cycle for patients with metastatic colorectal cancer enrolled in a phase I trial of oxaliplatin and capecitabine. An oxaliplatin specific neurotoxicity scale was used to grade toxicity.

Results

Eighty-six adult patients with colorectal cancer were evaluated. Acute neuropathy symptoms included voice changes, visual alterations, pharyngo-laryngeal dysesthesia (lack of awareness of breathing); peri-oral or oral numbness, pain and symptoms due to muscle contraction (spasm, cramps, tremors). When the worst neurotoxicity per patient was considered, grade 1/2/3/4 dysesthesias and paresthesias were seen in 71/12/5/0 and 66/20/7/1 percent of patients. By cycles 3, 6, 9, and 12, oxaliplatin dose reduction or discontinuation was needed in 2.7%, 20%, 37.5% and 62.5% of patients.

Conclusion

Oxaliplatin-associated acute neuropathy causes a variety of distressing, but transient, symptoms due to peripheral sensory and motor nerve hyperexcitability. Chronic neuropathy may be debilitating and often necessitates dose reductions or discontinuation of oxaliplatin. Patients should be warned of the possible spectrum of symptoms and re-assured about the transient nature of acute neurotoxicity. Ongoing studies are addressing the treatment and prophylaxis of oxaliplatin neurotoxicity.
Effects of DNA mass on multiple displacement whole genome amplification and genotyping performance
Authors: Bergen Andrew W , Qi Ying , Haque Kashif A , Welch Robert A , Chanock Stephen J
Published: September 2005

Background

Whole genome amplification (WGA) promises to eliminate practical molecular genetic analysis limitations associated with genomic DNA (gDNA) quantity. We evaluated the performance of multiple displacement amplification (MDA) WGA using gDNA extracted from lymphoblastoid cell lines (N = 27) with a range of starting gDNA input of 1–200 ng into the WGA reaction. Yield and composition analysis of whole genome amplified DNA (wgaDNA) was performed using three DNA quantification methods (OD, PicoGreen® and RT-PCR). Two panels of N = 15 STR (using the AmpFlSTR® Identifiler® panel) and N = 49 SNP (TaqMan®) genotyping assays were performed on each gDNA and wgaDNA sample in duplicate. gDNA and wgaDNA masses of 1, 4 and 20 ng were used in the SNP assays to evaluate the effects of DNA mass on SNP genotyping assay performance. A total of N = 6,880 STR and N = 56,448 SNP genotype attempts provided adequate power to detect differences in STR and SNP genotyping performance between gDNA and wgaDNA, and among wgaDNA produced from a range of gDNA templates inputs.

Results

The proportion of double-stranded wgaDNA and human-specific PCR amplifiable wgaDNA increased with increased gDNA input into the WGA reaction. Increased amounts of gDNA input into the WGA reaction improved wgaDNA genotyping performance. Genotype completion or genotype concordance rates of wgaDNA produced from all gDNA input levels were observed to be reduced compared to gDNA, although the reduction was not always statistically significant. Reduced wgaDNA genotyping performance was primarily due to the increased variance of allelic amplification, resulting in loss of heterozygosity or increased undetermined genotypes. MDA WGA produces wgaDNA from no template control samples; such samples exhibited substantial false-positive genotyping rates.

Conclusion

The amount of gDNA input into the MDA WGA reaction is a critical determinant of genotyping performance of wgaDNA. At least 10 ng of lymphoblastoid gDNA input into MDA WGA is required to obtain wgaDNA TaqMan® SNP assay genotyping performance equivalent to that of gDNA. Over 100 ng of lymphoblastoid gDNA input into MDA WGA is required to obtain optimal STR genotyping performance using the AmpFlSTR® Identifiler® panel from wgaDNA equivalent to that of gDNA.
Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons
Authors: Tenenbaum Alexander , Motro Michael , Fisman Enrique Z
Published: September 2005

There are three peroxisome proliferator-activated receptors (PPARs) subtypes which are commonly designated PPAR alpha, PPAR gamma and PPAR beta/delta. PPAR alpha activation increases high density lipoprotein (HDL) cholesterol synthesis, stimulates "reverse" cholesterol transport and reduces triglycerides. PPAR gamma activation results in insulin sensitization and antidiabetic action. Until recently, the biological role of PPAR beta/delta remained unclear. However, treatment of obese animals by specific PPAR delta agonists results in normalization of metabolic parameters and reduction of adiposity. Combined treatments with PPAR gamma and alpha agonists may potentially improve insulin resistance and alleviate atherogenic dyslipidemia, whereas PPAR delta properties may prevent the development of overweight which typically accompanies "pure" PPAR gamma ligands. The new generation of dual-action PPARs – the glitazars, which target PPAR-gamma and PPAR-alpha (like muraglitazar and tesaglitazar) are on deck in late-stage clinical trials and may be effective in reducing cardiovascular risk, but their long-term clinical effects are still unknown. A number of glitazars have presented problems at a late stage of clinical trials because of serious side-effects (including ragaglitazar and farglitazar). The old and well known lipid-lowering fibric acid derivative bezafibrate is the first clinically tested pan – (alpha, beta/delta, gamma) PPAR activator. It is the only pan-PPAR activator with more than a quarter of a century of therapeutic experience with a good safety profile. Therefore, bezafibrate could be considered (indeed, as a "post hoc" understanding) as an "archetype" of a clinically tested pan-PPAR ligand. Bezafibrate leads to considerable raising of HDL cholesterol and reduces triglycerides, improves insulin sensitivity and reduces blood glucose level, significantly lowering the incidence of cardiovascular events and new diabetes in patients with features of metabolic syndrome. Clinical evidences obtained from bezafibrate-based studies strongly support the concept of pan-PPAR therapeutic approach to conditions which comprise the metabolic syndrome. However, from a biochemical point of view, bezafibrate is a PPAR ligand with a relatively low potency. More powerful new compounds with pan-PPAR activity and proven long-term safety should be highly effective in a clinical setting of patients with coexisting relevant lipid and glucose metabolism disorders.
Identification of unique reciprocal and non reciprocal cross packaging relationships between HIV-1, HIV-2 and SIV reveals an efficient SIV/HIV-2 lentiviral vector system with highly favourable features for in vivo testing and clinical usage
Authors: Strappe Padraig M , Hampton David W , Brown Douglas , Cachon-Gonzalez Begona , Caldwell Maeve , Fawcett James W , Lever Andrew ML
Published: September 2005

Background

Lentiviral vectors have shown immense promise as vehicles for gene delivery to non-dividing cells particularly to cells of the central nervous system (CNS). Improvements in the biosafety of viral vectors are paramount as lentiviral vectors move into human clinical trials. This study investigates the packaging relationship between gene transfer (vector) and Gag-Pol expression constructs of HIV-1, HIV-2 and SIV. Cross-packaged vectors expressing GFP were assessed for RNA packaging, viral vector titre and their ability to transduce rat primary glial cell cultures and human neural stem cells.

Results

HIV-1 Gag-Pol demonstrated the ability to cross package both HIV-2 and SIV gene transfer vectors. However both HIV-2 and SIV Gag-Pol showed a reduced ability to package HIV-1 vector RNA with no significant gene transfer to target cells. An unexpected packaging relationship was found to exist between HIV-2 and SIV with SIV Gag-Pol able to package HIV-2 vector RNA and transduce dividing SV2T cells and CNS cell cultures with an efficiency equivalent to the homologous HIV-1 vector however HIV-2 was unable to deliver SIV based vectors.

Conclusion

This new non-reciprocal cross packaging relationship between SIV and HIV-2 provides a novel way of significantly increasing bio-safety with a reduced sequence homology between the HIV-2 gene transfer vector and the SIV Gag-Pol construct thus ensuring that vector RNA packaging is unidirectional.
Pregnancy and delivery while receiving vagus nerve stimulation for the treatment of major depression: a case report
Authors: Husain Mustafa M , Stegman Diane , Trevino Kenneth
Published: September 2005

Background

Depression during pregnancy can have significant health consequences for the mother and her infant. Antidepressant medications, which pass through the placenta, may increase the risk of low birth weight and preterm delivery. The use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy may induce serotonergic symptoms in the infant after delivery. Antidepressant medications in breast milk may also be passed to an infant. Vagus nerve stimulation (VNS) therapy is an effective non-pharmacologic treatment for treatment-resistant depression (TRD), but little information exists regarding the use of VNS therapy during pregnancy.

Case presentation

The patient began receiving VNS therapy for TRD in March 1999. The therapy was effective, producing substantial reductions in depressive symptoms and improvement of function. In 2002, the patient reported that she was pregnant. She continued receiving VNS therapy throughout her pregnancy, labor, and delivery, which enabled the sustained remission of her depression. The pregnancy was uneventful; a healthy daughter was delivered at full term.

Conclusion

In this case, VNS therapy provided effective treatment for TRD during pregnancy and delivery. VNS was safe for the patient and her child.
Open label phase II trial of single, ascending doses of MRA in Caucasian children with severe systemic juvenile idiopathic arthritis: proof of principle of the efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of prolonged clinical improvement
Authors: Woo Patricia , Wilkinson Nicholas , Prieur Anne-Marie , Southwood Taunton , Leone Valentina , Livermore Polly , Wythe Helena , Thomson David , Kishimoto Tadamitsu
Published: September 2005

Eighteen Caucasian (white, Middle East and Asian) children diagnosed by paediatric rheumatologists in the UK and France as having systemic juvenile idiopathic arthritis (sJIA) were enrolled in this open label, single dose trial. All patients had evidence of continued symptoms and disease activity for at least three months while receiving >0.2 mg/kg/day of prednisolone, or its equivalent, prior to recruitment. Twelve patients also received methotrexate (≤20 mg/m2/week). The patients were divided into three groups receiving 2, 4 or 8 mg/kg of MRA (tocilizumab) by intravenous infusion. No evidence of dose-limiting toxicity was observed and there were no dose-limiting safety issues. MRA appeared to be dramatically effective, with clinical and laboratory responses observed by 48 h post infusion, and these improvements continued well after serum MRA was undetectable. Eleven patients achieved the JIA definition of improvement (at least 3 of 6 core set criteria with a 30% improvement and no more than one worsened by 30%) and eight achieved ≥50% improvement. There were no observable differences with age. Clinical improvement in these children was observed for up to eight weeks, supporting the hypothesis that IL-6 is a key cytokine in the upregulation of genes crucial in the inflammation processes of sJIA, and the possibility of sequestration of MRA in the extra-vascular compartment needs to be considered.
Analytic solution of ray-tracing equations for a linearly inhomogeneous and elliptically anisotropic velocity model
Authors: Rogister Yves , Slawinski Michael A.
Published: September 2005

We study wave propagation in anisotropic inhomogeneous media. Specifically, we formulate and analytically solve the ray-tracing equations for the factorized model with wavefront velocity increasing linearly with depth and depending elliptically on direction. We obtain explicit expressions for traveltime, wavefront (phase) angle, and ray (group) velocity and angle, and study these seismological quantities for a model that successfully describes field measurements in the Western Canada Basin. By considering numerical examples, we also show that the difference between the wavefront and ray velocities depends only slightly on the anisotropy parameter, whereas the difference between the wavefront and ray angles is, in a first-order approximation, linear in the anisotropy parameter.
Iterative use of the Bruggeman-Hanai-Sen mixing model to determine water saturations in sand
Authors: Johnson Raymond H. , Poeter Eileen P.
Published: September 2005

The accuracy of the Bruggeman-Hanai-Sen (BHS) mixing model has been previously demonstrated for two-material mixtures during BHS model development. Using permittivities determined from modeling ground-penetrating radar (GPR) data, the BHS model has been iteratively applied to three-material mixtures of water, sand, and a dense, nonaqueous-phase liquid (DNAPL). However, the accuracy of this application has not been verified. A 10-cm air-line system driven by a network analyzer is used to measure bulk permittivitities when the water saturations in a sand are varied (frequency range of 20 to 200 MHz). Through iterative use of the BHS mixing model, the measured permittivities are used to calculate water saturations, which are compared to known saturation values. An iterative BHS mixing model for an air/water/sand system must consider which two-material end member (air/sand or water/sand) represents the matrix term in the original two-material BHS model. An air/sand matrix provides the best accuracy for low water saturations, and a water/sand matrix provides the best accuracy for high water saturations; thus, a new weighted model is developed. For a given porosity and a measured bulk permittivity, water saturation is most accurately determined by proportionally weighting the water saturation values determined using air/sand as the matrix and water/sand as the matrix in the BHS model.
Depth-consistent reflection tomography using PP and PS seismic data
Authors: Foss Stig-Kyrre , Ursin Bjørn , Hoop Maarten V. de
Published: September 2005

We present a method of reflection tomography for anisotropic elastic parameters from PP and PS reflection seismic data. The method is based upon the differential semblance misfit functional in scattering angle and azimuth (DSA) acting on common-image-point gathers (CIGs) to find fitting velocity models. The CIGs are amplitude corrected using a generalized Radon transform applied to the data. Depth consistency between the PP and PS images is enforced by penalizing any mis-tie between imaged key reflectors. The mis-tie is evaluated by means of map migration-demigration applied to the geometric information (times and slopes) contained in the data. In our implementation, we simplify the codepthing approach to zero-scattering-angle data only. The resulting measure is incorporated as a regularization in the DSA misfit functional. We then resort to an optimization procedure, restricting ourselves to transversely isotropic (TI) velocity models. In principle, depending on the available surface-offset range and orientation of reflectors in the subsurface, by combining the DSA with codepthing, the anisotropic parameters for TI models can be determined, provided the orientation of the symmetry axis is known. A proposed strategy is applied to an ocean-bottom-seismic field data set from the North Sea.
Least-squares joint imaging of multiples and primaries
Authors: Brown Morgan P. , Guitton Antoine
Published: September 2005

Multiple reflections contain subsurface reflectivity information which often complements that found in primary reflections. Previous attempts to combine the additional information by summing prestack images of the primaries and multiples have generally failed because of crosstalk leakage between the images. We present a general linear least-squares joint imaging of multiples-and primaries (LSJIMP) inversion method to simultaneously suppress crosstalk noise and combine pegleg multiples and primaries in a prestack sense. In general, LSJIMP is compatible with a wide variety of prestack imaging methods and can be extended to jointly image primaries and other embedded wave modes such as shear-wave conversions. We present a particular LSJIMP implementation that utilizes an efficient linear operator to model and image pegleg multiples in a true relative-amplitude sense. Applied to a given type of pegleg multiple in the data, our imaging operator produces an image directly comparable to primaries after NMO. Our operator's kinematic component is an extension of the NMO equation that independently images split peglegs in a moderately heterogeneous earth. Its amplitude component corrects multiples for their differences in angle-dependent reflection strength and illumination, relative to a primary. We test our LSJIMP implementation on 2D and 3D prestack field data examples and show that the method cleanly separates primaries and multiples and also uses joint information in the events to interpolate the signal in acquisition gaps.
3D multiple-source Werner deconvolution for magnetic data
Authors: Hansen R. O.
Published: September 2005

Werner deconvolution has been widely used for at least 30 years for rapid interpretation of magnetic data. Since 1993, a multiple-source generalization of the method has been known, and at least two implementations of the algorithm are in use. Recently, Werner deconvolution has been extended to three dimensions through the use of generalized Hilbert transforms. In this paper, a multiple-source extension of the 3D Werner algorithm is developed which also generalizes the 2D multiple-source algorithm. The implementation of this algorithm is tested on both 3D multiple-source synthetic data, for which good agreement with the model is obtained, and on complex data from the Albuquerque basin, which yields results corresponding well with other interpretations and with known geology.
Planned seismic imaging using explicit one-way operators
Authors: Ferguson Robert J. , Margrave Gary F.
Published: September 2005

A method is presented to compare the accuracy and computational cost of explicit one-way extrapolation operators as used in seismic imaging. For a given model, accuracy is measured in terms of lateral positioning error, and cost is calculated relative to the cost of the spatial fast Fourier transform. The result is a planned imaging scheme that achieves the greatest accuracy with respect to the velocity model for a fixed cost. To demonstrate, we use a 2D section of the EAGE/SEG salt model and assemble a suite of the most common operators. The data are imaged using each operator individually, and the results are compared to the result from the plan-based algorithm. The planned image is shown to return improved accuracy for no additional cost.
Elastic wave modeling in fractured media with an explicit approach
Authors: Zhang Jianfeng
Published: September 2005

This paper presents a numerical technique for modeling elastic-wave propagation in media with discrete distributions of fractures. The scheme is developed following the explicit treatments of fractures based on a linear-slip displacement-discontinuity model instead of using an effective-medium theory. The algorithm is implemented on an irregular numerical mesh by using the proposed integral forms of the elastic-momentum equations and displacement-discontinuity conditions together with a triangular-grid finite-difference operator. As a result, arbitrary nonplanar fractures can be explicitly represented on the mesh without extra computational cost. In contrast to schemes based on effective-medium theory, no stability problem arises here when incorporating fractures with any fracture compliance. The proposed scheme allows the background medium to be heterogeneous and, furthermore, allows the medium to differ on both sides of the fracture. In comparison with the seismic response calculation in the background medium in the absence of the fractures, the additional computational cost and memory requirements for incorporating many fractures are small. Examples of seismic-wave scattering from single horizontal and tilted fractures as well as a set of parallel tilted fractures demonstrate the good behavior of the proposed algorithm.
Determining subsurface fracture characteristics from azimuthal resistivity surveys: A case study at Nsawam, Ghana
Authors: Boadu Fred K. , Gyamfi Joseph , Owusu Emmanuel
Published: September 2005

We conducted azimuthal resistivity surveys (ARS) using the square-array configuration to characterize the subsurface fractured rock mass at selected farmland sites in Nsawam District, Ghana. This study is the first of its kind in Ghana, and it provides useful information for future hydrological studies of the area, where groundwater is suspected to be contaminated as a result of the indiscriminate use of pesticides and fertilizers by local farmers. We estimate the fracture orientation, fracture porosity, and coefficient of anisotropy of the fractured rock mass at the selected sites from the azimuthal resistivity measurements; the specific surface area is estimated from field geological mapping of outcrops. High correlations exist between the specific surface area and the real and imaginary parts of the measured resistivity of the fractured rock mass. Fractures at localities with relatively high values of coefficient of anisotropy possess relatively high fracture porosity and relatively low specific surface area and are thus more likely to be intensely fractured and permeable. Results from this integrated geological and geophysical study indicate two dominant fracture directions in the study area, with other minor orientations that may influence groundwater and contaminant transport. The dominant orientations of the fracture systems at Kitase are northwest-southeast in the northern part and northeast-southwest in the southern part. At Amanfrom, the fractures are oriented northwest-southeast, and at Nsakye they are northeast-southwest. These sources of information from a noninvasive geophysical method are useful in assessing the transport properties of the fractured rock mass in the study area.
Interpolation and gridding of aliased geophysical data using constrained anisotropic diffusion to enhance trends
Authors: Smith Richard S. , O'Connell Michael D.
Published: September 2005

Geophysical data are frequently collected with a fine sample interval along traverse lines but with a coarser sampling in the direction perpendicular to the traverses. This disparity in sampling intervals is particularly evident when magnetic data are collected simultaneously with airborne electromagnetic data. Interpolating this traverse data onto an evenly spaced 2D grid can result in aliasing artifacts. For example, narrow linear structures that trend at acute angles to the traverse lines are imaged as a thick/thin/thick feature, looking like a boudinage or string of beads. Applying the anisotropic diffusion process to the resulting grids of data removes the artifacts, but the grid values close to the traverses are altered significantly from their initial values. The altered values are therefore not faithful to the original traverse data. The anisotropic diffusion algorithm can be modified to constrain values close to the original traverses. This modification removes the aliasing artifacts and produces a data grid faithful to the original traverse data. Some small artifacts along the traverse lines in the final data grid become more evident when grids containing derivative data (such as the analytic signal) are generated from the new data grid. However, these small traverse-line artifacts can be removed with standard microleveling procedures. The constrained anisotropic diffusion process is iterative, and some experimentation is required to determine the appropriate number of iterations.
This issue of GEOPHYSICS
Authors: Schuster Gerard T.
Published: September 2005

In this article, the Editor of Geophysics provides an overview of all technical articles in this issue of the journal.
Unconventional mechanisms control cyclic respiratory gas release in flyingDrosophila
Authors: Lehmann Fritz-Olaf , Heymann Nicole
Published: September 2005

The high power output of flight muscles places special demands on the respiratory gas exchange system in insects. In small insects, respiration relies on diffusion, and for elevated locomotor performance such as flight,instantaneous gas exchange rates typically co-vary with the animal's metabolic activity. By contrast, under certain conditions, instantaneous release rate of carbon dioxide from the fruit fly Drosophila flying in a virtual-reality flight arena may oscillate distinctly at low frequency(0.37±0.055 Hz), even though flight muscle mechanical power output requires constant metabolic activity. Cross-correlation analysis suggests that this uncoupling between respiratory and metabolic rate is not driven by conventional types of convective flow reinforcement such as abdominal pumping,but might result from two unusual mechanisms for tracheal breathing. Simplified analytical modeling of diffusive tracheal gas exchange suggests that cyclic release patterns in the insect occur as a consequence of the stochastically synchronized control of spiracle opening area by the four large thoracic spiracles. Alternatively, in-flight motion analysis of the abdomen and proboscis using infra-red video imaging suggests utilization of the proboscis extension reflex (PER) for tracheal convection. Although the respiratory benefit of synchronized spiracle opening activity in the fruit fly is unclear, proboscis-induced tracheal convection might potentially help to balance the local oxygen supply between different body compartments of the flying animal.
Perfusion of the isolated trout heart coronary circulation with red blood cells: effects of oxygen supply and nitrite on coronary flow and myocardial oxygen consumption
Authors: Jensen F. B. , Agnisola C.
Published: September 2005

A method for perfusion of the isolated trout heart coronary circulation with red blood cells (RBCs) was developed. The method was used to analyse the influence of RBC perfusion on myocardial O2 supply and O2 consumption and to test the hypothesis that nitrite is converted to vasoactive nitric oxide in the RBC-perfused coronary circulation. Perfusion with RBCs significantly increased myocardial O2 supply and O2 consumption by increasing the incoming O2concentration and the O2 extraction. Coronary flow did not differ between RBC perfusion and saline perfusion, but RBC perfusion established a strong linear increase in myocardial O2 consumption with coronary flow. Nitric oxide was measured in the atrial effluent of the preparation. Perfusion with saline under hypoxic conditions was associated with NO production. The nitric oxide synthase inhibitor L-NA obliterated this NO production and significantly decreased coronary flow, showing that the NO was vasoactive and probably of endothelial origin. RBC perfusion at low PO2 similarly caused an L-NA-inhibitable NO production. The change in NO production upon subsequent nitrite addition, by contrast, was not inhibited by L-NA. Nitrite entered trout erythrocytes independent of degree of oxygenation, but the O2 saturation of RBCs showed a major decrease in the coronary circulation, and[NO2-] decreased while methaemoglobin rose, suggesting that deoxyHb-mediated reduction of nitrite to NO may have occurred. However,other possibilities (e.g. NO2-→NO conversion in myocardial cells) cannot be excluded. The NO formation associated with nitrite had no effect on coronary flow, possibly because NO was produced after the resistance vessels.
Does daily activity level determine muscle phenotype?
Authors: Hodgson John A. , Roy Roland R. , Higuchi Norio , Monti Ryan J. , Zhong Hui , Grossman Elena , Edgerton V. Reggie
Published: September 2005

The activation level of a muscle is presumed to be a major determinant of many mechanical and phenotypic properties of its muscle fibers. However, the relationship between the daily activation levels of a muscle and these properties has not been well defined, largely because of the lack of accurate and sustained assessments of the spontaneous activity levels of the muscle. Therefore, we determined the daily activity levels of selected rat hindlimb muscles using intramuscular EMG recordings. To allow comparisons across muscles having varying activity levels and/or muscle fiber type compositions,we recorded EMG activity in a predominantly slow plantarflexor (soleus), a predominantly fast plantarflexor (medial gastrocnemius, MG), a predominantly fast ankle dorsiflexor (tibialis anterior, TA) and a predominantly fast knee extensor (vastus lateralis, VL) in six unanesthetized rats for periods of 24 h. EMG activity levels were correlated with the light:dark cycle, with peak activity levels occurring during the dark period. The soleus was the most active and the TA the least active muscle in all rats. Daily EMG durations were highest for soleus (11–15 h), intermediate for MG (5–9 h) and VL (3–14 h) and lowest for TA (2–3 h). Daily mean EMG amplitudes and integrated EMG levels in the soleus were two- to threefold higher than in the MG and VL and seven- to eightfold higher than in the TA. Despite the three- to fourfold difference in activation levels of the MG and VL vs the TA, all three predominantly fast muscles have been reported to have a similar, very low percentage of slow fibers. Comparing these relative EMG levels to the published fiber type profiles of these muscles yields a very poor relationship between daily activity level and fiber type composition in the same muscles across several species. Although it is clear that changing the levels of activity can modulate the expression of the myosin phenotype,these results indicate that factors other than activation must play critical roles in determining and maintaining normal phenotypic properties of skeletal muscle fibers.