bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Detection of K-ras Mutations in Bile by Peptide Nucleic Acid-mediated PCR Clamping and Melting Curve Analysis: Comparison with Restriction Fragment Length Polymorphism Analysis
Authors: Chen Chiung-Yu , Shiesh Shu-Chu , Wu Sheu-Jen
Published: February 2004

Background: Current methods for detection of K-ras gene mutations are time-consuming. We aimed to develop a one-step PCR technique using fluorescent hybridization probes and competing peptide nucleic acid oligomers to detect K-ras mutations in bile and to compare the efficacy with restriction fragment length polymorphism (RFLP) analysis.

Methods: Bile samples were obtained from 116 patients with biliary obstruction, including gallstones (n = 64), benign biliary strictures (n = 6), pancreatic cancer (n = 20), and cholangiocarcinoma (n = 26). The DNA was extracted and subjected to K-ras mutation analysis by real-time PCR and RFLP analysis. Mutations were confirmed by direct sequencing. The sensitivity and specificity were calculated according to the clinical results.

Results: The analysis time for real-time PCR was <1 h, whereas RFLP analysis took more than 2 days. With the sensor probe designed for the GAT (G12D) mutant in codon 12 of the K-ras gene, the real-time PCR method also detected the GTT (G12V) mutant. In contrast, a specific sensor probe for the TGT (G12C) mutant detected GAT (G12D), AGT (G12S), and GTT (G12V) mutants in addition to the TGT mutant. The real-time PCR assay allowed the detection of mutation in a 3000-fold excess of wild-type bile DNA. In bile, K-ras codon 12 mutations were detected in 16 of 46 malignant cases by real-time PCR with the TGT probe and 15 by RFLP analysis. All benign cases were wild type.

Conclusion: Real-time PCR with a cysteine-specific (TGT) sensor probe can rapidly detect K-ras gene mutations in bile and diagnose malignant biliary obstruction with high specificity.
Measurement of Plasma Free Metanephrine and Normetanephrine by Liquid Chromatography–Tandem Mass Spectrometry for Diagnosis of Pheochromocytoma
Authors: Lagerstedt Susan A , O’Kane Dennis J , Singh Ravinder J
Published: February 2004

Background: Quantification of plasma free metanephrines is usually accomplished by HPLC with electrochemical detection, but sample preparation is labor-intensive and time-consuming, run times are long, and interfering substances sometimes obscure the relevant peaks. The aim of this study was to develop a sensitive and specific LC-MS/MS method for plasma free metanephrines.

Methods: After solid-phase extraction, chromatographic separation of normetanephrine (NMN) and metanephrine (MN) was accomplished by use of a cyano analytical column. NMN, MN, d3-NMN, and d3-MN positive ions were detected in the multiple-reaction monitoring mode using the specific transitions m/z 166→134, 180→148, 169→137, and 183→151, respectively, with an atmospheric pressure chemical ionization source.

Results: Multiple calibration curves exhibited consistent linearity and reproducibility. Interassay imprecision values (CV; n = 20) for NMN at 0.64, 1.9, and 2.7 nmol/L were 6.6%, 7.8%, and 13%, respectively. Interassay CV for MN at 0.60, 1.2, and 2.1 nmol/L (n = 20) were 9.2%, 6.8%, and 9.8%, respectively. The mean recoveries of NMN and MN relative to the internal standard were 100% and 96%, respectively. The assays were linear between 0.20 and 10.0 nmol/L. Deming regression of HPLC and LC-MS/MS results yielded slopes of 0.93 (95% confidence interval, 0.89–0.98) and 0.89 (0.85–0.93) and y-intercepts of −0.16 and 0.03 nmol/L for NMN (n = 132) and MN (n = 92), respectively.

Conclusions: This novel LC-MS/MS approach provides a precise, rapid, and specific alternative method to HPLC for the quantification of the low nanomolar concentrations of free metanephrines in plasma.
Quality Assessment of Interpretative Commenting in Clinical Chemistry
Authors: Lim Ee Mun , Sikaris Ken A , Gill Janice , Calleja John , Hickman Peter E , Beilby John , Vasikaran Samuel D
Published: February 2004

Background: Clinical interpretation of laboratory results is an integral part of clinical chemistry. However, the performance goals for assessing interpretative commenting in this discipline have not been as well established as for the quality of analytical requirements.

Methods: We present a review of the 10 case reports circulated in the 2002 Patient Report Comments Program by the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists Chemical Pathology Group of RCPA-Quality Assurance Programs Pty Ltd. Participants were expected to add an interpretative comment to a set of results accompanied by brief clinical details. Comments received were broken down into components that were translated into key phrases. An expert panel evaluated the appropriateness of the key phrases and proposed a suggested composite comment. A case summary/rationale was also returned to participants.

Results: There was considerable diversity in the range of interpretative comments received for each case report. Although the majority of comments received were felt to be acceptable by the expert panel, some comments were felt to be inappropriate, misleading, or in a few instances, dangerous.

Conclusion: The golden rule in medicine is “do no harm”. Although there is no objective evidence that interpretive comments help to improve patient outcomes, if comments are added to reports it is important that they reflect accepted practice and current guidelines. It is of concern that a large proportion of comments returned were considered to be inappropriate and/or misleading. The Patient Report Comments Program has highlighted the need to consider limiting commenting to persons with clear expertise.
Potential Clinical Utility of a New IRMA for Parathyroid Hormone in Postmenopausal Patients with Primary Hyperparathyroidism
Authors: Carnevale Vincenzo , Dionisi Simona , Nofroni Italo , Romagnoli Elisabetta , Paglia Federica , De Geronimo Simona , Pepe Jessica , Clemente Giovanni , Tonnarini Gianfranco , Minisola Salvatore
Published: February 2004

Background: A new commercially available (so-called second-generation) IRMA for parathyroid hormone (PTH) separately detects intact PTH and its N-truncated fragments; however, no studies have compared the first- and second-generation IRMAs for PTH in patients with primary hyperparathyroidism (PHPT) to assess their respective diagnostic accuracies.

Methods: We concomitantly investigated 39 postmenopausal patients with PHPT and a control group of 70 healthy postmenopausal women matched for age, renal function, and vitamin D status. In all individuals, PTH was measured with a classic IRMA (PTH-S; DiaSorin Inc.), which uses antibodies directed against epitopes 1–34 and 39–84, and a new method (Scantibodies Laboratory. Inc.), which uses antibodies against epitopes 1–4 and 39–84 (PTH-W) and epitopes 7–34 and 39–84 (PTH-T). We also assayed serum PTH in 10 PHPT patients every 24 h for 5 days after successful surgery.

Results: The different assays gave serum PTH values that were >2 SD higher than values for the control population in 59% (PTH-S), 77% (PTH-W), and 82% (PTH-T) of patients with PHPT. However, ROC curve analysis showed no significant differences among the three PTH assays, demonstrating overlapping diagnostic sensitivities. In PHPT patients, the correlation among the assays was highly significant (r = 0.91–0.92; P <0.001). The ratio PTH-W:PTH-T × 100 showed a gaussian distribution in both PHPT patients and controls, whose mean (SD) values [63.4 (13.3)% vs 64.5 (9.5)%, respectively] did not differ significantly. After parathyroidectomy, the mean percentages of variation in PTH detected with all of the assays were quite similar.

Conclusions: The distribution of the PTH-W:PTH-T ratio in patients and controls suggests that PHPT does not markedly influence the rate at which biologically inactive fragments are generated by central or peripheral cleavage of PTH. The similar postoperative curves seem to contradict the hypothesized effect of acute hypocalcemia in modulating the central secretion of hormonal fragments. Our results indicate that the three investigated assays have similar diagnostic sensitivities in PHPT.
Pyrosequencing Technology as a Method for the Diagnosis of Multiple Endocrine Neoplasia Type 2
Authors: Kruckeberg Kent E , Thibodeau Stephen N
Published: February 2004

Background: Multiple endocrine neoplasia type 2 (MEN2) is a cancer syndrome with well-characterized causative mutations. Missense mutations in ∼15 codons of the RET gene have been linked to disease phenotypes in the vast majority of cases. These missense mutations range from very simple single nucleotide base changes to more numerous changes at a given codon; they therefore are often tested for by more than one DNA-based diagnostic method. We developed and evaluated a Pyrosequencing™ technology-based approach for MEN2 mutation testing that allows both simple and complex mutations to be analyzed on one platform.

Methods: Archived DNA from peripheral blood of patients referred to the Mayo Clinic Molecular Genetics laboratory for MEN2 testing was selected. One to all of codons 609, 611, 618, 620, 630, 634, 768, 804, and 918 were analyzed by Pyrosequencing technology to match the original analysis of each patient. Template PCRs were set up using an automated liquid handler; the subsequent post-PCR preparation step was performed manually, and the sequencing was performed by a PSQ 96 instrument. Samples were tested in batch sizes expected to occur routinely.

Results: We analyzed samples from 217 patients who previously tested negative for MEN2 and 230 patients who previously tested positive, for a total of 1449 sequencing reactions. One discrepant result was found (100% concordant for negatives and 99.6% concordant for positives). A total of 37 unique mutations or alterations of unknown significance were analyzed.

Conclusion: Pyrosequencing technology offers an accurate, nonisotopic, simple, and rapid method for the analysis of DNA from patients suspected of having MEN2.
Distribution and Correlates of C-Reactive Protein Concentrations among Adult US Women
Authors: Ford Earl S , Giles Wayne H , Mokdad Ali H , Myers Gary L
Published: February 2004

Background: Understanding the distribution of C-reactive protein (CRP) concentration among adult women in the US helps to establish the magnitude of women at increased risk for cardiovascular disease.

Methods: We examined the distribution and correlates of CRP, using data from 2205 women ≥20 years of age from the National Health and Nutrition Examination Survey 1999–2000. CRP was measured with a high-sensitivity latex-enhanced turbidimetric assay.

Results: CRP concentration ranged from 0.1 to 296.0 mg/L (median, 2.7 mg/L). After exclusion of women with a CRP concentration >10 mg/L, the median was 2.2 mg/L. Approximately 25.7% of women, representing ∼26.8 million women, did not report using hormone replacement therapy and had a CRP concentration >3.0 to 10 mg/L, a category considered to indicate high risk for cardiovascular disease. Multiple linear regression analysis included age, race or ethnicity, education, smoking status, total cholesterol concentration, triglyceride concentration, systolic blood pressure, waist circumference, and concentrations of glucose, insulin, c-peptide, and glycated hemoglobin. CRP concentration varied by race or ethnicity (Mexican American > white) and hormone replacement therapy (users > nonusers). In addition, significant and independent associations existed between CRP and waist circumference, total cholesterol and triglyceride concentrations, and systolic blood pressure but not age, smoking status, alcohol use, insulin concentration, glycated hemoglobin, and c-peptide concentration.

Conclusion: Large numbers of US women have an increased concentration of CRP.
Characterization of Amplifiable, Circulating RNA in Plasma and Its Potential as a Tool for Cancer Diagnostics
Authors: El-Hefnawy Talal , Raja Siva , Kelly Lori , Bigbee William L , Kirkwood John M , Luketich James D , Godfrey Tony E
Published: February 2004

Background: Several recent reports have described the detection of circulating, cancer-related RNA molecules in serum or plasma from cancer patients, but little is known about the biology of this extracellular RNA. We aimed to determine how RNA is protected against degradation in serum, to optimize RNA isolation from large volumes of serum, and to test our optimized assays for serum-based cancer detection.

Methods: We used quantitative reverse transcription-PCR (QRT-PCR) analysis to investigate the isolation and biology of extracellular plasma RNA. We then examined the presence of amplifiable RNA transcripts in plasma and serum from controls and from patients with esophageal cancer and malignant melanoma.

Results: We found that extracellular RNA in plasma is highly degraded and can be isolated most efficiently by guanidinium–phenol extraction followed by precipitation. Extracellular RNA is stable in serum for up to 3 h but is destroyed immediately by addition of detergents. Extracellular RNA can be captured on 0.2 μm filters, allowing concentration of RNA from several milliliters of plasma. When we concentrated RNA from up to 4 mL of serum, detection of cancer-related transcripts in serum from cancer patients and controls was infrequent and inconsistent.

Conclusions: Extracellular RNA is most likely protected within protein or lipid vesicles, possibly apoptotic bodies, which can be disrupted by detergents. Despite optimizing many aspects of plasma RNA detection, we were unable to reproducibly detect cancer-related transcripts. Our data suggest that measurement of circulating RNA may not be a good approach to early cancer diagnosis.
Association of Serum Carotenoids and Tocopherols with γ-Glutamyltransferase: The Cardiovascular Risk Development in Young Adults (CARDIA) Study
Authors: Lee Duk-Hee , Gross Myron D , Jacobs David R
Published: February 2004

Background: Our previous studies suggest that serum γ-glutamyltransferase (GGT) activity may be related to oxidative stress, supporting findings of experimental studies. To further examine the role of GGT in relation to oxidative stress, we investigated the association between serum carotenoids and tocopherols, which have antioxidant properties, and serum GGT.

Methods: Study participants were 3128 black and white men and women 17–35 years of age in 1985–1986. Serum carotenoids and tocopherols were measured at years 0 and 7, and serum GGT was measured at years 0 and 10.

Results: Circulating concentrations of α-carotene, β-carotene, and β-cryptoxanthin inversely predicted the serum GGT concentration measured 10 years later in a dose–response manner (P for trend <0.01). Year 0 zeaxanthin/lutein was weakly inversely associated with year 10 GGT (P for trend = 0.08), and year 0 lycopene was unrelated to year 10 GGT. Adjusted geometric means of serum GGT at year 10 according to quintile of the sum of four carotenoids at year 0 (α-carotene, β-carotene, β-cryptoxanthin, and zeaxanthin/lutein) were 19.9, 19.4, 18.9, 17.8, and 17.3 U/L (P for trend <0.01). Year 0 α-tocopherol was also a significant inverse predictor of year 10 serum GGT concentration (P for trend = 0.03), whereas γ-tocopherol showed an inconsistent or possibly U-shaped association. However, year 0 serum GGT did not predict serum antioxidants measured 7 years later.

Conclusion: Our present findings support the contention that serum GGT concentration is a marker related with oxidative stress.
Eudesmane Derivatives from Hieracium intybaceum
Authors: Grass Sandra , Zidorn Christian , Ellmerer Ernst P. , Stuppner Hermann
Published: March 2004

Two new eudesmanolides, 4β‐H,3β‐(β‐D‐glucopyranosyloxy)eudesma‐1,11(13)‐dien‐12,6‐olide (5a) and 3β‐D‐glucopyranosyloxyeudesma‐1,4(15),11(13)‐trien‐12,6‐olide (5b), as well as two related, known compounds, tuberiferin (7a) and dehydrobrachylaenolide (7b), were isolated from the CH2Cl2 extract of subaerial parts of Hieracium intybaceum All. Compounds 6a, 6b, 8a, and 8b, the Me esters of the corresponding sesquiterpenic acids related to 5a, 5b, 7a, and 7b, respectively, were obtained as artifacts during the isolation process. Additionally, linoleic acid (1), linolenic acid (2), the lignane syringaresinol 4′‐O‐β‐D‐glucopyranoside (3), and the guaianolide dehydrocostus lactone (4) were also isolated from H. intybaceum. Structure elucidations were based on mass spectrometry and extensive 1D‐ and 2D‐NMR spectroscopy.
Two‐photon imaging of brain pericytes in vivo using dextran‐conjugated dyes
Authors: Hirase Hajime , Creso Judith , Singleton Malaika , Barthó Peter , Buzsáki György
Published: March 2004

Pericytes in the central nervous system (CNS) are hypothesized to be involved in important circulatory functions, including local blood flow regulation, angiogenesis, immune reaction, and regulation of blood‐brain barrier. Despite these putative functions, functional correlates of pericytes in vivo are scarce. We have labeled CNS pericytes using the dextran‐conjugated fluorescent calcium indicator Calcium Green I and imaged them in somatosensory cortex of the mouse in vivo. Intracellular calcium concentration in pericytes showed spontaneous surges lasting for several seconds. Furthermore, population bursts of neuronal activity were associated with increased Ca2+ signal in a portion of the pericytes. Selective in vivo labeling of pericytes with functional markers may help reveal their physiological function in neuronal activity‐associated regulation of local cerebral blood flow. © 2004 Wiley‐Liss, Inc.
Nitric oxide as a radiosensitizer: Evidence for an intrinsic role in addition to its effect on oxygen delivery and consumption
Authors: Jordan Bénédicte F. , Sonveaux Pierre , Feron Olivier , Grégoire Vincent , Beghein Nelson , Dessy Chantal , Gallez Bernard
Published: March 2004

Different nitric oxide (NO)‐mediated treatments (e.g., isosorbide dinitrate, insulin and electrical stimulation of the host tissue) have been investigated for their effects on tumor oxygenation and radiation sensitivity. We further address the issue of the role played by modulation of the NO‐pathway in tumor radiosensitivity. For this purpose, the local concentration of NO was monitored after treatment in FSaII tumors and a comparison between the sensitivity of LLC tumors implanted both on eNOS−/− and wild‐type (WT) mice was carried out. First, we demonstrate the central role played by eNOS in the radiosensitizing effect after application of insulin treatment and electrical stimulation: a significant increase in tumor NO content is induced by these treatments and the increase in tumor oxygenation, as well as the radiosensitizing effect are abolished in eNOS knock‐out mice, in contrast to WT mice. Second, by comparing the level of oxygen and NO achieved in tumors after NO‐mediated treatments and carbogen, we provide evidence that these NO‐mediated treatments are not simply acting by a single oxygen effect. These treatments induced significant regrowth delays compared to carbogen, despite a smaller increase in tumor oxygenation. For the NO‐mediated treatments, there was a direct correlation between the NO content and the radiosensitizing effect. These data strongly suggest that NO is a complementary factor additive to oxygen in determining the sensitivity to irradiation and we therefore propose that NO acts as an intrinsic radiosensitizer in vivo. © 2004 Wiley‐Liss, Inc.
Aurora A, Meiosis and Mitosis
Authors: Crane Richard , Gadea Bedrick , Littlepage Laurie , Wu Hua , Ruderman Joan V
Published: February 2004

Summry— The Aurora family kinases are pivotal to the successful execution of cell division. Together they ensure the formation of a bipolar mitotic spindle, accurate segregation of chromosomes and the completion of cytokinesis. They are also attractive drug targets, being frequently deregulated in cancer and able to transform cells in vitro. In this review, we summarize current knowledge about the three family members, Aur‐A, Aur‐B and Aur‐C. We then focus on Aur‐A, its roles in mitotic progression, and its emerging roles in checkpoint control pathways. Aur‐A activity can be controlled at several levels, including phosphorylation, ubiquitin‐dependent proteolysis and interaction with both positive regulators, such as TPX2, and negative ones, like the tumor suppressor protein p53. In addition, work in Xenopus oocytes and early embryos has revealed a second role for Aur‐A, directing the polyadenylation‐dependent translation of specific mRNAs important for cell cycle progression. This function extends to post‐mitotic neurons, and perhaps even to cycling somatic cells.
THE TENTH OSCILLATOR: THE WORK OF CATHY BERBERIAN 1958–1966
Authors: Osmond-Smith David
Published: March 2004

In future, those who look to anniversaries as a bulwark against the solvent flow of time will find their thoughts directed at once to Cathy Berberian who died 20 years ago in 1983, and to Luciano Berio, who died in 2003. This is apt enough. Their marriage lasted only fourteen years, from 1950 to 1964. But their creative trajectories were inextricably entwined. One does not get far in discussing the work of one without invoking the other.
Lindberg, Concerto for Orchestra, Barbican, London
Authors: Anderson Martin
Published: March 2004

There would hardly seem to be a composer better placed to write a concerto for orchestra than Magnus Lindberg: his complete mastery of orchestral texture – demonstrated in a string of modern classics, Joy (1989–90), Arena (1994–95), Feria (1997) and Cantigas (1998–99) among them – makes it a wonder he hasn't tackled the genre before now. Indeed, he quietly billed the magnificent Aura (1994–95) as a concerto for orchestra, although in reality it's as good a symphony as anyone has written this past half-century – my suspicion is that the label allowed him to dodge the issue.
International regime conflict in trade and environment: the Biosafety Protocol and the WTO
Authors: WINHAM GILBERT R.
Published: March 2004

Trade and environment constitute regimes in international relations: they are vehicles for cooperation between nation states that permit governments to address various subjects such as commercial non-discrimination, reduction of pollution, reciprocity and sustainable development. The issues of food safety and agricultural biotechnology (i.e., genetically modified organisms or GMOs) have been raised in both regimes, and have been managed in different and arguably inconsistent manners. In the trade regime, food safety and ag-biotech are mainly subject to the US-backed principle of ‘scientific risk assessment’ established in the WTO's Sanitary and Phytosanitary Agreement, while in the environment regime they would likely be addressed through the more politically based ‘precautionary principle’, promoted by the EU and represented in the Cartagena Protocol on Biosafety. Both the trade and environment regimes are rules-based, but conflict between them diminishes the force of precision and obligation needed to make rules effective. Furthermore, there is a danger that regime conflict could expand, thereby reducing the opportunity to promote an optimal relationship between science and society in the future.
Security and predictability under WTO law
Authors: WEISS WOLFGANG
Published: March 2004

This article focuses on the interpretation and application of law in WTO dispute settlement from the angle of legal certainty and predictability. An analysis of the interpretation of WTO law shows that in general it does not differ from the interpretation of other public international law as interpretative rules well known in international law are applied. This together with the consistence provided by the respect of earlier panel and Appellate Body reports safeguard legal certainty. Furthermore, legal certainty and predictability requires clarity in the law applicable in WTO dispute settlement, in particular as regards non-WTO law. It will be shown that apart from peremptory norms of public international law (ius cogens), the relevance of international law outside WTO law is limited. Non-WTO treaty law must not be applied except if referred to by WTO law or incorporated therein. Apart from that international law of any kind can only be considered when interpreting WTO law. In certain circumstances this applies even to non-WTO treaty law to which not all WTO members are parties. Due to the as yet limited importance of non-WTO law, legal certainty and predictability also depend on the issue of conflict of norms, which also is relevant as far as the interrelationship of the different WTO agreements is concerned. In this regard predictability and legal certainty cannot be fully reached.
Cluster observations of quasi‐periodic impulsive signatures in the dayside northern lobe: High‐latitude flux transfer events?
Authors: Thompson S. M. , Kivelson M. G. , Khurana K. K. , Balogh A. , Réme H. , Fazakerley A. N. , Kistler L. M.
Published: February 2004

We report on a series of quasi‐periodic reversals in GSM BZ observed by the four Cluster spacecraft in the northern dayside lobe poleward of the cusp on 23 February 2001. During an interval of about 35 min, multiple reversals (negative to positive) in BZ of approximately 1‐min duration with an approximate 8‐min recurrence time were observed. The individual structures do not resemble low‐latitude flux transfer events (FTE) [Russell and Elphic, 1979] but the 8‐min recurrence frequency suggests that intermittent reconnection may be occurring. Measurements (appropriately lagged) of the solar wind at ACE show that the IMF was southward‐oriented with a strong BX and that a modest dynamic pressure increase occurred as the events started. The multi‐point observations afforded by the Cluster spacecraft were used to infer the motion (direction and speed) of the observed magnetic field reversals. The associated currents were also calculated and they are consistent with the spatial confinement of the observed magnetic field reversals. We propose that the observed reversals are due to flux tubes reconnecting with closed field lines on the dayside. Ancillary data from the Cluster Ion Spectrometry (CIS) and Plasma Electron And Current Experiment (PEACE) instruments were used to develop a physical picture of the reversals.
Corecruitment of the Grg4 repressor by PU.1 is critical for Pax5‐mediated repression of B‐cell‐specific genes
Authors: Linderson Ylva , Eberhard Dirk , Malin Stephen , Johansson Annica , Busslinger Meinrad , Pettersson Sven
Published: March 2004

PU.1 and Pax5 are important regulators of immunoglobulin heavy‐chain (IgH) gene expression in B lineage cells. We have previously shown that PU.1 can potentiate the transcription of an IgH HS1,2 enhancer‐linked reporter gene, and that Pax5 represses the same enhancer in transient transfection assays. Here we report that PU.1, like Pax5, can recruit and physically interact with a member of the Groucho family of co‐repressors, Grg4. As a consequence, PU.1 in conjunction with Pax5 represses enhancer function in a position‐dependent manner when Grg4 is recruited. Interestingly, Grg4 levels decrease following B‐cell activation, suggesting temporal regulation of Grg4. Moreover, the joining‐chain promoter, with an activity pattern and architecture resembling HS1,2, can also be repressed by the combinatorial action of Pax5/PU.1/Grg4. These data indicate that Pax5 depends on PU.1, acting in cis, for stable recruitment of Grg co‐repressors to B‐cell‐specific genes.
Overview of large helical device diagnostics (invited)
Authors: Sudo S. , Nagayama Y. , Emoto M. , Goto M. , Hamada Y. , Ida K. , Ido T. , Iguchi H. , Inagaki S. , Isobe M. , Kawahata K. , Khlopenkov K. , Masuzaki S. , Minami T. , Morita S. , Muto S. , Nakanishi H. , Narihara K. , Nishizawa A. , Ohdachi S. , Osakabe M. , Ozaki T. , Peterson B. J. , Sakakibara S. , Sasao M. , Sato K. , Shoji M. , Tanaka K. , Toi K. , Tokuzawa T. , Watanabe K. , Watanabe T. , Yamada I. ,   LHD Team, Ashikawa N. , Kobuchi T. , Liang Y. , Tamura N. , Sasao H. , Ejiri A. , Okajima S. , Mase A. , Tsuji-Iio S. , Akiyama T. , Zanza V. , Bracco G. , Sibio A. , Tilia B. , Krasilnikov A. V. , Lyon J. F. , Vyacheslavov L. N. , Wurden G. A.
Published: February 2004

The Large Helical Device (LHD) is the largest helical machine with superconducting coils. Key diagnostics issues for LHD are: (a) capability for multidimensional measurements because of the nonaxisymmetric toroidal plasma; (b) measurements of the electric field; (c) cross check of fundamental parameters using different methods; (d) advanced measurements appropriate for steady-state operation; and (e) a satisfactory data acquisition system. The design and research and development of plasma diagnostics were carried out taking these issues into consideration. As a result, the present status of diagnostics is described: diagnostics for LHD operation, fundamental diagnostics for plasma performance, diagnostics for physics subjects, innovative diagnostics and diagnostics for long-pulse operation. The LHD experiment started in March, 1998. Since then, the development of diagnostics has kept pace with the experimental campaigns.
Installation of an advanced heavy ion beam diagnostic on the TJ-II stellarator
Authors: Bondarenko I. S. , Chmuga A. A. , Dreval N. B. , Khrebtov S. M. , Komarov A. D. , Kozachok A. S. , Krupnik L. I. , Coelho P. , Cunha M. , Gonçalves B. , Malaquias A. , Nedzelskiy I. S. , Varandas C. A. F. , Hidalgo C. , Garcia-Cortes I. , Melnikov A. V.
Published: February 2004

An advanced 200 keV heavy ion beam diagnostic has been developed for the TJ-II stellarator based on the simultaneous utilization of a 30° Proca–Green electrostatic energy analyzer and a multiple cell array detector. This innovative design allows instantaneous measurements of plasma potential and electron density profiles together with their respective fluctuations. In this article we present a description of the main parts of a heavy ion beam diagnostic (injection system, detectors, and control and data acquisition system) and the results obtained during the first operation on TJ-II. The problems of plasma loading of the detectors and hard x-ray generation associated with the probing beam are reported.
Study of structural effects of Langmuir probe array on edge fluctuation measurement in the compact helical system heliotron/torsatron
Authors: Ohkuni K. , Toi K. ,   Compact Helical System Group
Published: February 2004

A new type of Langmuir probe array is installed on the compact helical system heliotron/torsatron for the study of edge plasma turbulence. The probe array consists of four sets of the standard triple probes which are composed by four electrodes. Each triple probe set is slightly displaced both in the toroidal and poloidal directions to minimize the shadow effects among these probe sets. In order to investigate the structural effects of Langmuir probe arrays, the results obtained by this new probe array are compared with the results previously obtained by the old probe array where the triple probe sets were displaced only in the poloidal direction from each other. Stationary plasma parameters near the plasma edge such as electron temperature, density, and plasma potential were consistently obtained by two probe arrays. However, the new probe array displaced toroidally is more reliable to measure the particle flux induced by fluctuations where accurate measurement of the poloidal electric field fluctuations is required, compared with the old probe array.
A system for Alfvén-eigenmode spectroscopy using electrodes inserted into the compact helical system heliotron/torsatron plasma
Authors: Matsunaga G. , Toi K. ,   CHS Group
Published: February 2004

A system for Alfvén-eigenmode spectroscopy in the compact helical system heliotron/torsatron is presented. In this system, four electrodes inserted near the last closed flux surface are employed as the exciter of Alfvén eigenmodes (AEs). A set of magnetic probes is employed as the detectors of excited magnetic fluctuations. An alternating current path along the confinement magnetic field line is generated in the plasma edge between two electrodes which intersect with a specified magnetic field line. Another two electrodes also produce another current path. The polarity between these two current paths is adjusted to specify the toroidal mode number of the excited field perturbations. The frequency of the alternating current is in the range of 10–250 kHz. The possibility of the excitation of AEs by this system is discussed.
Diamagnetism measurements in the Hanbit magnetic mirror device
Authors: Bak J. G. , Lee S. G. , Kim B. C. , Hong J. , Yang J. G. , Kwon M. ,   the Hanbit Project Team, Chung Jinil
Published: February 2004

The diamagnetic effect is measured by using the diamagnetic loop with a compensation loop in the central cell of the Hanbit magnetic mirror device. To ensure reliable measurement, the influence of nearby conductors on the diamagnetic loop signal is investigated, and the output voltages during a pulsed vacuum field are measured to calibrate the loops installed inside the central cell. The diamagnetic measurement is carried out during rf discharges with a frequency of 3.75 MHz and heating power of up to 150 kW. In the measurement, the vacuum field of 0.126 T is applied in the central cell. The results from the experimental measurements are presented.
Atomic beam diagnostics for characterization of edge plasma in TJ-II stellarator
Authors: Brañas B. , Tafalla D. , Tabarés F. L. , Ortiz P.
Published: February 2004

He and Li beams have been installed and set into operation at the TJ-II stellarator with the aim of measuring electron temperature and density profiles in the edge and scrape-off layer regions of the plasma. The effusive thermal Li beam penetrates up to a normalized effective radius of ρ=0.6–0.7 in typical electron cyclotron heated plasmas. Density profiles deduced from the Li beam are wider than those obtained from extrapolation of the profile measured by Thomson scattering. The He beam is a pulsed supersonic one. Simultaneous detection of three emission lines (667.2, 706.5, and 728.1 nm) is made with a set of three photomultipliers. First He beam measurements of ne and Te in TJ-II are presented and the agreement among results of different plasma edge diagnostics is discussed.
Optimal foil shape for neutron time-of-flight measurements using elastic recoils
Authors: Hicks D. G. , Li C. K. , Séguin F. H. , Frenje J. A. , Petrasso R. D. , Sangster T. C.
Published: February 2004

The basis for a time-of-flight neutron spectrometer for inertial confinement fusion (ICF) experiments using recoils from a shaped scattering foil is presented. It is shown that the number of elastic recoils can be substantially increased by utilizing a large scattering foil in the shape of an ellipsoid, with the curvature of the ellipsoid being determined by the mass of the recoil particle. This shape allows the time-of-flight dispersion — present originally in the neutrons — to be maintained in the recoils despite the large foil area. The feasibility of using this design on current ICF experiments is discussed.
Two-dimensional full-wave simulation of microwave reflectometry on Alcator C-Mod
Authors: Lin Y. , Irby J. H. , Nazikian R. , Marmar E. S. , Mazurenko A.
Published: February 2004

A new two-dimensional full-wave code has been developed to simulate ordinary (O) mode reflectometry signals caused by plasma density fluctuations. The code uses the finite-difference time-domain method with a perfectly matched layer absorption boundary to solve Maxwell’s equations. Huygens wave sources are incorporated to generate Gaussian beams. The code has been used to simulate the reflectometer measurement of the quasicoherent mode (60–250 kHz) associated with enhanced Dα (EDA) H modes in the Alcator C-Mod tokamak. It is found that an analysis of the realistic experimental layout is essential for the quantitative interpretation of the mode amplitude.
Singular spectrum analysis as a tool for plasma fluctuations analysis
Authors: Marrelli L. , Bilato R. , Franz P. , Martin P. , Murari A. , O’Gorman M.
Published: February 2004

We describe the application of the singular spectrum analysis (SSA), an advanced adaptive statistical technique, to denoise experimental signals and to remove trends in order to isolate the relevant fluctuating components. We illustrate a fast denoising algorithm and show its performances relatively to synthetic and experimental signals of the soft x-ray (SXR) spectrometer and the polarimeter installed in the reversed field experiment (RFX) device. As a further application, we report a first estimate of the electron temperature fluctuations in the core of the RFX experiment. They have been performed with a multifilter SXR spectrometer and applying SSA for the first time in plasma physics the singular spectrum analysis. We find that temperature fluctuations are typically not larger than a few percent and are well correlated with magnetic fluctuations.
Design and fabrication of a vacuum ultraviolet pinhole camera based on thin phosphor screens (abstract)
Authors: Baciero A. , Zurro B. , McCarthy K. J. , De la Fuente M. C. , Burgos C.
Published: February 2004

A compact and highly sensitive pinhole camera has been developed for acquiring broadband vacuum ultraviolet (VUV) emission profiles of plasmas in the TJ-II. Its principal purpose is to obtain profiles with sufficiently high resolution so as to aid in the search for topological structures in stellarator plasmas. It can also be used to support experiments such as impurity injection by laser ablation. The original and purpose-designed camera reported here provides optimum sensitivity over a broad spectral range. In the camera vacuum chamber, plasma radiation passes through a pinhole and a filter before impinging on a 5×30 mm area of a P-46 phosphor screen. Thin screens of this material were extensively characterized using calibrated monochromatic VUV sources and it was found that their response is maximized when operated in reflection mode.1 Luminescent light emitted from the vacuum side of the screen is then focused by a toroidal mirror (the pinhole is cut in its center) onto the outside of a quartz window which is mounted on the side of camera. Finally, this intermediate image is relayed onto the surface of a gated and intensified linear photodiode array (25 μm by 25 mm) having 700 active pixels. This system is capable of obtaining radial VUV profiles every 12 ms and of recording them in ⩾100 ns.
Multichannel spectroscopy diagnostic for helium line intensity ratio measurements (abstract)
Authors: Punzmann H. , Shats M. G. , Solomon W. M.
Published: February 2004

A multichannel spectroscopy diagnostic has been designed to measure the electron temperature and density in radiation-dominated helium plasma in the H-1 heliac. The diagnostic principle relies on the well-known technique of measuring neutral helium line intensity ratios. A 2×10 optical fiber matrix (1 mm fiber diameter) is imaged into the plasma and collects light from ten chords. Two sets of ten-fiber arrays are coupled to the input slits of two monochrometers. The output slits are coupled to photomultiplier tubes through another two ten-fiber arrays. Several pairs of neutral helium spectral lines are used to measure time and spatially resolved Te and ne. The effect of structures and magnetic islands on the plasma profiles is investigated using this diagnostic.
Real-time measurement of toroidal rotation (abstract)
Authors: Paul S. F. , Cates C. , Mauel M. , Maurer D. , Navratil G. , Shilov M.
Published: February 2004

One of the important goals in Columbia’s HBT-EP tokamak program is the improvement in the stability of tokamak plasmas by controlling the bulk plasma flow relative to the conducting wall. The method for active plasma flow control in HBT-EP is the application of oscillating resonant magnetic perturbations to oppose the velocity of magnetic islands at the q=2 surface. Real time (10 kHz) feedback control without inserting a material probe necessitates the use of an optical toroidal rotation measurement whose data is available during the shot. This is being accomplished in a novel way by seeding the deuterium plasma with 5%–10% helium and measuring the Doppler shift of the chord-integrated emission of the He II (n=4→3) line at 4686 Å. Since the electron temperature is expected to be about 30 eV at the q=2 surface, helium is not fully stripped. The shift in wavelength is calculated by measuring the change in intensity as the line moves across the passband of an interference filter that varies linearly. Filters with less than 0.2% variation from a perfectly linear slope have been obtained. Fluctuations in the plasma emission are removed by having two detectors observe the same volume of plasma. This is achieved by splitting the optical view with a ‘Y’ composed of randomized optical fibers. One detector views the plasma through a filter whose passband has a negative slope and the other channel views it through a positive-slope filter. Systematic differences such as detector sensitivity, amplifier gain, fiber losses, etc. are compensated by normalizing each signal to the signal at a particular reference time. The ratio of signals at two different times does not depend on any detector or circuit characteristic that remains constant. The Doppler shift, relative to the reference time, is a function only of the slope of the filter’s transmission. The Doppler shift at the He II impurity emisson line is 0.25 Å for a toroidal rotation of 3 km/s, and the slope of the filter passband is 8%–10% per Å, resulting in a 4% variation in signal level relative to the other channel.
DMX: An absolutely calibrated time-resolved broadband soft x-ray spectrometer designed for MJ class laser-produced plasmas (invited)
Authors: Bourgade J. L. , Villette B. , Bocher J. L. , Boutin J. Y. , Chiche S. , Dague N. , Gontier D. , Jadaud J. P. , Savale B. , Wrobel R. , Turner R. E.
Published: February 2004

In high flux (1013–15 W/cm2) laser-plasma interaction, a large part of the incoming laser energy is radiated into soft x-rays. To determine both the shape of this spectrum and the conversion efficiency, we have designed and tested an absolutely calibrated broadband soft x-ray spectrometer with a high temporal resolution (100 ps). The detector in this spectrometer is a new coaxial x-ray diode coupled with a fast single shot oscilloscope (French IN7100 with 7 GHz frequency response cutoff). Both absolute calibrations (x-ray response of diodes) and relative calibrations (filters and mirrors) have used the French synchrotron beam lines at Laboratoire pour l’utilisation du Rayonnement Electromagnétique (LURE) in Orsay. The initial version of this instrument was first successfully implemented on laser plasmas experiments at the Phébus facility in France and an improved version is now operating at the Omega laser facility in Rochester, New York. The emitted x-ray spectrum is absolutely measured in 18 broad bands from 50 eV up to 20 keV. The softer bands (<1.5 keV) combine mirror and filter responses coupled with the coaxial diode response to improve hard x-ray rejection. Intermediate energy channels (1.5 keV<hν<5 keV) used only a filter and coaxial diode. For the hardest channels (>5 keV) we replace the x-ray diode (not sufficiently sensitive) with a photoconductive detector (neutron-damaged GaAs). An equivalent instrument will be designed for the future National Ignition Facility (NIF) in the United States and the Laser Mégajoule (LMJ) in France.
Vibrational spectrum in the vicinity of a local mode in linear chains with isotopic impurities
Authors: Ivanov M. A. , Skripnik Yu. V. , Molodid V. S.
Published: February 2004

The vibrational spectrum in the vicinity of the frequency of a local vibration of an isolated light isotopic impurity in a one-dimensional disordered chain containing such impurities is calculated numerically. Chains consisting of 108–109 atoms, corresponding to macroscopic samples several centimeters in size, are used. A complex hierarchical structure of the spectrum is obtained for this system. The results of the numerical calculations are compared with simple analytical expressions. It is shown that the smoothed density of states in a narrow neighborhood of the local mode can be obtained to sufficient accuracy from arguments based on separating out the nearest neighbor of the chosen impurity atom. It turns out that the expression for the density of states obtained in that manner gives an acceptable result not only outside but also inside the region of concentration broadening of the local mode.
Towards an embryocentric world: the current and potential uses of embryo technologies in dairy production
Authors: Hansen Peter J. , Block Jeremy
Published: February 2004

Structural features of the dairy industry make it well situated to use embryo technologies as tools for enhancing the genetic merit of dairy cattle and improving fertility. Technologies dependent upon embryo transfer have the potential to increase the efficiency of quantitative genetic selection as well as marker-assisted selection, simplify cross-breeding and germplasm conservation procedures and allow incorporation of transgenes into dairy cattle. In addition, embryo technologies may prove useful in improving fertility in infertile populations of lactating cows. The realisation of the promise of embryo technologies has been constrained by suboptimal efficiency in the production of embryos, alterations in embryonic and fetal survival and development associated with in vitro embryo production and cloning, as well as other technical and societal concerns. Solutions to many of these constraints are possible and the use of embryo technologies in both nucleus and commercial herds is likely to increase. Eventually, embryo transfer may compete with artificial insemination as a dominant method for establishing pregnancies in dairy cattle.