bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Common SCN5A Variant Alters the Responsiveness of Human Sodium Channels to Class I Antiarrhythmic Agents
Authors: SHURAIH MOSSAAB , AI TOMOHIKO , VATTA MATTEO , SOHMA YOSHIRO , MERKLE EILEEN M. , TAYLOR ERICA , LI ZHAOHUI , XI YUTAO , RAZAVI MEHDI , TOWBIN JEFFREY A. , CHENG JIE 
Published: February 2007

Background: The potential pathophysiological role of common SCN5A polymorphisms in cardiac arrhythmias has been increasingly recognized. However, little is known about the impact of those polymorphisms on the pharmocological response of hNav1.5 to various antiarrhythmic agents. Methods and Results: The known SCN5A polymorphism, S524Y, was studied in comparison with the wild type (WT) define the SCN5A‐Q1077del variant. The ion channel gating kinetics and pharmacology were evaluated using whole‐cell patch‐clamp methods in HEK‐293 cells. Consistent with a previous report, the basal ion channel gating kinetics of S524Y were indistinguishable from the WT. Quinidine (20 μM) caused similar extent of tonic block reduction of sodium currents at –120 mV in WT and S524Y. Surprisingly, quinidine (20 μM) exerted a more use‐dependent block by a 10 Hz pulse train in S524Y than in WT at 22°C (Ki: WT, 51.3 μM; S524Y, 20.3 μM). S524Y significantly delayed recovery from the use‐dependent block, compared with the WT (τ= 88.6 ± 7.9 s vs 41.9 ± 6.6 s, P < 0.005). Under more physiological conditions using a 2 Hz pulse train at 37°C, S524Y similarly enhanced the use‐dependent block by quinidine. In addition, S524Y enhanced the use‐dependent block by flecainide (12.5 μM), but not by mexiletine (100 μM). Conclusion: A common SCN5A polymorphism, S524Y, can enhance a use‐dependent block by class Ia and Ic antiarrhythmic agents. Our findings may have clinical implications in pharmacological management of cardiac arrhythmias since this common SCN5A polymorphism might be a contributing factor to the variable antiarrhythmic response.
Borderline ovarian tumors
Authors: GHAEMMAGHAMI Fatemeh , ASHRAF‐GANJOOIE Tahereh , IRAVANLOO Giti 
Published: February 2007

AbstractBorderline ovarian tumors account for approximately 15% of all epithelial ovarian tumors. In the early 1970s, borderline tumors were categorized as either serous or mucinous with overall survival rates of 75–90%. Since then, it has been recognized that the two categories are heterogonous. There are now many different groups following the recognition of serous tumors with microinvasion, non‐invasive and invasive peritoneal implants and a micropapillary pattern, and of mucinous tumors with microinvasion, intraepithelial carcinoma and pseudomyxoma peritoneal implants, in addition to further delineation of endometrial, clear cell and transitional cell tumors with atypical proliferation. This review outlines the most recent information regarding the epidemiology, pathology and clinical management of borderline tumors. Surgical management to excise all visible tumors remains the cornerstone of therapy. Because borderline ovarian tumors often occur in reproductive‐age women, fertility is an important issue. Conservative surgery is a safe in carefully selected patients. Effective non‐surgical therapies are yet to be identified.
Are the GFRUP’s recommendations for withholding or withdrawing treatments in critically ill children applicable? Results of a two-year survey
Authors: Cremer R , Binoche A , Noizet O , Fourier C , Leteurtre S , Moutel G , Leclerc F 
Published: February 2007

Objective:To evaluate feasibility of the guidelines of the Groupe Francophone de Réanimation et Urgence Pédiatriques (French-speaking group of paediatric intensive and emergency care; GFRUP) for limitation of treatments in the paediatric intensive care unit (PICU).Design:A 2-year prospective survey.Setting:A 12-bed PICU at the Hôpital Jeanne de Flandre, Lille, France.Patients:Were included when limitation of treatments was expected.Results:Of 967 children admitted, 55 were included with a 2-day median delay. They were younger than others (24v60 months), had a higher paediatric risk of mortality (PRISM) score (14v4), and a higher paediatric overall performance category (POPC) score at admission (2v1); all p<0.002. 34 (50% of total deaths) children died. A limitation decision was made without meeting for 7 children who died: 6 received do-not-resuscitate orders (DNROs) and 1 received withholding decision. Decision-making meetings were organised for 31 children, and the following decisions were made: 12 DNROs (6 deaths and 6 survivals), 4 withholding (1 death and 3 survivals), with 14 withdrawing (14 deaths) and 1 continuing treatment (survival). After limitation, 21 (31% of total deaths) children died and 10 survived (POPC score 4). 13 procedures were interrupted because of death and 11 because of clinical improvement (POPC score 4). Parents’ opinions were obtained after 4 family conferences (for a total of 110 min), 3 days after inclusion. The first meeting was planned for 6 days after inclusion and held on the 7th day after inclusion; 80% of parents were immediately informed of the decision, which was implemented after half a day.Conclusions:GFRUPs procedure was applicable in most cases. The main difficulties were anticipating the correct date for the meeting and involving nurses in the procedure. Children for whom the procedure was interrupted because of clinical improvement and who survived in poor condition without a formal decision pointed out the need for medical criteria for questioning, which should systematically lead to a formal decision-making process.
On the Physical Aspect of Heraclitus' Psychology
Authors: Betegh Gábor 
Published: February 2007

AbstractThe paper first discusses the metaphysical framework that allows the soul's integration into the physical world. A close examination of B36, supported by the comparative evidence of some other early theories of the soul, suggests that the word psuchê could function as both a mass term and a count noun for Heraclitus. There is a stuff in the world, alongside other physical elements, that manifests mental functions. Humans, and possibly other beings, show mental functions in so far as they have a portion of that stuff. Turning to the physical characterization of the soul, the paper argues that B36 is entirely consistent with the ancient testimonies that say that psuchê for Heraclitus is exhalation. But exhalations cover all states of matter from the lowest moist part of atmospheric air to the fire of celestial bodies. If so, psuchê for Heraclitus is both air and fire. The fact that psuchê can manifest the whole range of physical properties along the dry-wet axis guarantees that souls can show different intellectual and ethical properties as well. Moreover, Sextus Empiricus, supported by some other sources, provides us with an answer how portions of soul stuff are individuated into individual souls. The paper closes with a brief discussion of the question whether, and if so with what qualifications, we can apply the term 'physicalism' to Presocratic theories of the soul.
Tides and the Climate: Some Speculations
Authors: Munk Walter , Bills Bruce 
Published: February 2007

AbstractThe important role of tides in the mixing of the pelagic oceans has been established by recent experiments and analyses. The tide potential is modulated by long-period orbital modulations. Previously, Loder and Garrett found evidence for the 18.6-yr lunar nodal cycle in the sea surface temperatures of shallow seas. In this paper, the possible role of the 41 000-yr variation of the obliquity of the ecliptic is considered. The obliquity modulation of tidal mixing by a few percent and the associated modulation in the meridional overturning circulation (MOC) may play a role comparable to the obliquity modulation of the incoming solar radiation (insolation), a cornerstone of the Milanković theory of ice ages. This speculation involves even more than the usual number of uncertainties found in climate speculations.
Decadal Spinup of the South Pacific Subtropical Gyre
Authors: Roemmich D. , Gilson J. , Davis R. , Sutton P. , Wijffels S. , Riser S. 
Published: February 2007

Abstract
An increase in the circulation of the South Pacific Ocean subtropical gyre, extending from the sea surface to middepth, is observed over 12 years. Datasets used to quantify the decadal gyre spinup include satellite altimetric height, the World Ocean Circulation Experiment (WOCE) hydrographic and float survey of the South Pacific, a repeated hydrographic transect along 170°W, and profiling float data from the global Argo array. The signal in sea surface height is a 12-cm increase between 1993 and 2004, on large spatial scale centered at about 40°S, 170°W. The subsurface datasets show that this signal is predominantly due to density variations in the water column, that is, to deepening of isopycnal surfaces, extending to depths of at least 1800 m. The maximum increase in dynamic height is collocated with the deep center of the subtropical gyre, and the signal represents an increase in the total counterclockwise geostrophic circulation of the gyre, by at least 20% at 1000 m. A comparison of WOCE and Argo float trajectories at 1000 m confirms the gyre spinup during the 1990s. The signals in sea surface height, dynamic height, and velocity all peaked around 2003 and subsequently began to decline. The 1990s increase in wind-driven circulation resulted from decadal intensification of wind stress curl east of New Zealand—variability associated with an increase in the atmosphere’s Southern Hemisphere annular mode. It is suggested (based on altimetric height) that midlatitude gyres in all of the oceans have been affected by variability in the atmospheric annular modes on decadal time scales.
Is the World Ocean Warming? Upper-Ocean Temperature Trends: 1950–2000
Authors: Harrison D. E. , Carson Mark 
Published: February 2007

Abstract
Subsurface temperature trends in the better-sampled parts of the World Ocean are reported. Where there are sufficient observations for this analysis, there is large spatial variability of 51-yr trends in the upper ocean, with some regions showing cooling in excess of 3°C, and others warming of similar magnitude. Some 95% of the ocean area analyzed has both cooled and warmed over 20-yr subsets of this period. There is much space and time variability of 20-yr running trend estimates, indicating that trends over a decade or two may not be representative of longer-term trends. Results are based on sorting individual observations in World Ocean Database 2001 into 1° × 1° and 2° × 2° bins. Only bins with at least five observations per decade for four of the five decades since 1950 are used. Much of the World Ocean cannot be examined from this perspective. The 51-yr trends significant at the 90% level are given particular attention. Results are presented for depths of 100, 300, and 500 m. The patterns of the 90% significant trends are spatially coherent on scales resolved by the bin size. The vertical structure of the trends is coherent in some regions, but changes sign between the analysis depths in a number of others. It is suggested that additional attention should be given to uncertainty estimates for basin average and World Ocean average thermal trends.
Antarctic Circumpolar Current Transport Variability during 2003–05 from GRACE
Authors: Zlotnicki Victor , Wahr John , Fukumori Ichiro , Song Yuhe T. 
Published: February 2007

Abstract
Gravity Recovery and Climate Experiment (GRACE) gravity data spanning January 2003–November 2005 are used as proxies for ocean bottom pressure (BP) averaged over 1 month, spherical Gaussian caps 500 km in radius, and along paths bracketing the Antarctic Circumpolar Current’s various fronts. The GRACE BP signals are compared with those derived from the Estimating the Circulation and Climate of the Ocean (ECCO) ocean modeling–assimilation system, and to a non-Boussinesq version of the Regional Ocean Model System (ROMS). The discrepancy found between GRACE and the models is 1.7 cmH2O (1 cmH2O ∼ 1 hPa), slightly lower than the 1.9 cmH2O estimated by the authors independently from propagation of GRACE errors. The northern signals are weak and uncorrelated among basins. The southern signals are strong, with a common seasonality. The seasonal cycle GRACE data observed in the Pacific and Indian Ocean sectors of the ACC are consistent, with annual and semiannual amplitudes of 3.6 and 0.6 cmH2O (1.1 and 0.6 cmH2O with ECCO), the average over the full southern path peaks (stronger ACC) in the southern winter, on days of year 197 and 97 for the annual and semiannual components, respectively; the Atlantic Ocean annual peak is 20 days earlier. An approximate conversion factor of 3.1 Sv (Sv ≡ 106 m3 s−1) of barotropic transport variability per cmH2O of BP change is estimated. Wind stress data time series from the Quick Scatterometer (QuikSCAT), averaged monthly, zonally, and over the latitude band 40°–65°S, are also constructed and subsampled at the same months as with the GRACE data. The annual and semiannual harmonics of the wind stress peak on days 198 and 82, respectively. A decreasing trend over the 3 yr is observed in the three data types.
Comparison of the effectiveness of two programmes on older adults at risk of falling: unsupervised home exercise and supervised group exercise
Authors: Donat Hülya , Özcan Ayşe 
Published: February 2007

Objective: To compare the effectiveness of unsupervised home and supervised group exercise on parameters related to risk of falling among older adults. Design: Prospective, single-blind, randomized and controlled trial. Setting: Nursing home. Subjects: The subjects were selected from 535 independent individuals who resided in a nursing home. Forty-two older adults, aged > 65 years, with risk of falling were recruited, and 32 of them completed the study. Intervention: The 42 subjects were divided into two groups (unsupervised home exercise and supervised exercise group) randomly. Exercise sessions were performed three times a week for a period of eight weeks. Main measures: Measurements were taken at baseline and after the completion of the exercise programme. The fear of falling was evaluated using a visual analogue scale, quadriceps muscle strength was measured with a dynamometer, flexibility was assessed with the sit and reach test, functional mobility was determined using the Timed Up and Go Test, balance was evaluated using one-leg and tandem standing, and Berg Balance Scale and proprioception was assessed with knee position sense. Results: Thirty-two subjects (unsupervised home exercise n = 15, supervised group exercise n = 17) completed the exercise programme and all of the measurements. The unsupervised home exercise group showed significant improvement in balance, functional mobility and flexibility (P > 0.05). In addition to balance, functional mobility and flexibility, the supervised exercise group also showed significant improvements in both strength and proprioception (P > 0.05). Conclusions: Supervised group exercise is more effective at reducing the risk factors related to falling among older adults living in a nursing home than is unsupervised home exercise.
Development and validation of the Generalized Anxiety Disorder Inventory (GADI)
Authors: Argyropoulos Spilios V. , Ploubidis George B. , Wright Tamsin S. , Palm Marisha E. , Hood Sean D. , Nash Jon R. , Taylor A. Clare , Forshall Sam W. , Anderson Ian M. , Nutt David J. , Potokar John P. 
Published: February 2007

The psychometric tools used for the assessment of generalized anxiety disorder (GAD) either do not conform to the current concept of the condition or have important limitations. We aimed to develop and validate a new questionnaire for the assessment of symptom profile and severity of GAD. An original pool of potential scale items was subjected to a series of studies in non-clinical and clinical populations, in order to determine the final composition of the scale. The psychometric properties of the new scale, the Generalized Anxiety Disorder Inventory (GADI), were evaluated using a factor analytic model suitable for ordinal data and the Graded Response Model. The precision of measurement of the GADI was quantified through the item information functions. A total of 197 outpatients and 522 non-clinical subjects participated in four studies and completed the GADI. The final 18-item scale was derived from an original pool of 30 potential items. The GADI showed good reliability, convergent and divergent validity. The scale comprises three factors, relating to cognitive, somatic and sleep symptoms. It accurately distinguished GAD patients from non-patient controls. The cognitive factor also distinguished GAD from other anxiety disorders and depression. The GADI is a useful tool in the assessment of the breadth of symptoms and the severity of generalized anxiety disorder in clinical settings.
Evidence that the Pim1 kinase gene is a direct target of HOXA9
Authors: Hu Yu-Long , Passegué Emmanuelle , Fong Stephen , Largman Corey , Lawrence Hugh Jeffrey 
Published: February 2007

AbstractThe HOXA9 homeoprotein exerts dramatic effects in hematopoiesis. Enforced expression of HOXA9 enhances proliferation of primitive blood cells, expands hematopoietic stem cells (HSCs), and leads to myeloid leukemia. Conversely, loss of HOXA9 inhibits proliferation and impairs HSC function. The pathways by which HOXA9 acts are largely unknown, and although HOXA9 is a transcription factor, few direct target genes have been identified. Our previous study suggested that HOXA9 positively regulates Pim1, an oncogenic kinase. The hematologic phenotypes of Hoxa9- and Pim1-deficient animals are strikingly similar. Here we show that HOXA9 protein binds to the Pim1 promoter and induces Pim1 mRNA and protein in hematopoietic cells. Pim1 protein is diminished in Hoxa9−/− cells, and Hoxa9 and Pim1 mRNA levels track together in early hematopoietic compartments. Induction of Pim1 protein by HOXA9 increases the phosphorylation and inactivation of the proapoptotic BAD protein, a target of Pim1. Hoxa9−/− cells show increased apoptosis and decreased proliferation, defects that are ameliorated by reintroduction of Pim1. Thus Pim1 appears to be a direct transcriptional target of HOXA9 and a mediator of its antiapoptotic and proproliferative effects in early cells. Since HOXA9 is frequently up-regulated in acute myeloid leukemia, Pim1 may be a therapeutic target in human disease.
β-Trcp mediates ubiquitination and degradation of the erythropoietin receptor and controls cell proliferation
Authors: Meyer Laure , Deau Bénédicte , Forejtníková Hana , Duménil Dominique , Margottin-Goguet Florence , Lacombe Catherine , Mayeux Patrick , Verdier Frédérique 
Published: February 2007

AbstractControl of intensity and duration of erythropoietin (Epo) signaling is necessary to tightly regulate red blood cell production. We have recently shown that the ubiquitin/proteasome system plays a major role in the control of Epo-R signaling. Indeed, after Epo stimulation, Epo-R is ubiquitinated and its intracellular part is degraded by the proteasome, preventing further signal transduction. The remaining part of the receptor and associated Epo are internalized and degraded by the lysosomes. We show that β-Trcp is responsible for Epo-R ubiquitination and degradation. After Epo stimulation, β-Trcp binds to the Epo-R. This binding, like Epo-R ubiquitination, requires Jak2 activation. The Epo-R contains a typical DSG binding sequence for β-Trcp that is highly conserved among species. Interestingly, this sequence is located in a region of the Epo-R that is deleted in patients with familial polycythemia. Mutation of the serine residue of this motif to alanine (Epo-RS462A) abolished β-Trcp binding, Epo-R ubiquitination, and degradation. Epo-RS462A activation was prolonged and BaF3 cells expressing this receptor are hypersensitive to Epo, suggesting that part of the hypersensitivity to Epo in familial polycythemia could be the result of the lack of β-Trcp recruitment to the Epo-R.
The coding/non-coding overlapping architecture of the gene encoding the Drosophila pseudouridine synthase
Authors: Riccardo Sara , Tortoriello Giuseppe , Giordano Ennio , Turano Mimmo , Furia Maria 
Published: February 2007

Abstract

Background
In eukaryotic cells, each molecule of H/ACA small nucleolar RNA (snoRNA) assembles with four evolutionarily conserved core proteins to compose a specific ribonucleoprotein particle. One of the four core components has pseudouridine synthase activity and catalyzes the conversion of a selected uridine to pseudouridine. Members of the pseudouridine synthase family are highly conserved. In addition to catalyzing pseudouridylation of target RNAs, they carry out a variety of essential functions related to ribosome biogenesis and, in mammals, to telomere maintenance. To investigate further the molecular mechanisms underlying the expression of pseudouridine synthase genes, we analyzed the transcriptional activity of the Drosophila member of this family in great detail.

Results
The Drosophila gene for pseudouridine synthase, minifly/Nop60b (mfl), encodes two novel mRNAs ending at a downstream poly(A) site. One species is characterized only by an extended 3'-untranslated region (3'UTR), while a minor mRNA encodes a variant protein that represents the first example of an alternative subform described for any member of the family to date. The rare spliced variant is detected mainly in females and is predicted to have distinct functional properties. We also report that a cluster comprising four isoforms of a C/D box snoRNA and two highly related copies of a small ncRNA gene of unknown function is intron-encoded at the gene-variable 3'UTRs. Because this arrangement, the alternative 3' ends allow mfl not only to produce two distinct protein subforms, but also to release different ncRNAs. Intriguingly, accumulation of all these intron-encoded RNAs was found to be sex-biased and quantitatively modulated throughout development and, within the ovaries, the ncRNAs of unknown function were found not ubiquitously expressed.

Conclusion
Our results expand the repertoire of coding/non-coding transcripts derived from the gene encoding Drosophila pseudouridine synthase. This gene exhibits a complex and interlaced organization, and its genetic information may be expressed as different protein subforms and/or ncRNAs that may potentially contribute to its biological functions.