bluuebunny/crossref_metadata_2025 huggingface dataset:
Sound‐channel observations of ice‐generated tremor in the Indian Ocean
Authors: Chapp Emily , Bohnenstiehl DelWayne R. , Tolstoy Maya
Published: June 2005

Mid to low southern latitude hydrophone stations within the Indian Ocean have recorded two distinct types of low‐frequency (<100 Hz) tremor that can be correlated with drifting icebergs and glacial features along the Wilkes Land coast of eastern Antarctica. The most common of these signals is a variable harmonic tremor (VHT), with spectral peaks that exhibit frequency fluctuations through time. These signals typically display a 4 to 10 Hz fundamental frequency and may have as many as ten harmonic bands. Individual VHT signal packets have durations of up to ∼30 min and occur throughout the year in clusters that continue for hours to days. A second, less commonly observed signal is characterized by shorter duration (25 to 90 s) pulses with a convex‐upward spectrogram appearance. These cusped pulse tremors (CPT) often exhibit a near‐uniform pulse spacing, with episodes continuing for minutes to hours. Tremor received levels at hydrophones near 32°S, 114°E and 7°S, 72°E reach as high as 142 and 133 dB re 1 μPa (peak to peak), respectively. Propagation likely occurs as a sea surface–reflected phase at high latitudes and a sound channel phase north of the convergence zone, with low‐frequency transmission loss estimates suggesting maximum acoustic source levels of ∼245 dB re 1 μPa at 1 m. Source locations for a subset of the loudest VHT signals correlate with the satellite‐derived locations of a large iceberg (B‐15D) that migrated westward along the Wilkes Land shelf region during 2002 and early 2003. Most VHT sources, however, cannot be correlated with known iceberg locations, suggesting that these signals also may be sourced from smaller unnamed icebergs and/or associated with outlet glaciers distributed along the Wilkes Land coast. CPT signals have a more limited spatial distribution, originating from five specific regions where ice streams are observed. The harmonic nature of both signal types is consistent with the resonance of an ice layer or fluid‐filled cavity within an ice mass.
Comparison of SuperDARN radar boundaries with DMSP particle precipitation boundaries
Authors: Sotirelis T. , Ruohoniemi J. M. , Barnes R. J. , Newell P. T. , Greenwald R. A. , Skura J. P. , Meng C.‐I.
Published: June 2005

Auroral boundary algorithms for SuperDARN ionospheric convection observations are introduced. Both the equatorward boundary of scatter (EBS) and the convection reversal boundary (CRB) are found and compared with boundaries based on DMSP particle precipitation observations. These comparisons provide an intercalibration between the two schemes and insight into the relationship between disparate phenomena. The EBS is reliably poleward of the equatorward boundary of precipitation (EBP) at most local times but centers well on the equatorwardmost precipitation between 1600 and 2200 MLT when within 8° latitude of the radar station, indicating a correspondence with the SLERPS (slow long‐lived E region plasma structures) of Jayachandran. Near dawn the EBS coincides better with the structured–unstructured boundary (SUB) than the EBP, as one might expect if the ionospheric irregularities responsible for this scatter were produced by the gradient‐drift instability. The CRB correlates well with the open‐closed boundary (OCB) as seen by DMSP. There is, however, an equatorward offset of the CRB relative to the OCB that varies from zero near noon to ∼1° near dawn and dusk and is largest near midnight. This offset is consistent with a small viscous‐like interaction between the magnetosheath and the low‐latitude boundary layer, resulting in a degree of antisunward flow on closed field lines. The offset decreases under the influence of southward interplanetary magnetic field, as one might expect if increased dayside merging interfered with this effect.
Distinct element modeling of hydraulically fractured Lac du Bonnet granite
Authors: Al‐Busaidi A. , Hazzard J. F. , Young R. P.
Published: June 2005

The aim of this study is to better understand the mechanics of fracture development and propagation during hydraulic fracturing. This paper presents some development and applications of discrete particle modeling of this problem. A discontinuum modeling approach idealizes the material as separate particles bonded together at their contact points and utilizes the breakage of individual structural units or bonds to represent damage. The numerical models are correlated with existing hydrofracture laboratory experiments, which are presented in other publications. A simulation of a laboratory‐scale hydrofracture experiment and the acoustic emission (AE) data from the experiment is used to validate the synthetic AEs produced in the hydrofracture model. This technique has been used to examine the mechanics of fracture initiation and time and spatial distributions of AE. The modeling results demonstrate that the mechanism of hydraulically induced fracture in the Lac du Bonnet (LdB) granite core sample is predominantly tensile failure and that the shear cracks recorded in the hydrofracture experiment were due to slip on preexisting fractures. Numerical modeling of hydrofracture on homogeneous and heterogeneous synthetic samples seems to capture much of the behavior observed in the laboratory hydrofracture experiments.
Evaluation of the mesoscale model/land surface model (MM5/LSM) coupled model for East Asian summer monsoon simulations
Authors: Kang Hyun‐Suk , Cha Dong‐Hyun , Lee Dong‐Kyou
Published: June 2005

In this paper, a regional climate model (Seoul National University Regional Climate Model (SNURCM)) was configured by coupling an advanced land surface model with the Penn State University/National Center for Atmospheric Research mesoscale model. A spectral nudging technique was also implemented to reduce systematic biases resulting from the incomplete treatment of the downscaling problem in the classical lateral boundary condition. To evaluate the capability of the SNURCM, the East Asian summer monsoon (EASM) cases in 1991 and 1994 were simulated. The SNURCM simulated the large anomalous features in the summers of 1991 and 1994, in terms of precipitation and atmospheric circulations. The model also reproduced regional details in the horizontal distribution of precipitation with a certain degree of systematic biases. The model tended to simulate different atmospheric vertical structures over land versus ocean. Surface air temperature was also simulated reasonably in terms of spatial pattern, but a cold bias appeared over most of East Asia. The atmospheric circulations associated with the monsoon precipitation were well captured in the simulations, and the temporal evolutions of monsoon circulation and precipitation were also reasonably simulated. We also analyzed the hydrology and energy budget to investigate the reasons for the systematic model bias and extreme climate events occurring in the summer of 1991 and 1994. An experiment without the spectral nudging for the 1991 EASM case was also performed to assess the impacts of spectral nudging in the EASM simulation. The spectral nudging technique played a significant role in reducing the deviation of the model solutions from large‐scale driving forces. It contributes to improve model performance not only in simulating the mean features but also in capturing individual weather precipitation events. Without the spectral nudging, the weakened subtropical high did not simulate the low‐level confluent monsoon flows properly near the monsoon precipitation areas, and consequently resulted in significant precipitation bias from observation.
Evaluation of Last Glacial Maximum sea surface temperature reconstructions through their influence on South American climate
Authors: Vizy Edward K. , Cook Kerry H.
Published: June 2005

The consistency of land‐based and ocean‐based Last Glacial Maximum (LGM) proxy evidence on and near South America is evaluated by utilizing a regional climate model (RCM). The relatively high resolution of the RCM brings model output closer to the spatial scales of the geological reconstructions. This is important because proxy sites only a few tens of kilometers apart can yield markedly different interpretations of LGM climate. Along with differences in orbital parameters, CO2 concentrations, and vegetation, four versions of LGM sea surface temperatures (SSTs) (Climate: Long‐Range Investigation, Mapping, and Prediction (CLIMAP), Schäfer‐Neth and Paul's (2003) core version, Paul and Schäfer‐Neth's (2003) line version, and coupled GCM output from Shin et al. (2003)), are used to generate four realizations of the LGM climate in the model. Mean annual surface temperature, mean temperature of the coldest month, and aridity differences from a present‐day simulation are compared with the geological reconstructions over South America to evaluate the consistency of the land and ocean‐based reconstructions. Model results suggest that the tropical Atlantic during the LGM was not significantly cooler than CLIMAP's original estimates. Simulations utilizing tropical Atlantic LGM SSTs cooler than CLIMAP estimates yield unrealistically warm LGM surface conditions over the equatorial Amazon basin. Reductions in evaporation and the atmosphere's moisture content over too‐cold tropical oceans lead to a reduction in cloud cover over the Amazon and increases in solar heating of the surface. All of the LGM SST simulations produce drier conditions over tropical South America; however, the extent of the aridity is associated with the degree of cooling in the surrounding oceans, especially the tropical Atlantic. The “line” version LGM SSTs of Paul and Schäfer‐Neth (2003) are recommended.
Interannual variation of 13C in tropospheric methane: Implications for a possible atomic chlorine sink in the marine boundary layer
Authors: Allan W. , Lowe D. C. , Gomez A. J. , Struthers H. , Brailsford G. W.
Published: June 2005

We present methane mixing ratio and δ13C time series measured at Baring Head, New Zealand, and Scott Base, Antarctica, over the years 1991–2003. These data demonstrate that the apparent kinetic isotope effect (KIE) of the methane atmospheric sink (derived from the amplitudes of the mixing ratio and δ13C seasonal cycles) is generally much larger than would be expected if the sink were the hydroxyl radical alone and has changed significantly during the observation period on a timescale of ∼3 years. We show using a global transport model that this technique for deriving the KIE should be quite accurate for a single atmospheric sink and that the change with time is unlikely to arise from El Niño–Southern Oscillation transport effects. We infer that a sink in addition to hydroxyl is required. A strong candidate for this extra sink is atomic chlorine in the marine boundary layer (MBL). We derive the amplitude of the chlorine concentration seasonal cycle that would fully account for the apparent KIE. This amplitude ranges from ∼104 atom cm−3 in 1994–1996 to about 3 × 103 atom cm−3 in 1998–2000. If the KIE is enhanced throughout the free troposphere, the seasonal mean concentrations of atomic chlorine required in the MBL would be about 3 × 104 atom cm−3 in 1994–1996 and ∼104 atom cm−3 in 1998–2000.
Generalized Chebyshev arrays
Authors: El‐Hajj Ali , Kabalan Karim Y. , Al‐Husseini Mohammed
Published: June 2005

In this paper, a class of uniformly spaced linear arrays that we call the generalized Chebyshev arrays is introduced. For the proposed arrays, the array factor is the product of the array factors of several conventional Chebyshev arrays, the directivity is higher than that of the conventional and the modified Chebyshev arrays, and the beam width and the excitation currents ratio are smaller than those of the modified Chebyshev arrays. The sidelobes in the pattern of a generalized Chebyshev array are not of equal magnitude, but the maximal sidelobe level is controllable. Methods for computing the excitation currents, half‐power beam width, and optimum element spacing of these arrays are developed, and exact values of their directivity are obtained. The features of the proposed arrays are illustrated through numerical examples.
Radiation belt data assimilation with an extended Kalman filter
Authors: Naehr S. M. , Toffoletto F. R.
Published: June 2005

Kalman filtering provides an elegant framework for assimilating observational data into time‐dependent theoretical models. This paper explores the application of this approach to specify and forecast the radiation belt particle distribution. The Kalman filter is first outlined in a general form. A data assimilation algorithm is then derived for a simple radiation belt forecast model driven by radial diffusion. The model assimilates particle flux measurements from spacecraft in the equatorial plane, using an external magnetic field model to calculate adiabatic invariants and phase space density. The algorithm is tested in a series of virtual experiments, with data from an idealized magnetic storm simulation. Compared to assimilation by direct insertion of data, the Kalman filter more accurately reconstructs the global particle distribution from sparse observational data. We examine the response of the filter to errors in the observations, magnetic field model, and forecast model and discuss the application of this approach to more realistic models and data sets.
Predicting shoreline changes: A case study in Rio Grande do Sul, Brazil
Authors: Williams Jon J. , Esteves Luciana S.
Published: June 2005

A simple model is used to predict shoreline changes and uses the coast of Rio Grande do Sul (Brazil) as a case study. A continuity model is used to calculate changes in shoreline position attributable to longshore sediment transport (LST). The model is based on calculations of net LST using WAM hindcaste data in the CERC formula from 1997 to 2002. The model was able to reproduce most of the observed oscillations in shoreline during this period. The simulation demonstrated that reversals in shoreline displacements from erosion to accretion or vice‐versa could be explained at first order by changes in the wave climate. The results demonstrate that relatively small changes in the wave climate can significantly affect coastal position and that these changes are broadly predictable over short to medium‐term periods.
Hydrogen sulfide causes vanilloid receptor 1‐mediated neurogenic inflammation in the airways
Authors: Trevisani Marcello , Patacchini Riccardo , Nicoletti Paola , Gatti Raffaele , Gazzieri David , Lissi Nicola , Zagli Giovanni , Creminon Christophe , Geppetti Pierangelo , Harrison Selena
Published: June 2005

Hydrogen sulfide (H2S) is described as a mediator of diverse biological effects, and is known to produce irritation and injury in the lung following inhalation. Recently, H2S has been found to cause contraction in the rat urinary bladder via a neurogenic mechanism. Here, we studied whether sodium hydrogen sulfide (NaHS), used as donor of H2S, produces responses mediated by sensory nerve activation in the guinea‐pig airways.

NaHS evoked an increase in neuropeptide release in the airways that was significantly attenuated by capsaicin desensitization and by the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine. In addition, NaHS caused an atropine‐resistant contraction of isolated airways, which was completely prevented by capsaicin desensitization. Furthermore, NaHS‐induced contraction was reduced by TRPV1 antagonism (ruthenium red, capsazepine and SB366791), and was abolished by pretreatment with the combination of tachykinin NK1 (SR140333) and NK2 (SR48968) receptor antagonists.

In anesthetized guinea‐pigs, intratracheal instillation of NaHS increased the total lung resistance and airway plasma protein extravasation. These two effects were reduced by TRPV1 antagonism (capsazepine) and tachykinin receptors (SR140333 and SR48968) blockade.

Our results provide the first pharmacological evidence that H2S provokes tachykinin‐mediated neurogenic inflammatory responses in guinea‐pig airways, and that this effect is mediated by stimulation of TRPV1 receptors on sensory nerves endings. This novel mechanism may contribute to the irritative action of H2S in the respiratory system.

British Journal of Pharmacology (2005) 145, 1123–1131. doi:10.1038/sj.bjp.0706277; published online 6 June 2005
A Ser/Thr cluster within the C‐terminal domain of the rat prostaglandin receptor EP3α is essential for agonist‐induced phosphorylation, desensitization and internalization
Authors: Neuschäfer‐Rube Frank , Hermosilla Ricardo , Kuna Manuela , Pathe‐Neuschäfer‐Rube Andrea , Schülein Ralf , Püschel Gerhard Paul
Published: June 2005

Two isoforms of the rat prostaglandin E2 receptor, rEP3α‐R and rEP3β‐R, differ only in their C‐terminal domain. To analyze the function of the rEP3‐R C‐terminal domain in agonist induced desensitization, a cluster of Ser/Thr residues in the C‐terminal domain of the rEP3α‐R was mutated to Ala and both isoforms and the receptor mutant (rEP3α‐ST341‐349A‐R) were stably expressed in HEK293 cells.

All rEP3‐R receptors showed a similar ligand‐binding profile. They were functionally coupled to Gi and reduced forskolin‐induced cAMP‐formation.

Repeated exposure of cells expressing the rEP3α‐R isoform to PGE2 reduced the agonist induced inhibition of forskolin‐stimulated cAMP‐formation by 50% and led to internalization of the receptor to intracellular endocytotic vesicles. By contrast, Gi‐response as well as plasma membrane localization of the rEP3β‐R and the rEP3α‐ST341‐349A‐R were not affected by prior agonist‐stimulation.

Agonist‐stimulation of HEK293‐rEP3α‐R cells induced a time‐ and dose‐dependent phosphorylation of the receptor most likely by G protein‐coupled receptor kinases and not by protein kinase A or protein kinase C. By contrast, upon agonist‐stimulation the rEP3β‐R was not phosphorylated and the rEP3α‐ST341‐349A‐R was phosphorylated only weakly.

These results led to the hypothesis that agonist‐induced desensitization of the rEP3α‐R isoform is mediated most likely by a GRK‐dependent phosphorylation of Ser/Thr residues 341–349. Phosphorylation then initiates uncoupling of the receptor from Gi protein and receptor internalization.

British Journal of Pharmacology (2005) 145, 1132–1142. doi:10.1038/sj.bjp.0706282
Molecular and pharmacological characteristics of transient voltage‐dependent K+ currents in cultured human pulmonary arterial smooth muscle cells
Authors: Iida Haruko , Jo Taisuke , Iwasawa Kuniaki , Morita Toshihiro , Hikiji Hisako , Takato Tsuyoshi , Toyo‐oka Teruhiko , Nagai Ryozo , Nakajima Toshiaki
Published: June 2005

The A‐type voltage‐dependent K+ current (IA) has been identified in several types of smooth muscle cells including the pulmonary artery (PA), but little is known about the pharmacological and molecular characteristics of IA in human pulmonary arterial smooth muscle cells (hPASMCs). We investigated IA expressed in cultured PASMCs isolated from the human main pulmonary artery, using patch‐clamp techniques, reverse transcriptase–polymerase chain reaction (RT–PCR), quantitative real‐time RT–PCR and immunocytochemical studies.

With high EGTA and ATP in the pipette, the outward currents were dominated by a transient K+ current (IA), followed by a relatively small sustained outward current (IK).

IA was inhibited by 4‐aminopyridine (4‐AP) concentration‐dependently, and could be separated pharmacologically into two components by tetraethylammonium (TEA) sensitivity. A component was sensitive to TEA, and the second component was insensitive to TEA.

IA was inhibited by blood depressing substrate (BDS)‐II, a specific blocker of KV3.4 subunit, and phrixotoxin‐II, a specific blocker of KV4.2 and 4.3.

Flecainide inhibited IA concentration‐dependently, but it inhibited it preferentially in the presence of TEA (TEA‐insensitive IA).

Systematic screening of expression of KV genes using RT–PCR showed the definite presence of transcripts of the IA‐encoding genes for KV3.4, KV4.1, KV4.2 and KV4.3 as well as the IK‐encoding genes for KV1.1, KV1.5 and KV2.1. The real‐time RT–PCR analysis showed that the relative abundance of the encoding genes of IA α‐subunit and KV channel‐interacting proteins (KChIPs) was KV4.2>KV3.4>KV4.3 (long)>KV4.1, and KChIP3≫KChIP2, respectively.

The presence of KV3.4, KV4.2 and KV4.3 proteins was also demonstrated by immunocytochemical studies, and confirmed by immunohistochemical staining using intact human PA sections.

These results suggest that IA in cultured hPASMCs consists of two kinetically and pharmacologically distinct components, probably KV3.4 and KV4 channels.

British Journal of Pharmacology (2005) 146, 49–59. doi:10.1038/sj.bjp.0706285
Caveolin‐1 gene knockout impairs nitrergic function in mouse small intestine
Authors: El‐Yazbi Ahmed F , Cho Woo‐Jung , Boddy Geoffrey , Daniel Edwin E
Published: June 2005

Caveolin‐1 is a plasma membrane‐associated protein that is responsible for caveolae formation. It plays an important role in the regulation of the function of different signaling molecules, among which are the different isoforms of nitric oxide synthase (NOS).

Nitric oxide (NO) is known to be an important inhibitory mediator in the mouse gut. Caveolin‐1 knockout mice (Cav1−/−) were used to examine the effect of caveolin‐1 absence on the NO function in the mouse small intestine (ileum and jejunum) compared to their genetic controls and BALB/c controls.

Immunohistochemical staining showed loss of caveolin‐1 and NOS in the jejunal smooth muscles and myenteric plexus interstitial cells of Cajal (ICC) of Cav1−/− mice; however, nNOS immunoreactive nerves were still present in myenteric ganglia.

Under nonadrenergic noncholinergic (NANC) conditions, small intestinal tissues from Cav1−/− mice relaxed to electrical field stimulation (EFS), as did tissues from control mice. Relaxation of tissues from control mice was markedly reduced by N‐omega‐nitro‐L‐arginine (10−4 M), but relaxation of Cav1−/− animals was affected much less. Also, Cav1−/− mice tissues showed reduced relaxation responses to sodium nitroprusside (100 μM) compared to controls; yet there were no significant differences in the relaxation responses to 8‐bromoguanosine‐3′ : 5′‐cyclic monophosphate (100 μM).

Apamin (10−6 M) significantly reduced relaxations to EFS in NANC conditions in Cav1−/− mice, but not in controls.

The data from this study suggest that caveolin‐1 gene knockout causes alterations in the smooth muscles and the ICC, leading to an impaired NO function in the mouse small intestine that could possibly be compensated by apamin‐sensitive inhibitory mediators.

British Journal of Pharmacology (2005) 145, 1017–1026. doi:10.1038/sj.bjp.0706289
A Critical Analysis of Decision Support Systems Research
Authors: Arnott David , Pervan Graham
Published: June 2005

This paper critically analyses the nature and state of decision support systems (DSS) research. To provide context for the analysis, a history of DSS is presented which focuses on the evolution of a number of sub-groupings of research and practice: personal DSS, group support systems, negotiation support systems, intelligent DSS, knowledge management-based DSS, executive information systems/business intelligence, and data warehousing. To understand the state of DSS research an empirical investigation of published DSS research is presented. This investigation is based on the detailed analysis of 1,020 DSS articles published in 14 major journals from 1990 to 2003. The analysis found that DSS publication has been falling steadily since its peak in 1994 and the current publication rate is at early 1990s levels. Other findings include that personal DSS and group support systems dominate research activity and data warehousing is the least published type of DSS. The journal DSS is the major publishing outlet; US ‘Other’ journals dominate DSS publishing and there is very low exposure of DSS in European journals. Around two-thirds of DSS research is empirical, a much higher proportion than general IS research. DSS empirical research is overwhelming positivist, and is more dominated by positivism than IS research in general. Design science is a major DSS research category. The decision support focus of the sample shows a well-balanced mix of development, technology, process, and outcome studies. Almost half of DSS papers did not use judgement and decision-making reference research in the design and analysis of their projects and most cited reference works are relatively old. A major omission in DSS scholarship is the poor identification of the clients and users of the various DSS applications that are the focus of investigation. The analysis of the professional or practical contribution of DSS research shows a field that is facing a crisis of relevance. Using the history and empirical study as a foundation, a number of strategies for improving DSS research are suggested.
The Adoption and use of Collaboration Information Technologies: International Comparisons
Authors: Bajwa Deepinder S. , Lewis L. Floyd , Pervan Graham , Lai Vincent S.
Published: June 2005

Information technology (IT) applications to support group decision processes have been of considerable interest over the years. With the emergence of virtual team arrangements and the advent of emerging information and networking technologies, an increasing amount of attention is now being aimed at understanding collaboration among group members, as they make decisions to accomplish tasks. Effective and efficient collaboration is critical from a decision quality and decision timeliness standpoint. Commonly known as collaborative information technologies (CITs), many technology solutions have the capability to enhance collaboration and facilitate group decisions in task accomplishment by enabling better communication, sharing of information, ideas, expertise, and evaluating alternatives, irrespective of time and distance barriers. Many studies have investigated such individual CIT solutions in different regional settings. However, despite the fact that no single medium can support collaboration in different types of tasks, there is a scarcity of research investigating the adoption and use of multiple CIT options across regions. This paper builds upon innovation diffusion theory and tests a research model to validate five antecedents of collective adoption and use of seven CITs in the US, Australia, and Hong Kong. Sub-sample analyses of data collected from 344 organizations in these three regions suggest that not only do adoption and use patterns of some CIT solutions vary across regions but so do the antecedents that explain their proliferation. Implications of our findings are discussed for practitioners and researchers.
A Semiotic Information Quality Framework: Development and Comparative Analysis
Authors: Price Rosanne , Shanks Graeme
Published: June 2005

An organization depends on quality information for effective operations and decisionmaking. However, there is still no agreement as to how quality should be defined in terms of specific quality categories and criteria. Proposed information quality frameworks have limitations with respect to either consistency, resulting from a non-theoretical approach to framework development, or scope, considering only objective but not subjective information quality perspectives. In this paper, we describe a unique research approach to framework development that addresses these problems and compare it to those used previously for other frameworks. Semiotic theory, the philosophical theory of signs, is used to ensure rigor and scope. It provides a theoretical basis for framework structure - quality categories and their criteria - and for integrating objective and subjective quality views. Empirical refinement based on academic, practitioner, and end-user focus groups is then used to ensure relevance.
A Case in Customizing E-Learning
Authors: Neville Karen , Heavin Ciara , Walsh Eoin
Published: June 2005

Organizational change in today's competitive landscape is no longer just an option, but a fundamental strategy for success. In order to be the premier player in this type of competitive landscape, customer focus has to become a priority, and bearing this in mind both academia and competitive organizations have one key objective in common. Their current focus is on implementing successful support systems in order to meet their end-users’ needs. As early as 1995, University College Cork (a Third-level Irish university) introduced on-line support to provide learning material for students ranging from full/part-time undergraduates and postgraduates to distance-learners. However, students identified a need for more support, the type that only a more interactive system can provide. This paper focuses on the evolution of e-learning and learning management systems (LMS) in considering e-learning as the academic equivalent to the customer relationship management (CRM) challenge. This research outlines the different characteristics necessary for the successful management of the learning process and the support needed by students, through the investigation of current research and the analysis of the case environment. It also highlights the potential of the system to overcome the physical barriers of the traditional classroom aligning the key critical factors necessary for e-learning with those of CRM. Through the adoption of the CRM philosophy, the system presented here strengthened its link between the different actors and additionally provided the university with a more in-depth view of its target audience.
Are Decision Support Systems Getting People to Conform? The Impact of Work Organisation and Segmentation on User Behaviour in a French Bank
Authors: Rowe Frantz
Published: June 2005

The longitudinal study of the most sophisticated decision support system (DSS) for the management of debit accounts provides new answers to the question of conformity in French banking. In 2003, the analysis of 45 observations and qualitative interviews showed that the advisor maintains his free appreciation of risk. However, even if conformity does not exist, the results on the modification range show that the DSS does exert an influence on user behaviour. In addition, the interpretation and acceptance of DSS recommendation are different according to the type of portfolio managed and how the work is organised. The less the financial advisor knows the client, the greater the influence of the DSS. Recent decisions regarding the division of labour for the management of lower segments heighten the risk that DSS used without knowing the client leads to more conformity, or at least to what we conceptualise as strategic conformity, and a taylorisation of services.
BRCA2 BRC motifs bind RAD51–DNA filaments
Authors: Galkin Vitold E. , Esashi Fumiko , Yu Xiong , Yang Shixin , West Stephen C. , Egelman Edward H.
Published: June 2005

Germ-line mutations in
BRCA2
account for approximately half the cases of autosomal dominant familial breast cancers. BRCA2 has been shown to interact directly with RAD51, an essential component of the cellular machinery for homologous recombination and the maintenance of genome stability. Interactions between BRCA2 and RAD51 take place by means of the conserved BRC repeat regions of BRCA2. Previously, it was shown that peptides corresponding to BRC3 or BRC4 bind RAD51 monomers and block RAD51–DNA filament formation. In this work, we further analyze these interactions and find that at lower molar ratios BRC3 or BRC4 actually bind and form stable complexes with RAD51–DNA nucleoprotein filaments. Only at high concentrations of the BRC repeats are filaments disrupted. The specific protein–protein contacts occur in the RAD51 filament by means of the N-terminal domain of RAD51 for BRC3 and the nucleotide-binding core of RAD51 for BRC4. These observations show that the BRC repeats bind distinct regions of RAD51 and are nonequivalent in their mode of interaction. The results provide insight into why mutation in just one of the eight BRC repeats would affect the way that BRCA2 protein interacts with the RAD51 filament. Disruption of a single RAD51 interaction site, one of several simultaneous interactions occurring throughout the BRC repeat-containing exon 11 of BRCA2, might modulate the ability of RAD51 to promote recombinational repair and lead to an increased risk of breast cancer.
S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities
Authors: Martínez-Ruiz Antonio , Villanueva Laura , de Orduña Cecilia González , López-Ferrer Daniel , Higueras María Ángeles , Tarín Carlos , Rodríguez-Crespo Ignacio , Vázquez Jesús , Lamas Santiago
Published: June 2005

Nitric oxide is implicated in a variety of signaling pathways in different systems, notably in endothelial cells. Some of its effects can be exerted through covalent modifications of proteins and, among these modifications, increasing attention is being paid to S-nitrosylation as a signaling mechanism. In this work, we show by a variety of methods (ozone chemiluminescence, biotin switch, and mass spectrometry) that the molecular chaperone Hsp90 is a target of S-nitrosylation and identify a susceptible cysteine residue in the region of the C-terminal domain that interacts with endothelial nitric oxide synthase (eNOS). We also show that the modification occurs in endothelial cells when they are treated withS-nitroso-l-cysteine and when they are exposed to eNOS activators. Hsp90 ATPase activity and its positive effect on eNOS activity are both inhibited by S-nitrosylation. Together, these data suggest that S-nitrosylation may functionally regulate the general activities of Hsp90 and provide a feedback mechanism for limiting eNOS activation.
Evolutionary analysis of the well characterized
endo16
promoter reveals substantial variation within functional sites
Authors: Balhoff James P. , Wray Gregory A.
Published: June 2005

The evolutionary mechanisms that operate on genetic variation within transcriptional regulatory sequences are not well understood. We present here an evolutionary analysis of an exceptionally well characterized cis-regulatory region, the
endo16
promoter of the purple sea urchin. Segregating variation reveals striking differences in the intensity of negative selection among regulatory modules, reflecting their distinct functional roles. Surprisingly, transcription-factor-binding sites are as polymorphic and as likely to contain fixed differences as flanking nucleotides. Whereas nucleotides in protein-binding sites in the most proximal regulatory module exhibit reduced variation, those in other modules tend to be more polymorphic than putatively nonfunctional nucleotides. Two unrelated large insertions at the same position within the promoter are segregating at low frequencies; one is a strong ectodermal repressor that contains 16 verified transcription-factor-binding sites. These results demonstrate that a simple relationship between conservation and function does not exist within this cis-regulatory region and highlight significant population heterogeneity in the fine structure of a well understood promoter.
The primary mechanism of the IL-10-regulated antiinflammatory response is to selectively inhibit transcription
Authors: Murray Peter J.
Published: June 2005

The antiinflammatory cytokine IL-10 inhibits the production of multiple, diverse inflammatory mediators from activated macrophages and dendritic cells, a process requiring STAT3 activation. However, the mechanisms involved in the broad inhibitory effects of IL-10 are controversial. I eliminated the contribution of the major confounding variable to understanding the antiinflammatory response, the 3′ UTR region of inflammatory mediator genes, through knock-in mutation and analysis of the effects of IL-10 on transcription rate of inflammatory genes. IL-10 activates STAT3 to act indirectly by selectively inhibiting gene transcription independent of general effects on NF-κB or posttranscriptional mRNA processing through a process that reduces the overall transcriptional rate of specific genes.
Glutamatergic reinnervation through peripheral nerve graft dictates assembly of glutamatergic synapses at rat skeletal muscle
Authors: Brunelli Giorgio , Spano PierFranco , Barlati Sergio , Guarneri Bruno , Barbon Alessandro , Bresciani Roberto , Pizzi Marina
Published: June 2005

Acetylcholine is the main neurotransmitter at the mammalian neuromuscular junction (NMJ) where nicotinic acetylcholine receptors mediate the signaling between nerve terminals and muscle fibers. We show that under glutamatergic transmission, rat NMJ switches from cholinergic type synapse to glutamatergic synapse. Connecting skeletal muscle to the lateral white matter of the spinal cord by grafting the distal stump of the transected motor nerve produced functional muscle reinnervation. The restored neuromuscular activity became resistant to common curare blockers but sensitive to the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist. Analysis of the regenerated nerve disclosed new glutamatergic axons and the disappearance of cholinergic fibers. Many axons belonged to the supraspinal neurons located in the red nucleus and the brainstem nuclei. Finally, the innervated muscle displayed high expression and clustering of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits glutamate receptors 1 and 2. Our data suggest that supraspinal neurons can target skeletal muscle, which retains the plasticity to generate functional glutamatergic NMJ.
Visual memory needs categories
Authors: Olsson Henrik , Poom Leo
Published: June 2005

Capacity limitations in the way humans store and process information in working memory have been extensively studied, and several memory systems have been distinguished. In line with previous capacity estimates for verbal memory and memory for spatial information, recent studies suggest that it is possible to retain up to four objects in visual working memory. The objects used have typically been categorically different colors and shapes. Because knowledge about categories is stored in long-term memory, these estimations of working memory capacity have been contaminated by long-term memory support. We show that when using clearly distinguishable intracategorical items, visual working memory has a maximum capacity of only one object. Because attention is closely involved in the working memory process, our results add to other studies demonstrating capacity limitations of human attention such as inattentional blindness and change blindness.
Imaging individual retroviral fusion events: From hemifusion to pore formation and growth
Authors: Melikyan Gregory B. , Barnard Richard J. O. , Abrahamyan Levon G. , Mothes Walther , Young John A. T.
Published: June 2005

Viral fusion proteins catalyze merger of viral and cell membranes through a series of steps that have not yet been well defined. To elucidate the mechanism of virus entry, we have imaged fusion between single virions bearing avian sarcoma and leukosis virus (ASLV) envelope glycoprotein (Env) and the cell membrane. Viral particles were labeled with a lipophilic dye and with palmitylated enhanced YFP that was incorporated into the inner leaflet of the viral membrane. When individual virions were bound to target cells expressing cognate receptors, they transferred their lipids and contents only when exposed to low, but not neutral, pH. These data are consistent with the proposed two-step mechanism of ASLV entry that involves receptor-priming followed by low pH activation. Most importantly, lipid mixing commonly occurred before formation of a small fusion pore that was quickly and sensitively detected by pH-dependent changes in palmitylated enhanced YFP fluorescence. Nascent fusion pores were metastable and irreversibly closed, remained small, or fully enlarged, permitting nucleocapsid delivery into the cytosol. These findings strongly imply that hemifusion and a small pore are the key intermediates of ASLV fusion. When added before low pH treatment, a peptide designed to prevent Env from folding into a final helical-bundle conformation abolished virus-cell fusion and infection. Therefore, we conclude that, after receptor-activation, Env undergoes low pH-dependent refolding into a six-helix bundle and, in doing so, sequentially catalyzes hemifusion, fusion pore opening, and enlargement.
Variant surface glycoprotein RNA interference triggers a precytokinesis cell cycle arrest in African trypanosomes
Authors: Sheader Karen , Vaughan Sue , Minchin James , Hughes Katie , Gull Keith , Rudenko Gloria
Published: June 2005

Trypanosoma brucei
is a protozoan parasite that causes African sleeping sickness.
T. brucei
multiplies extracellularly in the bloodstream, relying on antigenic variation of a dense variant surface glycoprotein (VSG) coat to escape antibody-mediated lysis. We investigated the role of VSG in proliferation and pathogenicity by using inducible RNA interference to ablate
VSG
transcript down to 1-2% normal levels. Inhibiting VSG synthesis
in vitro
triggers a rapid and specific cell cycle checkpoint blocking cell division. Parasites arrest at a discrete precytokinesis stage with two full-length flagella and opposing flagellar pockets, without undergoing additional rounds of S phase and mitosis. A subset (<10%) of the stalled cells have internal flagella, indicating that the progenitors of these cells were already committed to cytokinesis when VSG restriction was sensed. Although there was no obvious VSG depletion
in vitro
after 24-h induction of
VSG
RNA interference, there was rapid clearance of these cells
in vivo
. We propose that a stringent block in VSG synthesis produces stalled trypanosomes with a minimally compromised VSG coat, which can be targeted by the immune system. Our data indicate that VSG protein or transcript is monitored during cell cycle progression in bloodstream-form
T. brucei
and describes precise precytokinesis cell cycle arrest. This checkpoint before cell division provides a link between the protective VSG coat and cell cycle progression and could function as a novel parasite safety mechanism, preventing extensive dilution of the protective VSG coat in the absence of VSG synthesis.
Linear-After-The-Exponential (LATE)-PCR: Primer design criteria for high yields of specific single-stranded DNA and improved real-time detection
Authors: Pierce Kenneth E. , Sanchez J. Aquiles , Rice John E. , Wangh Lawrence J.
Published: June 2005

Traditional asymmetric PCR uses conventional PCR primers at unequal concentrations to generate single-stranded DNA. This method, however, is difficult to optimize, often inefficient, and tends to promote nonspecific amplification. An alternative approach, Linear-After-The-Exponential (LATE)-PCR, solves these problems by using primer pairs deliberately designed for use at unequal concentrations. The present report systematically examines the primer design parameters that affect the exponential and linear phases of LATE-PCR amplification. In particular, we investigated how altering the concentration-adjusted melting temperature (
T
m
) of the limiting primer (
T
m
L
) relative to that of the excess primer (
T
m
X
) affects both amplification efficiency and specificity during the exponential phase of LATE-PCR. The highest reaction efficiency and specificity were observed when
T
m
L
-
T
m
X
≥ 5°C. We also investigated how altering
T
m
X
relative to the higher
T
m
of the double-stranded amplicon (
T
m
A
) affects the rate and extent of linear amplification. Excess primers with
T
m
X
closer to
T
m
A
yielded higher rates of linear amplification and stronger signals from a hybridization probe. These design criteria maximize the yield of specific single-stranded DNA products and make LATE-PCR more robust and easier to implement. The conclusions were validated by using primer pairs that amplify sequences within the cystic fibrosis transmembrane regulator (
CFTR
) gene, mutations of which are responsible for cystic fibrosis.
Thrombin inhibitors identified by computer-assisted multiparameter design
Authors: Riester Daniel , Wirsching Frank , Salinas Gabriela , Keller Martina , Gebinoga Michael , Kamphausen Stefan , Merkwirth Christian , Goetz Ruediger , Wiesenfeldt Martin , Stürzebecher Jörg , Bode Wolfram , Friedrich Rainer , Thürk Marcel , Schwienhorst Andreas
Published: June 2005

Here, we present a series of thrombin inhibitors that were generated by using powerful computer-assisted multiparameter optimization process. The process was organized in design cycles, starting with a set of randomly chosen molecules. Each cycle combined combinatorial synthesis, multiparameter characterization of compounds in a variety of bioassays, and algorithmic processing of the data to devise a set of compounds to be synthesized in the next cycle. The identified lead compounds exhibited thrombin inhibitory constants in the lower nanomolar range. They are by far the most selective synthetic thrombin inhibitors, with selectivities of >100,000-fold toward other proteases such as Factor Xa, Factor XIIa, urokinase, plasmin, and Plasma kallikrein. Furthermore, these compounds exhibit a favorable profile, comprising nontoxicity, high metabolic stability, low serum protein binding, good solubility, high anticoagulant activity, and a slow and exclusively renal elimination from the circulation in a rat model. Finally, x-ray crystallographic analysis of a thrombin–inhibitor complex revealed a binding mode with a neutral moiety in the S1 pocket of thrombin.
Inhibition of Stat3 activation in the endometrium prevents implantation: A nonsteroidal approach to contraception
Authors: Catalano Rob D. , Johnson Martin H. , Campbell Elizabeth A. , Charnock-Jones D. Stephen , Smith Stephen K. , Sharkey Andrew M.
Published: June 2005

Activation of the receptors for leukemia inhibitory factor (LIF) and IL-11 is essential for embryo attachment and decidualization in mice. Both receptors induce activation of the Stat family of signal transducers via the Jak/Stat pathway. Here, we aimed to establish whether activation of Stat3 in maternal endometrium is essential for successful implantation. Functional blockade of Stat3 before implantation, by injection into the uterine lumen of a cell-permeable Stat3 peptide inhibitor, reduced embryo implantation specifically by 70% (
P
< 0.001). Stat3 is phosphorylated in the luminal epithelium (LE) in response to LIF, and this phosphorylation was significantly reduced both
in vitro
and
in vivo
by the Stat3 inhibitor. The inhibitor also blocked induction by LIF of several LIF-regulated genes in the LE including Irg1, which has been shown previously to be essential for implantation. Successful implantation is therefore dependent on phosphorylation and activation of Stat3 in the endometrium before implantation. This finding provides a target for contraceptive development, based on selective blockade of signal transduction pathways essential for implantation. This study demonstrates that cell-permeable peptide inhibitors can be used effectively to target intracellular signaling pathways in the uterine LE.
Structure, function, and evolution of the tRNA endonucleases of Archaea: An example of subfunctionalization
Authors: Tocchini-Valentini Giuseppe D. , Fruscoloni Paolo , Tocchini-Valentini Glauco P.
Published: June 2005

We have detected two paralogs of the tRNA endonuclease gene of
Methanocaldococcus jannaschii
in the genome of the crenarchaeote
Sulfolobus solfataricus
. This finding has led to the discovery of a previously unrecognized oligomeric form of the enzyme. The two genes code for two different subunits, both of which are required for cleavage of the pre-tRNA substrate. Thus, there are now three forms of tRNA endonuclease in the Archaea: a homotetramer in some Euryarchaea, a homodimer in other Euryarchaea, and a heterotetramer in the Crenarchaea and the Nanoarchaea. The last-named enzyme, arising most likely by gene duplication and subsequent “subfunctionalization,” requires the products of both genes to be active.