bluuebunny/crossref_metadata_2025 huggingface dataset:
The Phytoestrogen Genistein Enhances Osteogenesis and Represses Adipogenic Differentiation of Human Primary Bone Marrow Stromal Cells
Authors: Heim M. , Frank O. , Kampmann G. , Sochocky N. , Pennimpede T. , Fuchs P. , Hunziker W. , Weber P. , Martin I. , Bendik I.
Published: November 2003

In the present study, we investigated the role of the phytoestrogen genistein and 17β-estradiol in human bone marrow stromal cells, undergoing induced osteogenic or adipogenic differentiation. Profiling of estrogen receptors (ERs)-α, -β1, -β2, -β3, -β4, -β5, and aromatase mRNAs revealed lineage-dependent expression patterns. During osteogenic differentiation, the osteoblast-determining core binding factor-α1 showed a progressive increase, whereas the adipogenic regulator peroxisome proliferator-activated receptor γ (PPARγ) was sequentially decreased. This temporal regulation of lineage-determining marker genes was strongly enhanced by genistein during the early osteogenic phase. Moreover, genistein increased alkaline phosphatase mRNA levels and activity, the osteoprotegerin:receptor activator of nuclear factor-κB ligand gene expression ratio, and the expression of TGFβ1. During adipogenic differentiation, down-regulation in the mRNA levels of PPARγ and CCAAT/enhancer-binding protein-α at d 3 and decreased lipoprotein lipase and adipsin mRNA levels at d 21 were observed after genistein treatment. This led to a lower number of adipocytes and a reduction in the size of their lipid droplets. At d 3 of adipogenesis, TGFβ1 was strongly up-regulated by genistein in an ER-dependent manner. Blocking the TGFβ1 pathway abolished the effects of genistein on PPARγ protein levels and led to a reduction in the proliferation rate of precursor cells. Overall, genistein enhanced the commitment and differentiation of bone marrow stromal cells to the osteoblast lineage but did not influence the late osteogenic maturation markers. Adipogenic differentiation and maturation, on the other hand, were reduced by genistein (and 17β-estradiol) via an ER-dependent mechanism involving autocrine or paracrine TGFβ1 signaling.
sFlt-1 Gene Therapy of Follicular Thyroid Carcinoma
Authors: Ye Caisheng , Feng Chong , Wang Shenming , Wang Kent Z. Q. , Huang Nancy , Liu Xiaoning , Lin Yongjie , Li Mengfeng
Published: November 2003

Tumor progression largely depends on blood supply and neovessel formation, and angiogenesis is emerging as a promising target for cancer therapy. Vascular endothelial growth factor (VEGF), a major proangiogenic molecule, stimulates angiogenesis via promoting endothelial proliferation, survival and migration. VEGF has been found to be up-regulated in various types of tumors and to be associated with tumor progression and poor prognosis. Inhibition of VEGF or its signaling pathway has been shown to suppress tumor angiogenesis and tumor growth. In the present study, we tested the antiangiogenic and antitumor effects of soluble VEGF receptor-1 [soluble Flt (sFlt)-1] on the growth of follicular thyroid carcinoma (FTC). We constructed a 293 embryonic kidney cell line (293-Flt1–3d) that expresses sFlt-1, which is composed of the first three extracellular domains of Flt-1. The 293-Flt1–3d cells inhibited the in vitro growth of human umbilical vein endothelial cells in a paracrine manner. The in vivo antitumor and antiangiogenic activities of the 293-Flt1–3d cells were tested. When 293-Flt1–3d cells were inoculated at a site remote to the FTC-133 tumor transplant, the growth of FTC-133 tumors were inhibited by 70.37%, as compared with the control treatment with 293 cells expressing control gene LacZ. Immunohistochemical analysis of microvessel densities in treated tumors demonstrated that 293-Flt1–3d cells robustly suppressed intratumoral angiogenesis. Our data suggest that a mammalian cell-mediated approach could effectively deliver sFlt-1 gene therapy and inhibit tumor angiogenesis and tumor growth.
Rapid, Nongenomic Effects of Aldosterone in the Heart Mediated by ε Protein Kinase C
Authors: Mihailidou Anastasia S. , Mardini Mahidi , Funder John W.
Published: November 2003

Aldosterone elevates Na+/K+/2Cl− cotransporter activity in rabbit cardiomyocytes within 15 min, an effect blocked by K-canrenoate and thus putatively mineralocorticoid receptor mediated. Increased cotransporter activity raises intracellular [Na+] sufficient to produce a secondary increase in Na+-K+ pump activity; when this increase in intracellular [Na+] is prevented, a rapid effect of aldosterone to lower pump activity is seen. Addition of transcription inhibitor actinomycin D did not change basal or aldosterone-induced lowered pump activity, indicating a direct, nongenomic action of aldosterone. We examined a possible role for protein kinase C (PKC) in the rapid nongenomic effects of aldosterone. Single ventricular myocytes and pipette solutions containing 10 mm intracellular [Na+] were used in patch clamp studies to measure Na+-K+ pump activity. Aldosterone lowered pump current, an effect abolished by ε PKC (εPKC) inhibition but neither αPKC nor scrambled εPKC; addition of εPKC activator peptide mimicked the rapid aldosterone effect. In rabbits chronically infused with aldosterone, the lowered pump current in cardiomyocytes was acutely (≤15 min) restored by εPKC inhibition. These studies show that rapid effects of aldosterone on Na+-K+ pump activity are nongenomic and specifically εPKC mediated; in addition, such effects may be prolonged (7 d) and long-lived (∼4 h isolated cardiomyocyte preparation time). The rapid, prolonged, long-lived effects can be rapidly (≤15 min) reversed by εPKC blockade, suggesting a hitherto unrecognized complexity of aldosterone action in the heart and perhaps by extension other tissues.
Carboxy Terminus of Glucose Transporter 3 Contains an Apical Membrane Targeting Domain
Authors: Inukai Kouichi , Shewan Annette M. , Pascoe Wendy S. , Katayama Shigehiro , James David E. , Oka Yoshitomo
Published: November 2003

We previously demonstrated that distinct facilitative glucose transporter isoforms display differential sorting in polarized epithelial cells. In Madin-Darby canine kidney (MDCK) cells, glucose transporter 1 and 2 (GLUT1 and GLUT2) are localized to the basolateral cell surface whereas GLUTs 3 and 5 are targeted to the apical membrane. To explore the molecular mechanisms underlying this asymmetric distribution, we analyzed the targeting of chimeric glucose transporter proteins in MDCK cells. Replacement of the carboxy-terminal cytosolic tail of GLUT1, GLUT2, or GLUT4 with that from GLUT3 resulted in apical targeting. Conversely, a GLUT3 chimera containing the cytosolic carboxy terminus of GLUT2 was sorted to the basolateral membrane. These findings are not attributable to the presence of a basolateral signal in the tails of GLUTs 1, 2, and 4 because the basolateral targeting of GLUT1 was retained in a GLUT1 chimera containing the carboxy terminus of GLUT5. In addition, we were unable to demonstrate the presence of an autonomous basolateral sorting signal in the GLUT1 tail using the low-density lipoprotein receptor as a reporter. By examining the targeting of a series of more defined GLUT1/3 chimeras, we found evidence of an apical targeting signal involving residues 473–484 (DRSGKDGVMEMN) in the carboxy tail. We conclude that the targeting of GLUT3 to the apical cell surface in MDCK cells is regulated by a unique cytosolic sorting motif.
FGF17b and FGF18 have different midbrain regulatory properties from FGF8b or activated FGF receptors
Authors: Liu Aimin , Li James Y. H. , Bromleigh Carrie , Lao Zhimin , Niswander Lee A. , Joyner Alexandra L.
Published: November 2003

Early patterning of the vertebrate midbrain and cerebellum is regulated by a mid/hindbrain organizer that produces three fibroblast growth factors (FGF8,FGF17 and FGF18). The mechanism by which each FGF contributes to patterning the midbrain, and induces a cerebellum in rhombomere 1 (r1) is not clear. We and others have found that FGF8b can transform the midbrain into a cerebellum fate, whereas FGF8a can promote midbrain development. In this study we used a chick electroporation assay and in vitro mouse brain explant experiments to compare the activity of FGF17b and FGF18 to FGF8a and FGF8b. First, FGF8b is the only protein that can induce the r1 gene Gbx2 and strongly activate the pathway inhibitors Spry1/2, as well as repress the midbrain gene Otx2. Consistent with previous studies that indicated high level FGF signaling is required to induce these gene expression changes,electroporation of activated FGFRs produce similar gene expression changes to FGF8b. Second, FGF8b extends the organizer along the junction between the induced Gbx2 domain and the remaining Otx2 region in the midbrain, correlating with cerebellum development. By contrast, FGF17b and FGF18 mimic FGF8a by causing expansion of the midbrain and upregulating midbrain gene expression. This result is consistent with Fgf17 and Fgf18 being expressed in the midbrain and not just in r1 as Fgf8 is. Third, analysis of gene expression in mouse brain explants with beads soaked in FGF8b or FGF17b showed that the distinct activities of FGF17b and FGF8b are not due to differences in the amount of FGF17b protein produced in vivo. Finally, brain explants were used to define a positive feedback loop involving FGF8b mediated upregulation of Fgf18, and two negative feedback loops that include repression of Fgfr2/3 and direct induction of Spry1/2. As Fgf17 and Fgf18 are co-expressed with Fgf8 in many tissues, our studies have broad implications for how these FGFs differentially control development.
Intranasal steroid sprays in the treatment of rhinitis: is one better than another?
Authors: Waddell A. N. , Patel S. K. , Toma A. G. , Maw A. R.
Published: November 2003

The treatment of allergic rhinitis has been revolutionized by the introduction of topical nasal steroids, which are one of the commonest prescriptions from otolaryngology departments. With so many different sprays available on the market, the literature was reviewed for the efficacy, side-effect profile and relative cost of each product and the following conclusions made:

(1) A meta-analysis of randomized controlled trials comparing the efficacy of intranasal corticosteroids and oral antihistamines in the treatment of allergic rhinitis showed a clear benefit in favour of intranasal steroids in relieving nasal symptoms.

(2) There is no clear evidence to support the suggestion that one steroid spray is more effective than another in the treatment of seasonal or perennial allergic rhinitis.

(3) All the sprays have a similar side-effect profile; the commonest being epistaxis with a reported incidence between 17 and 23 per cent. In all the clinical trials, the placebo spray had an appreciable rate of epistaxis of between 10 to 15 per cent.

(4) Fluticasone causes a reduction in endogenous cortisol secretion but no significant adrenal suppression was seen with triamcinolone, beclomethasone, budesonide or mometasone.

(5) There is little evidence that skeletal growth is restricted by the administration of topical nasal steroid sprays.

(6) There is considerable variation in the daily cost of each spray. Beclomethasone, dexamethasone and budesonide are significantly cheaper than fluticasone, mometasone or triamcinolone.
Improving outcomes in rhinocerebral mucormycosis - early diagnostic pointers and prognostic factors
Authors: Dhiwakar M. , Thakar A. , Bahadur S.
Published: November 2003

Rhinocerebral mucormycosis is an uncommon, rapidly progressive, highly fatal sinus infection, usually occurring in immunocompromised hosts. We describe our clinical experience with nine such consecutive cases managed at our centre, with emphasis on identifying early diagnostic and prognostic features. Perinasal cellulitis/paraesthesia was the most frequent early clinical sign of disease, being evident in at least six cases. Periorbital oedema, mucopurulent rhinorrhoea and nasal crusting were the other early manifestations. Concurrent computed tomography (CT) scan at this initial stage however revealed only minimal mucosal thickening of the sinuses in all four cases wherein it was done. Intracranial extension as evident on CT was the only adverse prognostic sign (p<0.05). The present report highlights the importance of early diagnosis and prompt institution of antifungal chemotherapy in ensuring a favourable outcome in rhinocerebral mucormycosis. However, initial CT is frequently near-normal and biopsy time-consuming and often not feasible. To optimize early diagnosis therefore, the clinician should be highly alert to certain subtle clinical signs, in the appropriate setting of an immunocompromised patient.
Massive subcutaneous emphysema following routine endotracheal intubation
Authors: Watters K. F. , Lacy P. D. , McConn Walsh R.
Published: November 2003

Upper aerodigestive tract injury after endotracheal intubation is a rare but serious complication. The case of a 57-year-old female, who developed extensive neck and pneumomediastinum following a knee arthroscopy under general anaesthesia, is presented. Possible mechanisms of injury and management options are discussed.
Removal of sub-mucosal foreign body (metal wire) from the pharynx using image intensifier
Authors: Bhatt C. , Reddy N. Vishnu Swaroop , Reddy T. N.
Published: November 2003

It is well known how difficult it is to localize a foreign body in the sub-mucosal tissues. This is a report of a male who swallowed a metal wire which lodged in the pharyngeal sub-mucosal tissue. The foreign body was localized using an image intensifier and removed successfully.
Magnetic resonance imaging of pleomorphic adenoma arising from the external auditory canal
Authors: Masumura Chisako , Horii Arata , Mishiro Yasuo , Inohara Hidenori , Kitahara Tadashi , Takashima Shodayu , Kubo Takeshi
Published: November 2003

Pleomorphic adenoma arising from the external auditory canal is a very rare neoplasm, and there has been no report on magnetic resonance (MR) imaging of pleomorphic adenoma of the external auditory canal. We report here a case of 65-year-old male with this tumour, measuring 12 mm in a diameter. Histopathology was confirmed from the specimen obtained at the surgical excision. MR revealed that the tumour had a well-defined margin showing hypointensity on T1-weighted images and hyperintensity on T2-weighted images relative to the parotid gland. The tumour was well enhanced by contrast material. No invasion to the surrounding tissue was observed. These MR findings were compatible with pleomorphic adenoma of the salivary gland origin. In treating pleomorphic adenoma of the external auditory canal, complete surgical excision is essential for the prevention of recurrence. It can be concluded that MR imaging is helpful for making a differential diagnosis of external auditory canal tumours and selection of adequate treatment.
How Critical are Critical Reviews? The Box Office Effects of Film Critics, Star Power, and Budgets
Authors: Basuroy Suman , Chatterjee Subimal , Ravid S. Abraham
Published: November 2003

The authors investigate how critics affect the box office performance of films and how the effects may be moderated by stars and budgets. The authors examine the process through which critics affect box office revenue, that is, whether they influence the decision of the film going public (their role as influencers), merely predict the decision (their role as predictors), or do both. They find that both positive and negative reviews are correlated with weekly box office revenue over an eight-week period, suggesting that critics play a dual role: They can influence and predict box office revenue. However, the authors find the impact of negative reviews (but not positive reviews) to diminish over time, a pattern that is more consistent with critics’ role as influencers. The authors then compare the positive impact of good reviews with the negative impact of bad reviews to find that film reviews evidence a negativity bias; that is, negative reviews hurt performance more than positive reviews help performance, but only during the first week of a film's run. Finally, the authors examine two key moderators of critical reviews, stars and budgets, and find that popular stars and big budgets enhance box office revenue for films that receive more negative critical reviews than positive critical reviews but do little for films that receive more positive reviews than negative reviews. Taken together, the findings not only replicate and extend prior research on critical reviews and box office performance but also offer insight into how film studios can strategically manage the review process to enhance box office revenue.
Antecedents and Consequences of Merit Pay Fairness for Industrial Salespeople
Authors: Ramaswami Sridhar N. , Singh Jagdip
Published: November 2003

How do salespeople make judgments of merit pay fairness? By what mechanisms do fairness judgments influence the performance and commitment of salespeople? Using equity and social exchange theories, the authors examine these questions for industrial salespeople who work in a Fortune 500 firm and provide four key findings. First, of the three dimensions of fairness judgments, they find the interactional fairness dimension to be relatively more important than procedural or distributive fairness in influencing job outcomes of salespeople. Second, supervisory behaviors have significant influence in shaping salespeople's fairness judgments, particularly judgments of distributive and interactional fairness. Third, the results underscore the contrasting mediating role of trust in supervisor and job satisfaction. Although trust in the supervisor is important in reducing salespeople's opportunistic behaviors, the authors find job satisfaction to be important in enhancing their loyalty to the organization. Fourth, salespeople's job performance is influenced directly by extrinsic factors such as fairness of current rewards and potential for rewards. In addition, the authors outline implications for theory and practice.
Sources and Financial Consequences of Radical Innovation: Insights from Pharmaceuticals
Authors: Sorescu Alina B. , Chandy Rajesh K. , Prabhu Jaideep C.
Published: November 2003

Radical innovations are engines of economic growth and the focus of much academic and practitioner interest, yet some fundamental questions remain unanswered. The authors use theoretical arguments on the risk associated with radical innovations, and the resources needed for them, to answer the following questions on the sources and financial consequences of radical innovation: (1) Who introduces a greater number of radical innovations: dominant or nondominant firms? (2) How great are the financial rewards to radical innovations, and how do these rewards vary across dominant and nondominant firms? (3) Is it only a firm's resources in the aggregate or also its focus and leverage of resources that make its innovations more financially valuable? and (4) Which are more valuable: innovations that incorporate a breakthrough technology or innovations that provide a substantial increase in customer benefits? The authors pool information from a disparate set of sources in the pharmaceutical industry to study these questions. Results indicate that a large majority of radical innovations come from a minority of firms. The financial rewards of innovation vary dramatically across firms and are tied closely to firms’ resource base. Firms that provide higher per-product levels of marketing and technology support obtain much greater financial rewards from their radical innovations than do other firms. Firms that have greater depth and breadth in their product portfolio also gain more from their radical innovations.
Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication
Authors: Krishnan Ramaswamy , Kopacz Monika , Ateshian Gerard A.
Published: November 2003

The objective of the current study was to measure the friction coefficient simultaneously with the interstitial fluid load support in bovine articular cartilage, while sliding against glass under a constant load. Ten visually normal 6‐mm‐diameter cartilage plugs harvested from the humeral head of four bovine shoulder joints (ages 2–4 months) were tested in a custom friction device under reciprocating linear motion (range of translation ± 2 mm; sliding velocity 1 mm/s), subjected to a 4.5 N constant load. The frictional coefficient was found to increase with time from a minimum value of μmin = 0.010 ± 0.007 (mean ± SD) to a maximum value of 0.243 ± 0.044 over a duration ranging from 920 to 19,870 s (median: 4,560 s). The corresponding interstitial fluid load support decreased from a maximum of 88.8 ± 3.8% to 8.7 ± 8.6%. A linear correlation was observed between the frictional coefficient and interstitial fluid load support (r2 = 0.96 ± 0.03). These results support the hypothesis that the temporal variation of the frictional coefficient correlates negatively with the interstitial fluid load support and that consequently interstitial fluid load support is a primary mechanism regulating the frictional response in articular cartilage. Fitting the experimental data to a previously proposed biphasic boundary lubrication model for cartilage yielded an equilibrium friction coefficient of μeq = 0.284 ± 0.044. The fraction of the apparent contact area over which the solid cartilage matrix was in contact with the glass slide was predicted at π = 1.7 ± 6.3%, significantly smaller than the solid volume fraction of the tissue, πs = 13.8 ± 1.8%. The model predictions suggest that mixed lubrication prevailed at the contact interface under the loading conditions employed in this study. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Influence of the Iceland mantle plume on crustal accretion at the inflated Reykjanes Ridge: Magma lens and low hydrothermal activity?
Authors: Chen Y. John
Published: November 2003

A simple ridge model is applied to the hot spot‐influenced, slow spreading Reykjanes Ridge in the North Atlantic to explore the effects of both mantle temperatures and hydrothermal cooling due to the Iceland mantle plume on the thermal structure and crustal accretion at this ridge. The objective of this study is not only to fit existing observations but also to raise important questions for future field programs to test. Does a magma chamber similar to that at the East Pacific Rise exist beneath the inflated Reykjanes Ridge north of the transition site at 59°N and if it does, at what depths? Modeling results of this study show that with increased magma supply a long‐lived magma chamber could be present at the lower crust if hydrothermal activity is comparable to elsewhere of the Mid‐Atlantic Ridge. More importantly, modeling results predict a shallow magma chamber beneath the inflated Reykjanes Ridge north of 59°N if it is associated with low hydrothermal activity. Since the recent observations of the extremely low incidence of high‐temperature vents along the Reykjanes Ridge was interpreted as the indication for the diffusive flow being the dominant mode of hydrothermal circulation there, not as the evidence for low hydrothermal activity, the questions raised here call for more field observations at the inflated Reykjanes Ridge north of 59°N against these testable model predictions and thus to resolve these important issues.
Role of diatoms in regulating the ocean's silicon cycle
Authors: Yool Andrew , Tyrrell Toby
Published: November 2003

Among phytoplankton the diatoms are strong competitors and contribute significantly to total global primary production. Aspects of their life history, notably their high sinking rates, make them important to the export flux of carbon into the ocean interior. Unlike the majority of other phytoplankton, they utilize silicic acid (=silicate) to construct their cell walls and are controlled by its availability and distribution. Here a simple model is developed to study the relationship between the diatoms and the ocean's silicon cycle. The ecological component of this model pits the slightly superior diatoms against all other algae, with both groups competing for phosphate while the diatoms additionally require silicic acid. The model agrees reasonably with observed distributions of nutrients and with their biogeochemical fluxes. While theoretically superior, the diatoms are held in check by the availability of silicic acid, allowing the persistence and numerical dominance of the other algae. The concentrations of both nutrients are homeostatically controlled by the phytoplankton, and resist perturbations. Analysis finds that primary production in the model is ultimately controlled by phosphate, with silicic acid abundance controlling the fraction of the total produced by diatoms. Sensitivity analyses using more ecologically detailed variants of the model find that these results are generally robust. The model's treatment of the “silica pump” hypothesis [Dugdale and Wilkerson, 1998] is also examined.
Very long period oscillations of Mount Erebus Volcano
Authors: Aster R. , Mah S. , Kyle P. , McIntosh W. , Dunbar N. , Johnson J. , Ruiz M. , McNamara S.
Published: November 2003

The exposed top of the conduit system at Mount Erebus Volcano, Ross Island, Antarctica, is a convecting lava (magma) lake hosting Strombolian eruptions caused by the explosive decompression of large (up to 5 m radius) gas slugs. Short‐period (SP; f ≥1 Hz) seismoacoustic eruption seismograms are accompanied by oscillatory very long period (VLP) signals observed in the near field by broadband seismometers 0.7 to 2.5 km from the lava lake. A variable VLP onset, preceding eruptions by several seconds, is followed by a repeatable VLP coda that persists for several minutes until the lava lake recovers to its preeruptive level. VLP signals are dominated by distinct decaying nonharmonic modes, the largest at periods of 20.7, 11.3, and 7.8 s, with respective source Q values of approximately 11, 18, and 4. Particle motions indicate a temporally evolving source producing increasingly vertical posteruptive displacements as the signal decays. VLP scalar moments, up to ∼5×1011 N m, exceed SP moments by an order of magnitude or more, suggesting distinct, though genetically related, SP and VLP source mechanisms. We conclude that VLP signals arise from excitation of a quasi‐linear resonator that is intimately associated with the conduit system and is excited by gravity and inertial forces associated with gas slug ascent, eruption, and magma recharge. VLP signal stability across hundreds of eruptions spanning 5 years, the persistence of the lava lake, and the rapid posteruptive lava lake recovery indicate a stable near‐summit magma reservoir and VLP source process.
Plasma blob events observed by KOMPSAT‐1 and DMSP F15 in the low latitude nighttime upper ionosphere
Authors: Park Jaeheung , Min Kyoung Wook , Lee Jae‐Jin , Kil Hyosub , Kim Vitaly P. , Kim Hee‐Jun , Lee Ensang , Lee Dae Young
Published: November 2003

In this paper we report plasma blob events (plasma density enhancements) that were observed from KOMPSAT‐1 (685‐km altitude, 2250 LT) and from DMSP F15 (840‐km altitude, 2130 LT) in the low‐latitude F region. The blobs were observed mostly along the ±15° magnetic latitudes. Their global distribution showed a seasonal‐longitudinal dependence similar to the distribution of the equatorial plasma bubbles. The blobs drifted upward relative to the ambient plasma, and the electron temperatures and H+ proportions were lower within the blobs compared to those in the background. The characteristics of the plasma blobs were similar to those of the equatorial plasma bubbles. Therefore, it is suggested that the blobs originated from the lower altitudes by a mechanism that drives an upward drift of the plasma bubbles. The blob events did not occur in a correlated way with the magnetic activity or daily variation of solar activity.
Inferring the scale height of the lunar nightside double layer
Authors: Halekas J. S. , Lin R. P. , Mitchell D. L.
Published: November 2003

Earlier analyses of Lunar Prospector (LP) data found that the shadowed lunar surface charges negative. The potential difference between the surface and LP has unexplained dependences on solar zenith angle and tip angle. The dependence on tip angle may arise because electrons with pitch angles close to the loss cone angle on field lines with higher tip angles encounter a smaller average potential before reflecting (the technique used to infer potentials relies upon loss cone angle measurements). The correlation may therefore be due to a systematic measurement error. However, since this “measurement error” depends upon the ratio of gyroradius to double layer scale height, it allows us to estimate the scale height. By comparing data with the results of particle tracing simulations, we estimate an average nightside scale height of a few km. This is somewhat larger than the electron Debye length, but much smaller than recent theoretical estimates.
Frequency of low‐ozone events over northwestern Europe in 1952–1963 and 1990–2000
Authors: Brönnimann Stefan , Hood Lon L.
Published: November 2003

The frequency of days with very low total ozone (<225 DU, termed LODs) over northwestern Europe is studied using data from 8 sites from 1952–1963 and 1990–2000. In autumn, the frequency of LODs was similar in both periods. However, in winter, LODs were much more frequent in 1990–2000 than in 1952–1963. The frequency of LODs is a function of both changes in atmospheric dynamics and changes in the mean ozone column. We used a statistical model to address the relative contributions of these two effects. Results show that the changing atmospheric circulation strongly contributed to the increased LOD frequency in winter. The model also suggests a strong effect of a different mean ozone column, but the uncertainty is larger. Because both total ozone and atmospheric dynamics changed little between the two periods in autumn, no large differences in LOD frequency were found during this season.
GPS measurement of postseismic deformation following the 1999 Chi‐Chi, Taiwan, earthquake
Authors: Yu Shui‐Beih , Hsu Ya‐Ju , Kuo Long‐Chen , Chen Horng‐Yue , Liu Chih‐Chung
Published: November 2003

In the 15‐month period (September 1999 to December 2000) after the 1999 Chi‐Chi, Taiwan, earthquake (Mw 7.6) about 80 campaign‐surveyed GPS stations in central Taiwan were occupied up to seven times. Furthermore, seven continuous GPS stations were put into operation in the epicentral region mostly within three weeks after the main shock. GPS data from these near‐field stations and some pre‐existing far‐field stations were utilized to study the postseismic deformation following the Chi‐Chi earthquake. The postseismic displacements of the GPS stations were approximated by a combination of an exponential transient decay function with a relaxation time of 86 days and a postseismic linear rate change. Stations on the hanging wall displayed west‐northwesterly horizontal displacements of up to 252 mm and uplift as large as 229 mm. Postseismic displacements are much larger to the south near the epicenter of Chi‐Chi main shock than in the north where the maximum coseismic displacement occurred. Stations on the footwall show only small displacements. The postseismic GPS data were inverted to infer the deeper fault geometry and afterslip distribution based on a four‐segment fault model with its shallow part constrained by coseismic fault geometry deduced from GPS and seismological studies. The optimal model requires the lower fault segment to be a horizontal plane at a depth of 10.4 km, consistent with a model based on GPS data taken during the first three months after the main shock and other geological or geophysical studies. The maximum afterslip (459 mm) occurs in the hypocentral region and in the northern part of the decollement. Slip of about 430 mm also occurs in the southern part of the decollement. The afterslip moment inferred from 15 months of GPS data is 4.7 × 1019 N m, approximately 2.3 times the seismic moment released by aftershocks. This implies that a major part of the postseismic deformation is aseismic.
Estimation of root water uptake parameters by inverse modeling with soil water content data
Authors: Hupet F. , Lambot S. , Feddes R. A. , van Dam J. C. , Vanclooster M.
Published: November 2003

In this paper we have tested the feasibility of the inverse modeling approach to derive root water uptake parameters (RWUP) from soil water content data using numerical experiments for three differently textured soils and for an optimal drying period. The RWUP of interest are the rooting depth and the bottom root length density. In a first step, a thorough sensitivity analysis was performed. This showed that soil water content dynamics is relatively insensitive to RWUP and that the sensitivity depends on the texture of the considered soil. For medium‐fine textured soil, the sensitivity is particularly low due to relatively high unsaturated hydraulic conductivity values. These ones allow a “compensating effect” to occur, i.e., vertical unsaturated water fluxes overshadowing in some way the root water uptake. In a second step, we analyzed the well‐posedness of the solution (stability and nonuniqueness) when only RWUP are optimized. For this case, the inverse problem is clearly ill‐posed except for the estimation of the rooting depth parameter for coarse and the very fine textured soils. In a third step, we addressed the case where RWUP are estimated simultaneously with additional parameters of the system (i.e., with soil hydraulic parameters). For this case, our study showed that the inverse problem is well‐posed for the coarse and very fine textured soils, allowing for the estimation of both RWUP of interest provided that a powerful global optimization algorithm is used. On the contrary, the estimation of RWUP is unfeasible for medium‐fine textured soil due to the “compensating effect” of the vertical unsaturated water flows. In conclusion, we can state that the inverse modeling approach can be applied to derive RWUP for some soils (coarse and very fine textured) and that the feasibility is strongly improved if the RWUP are simultaneously optimized with additional parameters. Nevertheless, more detailed research is needed to apply the inverse modeling approach to real cases for which additional issues are likely to be encountered such as soil heterogeneity and root dynamics.
An analytical method for predicting surface soil moisture from rainfall observations
Authors: Pan Feifei , Peters‐Lidard Christa D. , Sale Michael J.
Published: November 2003

A simple analytical method for estimating surface soil moisture directly from rainfall data is proposed and studied. Soil moisture dynamics are represented by a linear stochastic partial differential equation [Entekhabi and Rodriguez‐Iturbe, 1994]. A diagnostic equation is derived from the soil moisture dynamics equation by eliminating the diffusion term. The derived daily soil moisture function is a time‐weighted average of previous cumulative rainfall over a given period (e.g., >14 days). The advantage of this method is that information on the initial condition of soil moisture, which is often not available at all times and locations, is not needed. The loss coefficient in the diagnostic equation for soil moisture can be estimated from land surface characteristics and soil properties. The method for determining the averaging window size, the loss coefficient, and the infiltration coefficient are described and demonstrated. The soil moisture data observed during three field experiments, i.e., Monsoon'90, Washita'92, and SGP'97, are compared to the calculated soil moisture. The results indicate that the proposed method is robust and has the potential for useful soil moisture predictions.
How does rainfall become runoff? A combined tracer and runoff transfer function approach
Authors: Weiler Markus , McGlynn Brian L. , McGuire Kevin J. , McDonnell Jeffrey J.
Published: November 2003

Hydrographs are an enticing focus for hydrologic research: they are readily available hydrological data that integrate the variety of terrestrial runoff generation processes and upstream routing. Notwithstanding, new techniques to glean information from the hydrograph are lacking. After early approaches of graphically separating streamflow components, hydrograph separations in the past two decades have focused on tracers as a more objective means to separate the storm hydrograph. These tracer‐based methods provide process‐based information; however, their implicit assumptions limit their applicability and explanatory power. We present a new method for isotope hydrograph separation that integrates the instantaneous unit hydrograph and embraces the temporal variability of rainfall isotopic composition (one of the largest impediments to the standard use of isotopes as tracers). Our model computes transfer functions for event water and preevent water calculated from a time‐variable event water fraction. The transfer function hydrograph separation model (TRANSEP) provides coupled but constrained representations of transport and hydraulic transfer functions, overcoming limitations of other models. We illustrate the utility of TRANSEP by applying it to two rainfall events from a 17 ha catchment at Maimai in New Zealand, where 18O, rainfall, and runoff data were sampled with a high temporal resolution. We explore which runoff and tracer transfer function (exponential piston flow, gamma distribution, or two parallel linear reservoirs) gave the best results for the proposed model structure and for the example data set. Uncertainty analysis was used to determine if the parameters were identifiable and if the information available for applying TRANSEP was sufficient. The results of the best performing transfer function are considered in detail to identify model performance, illustrate individual event characteristics, and interpret runoff processes in the catchment.
Application of the theory of micromixing to groundwater reactive transport models
Authors: Robinson Bruce A. , Viswanathan Hari S.
Published: November 2003

This study extends and applies the theory of micromixing, first introduced in the chemical reaction engineering literature, to the topic of reactive transport in porous media. For all but the simplest linear kinetic and sorption models the fate and transport of a reactive solute depends on the residence times and the details of small‐scale mixing. The latter phenomenon, also called micromixing, is important because it brings into close proximity chemical species that react, and it controls the local concentrations in a flowing system. Solutes with reaction rates or sorption isotherms that depend on species concentration will therefore be affected by micromixing. Two models for micromixing are introduced, the minimum and maximum mixedness models, that provide bounds on the extent of reaction or retardation behavior within the constraints imposed by the residence time distribution (RTD) of a conservative solute in the same flow system. These mixing models prescribe the latest or earliest permissible mixing of parcels of fluid of different residence times, which in turn bounds the degree of reaction of a reactive solute for nonlinear rate laws or sorption isotherms. Simulation results using the bounding models show that micromixing effects are most important for nonlinear reaction curves, solute pulses of short duration, and systems with broad RTD curves. Use of these models is a straightforward and practical way to investigate the importance of a phenomenon for which data are seldom available and whose impact on groundwater reactive transport models has heretofore not been studied in a systematic, bounding manner.
Interleukin-1-receptor-associated kinase 2 (IRAK2)-mediated interleukin-1-dependent nuclear factor κB transactivation in Saos2 cells requires the Akt/protein kinase B kinase
Authors: CENNI Vittoria , SIRRI Alessandra , De Pol Anto , MARALDI Nadir Mario , MARMIROLI Sandra
Published: November 2003

The post-receptor pathway that leads to nuclear factor κB (NF-κB) activation begins with the assembly of a membrane-proximal complex among the interleukin 1 (IL-1) receptors and the adaptor molecules, myeloid differentiation protein 88 (MyD88), IL-1-receptor-associated kinases (IRAKs) and tumour-necrosis-factor-receptor-associated factor 6. Eventually, phosphorylation of the inhibitor of NF-κB (IκB) by the IκB kinases releases NF-κB, which translocates to the nucleus and modulates gene expression. In this paper, we report that IRAK2 and MyD88, but not IRAK1, interact physically with Akt, as demonstrated by co-immunoprecipitation and pull-down experiments. Interestingly, the association of Akt with recombinant IRAK2 is decreased by stimulation with IL-1, and is favoured by pre-treatment with phosphatase. Likewise, Akt association with IRAK2 is increased considerably by overexpression of PTEN (phosphatase and tensin homologue deleted on chromosome 10), while it is completely abrogated by overexpression of phosphoinositide-dependent protein kinase 1. These data indicate that Akt takes part in the formation of the signalling complex that conveys the signal from the IL-1 receptors to NF-κB, a step that is much more membrane-proximal than was reported previously. We also demonstrate that Akt activity is necessary for IL-1-dependent NF-κB transactivation, since a kinase-defective mutant of Akt impairs IRAK2- and MyD88-dependent, but not IRAK1-dependent, NF-κB activity, as monitored by a gene reporter assay. Accordingly, IRAK2 failed to trigger inducible nitric oxide synthase and IL-1β production in cells expressing dominant-negative Akt. However, NF-κB binding to DNA was not affected by inhibition of Akt, indicating that Akt regulates NF-κB at a level distinct from the dissociation of p65 from IκBα and its translocation to the nucleus, possibly involving phosphorylation of the p65 transactivation domain.
Family 18 chitinase–oligosaccharide substrate interaction: subsite preference and anomer selectivity of Serratia marcescens chitinase A
Authors: ARONSON Nathan N. , HALLORAN Brian A. , ALEXYEV Mikhail F. , AMABLE Lauren , MADURA Jeffry D. , PASUPULATI Lakshminarasimhulu , WORTH Catherine , VAN ROEY Patrick
Published: November 2003

The sizes and anomers of the products formed during the hydrolysis of chitin oligosaccharides by the Family 18 chitinase A (ChiA) from Serratia marcescens were analysed by hydrophilic interaction chromatography using a novel approach in which reactions were performed at 0 °C to stabilize the anomer conformations of the initial products. Crystallographic studies of the enzyme, having the structure of the complex of the ChiA E315L (Glu315→Leu) mutant with a hexasaccharide, show that the oligosaccharide occupies subsites −4 to +2 in the substrate-binding cleft, consistent with the processing of β-chitin by the release of disaccharide at the reducing end. Products of the hydrolysis of hexa- and penta-saccharides by wild-type ChiA, as well as by two mutants of the residues Trp275 and Phe396 important in binding the substrate at the +1 and +2 sites, show that the substrates only occupy sites −2 to +2 and that additional N-acetyl-d-glucosamines extend beyond the substrate-binding cleft at the reducing end. The subsites −3 and −4 are not used in this four-site binding mode. The explanation for these results is found in the high importance of individual binding sites for the processing of short oligosaccharides compared with the cumulative recognition and processive hydrolysis mechanism used to digest natural β-chitin.
Aromatic residues within the substrate-binding cleft of Bacillus circulans chitinase A1 are essential for hydrolysis of crystalline chitin
Authors: WATANABE Takeshi , ARIGA Yumiko , SATO Urara , TORATANI Tadayuki , HASHIMOTO Masayuki , NIKAIDOU Naoki , KEZUKA Yuichiro , NONAKA Takamasa , SUGIYAMA Junji
Published: November 2003

Bacillus circulans chitinase A1 (ChiA1) has a deep substrate-binding cleft on top of its (β/α)8-barrel catalytic domain and an interaction between the aromatic residues in this cleft and bound oligosaccharide has been suggested. To study the roles of these aromatic residues, especially in crystalline-chitin hydrolysis, site-directed mutagenesis of these residues was carried out. Y56A and W53A mutations at subsites −5 and −3, respectively, selectively decreased the hydrolysing activity against highly crystalline β-chitin. W164A and W285A mutations at subsites +1 and +2, respectively, decreased the hydrolysing activity against crystalline β-chitin and colloidal chitin, but enhanced the activities against soluble substrates. These mutations increased the Km-value when reduced (GlcNAc)5 (where GlcNAc is N-acetylglucosamine) was used as the substrate, but decreased substrate inhibition observed with wild-type ChiA1 at higher concentrations of this substrate. In contrast with the selective effect of the other mutations, mutations of W433 and Y279 at subsite −1 decreased the hydrolysing activity drastically against all substrates and reduced the kcat-value, measured with 4-methylumbelliferyl chitotrioside to 0.022% and 0.59% respectively. From these observations, it was concluded that residues Y56 and W53 are only essential for crystalline-chitin hydrolysis. W164 and W285 are very important for crystalline-chitin hydrolysis and also participate in hydrolysis of other substrates. W433 and Y279 are both essential for catalytic reaction as predicted from the structure.
Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A
Authors: DENECKE Bernd , GRÄBER Steffen , SCHÄFER Cora , HEISS Alexander , WÖLTJE Michael , JAHNEN-DECHENT Willi
Published: November 2003

Fetuins are serum proteins with diverse functions including the regulation of osteogenesis and inhibition of unwanted mineralization. Besides the α2-Heremans and Schmid glycoprotein/fetuin-A, the recently identified fetuin-B is a second member of the fetuin family [Olivier, Soury, Risler, Smih, Schneider, Lochner, Jouzeau, Fey and Salier (1999) Genomics 57, 352–364; Olivier, Soury, Ruminy, Husson, Parmentier, Daveau and Salier (2000) Biochem. J. 350, 589–597], which belongs to the cystatin superfamily. We compared the expressions of fetuin-B and fetuin-A at the RNA level and established that both genes are most highly expressed in liver tissue. Like fetuin-A, fetuin-B mRNA is also highly expressed in tongue and placenta tissues. We demonstrated for the first time that fetuin-B is also expressed at the protein level in sera and several organs of mouse, rat and human. We isolated contiguous genomic clones containing both fetuin-B and fetuin-A genes, indicating that these genes are closely linked at the genome level. The close proximity of both these genes may explain our observation that fetuin-B expression was decreased in fetuin-A-deficient mice. Unlike fetuin-A, the amount of fetuin-B protein in human serum varied with gender and was higher in females than in males. Functional analysis revealed that fetuin-B, similarly to fetuin-A, is an inhibitor of basic calcium phosphate precipitation, albeit less active when compared with fetuin-A. Therefore fetuin-B may have a function that is partly overlapping, if not identical, with the function of fetuin-A.