bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity and Seasonal Changes of Uncultured
Planctomycetales
in River Biofilms
Authors: Brümmer I. H. M. , Felske A. D. M. , Wagner-Döbler I.
Published: September 2004

Cell counts of planctomycetes showed that there were high levels of these organisms in the summer and low levels in the winter in biofilms grown in situ in two polluted rivers, the Elbe River and the Spittelwasser River. In this study 16S rRNA-based methods were used to investigate if these changes were correlated with changes in the species composition. Planctomycete-specific clone libraries of the 16S rRNA genes found in both rivers showed that there were seven clusters, which were distantly related to the genera
Pirellula
,
Planctomyces
, and
Gemmata
. The majority of the sequences from the Spittelwasser River were affiliated with a cluster related to
Pirellula
, while the majority of the clones from the Elbe River fell into three clusters related to
Planctomyces
and one deeply branching cluster related to
Pirellula
. Some clusters also contained sequences derived from freshwater environments worldwide, and the similarities to our biofilm clones were as high as 99.8%, indicating the presence of globally distributed freshwater clusters of planctomycetes that have not been cultivated yet. Community fingerprints of planctomycete 16S rRNA genes were generated by temperature gradient gel electrophoresis from Elbe River biofilm samples collected monthly for 1 year. Sixteen bands were identified, and for the most part these bands represented organisms related to the genus
Planctomyces.
The fingerprints showed that there was strong seasonality of most bands and that there were clear differences in the summer and the winter. Thus, seasonal changes in the abundance of
Planctomycetales
in river biofilms were coupled to shifts in the community composition.
AN OPTIC-FIBER INTERFEROMETER FOR THE DYNAMIC CHARACTERIZATION OF MICROSTRUCTURES
Authors: PENG CHONG , ZHANG PEIQIANG
Published: September 2004

This article describes a measurement system designed to evaluate the dynamic characteristics of micromechanical structures. The system is based on Active Homodyne demodulation M-Z optic-fiber interferometer and can measure out-of-plane movement with a sensitivity of 0.1 nm. To validate the system, vibration measurements have been carried on a typical MEMS structure — the sensitive elements of a kind of uncooled IR imaging system, an array of micromachined bimaterial cantilevers (micron dimensions) — and the results are compared with the ones from FEM model analysis and another measurement method which can be known as spectrum plane optic filtering. The three results agree with each other. The first natural frequencies of the structures are determined from data obtained by vibrating the structures using a PZT excitation system. The mode shapes and modal damping will be carried out soon after a scanning system is completed.
Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen
Authors: Stephens Gillian , Yan Yibing , Jandrot-Perrus Martine , Villeval Jean-Luc , Clemetson Kenneth J. , Phillips David R.
Published: September 2004

Glycoprotein (GP) VI, the primary collagen receptor on platelets, has been shown to have variable expression, possibly as a consequence of immune modulation. The present study was designed to determine the mechanism by which GP VI clearance occurs. We found that direct activation of GP VI both by a GP VI–specific antibody and by GP VI ligands (collagen and convulxin) reduced binding of biotinylated convulxin to the stimulated platelets. Analysis of immunoblots of platelets and supernatants showed that the stimulated platelets contained less GP VI, while the soluble fraction contained a 57-kDa cleavage product. Stimulation of platelets with PAR-1 agonists (TRAP peptide and thrombin) also caused GP VI cleavage, although the amount of GP VI loss was less than that observed with direct GP VI ligands. The metalloproteinase (MMP) inhibitors GM6001 and TAPI prevented both the clearance of GP VI from the platelet surface and the appearance of the soluble cleavage product. Induction of GP VI cleavage caused specific down-regulation of collagen-induced platelet aggregation, providing a mechanism for the modulation of platelet responsiveness to this important platelet agonist.
Long acting β2agonists for stable chronic obstructive pulmonary disease with poor reversibility: a systematic review of randomised controlled trials
Authors: Husereau Don , Shukla Vijay , Boucher Michel , Mensinkai Shaila , Dales Robert
Published: September 2004

Background

The long acting β2-agonists, salmeterol and formoterol, have been recommended, by some, as first line treatment of stable chronic obstructive pulmonary disease (COPD). We reviewed evidence of efficacy and safety when compared with placebo or anticholinergic agents in patients with poorly reversible COPD.

Methods

After searching MEDLINE, EMBASE, HealthSTAR, BIOSIS Previews, PASCAL, ToxFile, SciSearch, the Cochrane Library, and PubMed, as well as Web sites, selected journals, reference lists, and contacting drug manufacturers, two reviewers independently screened reports of randomised controlled trials of parallel or crossover design lasting four weeks or longer and including patients with a forced expiratory volume in one second (FEV1) ≤ 75% of predicted, a ratio of FEV1 to forced vital capacity (FVC) ≤ 88% of predicted, and < 15% improvement from baseline FEV1 after a dose of a β2 agonist. We included trials comparing salmeterol or formoterol with placebo or with ipratropium bromide and reporting one of these outcomes: lung function; exercise capacity; quality of life scores; dyspnea; exacerbations; rescue inhaler use; incidence of tachycardia, hypokalemia, or dry mouth. Two reviewers assessed the quality of included reports using the Jadad scale and allocation concealment, and abstracted data.

Results

Twelve trials satisfied our inclusion criteria; eight were high quality (Jadad score >2) and four were low quality (≤ 2). The adequacy of allocation concealment was unclear in all of them. We did not perform a meta-analysis due to differences in trial design and how outcomes were reported.

Two trials comparing salmeterol with ipratropium did not detect differences; one trial comparing formoterol and ipratropium described greater improvement with formoterol in morning PEFR (15.3 versus 7.1 l/min, p = 0.040).

Of twelve trials comparing long acting β2 agonists with placebo, six reported no improvement in exercise capacity, eleven reported improvements in FEV1 lung function (one reported no improvement), six reported less rescue inhaler usage (one reported no difference) and five reported improved dyspnea scores (two reported no improvement). Differences in quality of life were detected in one salmeterol trial ; however, two salmeterol, and one formoterol trial reported no differences. Adverse effects of interest were not reported.

Conclusion

In terms of clinical outcomes and safety, we could not find convincing evidence that salmeterol and formoterol have demonstrated advantages to ipratropium, a less expensive drug, for patients with stable COPD and poor reversibility. Compared to placebo, we found evidence of reduced rescue inhaler usage and improved spirometric outcomes without a significant impact on quality of life or exercise capacity.
Could a simple surgical intervention eliminate HIV infection?
Authors: Tepic Slobodan
Published: September 2004

Background

Human Immunodeficiency Virus (HIV) infection is a dynamic interaction of the pathogen and the host uniquely defined by the preference of the pathogen for a major component of the immune defense of the host. Simple mathematical models of these interactions show that one of the possible outcomes is a chronic infection and much of the modelling work has focused on this state.

Bifurcation

However, the models also predict the existence of a virus-free equilibrium. Which one of the equilibrium states the system selects depends on its parameters. One of these is the net extinction rate of the preferred HIV target, the CD4+ lymphocyte. The theory predicts, somewhat counterintuitively, that above a critical extinction rate, the host could eliminate the virus. The question then is how to increase the extinction rate of lymphocytes over a period of several weeks to several months without affecting other parameters of the system.

Testing the hypothesis

Proposed here is the use of drainage, or filtration, of the thoracic duct lymph, a well-established surgical technique developed as an alternative for drug immunosuppression for organ transplantation. The performance of clinically tested thoracic duct lymphocyte depletion schemes matches theoretically predicted requirements for HIV elimination.
Drosophila double-parkedis sufficient to induce re-replication during development and is regulated by cyclin E/CDK2
Authors: Thomer Marguerite , May Noah R. , Aggarwal Bhagwan D. , Kwok Garrick , Calvi Brian R.
Published: September 2004

It is important that chromosomes are duplicated only once per cell cycle. Over-replication is prevented by multiple mechanisms that block the reformation of a pre-replicative complex (pre-RC) onto origins in S and G2 phase. We have investigated the developmental regulation of Double-parked (Dup) protein, the Drosophila ortholog of Cdt1, a conserved and essential pre-RC component found in human and other organisms. We find that phosphorylation and degradation of Dup protein at G1/S requires cyclin E/CDK2. The N terminus of Dup, which contains ten potential CDK phosphorylation sites, is necessary and sufficient for Dup degradation during S phase of mitotic cycles and endocycles. Mutation of these ten phosphorylation sites, however, only partially stabilizes the protein,suggesting that multiple mechanisms ensure Dup degradation. This regulation is important because increased Dup protein is sufficient to induce profound rereplication and death of developing cells. Mis-expression has different effects on genomic replication than on developmental amplification from chorion origins. The C terminus alone has no effect on genomic replication,but it is better than full-length protein at stimulating amplification. Mutation of the Dup CDK sites increases genomic re-replication, but is dominant negative for amplification. These two results suggest that phosphorylation regulates Dup activity differently during these developmentally specific types of DNA replication. Moreover, the ability of the CDK site mutant to rapidly inhibit BrdU incorporation suggests that Dup is required for fork elongation during amplification. In the context of findings from human and other cells, our results indicate that stringent regulation of Dup protein is critical to protect genome integrity.
ATX-2, theC. elegansortholog of ataxin 2, functions in translational regulation in the germline
Authors: Ciosk Rafal , DePalma Michael , Priess James R.
Published: September 2004

Human ataxin 2 is a protein of unknown function that is implicated in the neurodegenerative disorder spinocerebellar ataxia type 2. We found that the C. elegans ortholog of ataxin 2, ATX-2, forms a complex with PAB-1, a cytoplasmic poly(A)-binding protein, and that ATX-2 is required for development of the germline. In the absence of ATX-2, proliferation of stem cells is reduced, and the germline is abnormally masculinized. These defects appear to result from inappropriate translational regulation that normally is mediated by the conserved KH-domain protein GLD-1. We find that MEX-3, a second KH-domain protein, exhibits a novel, ATX-2-dependent role in preventing inappropriate translation in the germline stem cells. Together, our results suggest that ATX-2 functions in translational regulation that is mediated by GLD-1 and MEX-3 proteins.
Met and Hgf signaling controls hypaxial muscle and lateral line development in the zebrafish
Authors: Haines Lynn , Neyt Christine , Gautier Philippe , Keenan David G. , Bryson-Richardson Robert J. , Hollway Georgina E. , Cole Nicolas J. , Currie Peter D.
Published: September 2004

Somites give rise to a number of different embryonic cell types, including the precursors of skeletal muscle populations. The lateral aspect of amniote and fish somites have been shown to give rise specifically to hypaxial muscle,including the appendicular muscle that populates fins and limbs. We have investigated the morphogenetic basis for formation of specific hypaxial muscles within the zebrafish embryo and larvae. Transplantation experiments have revealed a developmentally precocious commitment of cells derived from pectoral fin level somites to forming hypaxial and specifically appendicular muscle. The fate of transplanted somites cannot be over-ridden by local inductive signals, suggesting that somitic tissue may be fixed at an early point in their developmental history to produce appendicular muscle. We further show that this restriction in competence is mirrored at the molecular level, with the exclusive expression of the receptor tyrosine kinase met within somitic regions fated to give rise to appendicular muscle. Loss-of-function experiments reveal that Met and its ligand, hepatocyte growth factor, are required for the correct morphogenesis of the hypaxial muscles in which met is expressed. Furthermore, we demonstrate a requirement for Met signaling in the process of proneuromast deposition from the posterior lateral line primordia.
Predictive Factors of Stenosis after Stapled Colorectal Anastomosis: Prospective Analysis of 179 Consecutive Patients
Authors: Bannura Guillermo C. , Cumsille Miguel Angel G. , Barrera Alejandro E. , Contreras Jaime P. , Melo Carlos L. , Soto Daniel C.
Published: September 2004

The incidence, risk factors, and clinical relevance of stenosis of stapled colorectal anastomosis (CRA) were studied prospectively. Anastomotic stricture was defined as the inability of traversing the anastomosis with the rigid proctoscope. The population studied consisted of 179 patients (94 males) with an average age of 59.3 years (range: 20 to 91 years). The main indication for surgery was colorectal cancer in 59% of the cases, followed by diverticular disease in 23%. The first endoscopic control was performed before 4 months in 25% of the patients, between 5 and 10 months in 50%, and during the following 10 months in 25%. Stenosis was verified with the rigid instrument in 21.1% of the cases and with the flexible colonoscope in 4.4%. The barium enema performed in 12 cases confirmed a punctiform stenosis in 5 patients, 4 of whom had been asymptomatic. An endoscopic dilatation was performed on 5 of the 8 symptomatic patients, with one relapse that required an additional dilatation. In the univariate analysis only the lesser 4‐month interval was statistically significant (p = 0.033; odds ratio (OR) = 2.3; confidence interval (CI) 95% = 1.06 to 4.97). Male patients (p = 0.057; OR = 2.08; IC 95% = 0.97–4.44) show a tendency to CRA stricture that does not reach statistically significant levels. In the multivariate analysis, only sex (p = 0.04; OR = 4.11; IC 95% = 1.03 to 5.41) and the time interval (p = 0.012; OR = 2.87; IC 95% = 1.25 to 6.57) appear as independent variables in stenosis risk of a stapled CRA. The incidence of this complication depends on the criteria used for defining it. It is clinically relevant in no more than 5% of the patients. Five out of eight patients in category II were treated successfully with an endoscopic dilatation, while the other three improved spontaneously. Early stenosis, although frequent, is generally asymptomatic and disappears spontaneously. Considering the lack of correlation between the degree of stricture and its symptomatology, it is convenient to combine both the anatomic and the clinical criteria in the selection of candidates for an eventual therapeutic procedure.
Clinicopathologic and Prognostic Characterization of Poorly Differentiated Medullary‐type Gastric Adenocarcinoma
Authors: Otsuji Eigo , Kuriu Yoshiaki , Ichikawa Daisuke , Ochiai Toshiya , Okamoto Kazuma , Hagiwara Akeo , Yamagishi Hisakazu
Published: September 2004

Poorly differentiated medullary‐type gastric adenocarcinoma has been reported to differ biologically from poorly differentiated scirrhous adenocarcinoma, and we have characterized the differences in greater detail. Clinicopathologic comparisons were made between the former and latter tumor types as well as well‐differentiated gastric adenocarcinoma. Poorly differentiated medullary cancers were smaller, invaded less deeply, and were less likely to arise from the upper part of the stomach than scirrhous cancers. Poorly differentiated medullary cancers less often gave rise to lymph node and peritoneal metastases than scirrhous cancers but more often metastasized to the liver. Venous invasion was more common in medullary than scirrhous or well‐differentiated adenocarcinomas. Postoperative survival for patients with poorly differentiated medullary cancers was significantly better than for patients with scirrhous‐type cancers but did not differ significantly from survival with well‐differentiated adenocarcinoma. The most common cause of death was hematogenous metastasis in patients with medullary or well‐differentiated adenocarcinomas, whereas in patients with scirrhous cancer peritoneal metastasis was the most frequent cause. In conclusion, the biologic behavior of poorly differentiated medullary gastric adenocarcinoma was similar to that of well‐differentiated adenocarcinoma.
Meckel’s Diverticulum: Comparison of Incidental and Symptomatic Cases
Authors: Bani‐Hani Kamal E. , Shatnawi Nawaf J.
Published: September 2004

Although Meckel’s diverticulum is the commonest congenital gastrointestinal anomaly, there is still debate concerning the proper management of asymptomatic diverticula. Records of all patients whose Meckel’s diverticulum was resected at our hospitals between 1990 and 2002 were reviewed. Clinical characteristics, mode of presentations, and management for all patients were analyzed. Meckel’s diverticula were resected in 68 patients. Patients were divided into two groups: the incidental group included 40 patients (24 males) in whom the diagnosis of diverticula was incidental. The symptomatic group included 28 patients (20 males) who presented with diverticulum‐related complications. Preoperative diagnosis was possible in only four cases. In four patients from the symptomatic group, Meckel’s diverticula were found and left untouched during a previous laparotomy. There was no significant difference between the two groups with respect to gender (p = 0.48). Patients in the symptomatic group were significantly younger than patients in the incidental group (p = 0.002). The diverticula in the symptomatic group tended to be longer (p = 0.001) with a narrower base (p = 0.001) than the diverticula in the incidental group. A diameter of ≤ 2 cm was significantly associated with more complications (p = 0.01). Heterotopic tissue was present more significantly in the symptomatic group than the incidental group (p = 0.01). There was no significant difference in the morbidity rate between the two groups (p = 0.71), and there was no mortality in either group. Preoperative diagnosis of Meckel’s diverticulum is difficult and should be kept in mind in cases of acute abdomen. Resection of incidentally found diverticula is not associated with increased operative morbidity or mortality.
Spatially variable extension in southern Tibet based on GPS measurements
Authors: Chen Qizhi , Freymueller Jeffrey T. , Yang Zhiqiang , Xu Caijun , Jiang Weiping , Wang Qi , Liu Jingnan
Published: September 2004

We use Global Positioning System (GPS) data and kinematic block models to study the present‐day deformation of southern Tibet. GPS data from 33 sites in southern Tibet and Nepal surveyed between 1991 and 2000 reveal 13 ± 2 mm/yr of N110°E extension between Lhasa and Shiquanhe (80°E–91°E), of which 9.7 ± 3.0 mm/yr represents permanent extension of the Tibetan crust. The remaining ∼3 mm/yr results from elastic deformation from the locked, curving Main Himalayan Thrust fault. This extension is spatially nonuniform. One half to two thirds of the permanent extension is concentrated across the Yadong‐Gulu rift, with an opening rate of 6.5 ± 1.5 mm/yr; most of the remainder occurs on or near the Thakkola graben, with little extension across the rifts between them. Differential velocities of sites north and south of the Yarlung‐Zangbo suture in western Tibet imply that the suture or an adjacent structure may be active as a strike‐slip fault. A numerical model suggests that right‐lateral strike slip on the Yarlung‐Zangbo suture may extend from the Karakorum Fault Zone in the west at least to the Yadong‐Gulu rift in the east with ∼3 mm/yr slip rate, accommodating part of the eastward extrusion of Tibet. The convergence directions inferred from GPS are consistent with slip vectors of earthquakes; however, the rate of slip of India beneath Tibet along the Himalaya is lower than those previously estimated. We estimate a slip rate of 12.4 ± 0.4 mm/yr between longitudes 83°E and 88°E and 17 ± 1 and 19 ± 1 mm/yr in the western and eastern Himalaya, respectively. The variable slip rate correlates with the variable extension rate in southern Tibet, and we suggest that it results from variation in the deformation rate of the overriding Tibetan crust. We infer that the slower convergence rate in the central Himalaya is significant.
A coastal upwelling seesaw in the Atlantic Ocean as a result of the closure of the Central American Seaway
Authors: Prange M. , Schulz M.
Published: September 2004

Based on coupled climate model experiments, we suggest an antiphase relationship between the two major coastal upwelling zones in the Atlantic Ocean off northwestern and southwestern Africa. We describe this as an ‘upwelling seesaw’. The state of the coastal upwelling seesaw is controlled by variations in the oceanic meridional heat transfer between South and North Atlantic. In particular, we suggest that the Pliocene closure of the Central American Seaway induced a large‐scale redistribution of heat in the Atlantic Ocean, leading to an intensification (weakening) of upwelling off southwest (northwest) Africa.
Theoretical and numerical studies of density modulated whistlers
Authors: Eliasson B. , Shukla P. K.
Published: September 2004

Recently, observations from laboratory experiments, which are relevant to space observations as well, have conclusively revealed the amplitude modulation of whistlers by low‐frequency perturbations. Our objective here is to present theoretical and simulation studies of amplitude modulated whistler packets on account of their interaction with background low‐frequency density perturbations that are reinforced by the whistler ponderomotive force. Specifically, we show that nonlinear interactions between whistlers and finite amplitude density perturbations are governed by a nonlinear Schrödinger equation for the modulated whistlers, and a set of equations for arbitrary large amplitude density perturbations in the presence of the whistler ponderomotive force. The governing equations are solved numerically to show the existence of large scale density perturbations that are self‐consistently created by localized modulated whistler wavepackets. Our numerical results are found to be in good agreement with experimental results, as well as have relevance to observations from magnetized space plasmas.
Recent rapid thinning of the “Mer de Glace” glacier derived from satellite optical images
Authors: Berthier E. , Arnaud Y. , Baratoux D. , Vincent C. , Rémy F.
Published: September 2004

The rapid wastage of mountain glaciers and their contribution to sea level rise require worldwide monitoring of their mass balance. In this paper, we show that changes in glacier thickness can be accurately measured from satellite images. We use SPOT image pairs to build Digital Elevation Models (DEMs) of the Mont Blanc area (French Alps) for different years. To register the DEMs, we adjust their longitude, latitude and altitude over motionless areas. The uncertainty of the thickness change measurement is greatly reduced by averaging over areas covering altitude intervals of 50 m. Comparisons with topographic profiles and a differential DEM from aerial photographs obtained on the Mer de Glace indicate an overall accuracy of 1 m for the thickness change measurement. Below 2100 m, satellite DEMs show an evolution of the thinning rate from 1 ± 0.4 m.a−1 (years 1979–1994) to 4.1 ± 1.7 m.a−1 (2000–2003).
Liver delivery of NO by NCX‐1000 protects against acute liver failure and mitochondrial dysfunction induced by APAP in mice  THIS ARTICLE HAS BEEN RETRACTED
Authors: Fiorucci Stefano , Antonelli Elisabetta , Distrutti Eleonora , Mencarelli Andrea , Farneti Silvana , Soldato Piero Del , Morelli Antonio
Published: September 2004

NCX‐1000, (3α, 5β, 7β)‐3,7‐dihydroxycholan‐24oic acid[2‐methoxy‐4‐[3‐[4‐(nitroxy)butoxy]‐3‐oxo‐1‐propenyl]phenyl ester, is a nitric oxide (NO)‐derivative of ursodeoxyxholic acid (UDCA) that selectively release NO in the liver.

Here, we demonstrated that administering mice with 40 μmol kg−1 NCX‐1000, but not UDCA, improves liver histopathology and reduces mortality caused by 330 μmol kg−1 APAP from 60 to 25% (P<0.01). Administration of NCX‐1000, in a therapeutic manner, that is, 2 h after acetaminophen (APAP) intoxication reduced mortality, improved liver histopathology and prevented liver IFN‐γ, TNF‐α, Fas/Fas ligand and inducible nitric oxide synthase (iNOS) mRNA accumulation caused by APAP.

In vitro exposure of primary cultures of mouse hepatocytes to APAP, 6.6 mM, resulted in apoptosis followed by necrosis. Loss of cell viability correlates with early mitochondrial membrane potential (Δψm) hyperpolarization followed by depolarization and cytochrome c translocation from mitochondria to cytosol. APAP‐induced apoptosis associated with procaspase‐3 and ‐9 cleavage, appearance of truncated Bid and activation of poly(ADP‐ribose) polymerase (PARP).

Treating primary culture of hepatocytes with 5 μM cyclosporine and 10 μM trifluoperazine for eight resulted in significant reduction of apoptosis induced by APAP suggesting that loss of Δψm was mechanistically involved in apoptosis induced by APAP in vitro.

NCX‐1000, but not UDCA, concentration‐dependently (ED50=16 μM) protected against Δψm depolarization and reduced transition from apoptosis to necrosis caused by 6.6 mM APAP.

Treating primary cultures of hepatocytes with the NO‐donor DETA‐NO, 100 μM, reduced apoptosis induced by APAP and prevented caspase activation.

In conclusion, NCX‐1000 is effective in protecting against APAP‐induced hepatotoxicity when administered in a therapeutic manner. This protection may involve the inhibition of apoptosis and the maintenance of mitochondrial integrity.

British Journal of Pharmacology (2004) 143, 33–42. doi:10.1038/sj.bjp.0705780
Nephroprotection in Zucker diabetic fatty rats by vasopeptidase inhibition is partly bradykinin B2 receptor dependent
Authors: Schäfer Stefan , Schmidts Hans‐Ludwig , Bleich Markus , Busch Andreas E , Linz Wolfgang
Published: September 2004

Vasopeptidase inhibition (i.e., the simultaneous inhibition of both angiotensin‐converting enzyme (ACE) and neutral endopeptidase) can ameliorate diabetic nephropathy. We investigated whether this nephroprotection is mediated by the bradykinin B2 receptor.

In all, 43 obese Zucker diabetic fatty (ZDF/Gmi‐fa/fa) rats aged 21 weeks were separated into four groups and treated for 26 weeks with either placebo, the bradykinin B2 receptor antagonist icatibant (500 μg kg−1 day−1 s.c. infusion), the vasopeptidase inhibitor AVE7688 (45 mg kg−1 day−1 in chow), or AVE7688 plus icatibant. Nephropathy was assessed as albuminuria at age 31 and 39 weeks, and by histopathologic scoring at the end of the treatment period.

All animals had established diabetes mellitus (blood glucose >20 mmol l−1) and marked albuminuria at baseline. Blood glucose was not influenced by any treatment. Icatibant alone did not influence albuminuria (8.6±1.6 vs placebo 9.5±1.3 mg kg−1 h−1). AVE7688 reduced albuminuria at week 31 markedly to 1.1±0.1 mg kg−1 h−1 and reduced glomerular and tubulo‐interstitial kidney damage at week 47. In the AVE7688 plus icatibant group, proteinuria was significantly higher than in the AVE7688 only group (2.0±0.6 mg kg−1 h−1), but still reduced compared to placebo. In addition, icatibant partly antagonized the tubulo‐interstitial protection mediated by AVE7688.

We conclude that vasopeptidase inhibition provides nephroprotection in rats with type II diabetic nephropathy, which is partly mediated by bradykinin B2 receptor activation.

British Journal of Pharmacology (2004) 143, 27–32. doi:10.1038/sj.bjp.0705884
Nitric oxide donors inhibit 5‐hydroxytryptamine (5‐HT) uptake by the human 5‐HT transporter (SERT)
Authors: Bryan‐Lluka Lesley J , Papacostas Marisa H , Paczkowski Filip A , Wanstall Janet C
Published: September 2004

The aim was to test the hypothesis that nitric oxide (NO) donor drugs can inhibit the 5‐hydroxytryptamine (5‐HT) transporter, SERT.

The NO donors, MAHMA/NO (a NONOate; (Z)‐1‐[N‐methyl‐N‐[6‐(N‐methylammoniohexyl)‐amino]]diazen‐1‐ium‐1,2‐diolate), SIN‐1 (a sydnonimine; 5‐amino‐3‐(4‐morpholinyl)‐1,2,3‐oxadiazolium chloride), FK409 (an oxime; (±)‐(4‐ethyl‐2E‐(hydroxyimino)‐5‐nitro‐3E‐hexenamide)) and peroxynitrite, but not Angeli's salt (source of nitroxyl anion) or sodium nitrite, caused concentration‐dependent inhibition of the specific uptake of [3H]‐5‐HT in COS‐7 cells expressing human SERT.

Superoxide dismutase (150 U ml−1) plus catalase (1200 U ml−1), used to remove superoxide and hence prevent peroxynitrite formation, prevented the inhibitory effect of SIN‐1 (which generates superoxide) but not of MAHMA/NO or FK409.

The inhibitory effects of the NO donors were not affected by the free radical scavenger, hydroxocobalamin (1 mM) or the guanylate cyclase inhibitor, ODQ (1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one; 3 μM).

L‐Cysteine (1 mM; source of excess thiol residues) abolished or markedly reduced the inhibitory effects of MAHMA/NO, SIN‐1, FK409 and peroxynitrite.

It is concluded that inhibition of SERT by the NO donors cannot be attributed exclusively to NO free radical nor to nitroxyl anion. It does not involve guanosine‐3′,5′‐cyclic monophosphate, but may involve nitrosation of cysteine residues on the SERT protein. Peroxynitrite mediates the effect of SIN‐1, but not the other drugs.

Data in mice with hypoxic pulmonary hypertension suggest that SERT inhibitors may attenuate pulmonary vascular remodelling. Thus, NO donors may be useful in pulmonary hypertension, not only as vasodilators, but also because they inhibit SERT, provided they display this effect in vivo at appropriate doses.

British Journal of Pharmacology (2004) 143, 63–70. doi:10.1038/sj.bjp.0705904
Influence of agonist intrinsic activity on the desensitisation of β2‐adrenoceptor‐mediated responses in mast cells
Authors: Scola Anne‐Marie , Chong Lee K , Chess‐Williams Russell , Peachell Peter T
Published: September 2004

The aim of the present study was to determine whether the intrinsic activity of an agonist influences the extent of desensitisation of β2‐adrenoceptor‐mediated responses in human lung mast cells.

The effects of a wide range of β‐adrenoceptor agonists (10−10–10−5M) on the IgE‐mediated release of histamine from mast cells were determined. The intrinsic activity of agonists was established by comparing the maximal inhibitory response (Emax) of an agonist relative to the maximal response obtained with the full agonist, isoprenaline. The intrinsic activity order for the inhibition of histamine release was isoprenaline (1.0)>formoterol (0.94)>fenoterol (0.89)>terbutaline (0.84)>salbutamol (0.69)>clenbuterol (0.65)>salmeterol (0.30)>dobutamine (0.20).

There was a significant (P<0.05) positive correlation (r=0.81) between the extent to which β‐adrenoceptor agonists inhibited histamine release and the degree to which the agonists caused elevations in cAMP in mast cells.

Further studies investigated the effects of long‐term (24 h) incubation of mast cells with β‐adrenoceptor agonists on the subsequent ability of isoprenaline to inhibit histamine release. At concentrations of agonists selected to occupy a large percentage (88%) of β2‐adrenoceptors, there was a significant (P<0.05) correlation (r=0.73) between the relative intrinsic activity of agonists as inhibitors of histamine release and the extent of functional desensitisation induced by the agonists. At lower receptor occupancies, however, there was no correlation between the relative intrinsic activity of agonists and the extent of agonist‐induced desensitisation.

These data indicate that, under experimental conditions where high receptor occupancies prevail, agonist intrinsic activity influences the extent of desensitisation of β2‐adrenoceptor‐mediated responses in mast cells.

British Journal of Pharmacology (2004) 143, 71–80. doi:10.1038/sj.bjp.0705905
P2Y2‐receptor‐mediated activation of a contralateral, lanthanide‐sensitive calcium entry pathway in the human airway epithelium
Authors: Bahra Parmjit , Mesher Jonathan , Li Su , Poll Christopher T , Danahay Henry
Published: September 2004

Receptor‐mediated calcium entry (RMCE) was examined in well‐differentiated cultures of normal human bronchial epithelial cells (HBECs). Changes in intracellular free Ca2+ ([Ca2+]i) were quantified using fluorescence ratio imaging of Fura‐2‐loaded cells during perfusion with Ca2+ mobilizing agonists.

Initial studies revealed an agonist potency of ATP=uridine triphosphate (UTP) >ADP=uridine diphosphate, consistent with purinergic activation of an apical P2Y2‐receptor mediating the increase in [Ca2+]i in HBECs.

Apical UTP (30 μM) induced a sustained period of elevated [Ca2+]i between 300 and 600 s following agonist stimulation that extracellular Ca2+ free studies indicated was dominated by Ca2+ influx.

RMCE was inhibited by 100 nM La3+ (83±3%) or Gd3+ (95±7%) (P<0.005, n=4–11) and was partially attenuated by Ni2+ (1 mM) (58.7±5.0%, P<0.005, n=9).

RMCE was also partially sensitive (< 25% inhibition, P<0.01) to the cation channel blockers SKF96365 (30 μM) and econazole (30 μM), but was insensitive to both verapamil (1 μM) and ruthenium red (10 μM).

Using either a sided Ca2+ readdition protocol or unilateral La3+, established that the RMCE pathway was located exclusively on the basolateral membrane.

The pharmacological sensitivity of the P2Y2‐receptor activated Ca2+ entry pathway in the human airway epithelium is inconsistent with the established profile of TRP channel families and is therefore likely to be of an as‐yet uncharacterized molecular identity.

British Journal of Pharmacology (2004) 143, 91–98. doi:10.1038/sj.bjp.0705913
Magnetophotoluminescence study of the influence of substrate orientation and growth interruption on the electronic properties of InAs∕GaAs quantum dots
Authors: Godefroo S. , Maes J. , Hayne M. , Moshchalkov V. V. , Henini M. , Pulizzi F. , Patanè A. , Eaves L.
Published: September 2004

We have used photoluminescence in pulsed (⩽50T) and dc (⩽12T) magnetic fields to investigate the influence of substrate orientation and growth interruption (GI) on the electronic properties of InAs∕GaAs quantum dots, grown by molecular beam epitaxy at 480°C. Dot formation is very efficient on the (100) substrate: electronic confinement is already strong without GI and no significant change in confinement is observed with GI. On the contrary, for the (311)B substrate strong confinement of the charges only occurs after a GI is introduced. When longer GIs are applied the dots become higher.
Energetic model of ferromagnetic hysteresis: Isotropic magnetization
Authors: Hauser Hans
Published: September 2004

The model is based on considerations of energy balance and statistical domain behavior. The parameters are related to macroscopic hysteresis features such as coercivity, initial susceptibility, saturation, and remanence and identification strategies are presented for static and dynamic magnetization processes. Furthermore, the model parameters are related to spontaneous magnetization, magnetocrystalline anisotropy, magnetostriction, and microstructure geometry which assist in the interpretation of the hysteresis dependence on stress, temperature, and direction of magnetization. Examples and predictions are the magnetization reversal in low dimensional structures, stress demagnetization, temporary decay of magnetization, Barkhausen noise, and the behavior of materials with multiple phases. Finally, the fictitious statistical domains (or unit magnetization reversals) are related to the magnetic spin moments, which enables a quantum-mechanical interpretation of the model.
Using a quartz crystal microbalance to probe formation of Xe hydrate in thin ice films
Authors: Chan J. , Forrest J. A. , Torrie B. H.
Published: September 2004

We have demonstrated the ability of the quartz crystal microbalance to successfully measure the formation and dissociation of thin films of Xe hydrate formed from ice films in the presence of Xe gas or from a cooled mixture of water vapor and Xe gas. By monitoring the uptake of mass, we have measured the formation of Xe hydrates on ice films in the temperature range 180<T<251K. Analysis of the mass uptake reveals a final sample that has 60% by weight of Xe, in good agreement with a fully hydrated sample. The formation and dissociation conditions suggest that there is a critical temperature T0∼255K beyond which thin films of Xe hydrate are not stable.
Nonohmic behavior of SnO2-MnO polycrystalline ceramics. I. Correlations between microstructural morphology and nonohmic features
Authors: Bueno P. R. , Orlandi M. O. , Simões L. G. P. , Leite E. R. , Longo E. , Cerri J. A.
Published: September 2004

This report discusses important microstructural features of SnO2.MnO-based polycrystalline ceramics. The influence of the sintering time and the concentration of donor Nb2O5 on the microstructure of these ceramics are investigated, and the correlation between the microstructural features and nonohmic behavior are also discussed. High resolution analytical electron microscopy was used for a detailed characterization of the microstructure and grain boundary chemistry of the compositions, revealing that SnO2-MnO dense ceramics consist of two phases, SnO2 grains and Mn2SnO4, precipitated mainly at triple grain points. In addition, two types of SnO2-SnO2 grain boundary were identified: type I, Mn-rich and thin, and type II, Mn-poor and thick. Changes in Mn concentrations at the grain boundaries are ascribed to both grain misorientation and Mn diffusivity along the grain boundary. The identification of two kinds of junctions in SnO2-MnO has significant implications in the material’s nonohmic behavior, as will be discussed in detail here and in Part II, and is important in understanding the sintering mechanism and microstructural formation of SnO2 ceramics.
Low-frequency flux noise in current-carrying high critical temperature superconducting films
Authors: Kuriki S. , Kawaguchi Y. , Takahashi K. , Matsuda M.
Published: September 2004

The low-frequency flux noise of a narrow current-carrying superconducting film is measured in order to examine the flux noise induced by shielding current in directly coupled high critical temperature superconducting quantum interference devices. Reversible flux noise is found to appear during the application of current above a threshold level, but to disappear when the current is removed. However, as the current is increased beyond a second threshold, where the strip enters a flux creep∕flow state, a flux noise occurs that remains after the current is removed. The threshold current for the onset of the reversible flux noise strongly depends on the edge-shape processing applied to the strip. The sources of the reversible and remaining flux noises are discussed on the basis of existing models of vortex penetration and pinning in a superconducting thin film.
Molecular dynamics simulation of dislocations in wurtzite-type GaN crystal
Authors: Harafuji Kenji , Tsuchiya Taku , Kawamura Katsuyuki
Published: September 2004

Microscopic dislocation structures in wurtzite-type GaN crystal have been studied by the use of molecular dynamics simulation. Parameters for a two-body interatomic potential are determined by the Hartree-Fock ab initio method. A dislocation is generated by the coalescence of the facing planes of a semi-infinite trench structure in the crystal. Six types of trench structures with different depth-directions and extension-directions are examined. Temperatures of 1000 and 1500K are considered. A core structure with an eightfold ring has been confirmed for edge dislocations along the c axis, though there appear a few atoms that are shifted from the ring core structure. The ring core structure is consistent with reported theoretical expectations and experimental observations. A tenfold ring core structure is also observed for edge dislocations along the c axis. A screw dislocation is generated by an attracting force between gallium and nitrogen atoms across the trench space when the attracting force has a large component parallel to the trench extension direction.
Surface passivation of n-GaN by nitrided-thin-Ga2O3∕SiO2 and Si3N4 films
Authors: Bae Choelhwyi , Krug Cristiano , Lucovsky Gerald , Chakraborty Arpan , Mishra Umesh
Published: September 2004

The electrical characteristics of n-GaN∕nitrided-thin-Ga2O3∕SiO2 and n-GaN∕Si3N4 metal-insulator-semiconductor (MIS) capacitors have been compared, and the work-function difference ϕms and effective dielectric-fixed charge density Qf,eff have been determined. Oxide samples showed lower interface trap level density Dit, lower leakage current, and better reproducibility compared to the nitride samples. The superior properties of the oxide samples are partially attributed to the nitrided-thin-Ga2O3 layer (∼0.6-nm-thick). ϕms and Qf,eff were determined, respectively, as 0.13V and 1.0×1012qcm−2 in oxide and 0.27V and −3.6×1011qcm−2 in nitride samples using flatband voltage versus dielectric thickness data. True dielectric-fixed charge density and location of the major amount of fixed charge are discussed based on Qf,eff, Dit, and spontaneous polarization of n-GaN.
Investigation of laser-ablated ZnO thin films grown with Zn metal target: A structural study
Authors: Fouchet A. , Prellier W. , Mercey B. , Méchin L. , Kulkarni V. N. , Venkatesan T.
Published: September 2004

High quality ZnO thin films were grown using the pulsed laser deposition technique on (0001) Al2O3 substrates in an oxidizing atmosphere, using a Zn metallic target. We varied the growth conditions such as the deposition temperature and the oxygen pressure. First, using a battery of techniques such as x-ray diffraction, Rutherford-backscattering spectroscopy, and atomic force microscopy, we evaluated the structural quality, the stress, and the degree of epitaxy of the films. Second, the relations between the deposition conditions and the structural properties that are directly related to the nature of the thin films are discussed qualitatively. Finally, a number of issues on how to get good-quality ZnO films are addressed.
Thermal hysteresis of nonlinear ultrasonic attenuation in lithium niobate
Authors: Breazeale Mack A. , Ostrovskii Igor V. , McPherson Michael S.
Published: September 2004

A type of nonlinear ultrasound attenuation in ferroelectric crystals is reported. It consists of a strong hysteresis under thermal cycling, a nonexponential echo train pattern which cannot be explained by a nonparallelism of the samples, and decreasing of the insertion losses under increasing temperature. The hysteresis behavior suggests involvement of crystal lattice defects.
The energy-fine structure of GaInNAs∕GaAs multiple quantum wells grown at different temperatures and postgrown annealed
Authors: Kudrawiec R. , Pavelescu E.-M. , Andrzejewski J. , Misiewicz J. , Gheorghiu A. , Jouhti T. , Pessa M.
Published: September 2004

We report photoreflectance investigations of the energy-fine structure of GaInNAs∕GaAs multiple quantum wells (MQWs) grown at different temperatures and postgrown treated by rapid thermal annealing (RTA). A “splitting” of the ground and excited QW transitious due to the presence of different nitrogen nearest-neighbor environments, i.e., N-Ga4−mInm(0⩽m⩽4) short-range-order clusters, has been observed. The RTA induces a nitrogen redistribution between the five possible N-Ga4−mInm configurations and thus leads to a blueshift of QW transitions. The magnitude of the blueshift and its dependence on the growth temperature and annealing temperature are investigated in this paper.
Modulated photothermal radiometry applied to semitransparent samples: Models and experiments
Authors: André S. , Rémy B. , Maillet D. , Degiovanni A. , Serra J.-J.
Published: September 2004

Mathematical modeling is presented of the combined conductive and radiative heat transfer occurring in a semitransparent material (STM) subjected to a periodic heat flux. The models rely on the quadrupole method, which is a very powerful tool to obtain analytical solutions in the Fourier or Laplace domain. Photoacoustic or photothermal radiometry techniques are reviewed. Two groups of methods are discussed depending on whether the sample has natural or opaque interfaces to simulate radiative exchanges with the surroundings. The metrological problem of measuring the phonic thermal diffusivity of semitransparent materials is investigated. Theoretical simulations are given. They explain some typical features of the phase-lag signal of temperature responses. Experimental measurements on pure silica validate the results and prove that these methods are efficient for the thermal characterization of STM.
Effect of annealing on refractive indices of radio-frequency magnetron sputtered waveguiding zinc oxide films on glass
Authors: Mehan Navina , Gupta Vinay , Sreenivas Kondepudy , Mansingh Abhai
Published: September 2004

The effects of annealing and gas composition on the refractive indices of zinc oxide films were studied in light of the structural properties. ZnO films (1μm) were deposited by rf magnetron sputtering in different oxygen:argon mixtures on glass and annealed at 380°C in air, at different times. Waveguide modes were excited in the films by prism coupling using a He-Ne laser. The estimated values of the extraordinary and ordinary refractive indices of the films, which were close to the corresponding bulk values (ne=2.006, no=1.990), initially decreased with annealing time and later increased before becoming constant with further annealing. The variation in refractive indices was explained on the basis of contribution from both packing density p and lattice constant c of the films. The initial decrease in refractive indices was attributed to the observed lattice contraction, and the latter increase was explained in terms of the increase in packing density (p) of the films on annealing. A relation is proposed to estimate the refractive indices of films, which have the lattice constant c different from the bulk value.
Structural and multiferroic properties of BiFeO3 thin films at room temperature
Authors: Yun Kwi Young , Noda Minoru , Okuyama Masanori , Saeki Hiromasa , Tabata Hitoshi , Saito Keisuke
Published: September 2004

BiFeO 3 thin films have been prepared on Pt∕TiO2∕SiO2∕Si substrates under various oxygen pressures of 0.15–0.005Torr at a temperature of 450°C by pulsed-laser deposition. The effects of deposition pressure on their crystal structure and multiferroic properties have been investigated at room temperature. X-ray diffraction analysis (θ-2θ scans and 2-dimensional scans) shows that the BiFeO3 thin films consist of perovskite single phase with tetragonal crystal structure and space group P4mm. The c-axis lattice constant decreases (4.062–4.006Å) and c∕a ratio of the films decreases from 1.032 to 1.014 with a decrease in the oxygen pressure. The surface roughness and grain size of the films depend dramatically on oxygen pressures. The dielectric constant of the films decreases with decreasing oxygen pressure. The film deposited at 0.05Torr shows a stable current density and well-saturated hysteresis loop with twice the remanent polarization (2Pr) of 136μC∕cm2 and coercive field (2Ec) of 109kV∕cm. The BiFeO3 thin films also show the saturated weak ferromagnetic hysteresis loops with a small remanent magnetization.