bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase of thermal emission spectroscopy for properties measurements of delaminating thermal barrier coatings
Authors: Yu Fengling , Bennett Ted D.
Published: November 2005

Phase of thermal emission spectroscopy is developed for determining the thermal properties of thermal barrier coating (TBC) in the presence of thermal contact resistance between the coating and the substrate. In this method, a TBC sample is heated using a periodically modulated laser and the thermal emission from the coating is collected using an infrared detector. The phase difference between the heating signal and the emission signal is measured experimentally. A mathematical model is developed to predict the phase difference between the laser and the measured emission, which considers the coating properties and the thermal contact resistance of the interface. An electron-beam physical vapor deposition thermal barrier coating with local regions delaminated by laser shock is characterized using this technique. The measurements are made on two regions of the coating, one where good thermal contact between the coating and substrate exists and the other where the interface has been damaged by laser shock. The results for the thermal properties and thermal contact resistance of the interface are presented and compared.
Enhanced ferromagnetic phase diagram of epitaxial (Co,Mn) alloys on GaAs(001)
Authors: Zhang L. , Basiaga D. , O’Brien J. R. , Heiman D.
Published: November 2005

Alloys of Co1−xMnx were grown epitaxially on GaAs(001) substrates. Unlike bulk alloys, nanometer-thick layers are found to have a much higher Curie temperature and are ferromagnetic over a wider range of Mn concentration, extending from x=0 to 0.8. The enhanced ferromagnetism is attributed to the strained tetragonal lattice which is in registration with the GaAs(001) lattice. This demonstrates the utility of tailoring magnetic properties with strain-layer epitaxy.
Numerical experiments on flapping foils mimicking fish-like locomotion
Authors: Blondeaux Paolo , Fornarelli Francesco , Guglielmini Laura , Triantafyllou Michael S. , Verzicco Roberto
Published: November 2005

The results of numerical experiments aimed at investigating the topology of the vortex structures shed by an oscillating foil of finite span are described. The motion of the foil and its geometry are chosen to mimic the tail of a fish using the carangiform swimming. The numerical results have been compared with the flow visualizations of Freymuth [J. Fluids Eng. 111, 217 (1989)] and those of von Ellenrieder et al. [J. Fluid Mech.490, 129 (2003)]. The results show that a vortex ring is shed by the oscillating foil every half a cycle. The dynamics of the vortex rings depends on the Strouhal number St. For relatively small values of St, the interaction between adjacent rings is weak and they are mainly convected downstream by the free stream. On the other hand, for relatively large values of St, a strong interaction among adjacent rings takes place and the present results suggest the existence of reconnection phenomena, which create pairs of longitudinal counter-rotating vortices.
High dose Co-60 gamma irradiation of InGaN quantum well light-emitting diodes
Authors: Khanna Rohit , Han Sang Youn , Pearton S. J. , Schoenfeld D. , Schoenfeld W. V. , Ren F.
Published: November 2005

InGaN multiquantum-well light-emitting diodes (LEDs) in the form of unpackaged die with emission wavelengths from 410to510nm were irradiated with Co60 γ-rays with doses in the range 150–2000Mrad (Si). The forward turn-on voltage for all the irradiated LEDs was increased slightly (e.g., by only ∼0.1–0.15V for 500MRad dose irradiation) while the reverse breakdown voltage was unchanged within experimental error. The light output intensity for the 410nm diodes was decreased by 20% after a dose of 150MRad and 75% after ∼2GRad. The current transport in the LEDs was dominated by generation-recombination (ideality factor ∼2) both before and after irradiation. The morphology and appearance of the p and n-Ohmic metallization did not show any detectable change as a result of even the highest γ-ray dose.
Effect of nitrogen on band alignment in HfSiON gate dielectrics
Authors: Sayan S. , Nguyen N. V. , Ehrstein J. , Chambers J. J. , Visokay M. R. , Quevedo-Lopez M. A. , Colombo L. , Yoder D. , Levin I. , Fischer D. A. , Paunescu M. , Celik O. , Garfunkel E.
Published: November 2005

Nitridation of HfSiO films improves certain physical and electrical properties—when using gate stack layers—such as their crystallization temperature and their resistance to interdiffusion. We have studied the band alignment of HfSiO and HfSiON films by soft x-ray photoemission, oxygen K-edge x-ray absorption, and spectroscopic ellipsometry. Nitridation of HfSiO reduced the band gap by 1.50eV±0.05eV, and the valence- and conduction-band offsets by 1.2eV±0.1eV and 0.33eV±0.05eV, respectively. Although the band-gap reduction should lead to increased leakage, the barrier heights are still sufficient for proposed near-future complementary metal-oxide-semiconductor applications.
Transmission ion channeling analysis of isolated 60° misfit dislocations
Authors: Breese M. B. H. , Huang L. , Teo E. J. , King P. J. C. , Wilshaw P. R.
Published: November 2005

High-contrast transmission channeling images and linescans of isolated bunches and individual 60° misfit dislocations in thick partially relaxed Si1−xGex∕Si layers are presented. Changes in dislocation contrast with tilt angle are explained using a model of planar dechanneling by the two-edge components of 60° dislocations. By careful analysis of the tilting contrast, all of the four possible combinations of the two-edge components of the Burger’s vector of 60° dislocations may be distinguished.
Algorithm for high-resolution single-shot THz measurement using in-line spectral interferometry with chirped pulses
Authors: Yellampalle B. , Kim K. Y. , Rodriguez G. , Glownia J. H. , Taylor A. J.
Published: November 2005

Z. P. Jiang and X. C. Zhang demonstrated a single-shot THz diagnostic based on spectral encoding of a chirped optical probe pulse [Appl. Phys. Lett. 72, 1945 (1998)]. This technique is thought to have an inherent uncertainty principle-imposed temporal resolution limitations. In this letter, we describe a method to recover the THz field without distortions, surpassing previous resolution limitations. Our approach is based on interpreting the spectral encoding experiment as in-line spectral interferometry, analogous to Gabor’s in-line spatial holography [D. Gabor, Nature (London) 161, 777 (1948)]. We recover the THz field from the interferogram and the characterized probe by using Tikhonov regularization combined with lower and upper triangular decomposition.
The diagnosis and correction of sulfur deficiency and the management of sulfur requirements in New Zealand pastures: a review
Authors: Edmeades D. C. , Thorrold B. S. , Roberts A. H. C.
Published: November 2005

This review consolidates and updates our understanding of the diagnosis and correction of soil S deficiencies, and the management of S requirements for pastures, using both historical data from field trials and recent developments in the understanding of the sulfur (S) cycle in New Zealand pastoral soils. The basis for, and the practical implications of, a new quasi-equilibrium S model for pastures is discussed in terms of the size and changes in the pools of sulfate S, readily available extractable organic S (EOS) and total organic S over time and with the addition and removal of S through fertiliser and leaching. With this background, the use and interpretation of the 2 S soil tests are discussed. Historical data from field trials and the recent research on nutrient ratios are used to update the use of pasture S concentrations for diagnosing S deficiency. Historical data is also used to examine the distribution and size of pasture responses to S fertiliser and to define the biological S requirements for New Zealand soils. The effects of time, single or split, and annual or triennial applications of sulfate and S0 are reviewed and the suitability of current S0 fertilisers is discussed. Generalised fertiliser S strategies are then developed for the major soil groups, climate zones and farm types, based on all this information.
Effects of cover crop and straw mulching on no-tillage, no-fertilised, direct-sown rice cropping systems
Authors: Cho Young-Son
Published: November 2005

Field experiments were conducted to evaluate the effects of 4 rice farming systems (fallow, white clover (WC), rye and rye + WC) at 3 straw mulching levels (0, 500, 1000 g/m2) under no-till, direct-sown and unfertilised rice-based cropping systems in a temperate climate in Japan. From 1999 to 2001, white clover and rye were grown during winter (November–May) in Ehime Prefecture (33°57′N, 132°47′E, 15 m a.s.l.) to evaluate the effects on rice growth and yield-related characteristics. Seed germination was greatest in clover–rice cropping systems (60, 68%) followed by rye + WC–rice (56, 57%) for the 0 and 500 g/m2 mulching treatment, respectively. Rice yielded 1.26–4.12 t/ha in 2000 and 0.54–3.80 t/ha in 2001. Panicle number ranged from 84 to 248 and 47 to 323/m2 in 2000 and 2001, respectively. WC with light rice straw mulching in rotation with rice produced moderate rice yield in no-till, unfertilised, direct-sown rice-based cropping systems. Heavy mulching of rice straw in the WC and WC + rye is not recommended because it leads to a decrease in white clover biomass production. However, straw mulching in fallow–rice and rye–rice cropping systems is essential for improving seed germination and seedling establishment while providing nutrients to rice at later growth stages.
Rumen protected protein and fat produced from oilseeds and/or meals by formaldehyde treatment; their role in ruminant production and product quality: a review
Authors: Gulati S. K. , Garg M. R. , Scott T. W.
Published: November 2005

The nutritional characteristics of rumen-protected protein and fat supplements produced by formaldehyde treatment of oilseeds and meals are reviewed. The proportion of rumen undegraded protein (RUP) in different protein sources can be controlled by this process, bio-available lysine is 82–84% and the proportions of acid detergent and neutral detergent insoluble nitrogen are unchanged by formaldehyde treatment; this is in contrast to heat treatment of proteins where significant increases in these nitrogen components can occur if the RUP content exceeds 60% of the crude protein (CP). A RUP content of 75–80% of CP is optimal when using protein supplements for milk production, and for body growth in steers a lower RUP content is desirable (i.e. 50–55% of CP). Both the fat and protein constituents in rumen-protected fat supplements derived from the emulsification and formaldehyde treatment of oilseeds are highly protected from ruminal metabolism (75–90%) and are readily digested in the small intestine (90% for C18 unsaturated fatty acids, 82% for the essential amino acids). Protected fat/protein supplements are designed and fed to lactating and non-lactating ruminants to increase efficiency of production, enhance product quality, augment n-3, n-6 and n-9 fatty acid content of meat and milk, and to improve reproductive performance. The challenges and potential role for these protected fat/protein supplements in improving productivity and quality of ruminant derived foods are discussed.
Oxygen budget for an urban estuary
Authors: Connell DW , Morton HC , Bycroft BM
Published: November 2005

Various processes affecting the dissolved oxygen content of waters of the Norman Creek estuary, Brisbane, were measured or estimated and standardized for the mid tide daylight situation. Over a 9-week period, accrual, aeration and photosynthetic processes resulted in the daily addition of 76,225 and 214 kg oxygen, respectively, and export, deaeration, biochemical oxygen demand, plant respiration and benthic respiration in the daily loss of 30, 89, 91, 97 and 335 kg oxygen, respectively. These processes are highly dynamic, with substantial daily turnover in the water mass. Benthic sediments; enriched with organic matter, exercise a major influence on the dissolved oxygen content of the water.
Ammonia and phosphate excretion by zooplankton from the inshore waters of the Great Barrier Reef. II. Their in situ contributions to nutrient regeneration
Authors: Ikeda T , Carleton JH , Mitchell AW , Dixon P
Published: November 2005

Zooplankton excretion was estimated by combining biomass data with experimental laboratory data on excretion rates at three stations, characterized by low nutrient levels, in the inshore waters of the Great Barrier Reef. Hourly ammonia excretion (as nitrogen) by net zooplankton (>205 �) was calculated to range from 11.9 to 22.6 � m-3 or from 1.6 to 5.0 g m-2 per year, and hourly phosphate excretion (as phosphorus) from 1.4 to 2.8 � m-3 or from 0.16 to 0.63 g m-2 per year. Hourly excretion of ammonia by microzooplankton ( < 205 �) was calculated to be 2.6 � m-3 (as nitrogen) and of phosphate 0.55 � m-3 (as phosphorus), values that were 15 and 27% of the excretion by net zooplankton, respectively. Combined excretion rates by net zooplankton and microzooplankton could supply only 9.0-29.2% of the nitrogen and 6.6-25.6% of the phosphorus for an assumed yearly primary production of carbon of 100 g m-2 (= 17.6 g m-2 of nitrogen and 2.5 g m-2 of phosphorus). Calculations from an empirical equation relating temperature to oxygen consumption by a bottom community indicated a high potential for benthic nutrient regeneration in reef inshore waters (27.1 g m-2 per year, as nitrogen). The bottom community therefore appears to be the most important source of nutrient regeneration within the area studied.
Calcineurin regulates bone formation by the osteoblast
Authors: Sun Li , Blair Harry C. , Peng Yuanzhen , Zaidi Neeha , Adebanjo Olugbenga A. , Wu Xue Bin , Wu Xing Yao , Iqbal Jameel , Epstein Solomon , Abe Etsuko , Moonga Baljit S. , Zaidi Mone
Published: November 2005

Two of the most commonly used immunosuppressants, cyclosporine A and tacrolimus (FK506), inhibit the activity of a ubiquitously expressed Ca
2+
/calmodulin-sensitive phosphatase, calcineurin. Because both drugs also cause profound bone loss in humans and in animal models, we explored whether calcineurin played a role in regulating skeletal remodeling. We found that osteoblasts contained mRNA and protein for all isoforms of calcineurin A and B. TAT-assisted transduction of fusion protein TAT-calcineurin Aα into osteoblasts resulted in the enhanced expression of the osteoblast differentiation markers
Runx-2
, alkaline phosphatase, bone sialoprotein, and osteocalcin. This expression was associated with a dramatic enhancement of bone formation in intact calvarial cultures. Calcineurin Aα
-/-
mice displayed severe osteoporosis, markedly reduced mineral apposition rates, and attenuated colony formation in 10-day
ex vivo
stromal cell cultures. The latter was associated with significant reductions in
Runx2
, bone sialoprotein, and osteocalcin expression, paralleled by similar decreases in response to FK506. Together, the gain- and loss-of-function experiments indicate that calcineurin regulates bone formation through an effect on osteoblast differentiation.
Decreased levels of CXC-chemokines in serum of benzene-exposed workers identified by array-based proteomics
Authors: Vermeulen Roel , Lan Qing , Zhang Luoping , Gunn Laura , McCarthy Diane , Woodbury Ronald L. , McGuire Marielena , Podust Vladimir N. , Li Guilan , Chatterjee Nilanjan , Mu Ruidong , Yin Songnian , Rothman Nathaniel , Smith Martyn T.
Published: November 2005

Benzene is an important industrial chemical and environmental contaminant that causes leukemia. To obtain mechanistic insight into benzene's mechanism of action, we examined the impact of benzene on the human serum proteome in a study of exposed healthy shoe-factory workers and unexposed controls. Two sequential studies were performed, each using sera from 10 workers exposed to benzene (overall mean benzene air level >30 ppm) and 10 controls. Serum samples were subjected to anion-exchange fractionation and bound to three types of ProteinChip arrays (Ciphergen Biosystems, Fremont, CA) [hydrophobic (H50), metal affinity (IMAC3-Cu), and cation exchange (WCX2)]. Protein-expression patterns were detected by surface-enhanced laser desorption/ionization (SELDI)-TOF MS. Three proteins (4.1, 7.7, and 9.3 kDa) were consistently down-regulated in exposed compared with control subjects in both studies. All proteins were highly inversely correlated with individual estimates of benzene exposure (r> 0.75). The 7.7- and 9.3-kDa proteins were subsequently identified as platelet factor (PF)4 and connective tissue activating peptide (CTAP)-III. Initial proteomic results for PF4 and CTAP-III were subsequently confirmed in a single experiment using a ProteinChip-array-based immunoassay(Ciphergen Biosystems). The altered expression of the platelet-derived CXC-chemokines (40% and 63% for PF4 and CTAP-III, respectively) could not be explained by changes in absolute platelet counts. Thus, SELDI-TOF analysis of a limited number of exposed and unexposed subjects revealed that lowered expression of PF4 and CTAP-III proteins is a potential biomarker of benzene's early biologic effects and may play a role in the immunosuppressive effects of benzene.
The β
1a
subunit is essential for the assembly of dihydropyridine-receptor arrays in skeletal muscle
Authors: Schredelseker Johann , Di Biase Valentina , Obermair Gerald J. , Felder E. Tatiana , Flucher Bernhard E. , Franzini-Armstrong Clara , Grabner Manfred
Published: November 2005

Homozygous zebrafish of the mutant
relaxed
(
red
ts25
) are paralyzed and die within days after hatching. A significant reduction of intramembrane charge movements and the lack of depolarization-induced but not caffeine-induced Ca
2+
transients suggested a defect in the skeletal muscle dihydropyridine receptor (DHPR). Sequencing of DHPR cDNAs indicated that the α
1S
subunit is normal, whereas the β
1a
subunit harbors a single point mutation resulting in a premature stop. Quantitative RT-PCR revealed that the mutated gene is transcribed, but Western blot analysis and immunocytochemistry demonstrated the complete loss of the β
1a
protein in mutant muscle. Thus, the immotile zebrafish
relaxed
is a β
1a
-null mutant. Interestingly, immunocytochemistry showed correct triad targeting of the α
1S
subunit in the absence of β
1a
. Freeze-fracture analysis of the DHPR clusters in
relaxed
myotubes revealed an ≈2-fold reduction in cluster size with a normal density of DHPR particles within the clusters. Most importantly, DHPR particles in the junctional membranes of the immotile zebrafish mutant
relaxed
entirely lacked the normal arrangement in arrays of tetrads. Thus, our data indicate that the lack of the β
1a
subunit does not prevent triad targeting of the DHPR α
1S
subunit but precludes the skeletal muscle-specific arrangement of DHPR particles opposite the ryanodine receptor (RyR1). This defect properly explains the complete deficiency of skeletal muscle excitation-contraction coupling in β
1
-null model organisms.
Are Employment Zones Successful? Evidence From the First Four Years
Authors: Bruttel Oliver
Published: November 2005

The British Employment Service increasingly relies on private providers. Arguably, the Employment Zone initiative provides a radical example of contracting out. Since 2000, long-term unemployed people in 13 local areas have been receiving employment reintegration services through private providers. This article provides a comprehensive overview of this experience. It builds on existing evaluations and primary research through expert interviews and document analysis. It attempts to add new, original insights into the development of the market as well as the incentive mechanisms used to gear employment outcomes. It seems that the flexibility of private providers is indeed able to increase the effectiveness of placement services compared with Jobcentre Plus. Nevertheless, Employment Zones seem to suffer from the general deficiencies of ‘Work First’ policies.
Socio-economic Decline and Adaptation: South Yorkshire's Former Coalfields
Authors: Murray Robert , Baldwin James , Ridgway Keith , Winder Belinda
Published: November 2005

Two decades after the year-long miners' strike of 1984/5, this paper presents a contemporary account of the social and economic situation faced by ex-miners in South Yorkshire, uncovering those factors that continue to inhibit new employment and adaptation following the contraction of the coal industry. Forty-one in-depth qualitative interviews were conducted with men who had worked in the region's coal mining industry for varying periods of time. The interviews were designed to examine many of the problems that have emerged following deindustrialisation and assess appraisals of retraining provision and prospects for employment. Findings increase understanding of issues endemic to many former pit villages including continuing high levels of localised unemployment and disproportionately high numbers of incapacity benefit claimants. A greater understanding of the reluctance of individuals to adapt, retrain and seek new, alternative employment will lead to more successful methods of dealing with the problems associated with continuing economic inactivity in the region's former coalfield communities and has many important consequences for existing regeneration programmes and employment initiatives.
Mitogen‐Activated Protein Kinases Regulate Platelet‐Activating Factor‐Induced Hyperpermeability
Authors: YU PENG , HATAKEYAMA TAKUYA , ARAMOTO HARUO , MIYATA TETSURO , SHIGEMATSU HIROSHI , NAGAWA HIROKAZU , HOBSON ROBERT W. , DURÁN WALTER N.
Published: November 2005

Objective: The authors tested the hypothesis that p42/44‐ (ERK‐1/2) and/or p38‐mitogen‐activated protein kinases (MAPK) are in vivo regulatory elements in the platelet‐activating factor (PAF) activated signaling cascade that stimulates microvascular hyperpermeability.

Methods: FITC‐dextran 70 was used as the macromolecular tracer for microvascular permeability in the mouse mesenteric fat tissue. Interstitial integrated optical intensity (IOI) was used as an index of permeability.

Results: An application of 10−7 M PAF increased IOI from 23.1 ± 3.6 to 70.8 ± 7.4 (mean ± SEM). Inhibition of ERK‐1/2 with 3 μM and 30 μM AG126 reduced IOI to 32.3 ± 2.5. Similarly, inhibition of p38‐MAPK with 6 nM, 60 nM and 600 nM SB203580 lowered IOI to 29.1 ± 2.4.

Conclusions: The results demonstrate that ERK‐1/2 and p38MAPK participate in the signaling cascade that regulates PAF‐induced microvascular hyperpermeability in vivo.
p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death
Authors: Bjørkøy Geir , Lamark Trond , Brech Andreas , Outzen Heidi , Perander Maria , Øvervatn Aud , Stenmark Harald , Johansen Terje
Published: November 2005

Autophagic degradation of ubiquitinated protein aggregates is important for cell survival, but it is not known how the autophagic machinery recognizes such aggregates. In this study, we report that polymerization of the polyubiquitin-binding protein p62/SQSTM1 yields protein bodies that either reside free in the cytosol and nucleus or occur within autophagosomes and lysosomal structures. Inhibition of autophagy led to an increase in the size and number of p62 bodies and p62 protein levels. The autophagic marker light chain 3 (LC3) colocalized with p62 bodies and coimmunoprecipitated with p62, suggesting that these two proteins participate in the same complexes. The depletion of p62 inhibited recruitment of LC3 to autophagosomes under starvation conditions. Strikingly, p62 and LC3 formed a shell surrounding aggregates of mutant huntingtin. Reduction of p62 protein levels or interference with p62 function significantly increased cell death that was induced by the expression of mutant huntingtin. We suggest that p62 may, via LC3, be involved in linking polyubiquitinated protein aggregates to the autophagy machinery.
Spore number control and breeding in Saccharomyces cerevisiae
Authors: Taxis Christof , Keller Philipp , Kavagiou Zaharoula , Jensen Lars Juhl , Colombelli Julien , Bork Peer , Stelzer Ernst H.K. , Knop Michael
Published: November 2005

Spindle pole bodies (SPBs) provide a structural basis for genome inheritance and spore formation during meiosis in yeast. Upon carbon source limitation during sporulation, the number of haploid spores formed per cell is reduced. We show that precise spore number control (SNC) fulfills two functions. SNC maximizes the production of spores (1–4) that are formed by a single cell. This is regulated by the concentration of three structural meiotic SPB components, which is dependent on available amounts of carbon source. Using experiments and computer simulation, we show that the molecular mechanism relies on a self-organizing system, which is able to generate particular patterns (different numbers of spores) in dependency on one single stimulus (gradually increasing amounts of SPB constituents). We also show that SNC enhances intratetrad mating, whereby maximal amounts of germinated spores are able to return to a diploid lifestyle without intermediary mitotic division. This is beneficial for the immediate fitness of the population of postmeiotic cells.
Inferring functional information from domain co-evolution
Authors: Kim Yohan , Koyutürk Mehmet , Topkara Umut , Grama Ananth , Subramaniam Shankar
Published: November 2005

Motivation: Co-evolution is a powerful mechanism for understanding protein function. Prior work in this area has shown that co-evolving proteins are more likely to share the same function than those that do not because of functional constraints. Many of the efforts founded on this observation, however, are at the level of entire sequences, implicitly assuming that the complete protein sequence follows a single evolutionary trajectory. Since it is well known that a domain can exist in various contexts, this assumption is not valid for numerous multi-domain proteins. Motivated by these observations, we introduce a novel technique called Coevolutionary-Matrix that captures co-evolution between regions of two proteins. Instead of using existing domain information, the method exploits residue-level conservation to identify co-evolving regions that might correspond to domains.

Results: We show that the Coevolutionary-Matrix method can detect greater number of known functional associations for the Escherichia coli proteins when compared with earlier implementations of phylogenetic profiles. Furthermore, co-evolving regions of proteins detected by our method enable us to make hypotheses about their specific functions, many of which are supported by existing biochemical studies.

Contact:  shankar@sdsc.edu
The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling
Authors: Arnold Konstantin , Bordoli Lorenza , Kopp Jürgen , Schwede Torsten
Published: November 2005

Motivation: Homology models of proteins are of great interest for planning and analysing biological experiments when no experimental three-dimensional structures are available. Building homology models requires specialized programs and up-to-date sequence and structural databases. Integrating all required tools, programs and databases into a single web-based workspace facilitates access to homology modelling from a computer with web connection without the need of downloading and installing large program packages and databases.

Results: SWISS-MODEL workspace is a web-based integrated service dedicated to protein structure homology modelling. It assists and guides the user in building protein homology models at different levels of complexity. A personal working environment is provided for each user where several modelling projects can be carried out in parallel. Protein sequence and structure databases necessary for modelling are accessible from the workspace and are updated in regular intervals. Tools for template selection, model building and structure quality evaluation can be invoked from within the workspace. Workflow and usage of the workspace are illustrated by modelling human Cyclin A1 and human Transmembrane Protease 3.

Availability: The SWISS-MODEL workspace can be accessed freely at

Contact:  Torsten.Schwede@unibas.ch

Supplementary information: Supplementary data are available at Bioinformatics online.
Bacterial outer membrane vesicles and the host–pathogen interaction
Authors: Kuehn Meta J. , Kesty Nicole C.
Published: November 2005

Extracellular secretion of products is the major mechanism by which Gram-negative pathogens communicate with and intoxicate host cells. Vesicles released from the envelope of growing bacteria serve as secretory vehicles for proteins and lipids of Gram-negative bacteria. Vesicle production occurs in infected tissues and is influenced by environmental factors. Vesicles play roles in establishing a colonization niche, carrying and transmitting virulence factors into host cells, and modulating host defense and response. Vesicle-mediated toxin delivery is a potent virulence mechanism exhibited by diverse Gram-negative pathogens. The biochemical and functional properties of pathogen-derived vesicles reveal their potential to critically impact disease.
Slicer function of Drosophila Argonautes and its involvement in RISC formation
Authors: Miyoshi Keita , Tsukumo Hiroko , Nagami Tomoko , Siomi Haruhiko , Siomi Mikiko C.
Published: November 2005

Argonaute proteins play important yet distinct roles in RNA silencing. Human Argonaute2 (hAgo2) was shown to be responsible for target RNA cleavage (“Slicer”) activity in RNA interference (RNAi), whereas other Argonaute subfamily members do not exhibit the Slicer activity in humans. In Drosophila, AGO2 was shown to possess the Slicer activity. Here we show that AGO1, another member of the Drosophila Argonaute subfamily, immunopurified from Schneider2 (S2) cells associates with microRNA (miRNA) and cleaves target RNA completely complementary to the miRNA. Slicer activity is reconstituted with recombinant full-length AGO1. Thus, in Drosophila, unlike in humans, both AGO1 and AGO2 have Slicer functions. Further, reconstitution of Slicer activity with recombinant PIWI domains of AGO1 and AGO2 demonstrates that other regions in the Argonautes are not strictly necessary for small interfering RNA (siRNA)-binding and cleavage activities. It has been shown that in circumstances with AGO2-lacking, the siRNA duplex is not unwound and consequently an RNA-induced silencing complex (RISC) is not formed. We show that upon addition of an siRNA duplex in S2 lysate, the passenger strand is cleaved in an AGO2-dependent manner, and nuclease-resistant modification of the passenger strand impairs RISC formation. These findings give rise to a new model in which AGO2 is directly involved in RISC formation as “Slicer” of the passenger strand of the siRNA duplex.
Homologous recombination and nonhomologous end-joining repair pathways regulate fragile site stability
Authors: Schwartz Michal , Zlotorynski Eitan , Goldberg Michal , Ozeri Efrat , Rahat Ayelet , Sage Carlos le , Chen Benjamin P.C. , Chen David J. , Agami Reuven , Kerem Batsheva
Published: November 2005

Common fragile sites are specific loci that form gaps and constrictions on metaphase chromosomes exposed to replication stress, which slows DNA replication. These sites have a role in chromosomal rearrangements in tumors; however, the molecular mechanism of their expression is unclear. Here we show that replication stress leads to focus formation of Rad51 and phosphorylated DNA-PKcs, key components of the homologous recombination (HR) and nonhomologous end-joining (NHEJ), double-strand break (DSB) repair pathways, respectively. Down-regulation of Rad51, DNA-PKcs, or Ligase IV, an additional component of the NHEJ repair pathway, leads to a significant increase in fragile site expression under replication stress. Replication stress also results in focus formation of the DSB markers, MDC1 and γH2AX. These foci colocalized with those of Rad51 and phospho-DNA-PKcs. Furthermore, γH2AX and phospho-DNA-PKcs foci were localized at expressed fragile sites on metaphase chromosomes. These findings suggest that DSBs are formed at common fragile sites as a result of replication perturbation. The repair of these breaks by both HR and NHEJ pathways is essential for chromosomal stability at these sites.
Pollen development and fertilization in Arabidopsis is dependent on the MALE GAMETOGENESIS IMPAIRED ANTHERS gene encoding a Type V P-type ATPase
Authors: Jakobsen, Mia Kyed , Poulsen, Lisbeth R. , Schulz, Alexander , Fleurat-Lessard, Pierrette , Møller, Annette , Husted, Søren , Schiøtt, Morten , Amtmann, Anna , Palmgren, Michael G.
Published: November 2005

In flowering plants, development of the haploid male gametophytes (pollen grains) takes place in a specialized structure called the anther. Successful pollen development, and thus reproduction, requires high secretory activity in both anther tissues and pollen. In this paper, we describe a novel member of the eukaryotic type V subfamily (P5) of P-type ATPase cation pumps, the MALE GAMETOGENESIS IMPAIRED ANTHERS (MIA) gene. MIA protein is highly abundant in the endoplasmic reticulum and small vesicles of developing pollen grains and tapetum cells. T-DNA insertional mutants of MIA suffer from imbalances in cation homeostasis and exhibit a severe reduction in fertility. Mutant microspores fail to separate from tetrads and pollen grains are fragile with an abnormal morphology and altered cell wall structure. Disruption of MIA affects expression of genes essential for secretion as well as a high number of genes encoding cell wall proteins and membrane transporters. MIA functionally complements a mutant in the P5 ATPase homolog SPF1 from Saccharomyces cerevisiae, suggesting a common function for P5 ATPases in single and multicellular organisms. Our results suggest that MIA is required in the secretory pathway for proper secretion of vesicle cargo to the plasma membrane.
FGF-dependent Notch signaling maintains the spinal cord stem zone
Authors: Akai Jun , Halley Pam A. , Storey Kate G.
Published: November 2005

Generation of the spinal cord relies on proliferation of undifferentiated cells located in a caudal stem zone. Although fibroblast growth factor (FGF) signaling is required to maintain this cell group, we do not know how it controls cell behavior in this context. Here we characterize an overlooked expression domain of the Notch ligand, Delta1, in the stem zone and demonstrate that this constitutes a proliferative cell group in which Notch signaling is active. We show that FGF signaling is required for expression of the proneural gene cash4 in the stem zone, which in turn induces Delta1. We further demonstrate that Notch signaling is required for cell proliferation within the stem zone; however, it does not regulate cell movement out of this region, nor is loss of Notch signaling sufficient to drive neuronal differentiation within this tissue. These data identify a novel role for the Notch pathway during vertebrate neurogenesis in which signaling between high Delta1-expressing cells maintains the neural precursor pool that generates the spinal cord. Our findings also suggest a mechanism for the establishment of the cell selection process, lateral inhibition: Mutual inhibition between Delta/Notch-expressing stem zone cells switches to single Delta1-presenting neurons as FGF activity declines in the newly formed neuroepithelium.
Involvement of IP3 receptors in LTP and LTD induction in guinea pig hippocampal CA1 neurons
Authors: Taufiq Ahmed Mostafa , Fujii Satoshi , Yamazaki Yoshihiko , Sasaki Hiroshi , Kaneko Kenya , Li Jianmin , Kato Hiroshi , Mikoshiba Katsuhiko
Published: November 2005

The role of inositol 1, 4, 5-trisphosphate receptors (IP3Rs) in long-term
potentiation (LTP) and long-term depression (LTD) was studied in CA1 neurons
in guinea pig hippocampal slices. In standard solution, short tetanic
stimulation consisting of 15 pulses at 100 Hz induced LTP, while three short
trains of low-frequency stimulation (LFS; 200 pulses at 1 Hz) at 18-min
intervals or one long train of LFS (1000 pulses at 1 Hz) induced stable LTD in
both the slope of the field EPSP (S-EPSP) and the amplitude of the population
spike (A-PS). Bath application of 2-aminoethoxydiphenyl borate (2-APB), an
IP3R antagonist, or of α-methyl-4-carboxyphenylglycine (MCPG), a
wide-spectrum metabotropic glutamate receptor antagonist, during weak tetanic
stimulation significantly increased the magnitude of the LTP in both the
S-EPSP and A-PS. Three short trains of LFS or one long train of LFS delivered
in the presence of 2-APB or MCPG did not induce LTD, but elicited LTP. Based
on these results, we conclude that, in hippocampal CA1 neurons, IP3Rs play an
important role in synaptic plasticity by attenuating LTP and facilitating
LTD.
Cholinergic septo-hippocampal innervation is required for trace eyeblink classical conditioning
Authors: Fontán-Lozano Ángela , Troncoso Julieta , Múnera Alejandro , Carrión Ángel Manuel , Delgado-García José María
Published: November 2005

We studied the effects of a selective lesion in rats, with 192-IgG-saporin,
of the cholinergic neurons located in the medial septum/diagonal band (MSDB)
complex on the acquisition of classical and instrumental conditioning
paradigms. The MSDB lesion induced a marked deficit in the acquisition, but
not in the retrieval, of eyeblink classical conditioning using a trace
paradigm. Such a deficit was task-selective, as lesioned rats were able to
acquire a fixed-interval operant conditioning as controls, and was not due to
nonspecific motor alterations, because spontaneous locomotion and blink
reflexes were not disturbed by the MSDB lesion. The deficit in the acquisition
of a trace eyeblink classical conditioning was reverted by the systemic
administration of carbachol, a nonselective cholinergic muscarinic agonist,
but not by lobeline, a nicotinic agonist. These results suggest a key role of
muscarinic denervation on the acquisition of new motor abilities using trace
classical conditioning procedures. It might also be suggested that muscarinic
agents would be useful for the amelioration of some associative learning
deficits observed at early stages in patients with Alzheimer's disease.
Enhancement of auditory fear conditioning after housing in a complex environment is attenuated by prior treatment with amphetamine
Authors: Briand Lisa A. , Robinson Terry E. , Maren Stephen
Published: November 2005

Prior exposure to drugs of abuse has been shown to occlude the structural
plasticity associated with living in a complex environment. Amphetamine
treatment may also occlude some cognitive advantages normally associated with
living in a complex environment. To test this hypothesis we examined the
influence of prior exposure to amphetamine on fear conditioning in rats housed
in either a standard or complex environment. Housing in a complex environment
facilitated fear learning to an auditory conditioned stimulus (CS), but not to
the training context, relative to animals housed singly or in a social group.
Prior treatment with amphetamine eliminated this effect. These results
indicate that living in a complex environment facilitates conditional freezing
to an auditory CS, and that this effect is abolished by pretreatment with
amphetamine.
A latent cue preference based on sodium depletion in rats
Authors: Stouffer Eric M. , White Norman M.
Published: November 2005

Three experiments show latent (or incidental) learning of salt-cue
relationships using a conditioned cue-preference paradigm. Rats drank a salt
solution while confined in one compartment and water in an adjacent, distinct
compartment on alternate days. When given access to the two compartments with
no solutions present, sodium-deprived rats preferred their salt-paired
compartments; normal rats preferred their water-paired compartments. Reversing
the deprivation states of the two groups reversed their preferences. These
results show that rats can latently acquire associations between environmental
cues and the taste of salt, and can use this information flexibly to guide
behavior based upon internal cues produced by sodium deprivation.
Association between early postoperative coagulation activation and peri‐operative myocardial ischaemia in patients undergoing vascular surgery
Authors: Böttiger B. W. , Snyder‐Ramos S. A. , Lapp W. , Motsch J. , Aulmann M. , Schweizer M. , Layug E. L. , Martin E. , Mangano D. T. ,   the investigators of the Multicenter Study of Perioperative Ischemia (MCSPI) Research Group, Inc. and the Ischemia Research and Education Foundation
Published: November 2005

We investigated the association of peri‐operative myocardial ischaemia with activation of coagulation and endogenous fibrinolysis in patients undergoing vascular surgery. In 50 patients, continuous Holter monitoring was performed to assess peri‐operative myocardial ischaemia and 12‐lead electrocardiography was recorded preoperatively and 72 h postoperatively to assess myocardial infarction. Serial blood samples were drawn peri‐operatively to determine the concentrations of fibrin monomers (for activation of coagulation), d‐dimer (for endogenous fibrinolysis) and cardiac troponin T and I. Patients with myocardial ischaemia showed higher concentrations of fibrin monomers at 48 h, and higher concentrations of d‐dimer preoperatively and at 24 and 48 h postoperatively. In patients with peri‐operative myocardial ischaemia, strong positive correlations were observed between fibrin monomer and d‐dimer concentrations at 15 min and 4 h postoperatively, and cardiac troponins at 15 min and at 4, 24, 48 and 72 h postoperatively. Early postoperative activation of coagulation and fibrinolysis is associated with peri‐operative myocardial cell damage among patients who are at risk for, or have a history of, coronary artery disease plus peri‐operative myocardial ischaemia.
Linkage of Sevier thrusting episodes and Late Cretaceous foreland basin megasequences across southern Wyoming (USA)
Authors: Liu Shao‐Feng , Nummedal Dag , Yin Pei‐Gui , Luo Hong‐Jun
Published: November 2005

Deposition and subsidence analysis, coupled with previous structural studies of the Sevier thrust belt, provide a means of reconstructing the detailed kinematic history of depositional response to episodic thrusting in the Cordilleran foreland basin of southern Wyoming, western interior USA. The Upper Cretaceous basin fill is divided into five megasequences bounded by unconformities. The Sevier thrust belt in northern Utah and southwestern Wyoming deformed in an eastward progression of episodic thrusting. Three major episodes of displacement on the Willard‐Meade, Crawford and ‘early’ Absaroka thrusts occurred from Aptian to early Campanian, and the thrust wedge gradually became supercritically tapered. The Frontier Formation conglomerate, Echo Canyon and Weber Canyon Conglomerates and Little Muddy Creek Conglomerate were deposited in response to these major thrusting events. Corresponding to these proximal conglomerates within the thrust belt, Megasequences 1, 2 and 3 were developed in the distal foreland of southern Wyoming. Two‐dimensional (2‐D) subsidence analyses show that the basin was divided into foredeep, forebulge and backbulge depozones. Foredeep subsidence in Megasequences 1, 2 and 3, resulting from Willard‐Meade, Crawford and ‘early’ Absaroka thrust loading, were confined to a narrow zone in the western part of the basin. Subsidence in the broad region east of the forebulge was dominantly controlled by sediment loading and inferred dynamic subsidence. Individual subsidence curves are characterized by three stages from rapid to slow. Controlled by relationships between accommodation and sediment supply, the basin was filled with retrogradational shales during periods of rapid subsidence, followed by progradational coarse clastic wedges during periods of slow subsidence. During middle Campanian time (ca. 78.5–73.4 Ma), the thrust wedge was stalled because of wedge‐top erosion and became subcritical, and the foredeep zone eroded and rebounded because of isostasy. The eroded sediments were transported far from the thrust belt, and constitute Megasequence 4 that was mostly composed of fluvial and coastal plain depositional systems. Subsidence rates were very slow, because of post‐thrusting rebound, and the resulting 2‐D subsidence was lenticular in an east–west direction. During late Campanian to early Maastrichtian time, widespread deposits of coarse sediment (the Hams Fork Conglomerate) aggraded the top of the thrust wedge after it stalled, prior to initiation of ‘late’ Absaroka thrusting. Meanwhile Megasequence 5 was deposited in the Wyoming foreland under the influence of both the intraforeland Wind River basement uplift and the Sevier thrust belt.
Thrombophilia in pregnancy: a systematic review
Authors: Robertson L. , Wu O. , Langhorne P. , Twaddle S. , Clark P. , Lowe G. D. O. , Walker I. D. , Greaves M. , Brenkel I. , Regan L. , Greer I. A. ,   The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study.
Published: November 2005

Growing evidence suggests that thrombophilia is associated with venous thromboembolism (VTE) and adverse pregnancy outcomes. However, methodological limitations have made it difficult to obtain a clear overview of the overall risks. We conducted a systematic review to determine the risk of VTE and adverse pregnancy outcomes associated with thrombophilia in pregnancy. The effectiveness of prophylactic interventions during pregnancy was also evaluated. Major electronic databases were searched, relevant data abstracted and study quality assessed by two independent reviewers. Odds ratios (ORs) stratified by thrombophilia type were calculated for each outcome. A total of 79 studies were included in our review. The risks for individual thrombophilic defects were determined for VTE (ORs, 0·74–34·40); early pregnancy loss (ORs, 1·40–6·25); late pregnancy loss (ORs, 1·31–20·09); pre‐eclampsia (ORs, 1·37–3·49); placental abruption (ORs, 1·42–7·71) and intrauterine growth restriction (ORs, 1·24–2·92). Low‐dose aspirin plus heparin was the most effective in preventing pregnancy loss in thrombophilic women (OR, 1·62). Our findings confirm that women with thrombophilia are at risk of developing VTE and complications in pregnancy. However, despite the increase in relative risk, the absolute risk of VTE and adverse outcomes remains low. There is also a lack of controlled trials of antithrombotic intervention to prevent pregnancy complications. Thus, at present, universal screening for thrombophilia in pregnancy cannot be justified clinically.
PRIMA‐1 induces apoptosis in acute myeloid leukaemia cells with p53 gene deletion
Authors: Nahi H. , Merup M. , Lehmann S. , Bengtzen S. , Möllgård L. , Selivanova G. , Wiman K. G. , Paul C.
Published: November 2005

The p53 tumour suppressor gene located on chromosome 17p13 is the most frequently mutated gene in human tumours. About 5–8% of cases with acute myeloid leukaemia (AML) carry the p53 mutation. Recently, the compound p53‐dependent reactivation and induction of massive apoptosis (PRIMA‐1) has been shown to induce cytotoxic effects and apoptosis in human tumour cells by restoration of the transcriptional activity of mutated p53. This is believed to be mediated by a change in the conformation of mutated p53 protein, restoring DNA binding and activation of p53 target genes. We studied the effects of PRIMA‐1 and commonly used antileukaemic drugs on AML cells from 62 patients. Cells were obtained from peripheral blood or bone marrow and were exposed to PRIMA‐1, cytarabine, daunorubicin, chlorodeoxyadenosine and fludarabine. This study showed that PRIMA‐1 had cytotoxic effects on AML cells. Conventional AML drugs were less effective in cells with hemizygous p53 deletion. Interestingly, our data indicated that PRIMA‐1 was more effective in this subgroup of patients compared with patients with normal chromosome 17. Our data suggest that the concept of restoration of p53 protein by PRIMA‐1 or a PRIMA‐1‐based new drug may increase the efficacy of AML treatment in patients with p53 mutations.