bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the Expression of Molecular Chirality in the Self‐Assembly of a Peptidomimetic Organogelator
Authors: Becerril Jorge , Escuder Beatriu , Miravet Juan F. , Gavara Raquel , Luis Santiago V.
Published: February 2005

The expression of molecular chirality during the self‐assembly of an amino‐acid‐based macrocyclic organogelator (1) has been studied. The gelation behaviour of enantiopure samples, as well as mixtures of both enantiomers, of this compound have been studied and important differences have been found between them. For example, the enantiopure samples form gels whereas the racemates does not. Electron microscopy reveals the formation of helicoidal fibers of opposite handedness in the gels formed by pure enantiomers, whereas only straight ribbons are found in the racemate and most of the nonenantiopure mixtures. X‐ray powder diffraction shows an enantiospecific self‐assembly in the mixtures that indicates the formation of enantiopure aggregates in all cases. These results are rationalized by considering the influence of the aggregates size on the gelation ability as well as the chirality expression at the supramolecular level. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Capillary liquid chromatography with MS3 for the determination of enkephalins in microdialysis samples from the striatum of anesthetized and freely–moving rats
Authors: Baseski Holly M. , Watson Christopher J. , Cellar Nicholas A. , Shackman Jonathan G. , Kennedy Robert T.
Published: February 2005

In vivo microdialysis sampling was coupled to capillary liquid chromatography (LC)/electrospray ionization quadrupole ion trap mass spectrometry (MS) to monitor [Met]enkephalin and [Leu]enkephalin in the striatum of anesthetized and freely–moving rats. The LC system utilized a high‐pressure pump to load 2.5 µl samples and desalt the 25 µm i.d. by 2 cm long column in 12 min. Samples were eluted with a separate pump at ∼100 nl min−1. A rapid gradient effectively separated the endogenous neuropeptides in 4 min. A comparison was made for operating the mass spectrometer in the MS2 and MS3 modes for detection of the peptides. In standard solutions, the detection limits were similar at 1–2 pM (2–4 amol injected); however, the reproducibility was improved with MS3 as the relative standard deviation was <5% compared with 20% for MS2 for 60 pM samples. For dialysate solutions, reconstructed ion chromatograms and tandem mass spectra had much higher signal‐to‐noise ratios in the MS3 mode, resulting in more confident detection at in vivo concentrations. The method was successfully used to monitor the peptides under basal conditions and with stimulation of peptide secretion by infusion of elevated K+ concentration. Copyright © 2005 John Wiley & Sons, Ltd.
Human cerebrospinal fluid peptidomics
Authors: Yuan Xianglin , Desiderio Dominic M.
Published: February 2005

Cerebrospinal fluid (CSF) has frequently been extensively studied to explore several different central nervous system (CNS) disorders because it contains proteins, enzymes, hormones, neuropeptides and neurotransmitters that play critical regulatory roles in many different physiological processes. Individual neuropeptidergic systems in CSF have been studied. In theory, peptidomics offers a bird's‐eye, comprehensive and systems‐level approach to analyze all of the peptidergic systems that have been expressed in CSF at any given time. In this study, low molecular mass (Mr < 5 kDa) peptides were isolated by ultrafiltration. The isolated peptides, with or without trypsin digestion, were preferentially enriched with a solid‐phase extraction cartridge, and the peptides were separated with capillary liquid chromatography and analyzed with on‐line quadrupole time‐of‐flight mass spectrometry (MS). In this proof‐of‐principle study, the 20 representative MS‐characterized peptides were shown to be derived from 12 proteins, among which four proteins, amyloid‐like protein 1, secretogranin I, granin‐like neuroendocrine peptide precursor and neurosecretory protein VGF, have been shown elsewhere to be either associated with CNS disorders or to play a central role in the CNS. The long‐term goals of this peptidomics study are to monitor the changes (amount; modifications) of CSF peptides, clarify the aberrant processing of large intact protein precursors, elucidate the molecular mechanisms of CNS disorders and find biomarkers. This analytical method is effective for the analysis of the human lumbar CSF peptidome. Copyright © 2005 John Wiley & Sons, Ltd.
Quantification of the Aβ peptide in Alzheimer's plaques by laser dissection microscopy combined with mass spectrometry
Authors: Rüfenacht Pascal , Güntert Andreas , Bohrmann Bernd , Ducret Axel , Döbeli Heinz
Published: February 2005

The accumulation and aggregation of the beta‐amyloid peptide (Aβ) in the brain represents a key factor in the pathogenesis of Alzheimer's disease (AD). Many of the transgenic mouse models for AD exhibit an amyloid pathology with neuritic plaques but they typically vary by the type and abundance of plaques identified in their brains and by the onset and severity of cognitive impairment. Thus, an important consideration in the characterization of AD transgenic mouse models should be the quantitative evaluation of the amyloid load in the brain together with a detailed physico‐chemical analysis of Aβ from the deposited plaques. Here we present an analytical procedure to collect single amyloid plaques from anatomically defined brain regions by laser dissection microscopy that can be quantitatively assessed in their Aβ isoforms composition by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. Quantification was achieved by stable isotope dilution using calibrated 15N‐labeled Aβ standards that were spiked in the sample immediately after laser dissection. Using this method, we found that the amyloid loads in brain plaques isolated from the transgenic AD mouse model PS2APP or from human were similar. Total Aβ composition was estimated at ∼50–100 fmol per excised plaque disc, as confirmed by immunoblot analysis. N‐Terminal truncated Aβ isoforms were identified in both transgene and human amyloid plaques but with significantly elevated levels in human samples. Copyright © 2005 John Wiley & Sons, Ltd.
Proteomics and peptidomics in neuroscience. Experience of capabilities and limitations in a neurochemical laboratory
Authors: Paulson Linda , Persson Rita , Karlsson Gösta , Silberring Jerzy , Bierczynska‐Krzysik Anna , Ekman Rolf , Westman‐Brinkmalm Ann
Published: February 2005

The increasing use of proteomics has created a basis for new strategies to develop methodologies for rapid identification of protein patterns in living organisms. It has also become evident that proteomics has other potential applications than protein and peptide identification, e.g. protein characterization, with the aim of revealing their structure, function(s) and interactions of proteins. In comparative proteomics studies, the protein expression of a certain biological system is compared with another system or the same system under perturbed conditions. Global identification of proteins in neuroscience is extremely complex, owing to the limited availability of biological material and very low concentrations of the molecules. Moreover, in addition to proteins, there are number of peptides that must also be considered in global studies on the central nervous system. In this overview, we focus on and discuss problems related to the different sources of biological material and sample handling, which are part of all preparatory and analytical steps. Straightforward protocols are desirable to avoid excessive purification steps, since loss of material at each step is inevitable. We would like to merge the two worlds of proteomics/peptidomics and neuroscience, and finally we consider different practical and technical aspects, illustrated with examples from our laboratory. Copyright © 2005 John Wiley & Sons, Ltd.
Fourier transform infrared/attenuated total reflectance analysis of water diffusion in poly[styrene‐b‐isobutylene‐ b‐styrene] block copolymer membranes
Authors: Mountz David A. , Storey Robson F. , Mauritz Kenneth A.
Published: February 2005

A Fourier transform infrared/attenuated total reflectance technique was used to study the diffusion of water through poly(styrene‐b‐isobutylene‐b‐styrene) block copolymers (BCPs), as well as sulfonated (H+) and Na+‐sulfonated ionomer versions. Diffusion data were collected and interpreted for these membranes versus polystyrene block composition, degree of sulfonation, Na+ ion content in the ionomers, and the effect of initially dry versus prehydrated conditions. An “early time” diffusion coefficient, D, decreased with increasing percent polystyrene for a series of unmodified BCPs. D decreased with increasing degree of sulfonation, and with increasing ion content for the Na+‐exchanged samples and this was interpreted in terms of diffusion limitations caused by a strong tendency for ion hydration. The method also yielded information relating to the time evolution of water structure from the standpoint of degree of intermolecular hydrogen bonding. Membrane prehydration causes profound increases in D for both the unmodified BCP and sulfonated samples, as in plasticization. The simultaneous acquisition of information relating to interactions between water molecules and interactions of water molecules with functional groups on the host polymer matrix offers more information than conventional diffusion measurement techniques that simply count transported molecules. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 764–776, 2005
The use of the triangular test with response‐adaptive treatment allocation
Authors: Coad D. Stephen , Ivanova Anastasia
Published: February 2005

A clinical trial is considered in which two treatments with binary responses are to be compared. A popular sequential stopping rule, the triangular test, is studied when various response‐adaptive treatment allocation rules are applied, such as the recently proposed drop‐the‐loser rule, an urn randomization scheme. The paper extends previous work by Coad and Rosenberger, who combined the triangular test with the randomized play‐the‐winner rule. The purpose of the paper is to investigate to what extent the variability of an adaptive design affects the overall performance of the triangular test. The adaptive rules under consideration are described and some of their asymptotic properties are summarized. Simulation is then used to assess the performance of the triangular test when combined with the various adaptive rules. The main finding is that the drop‐the‐loser rule is the most promising of the adaptive rules considered in terms of a less variable allocation proportion and a smaller number of treatment failures. The use of this rule with the triangular test is beneficial compared with the triangular test with equal allocation, since it yields fewer treatment failures on average while providing comparable power with similar expected sample size. The results of an AIDS trial are used to illustrate the performance of the triangular test when combined with the drop‐the‐loser rule. Copyright © 2005 John Wiley & Sons, Ltd.
Statistical design and analysis of pharmacogenetic trials
Authors: Kelly Patrick J. , Stallard Nigel , Whittaker John C.
Published: February 2005

Pharmacogenetic trials investigate the effect of genotype on treatment response. When there are two or more treatment groups and two or more genetic groups, investigation of gene–treatment interactions is of key interest. However, calculation of the power to detect such interactions is complicated because this depends not only on the treatment effect size within each genetic group, but also on the number of genetic groups, the size of each genetic group, and the type of genetic effect that is both present and tested for. The scale chosen to measure the magnitude of an interaction can also be problematic, especially for the binary case.

Elston et al. proposed a test for detecting the presence of gene–treatment interactions for binary responses, and gave appropriate power calculations. This paper shows how the same approach can also be used for normally distributed responses. We also propose a method for analysing and performing sample size calculations based on a generalized linear model (GLM) approach. The power of the Elston et al. and GLM approaches are compared for the binary and normal case using several illustrative examples. While more sensitive to errors in model specification than the Elston et al. approach, the GLM approach is much more flexible and in many cases more powerful. Copyright © 2005 John Wiley & Sons, Ltd.
The prognosis of impaired left ventricular systolic function and heart failure in a middle‐aged and elderly population in an urban population segment of Copenhagen
Authors: Raymond Ilan , Mehlsen Jesper , Pedersen Frants , Dimsits Jeannett , Jacobsen Jørgen , Hildebrandt Per Rossen
Published: February 2005

Aims:

To determine the prognosis, total mortality and cardiac morbidity, of patients with left ventricular systolic dysfunction and heart failure (HF) in a general population sample.

Methods and results:

A total of 764 subjects, 432 females and 332 males, median age (range) 66 years (50–89), participated in this cross sectional survey. The study population was recruited from randomly selected general practitioners and stratified to include a minimum of 150 persons in each age decade stratum. Each participant filled in a heart failure questionnaire and ECG, blood tests and echocardiography were performed. Median (range) follow‐up was 1145 (51–1197) days. Subjects with LVEF≤0.40 had a significantly higher all‐cause mortality (27.8% vs. 5.6%, P<0.0001), admission rate for HF (25.0% vs. 1.9%, P<0.0001) and for other cardiac causes (25.0% vs. 6.3%, P<0.0001) than in subjects with LVEF>0.40. The age and gender adjusted 2‐year relative risk of death was 4.6 (95% C.I.=1.6–13.2). No significant difference in mortality was found between subjects with or without heart failure symptoms.

Conclusion:

Significantly higher mortality as well as cardiac morbidity was found in subjects with symptomatic and asymptomatic LV systolic dysfunction compared to those with normal systolic function. These conditions were among the strongest predictors of all‐cause mortality and cardiac morbidity.
Pilot assessment of the response of several pulmonary hemodynamic variables to sublingual sildenafil in candidates for heart transplantation
Authors: Gómez‐Sánchez Miguel Angel , de la Calzada Carlos Saenz , Subías Pilar Escribano , Jiménez Juan Francisco Delgado , Salvador María Lázaro , González Agustín Albarrán , Calvo Luis Cea
Published: February 2005

Objective:

To determine the acute vasodilator effect of sublingual sildenafil in heart transplant candidates with severe pulmonary hypertension due to severe left ventricular dysfunction (LVD).

Background:

Pulmonary hypertension confers an increased risk of early graft failure.

Patients and methods:

Seven patients, (mean age of 53±8) with severe LVD (mean EF: 19±1.7%, functional class III–IV) due to coronary artery disease, dilated cardiomyopathy and valvulopathy were evaluated for heart transplant. All patients presented a mean transpulmonary gradient >12 mmHg and pulmonary vascular resistances >2.5 W.U., despite full treatment for advanced heart failure. The following hemodynamic data were obtained at basal state and then 15, 30 and 45 min after administration of 100 mg of sublingual sildenafil: right atrial, mean pulmonary artery pressure (mPAP), mean pulmonary capillary wedge pressures, mean transpulmonary gradient (mTPG), blood pressure, cardiac output, pulmonary vascular resistances (PVR) and systemic vascular resistances. Sublingual sildenafil was given without changing the previous treatment of heart failure.

Results:

After 30 min of sublingual sildenafil, mPAP decreased from 37 (28–61) to 30 (16–42) mmHg and PVR decreased from 5.2 (1.9–13.8) to 2.5 (1.4–3.9) W.U. after 45 min. Mean TPG decreased from 19 (16–33) to 12 (8–14) mmHg at 45 min. Mean pulmonary capillary wedge pressure, cardiac output, systemic vascular resistances and mean blood pressure were unchanged. Sublingual sildenafil was well tolerated, with only transient facial flushing in 4 patients and mild headache in 2.

Conclusions:

Based on this initial study, sublingual sildenafil may be a useful alternative drug to perform acute vasodilator test in heart transplant candidates with significant pulmonary hypertension due to severe LVD. Nevertheless, further studies are warranted to confirm our results.
An 8‐year follow‐up study of acute admissions with heart failure in a multiethnic population
Authors: Sosin Michael D. , Bhatia Gurbir S. , Zarifis John , Davis Russell C. , Lip Gregory Y.H.
Published: February 2005

In 1994, we reported a cross‐sectional survey of acute heart failure admissions to a city centre hospital serving a multiethnic population and found ethnic differences in aetiological factors and short‐term (in‐patient) mortality. We analysed long‐term mortality data for this original survey cohort after 8 years’ follow‐up. At 8 years’ follow‐up, the total mortality was 90.5% amongst Europeans and 87.0% amongst non‐Europeans (log rank test, P=0.0705). The non‐European patients had significantly better survival at all time points until 6 years, after which the survival curves start to converge. In univariate analysis, age <75.6 years (that is, the median age of the whole cohort), use of beta‐blockers, use of ACE inhibitors, and absence of atrial fibrillation were significantly associated with increased survival. In addition, patients who had had an echocardiographic examination had significantly prolonged survival when compared to those who did not. Using a Cox multiple regression analysis, age, renal impairment, atrial fibrillation, absence of echocardiography, absence of beta‐blockers or ACE inhibitor use (and not ethnicity) remained significant predictors of mortality at 8 years. While this follow‐up study has suggested that survival following admission for acutely decompensated heart failure is not different between different ethnic groups when corrected for age, it is clear from the younger age of heart failure patients from ethnic minority groups and the relatively high prevalence, that the burden of heart failure is greater in these populations. Future observational and therapeutic trials in heart failure should include sufficient numbers of participants from ethnic minority groups to ensure that the results can be applied to the population at risk.
The Arctic ship Veslekari
Authors: Kjær Kjell-G. , Sefland Magnus
Published: February 2005

The ship Veslekari was launched in 1918 from Christian Jensen's shipyard near Kristiania (present-day Oslo), where Roald Amundsen's ship Maud had been built. Although primarily a sealer, she was also used extensively for other expeditions to the Arctic. She participated in several relief expeditions, including one in 1936 to Jan Mayen to evacuate people during a series of earthquakes, and another in 1939 to northeast Greenland to evacuate Count Gaston Micard, who was seriously ill. In 1928 Veslekari participated in the search for Roald Amundsen and his plane in the waters off Bjørnøya. Tryggve Gran, a member of Robert Falcon Scott's last expedition, sailed with her at that time. She was chartered four times as expedition ship for the American Arctic explorer Miss Louise A. Boyd. In the summer of 1940 Veslekari sailed to northeast Greenland to relieve Norwegian hunters and the crew of the Norwegian weather station, but she was impounded by British and Norwegian forces and taken to Scotland on order of the Norwegian government in London. She was chartered by the Ministry of War Transport and was based in Scotland and Iceland. In 1943 she was renamed HMS Bransfield and was prepared for service in the Antarctic. After the war she resumed sealing under Norwegian ownership until in 1961, when she was wrecked in the ice in the sealing ground off Newfoundland.
The Effect of Ursodeoxycholic Acid Therapy on Liver Fibrosis Progression in Primary Biliary Cirrhosis
Authors: Corpechot Christophe , Carrat Fabrice , Bonnand Anne-Marie , Poupon Renée Eugénie , Poupon Raoul
Published: February 2005

Ursodeoxycholic acid (UDCA) is the only approved treatment for primary biliary cirrhosis (PBC). However, the benefit from UDCA therapy on the progression of PBC from its early stage towards extensive fibrosis and cirrhosis has not been clearly shown. The aim of this study was to assess the effect of UDCA therapy on liver fibrosis progression in PBC. A Markov model was used to analyze the progression rates between early and late histologic stages in 103 patients with PBC enrolled in a randomized, double–blind, placebo–controlled trial of UDCA. Early stage was defined by the presence of portal and periportal lesions without extensive fibrosis, whereas late stage was defined by the presence of numerous septa, bridging fibrosis, or cirrhosis. A total of 162 pairs of liver biopsy specimens were studied. The model accurately described the observed data. UDCA therapy was associated with a 5–fold lower progression rate from early stage disease to extensive fibrosis or cirrhosis (7% per year under UDCA vs. 34% per year under placebo, P <.002), but was not associated with a significant difference in regression rates (3% per year under both UDCA and placebo). At 4 years, the probability of UDCA–treated patients to remain in early stage disease is 76% (95% confidence interval: 58%–88%), as compared with 29% (15%–52%) in placebo–treated patients. In conclusion, UDCA therapy significantly delays the progression of liver fibrosis in PBC. Markov modeling should prove useful in assessing the efficacy of future medical treatments in clinical trials involving histologic endpoints.
Results of Surgical and Nonsurgical Treatment for Small–Sized Hepatocellular Carcinomas: A Retrospective and Nationwide Survey in Japan
Authors: Arii Shigeki , Yamaoka Yoshio , Futagawa Syunji , Inoue Kyoichi , Kobayashi Kenichi , Kojiro Masamichi , Makuuchi Masatoshi , Nakamura Yasuni , Okita Kiwamu , Yamada Ryusaku
Published: February 2005

Hepatic resection (HX), percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TCAE) have all been used in the treatment of patients with small–sized hepatocellular carcinomas (HCCs). However, the indications for these therapeutic modalities remain unclear. Therefore, the first step to minimize the debate on these indications is to review the standard results from each treatment based on an extensive survey. The participants in this study were patients with HCCs less than 5 cm in diameter who were enrolled in The Liver Cancer Study Group of Japan. The survival rates in the HX (n = 8,010), PEI (n = 4,037), and TCAE (n = 841) groups were calculated in relation to the number of tumors and the clinical stage. In the clinical stage I cases with a solitary tumor less than 2 cm in diameter and in all clinical stages with a solitary tumor greater than 2 cm and in the clinical stage II cases with 2 tumors greater than 2 cm, the HX group showed higher survival rates than the nonsurgical groups. The HX group had a higher male/female ratio and a younger mean age than the PEI or TCAE group. The ratio of HBs antigen–positive cases/hepatitis C virus antibody–positive cases in the PEI group was lower than that in the corresponding HX group. In contrast, the PIVKA–II values in the HX group tended to be higher than in the PEI group. In conclusion, these findings will provide useful information for selection of a therapeutic modality for small–sized HCCs.
Comment on “Excitations in photoactive molecules from quantum Monte Carlo” [J. Chem. Phys. 121, 5836 (2004)]
Authors: Doltsinis Nikos L. , Fink Karin
Published: February 2005

It is shown that the qualitative differences between high-level ab initio calculations and restricted open-shell Kohn-Sham (ROKS) results for the lowest singlet excited electronic state of formaldimine along a particular isomerization path found by Schautz, Buda, and Filippi [J. Chem. Phys.121, 5836 (2004)] play a minor role in molecular dynamics simulations of photoisomerization at room temperature. In fact, ROKS yields, within its well-known limitations, a good representation of the physically relevant isomerization pathway.
Coherence spectroscopy in dissipative media: A Liouville space pathway approach
Authors: Ramakrishna S. , Seideman Tamar
Published: February 2005

We address the possibility of using coherent control tools to extract useful information about the interaction of a system with a dissipative environment. To that end we extend previous work, which developed a coherence spectroscopy based on two-pathway excitation phase control, from the isolated molecule limit to dense media. Specifically, we explore the properties of the channel phase, an observable of energy-domain two-pathway excitation experiments that was shown in the isolated molecule limit to carry information about the phase properties of the material system. Our analysis is based on the combination of steady state and time-dependent analytical perturbative approaches within the density matrix formalism, complemented by nonperturbative numerical simulations. We find that the channel phase carries significantly richer information in the presence of decoherence mechanisms than in their absence. In particular, rescattering events in the structured continuum introduce new features in the channel phase spectrum, whose structure conveys information about both the molecular continuum and the system bath interaction.
Quasiclassical study of Eley–Rideal and hot atom reactions of H atoms with Cl adsorbed on a Au(111) surface
Authors: Quattrucci Joseph G. , Jackson Bret
Published: February 2005

Using quasiclassical methods and a potential energy surface based on total energy calculations, we have found that H atoms react with Cl atoms adsorbed onto a Au(111) surface to produce HCl via Eley–Rideal (ER), hot atom (HA), and Langmuir–Hinschelwood (LH) pathways. We observe two ER mechanisms. At small normal incidence energies reaction results from a more or less direct collision with Cl, leading to a large amount of product vibration (ν=8), and relatively cold rotation and translation. In the second mechanism, more dominant at near-normal incidence and/or large incident energies, the H atom passes near Cl, recoils from the metal, and is pulled into orbit about Cl. This leads to broader product state distributions, and a more even distribution of the 3.0eV of available energy among the product degrees of freedom, similar to products formed via the HA pathway. Overall, ER processes tend to contribute less than 10% to the reactivity, and most of the HCl is formed via HA processes. There is an increase in HCl formation with surface temperature for both the ER and HA mechanisms, but this increase is relatively weak. We observe typically about 12% H atom sticking, which would lead to HCl formation via a LH process in the experiments, above 140K. We observe a weak forward scattering due to the direct ER component, as in the experiments. However, unlike the experiments, we observe a dip in our product angular distributions about θf=0°, which we ascribe to our quasiclassical approximation. While we tend to see more energy in the hot products than in the experiments, our product translational, rotational, and vibrational distributions are in relatively reasonable agreement with those measured. One major disagreement with experiment is that there is apparently a significant sticking of the H atom at low temperatures, leading to a large LH component. In addition, the ER and HA components increase much more strongly with temperature than in the calculations. It is possible that electon-hole pair excitations in the metal strongly relax both the H atom and the excited HCl molecules formed.
Antioxidation properties of Ti0.83Al0.17N prepared using plasma-enhanced atomic layer deposition
Authors: Lee Yong Ju , Kang Sang-Won
Published: February 2005

The high-temperature antioxidation behavior of Ti0.83Al0.17N prepared using plasma-enhanced atomic layer deposition (PEALD) with TiCl4, AlCl3, N2∕H2∕Ar, and NH3∕H2∕Ar radicals were studied. One cycle for depositing Ti0.83Al0.17N consisted of eight TiN cycles followed by two AlN cycles. After forming a 30-nm-thick Ti0.83Al0.17N film, the film was oxidized in ambient O2 at 650 °C for 30 min. The Ti0.83Al0.17N thin film showed good oxidation-resistance properties as compared with the pure TiN film prepared by PEALD. This is attributed to the Al2O3 layer formed on the surface of the Ti0.83Al0.17N. The Al2O3 layer serves as a barrier to oxygen diffusion, and protects the remaining nitride layer from being oxidized further.
Ab initio study of metal gate electrode work function
Authors: Park Seongjun , Colombo Luigi , Nishi Yoshio , Cho Kyeongjae
Published: February 2005

The work function of metal multilayers and monolayers on bulk metals was studied using the first principle pseudopotential method within the local density approximation in order to find a way to modulate the work function of metal gate electrodes. Various multilayer stacks and bilayer stacks of two systems, Al–Pt and Al–Ni, were examined. It was found that two or three layers of the metal are enough to shift the work function to that of the surface metal. Also, it was found that even a submonolayer could affect the work function of the bulk metal significantly.
Photoinduced resistivity changes in Bi0.4Ca0.6MnO3 thin films
Authors: Smolyaninova V. N. , Rajeswari M. , Kennedy R. , Overby M. , Lofland S. E. , Chen L. Z. , Greene R. L.
Published: February 2005

We report charge-ordered Bi0.4Ca0.6MnO3 thin films with charge-ordering temperature near room temperature, and observation of large photoinduced resistivity changes in these films associated with melting of the charge ordering by visible light. Films grown under small compressive strain exhibit the largest photoinduced resistivity changes. The lifetime of the photoinduced low-resistance state is on the order of half a minute. These photoinduced resistivity changes in thin films of Bi0.4Ca0.6MnO3 make them very promising for photonic device application.
The Respective Role of Low and High Spatial Frequencies in Supporting Configural and Featural Processing of Faces
Authors: Goffaux Valérie , Hault Barbara , Michel Caroline , Vuong Quoc C , Rossion Bruno
Published: February 2005

One distinctive feature of processing faces, as compared to other categories, is thought to be the large dependence on configural cues such as the metric relations among features. To test the role of low spatial frequencies (LSFs) and high spatial frequencies (HSFs) in configural and featural processing, subjects were presented with triplets of faces that were filtered to preserve either LSFs (below 8 cycles per face width), HSFs (above 32 cycles per face width), or the full frequency spectrum. They were asked to match one of two probe faces to a target face. The distractor probe face differed from the target either configurally, featurally, or both featurally and configurally. When the difference was at the configural level, performance was better with LSF faces than with HSF faces. In contrast, with a featural difference, a strong performance advantage was found for HSF faces as compared to LSF faces. These results support the dominant role that LSFs play in the configural processing of faces, whereas featural processing is largely dependent on HSFs.
T cell receptor (TCR) clustering in the immunological synapse integrates TCR and costimulatory signaling in selected T cells
Authors: Purtic Bozidar , Pitcher Lisa A. , van Oers Nicolai S. C. , Wülfing Christoph
Published: February 2005

During T cell activation, T cell receptors (TCR) cluster at the center of the T cell/antigen-presenting cell interface forming a key component of the immunological synapse. The function of this TCR clustering is still unresolved. A comprehensive search for such a function yielded a very limited and specific result. A micrometer-scale receptor clustering integrated the TCR and CD28 signals required for IL-2 secretion in primary 5C.C7 T cells, a low-affinity/avidity TCR system. 5C.C7 TCR signaling itself was not affected. In addition, central TCR accumulation was not required for any T cell effector function tested in three other TCR transgenic models. Central TCR accumulation thus had a specific role in signaling integration in low-affinity T cells.
Selective blockade of inhibitory Fcγ receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells
Authors: Dhodapkar Kavita M. , Kaufman Jacob L. , Ehlers Marc , Banerjee Devi K. , Bonvini Ezio , Koenig Scott , Steinman Ralph M. , Ravetch Jeffrey V. , Dhodapkar Madhav V.
Published: February 2005

The final differentiation or maturation of dendritic cells (DCs) in response to environmental stimuli influences their ability to both initiate immunity and determine the quality of the response to antigens. Circulating immune complexes and cell-bound immunoglobulins present in normal human sera represent a potential stimulus for inadvertent DC activation in the steady state and during autoimmunity. Here, we show that selective blockade of the inhibitory Fcγ receptor (FcγR) FcγRIIb with recently developed monoclonal antibodies leads to maturation of human monocyte-derived DCs, which depends on the presence of IgG in normal human plasma. Plasma, in the presence of an FcγRIIb blockade, caused the DCs to up-regulate the expression of costimulatory molecules and to produce the inflammatory mediator IL-12p70. FcγRIIb blockade of DCs loaded with tumor cells led to increased tumor-specific T cell immunity without the need for exogenous stimuli other than human plasma. Therefore, the activation status of DCs in the presence of normal human serum depends on the balance between activating and inhibitory FcγRs and can be enhanced by new antibodies that react selectively with FcγRIIb. These data suggest an approach for modifying this balance to enhance immunity to immune complexes and antibody-coated tumor cells and to silence DC activation by immune complexes in autoimmune states.
Transient changes of transforming growth factor-β expression in the small intestine of the pig in association with weaning
Authors: Mei Jie , Xu Ruo-Jun
Published: February 2005

It is well known that early weaning causes marked changes in intestinal structure and function, and transforming growth factor-β (TGF-β) is believed to play an important regulatory role in post-weaning adaptation of the small intestine. The present study examined the distribution and expression intensity of TGF-β in the small intestinal mucosa of pre- and post-weaning pigs using a specific immunostaining technique and Western blot analysis. The level of TGF-β in the intestinal mucosa, as estimated by Western blot analysis, did not change significantly during weaning. However, when examined by the immunostaining technique, TGF-β1 (one of the TGF-β isoforms dominantly expressed in the tissue) at the intestinal villus epithelium, particularly at the apical membrane of the epithelium, decreased significantly 4 d after weaning, while the staining intensity increased significantly at the intestinal crypts compared with that in pre-weaning pigs. These changes were transient, with the immunostaining intensity for TGF-β1 at the intestinal villi and the crypts returning to the pre-weaning level by 8 d post-weaning. The transient decrease in TGF-β1 level at the intestinal villus epithelium was associated with obvious intestinal villus atrophy and marked reduction of mucosal digestive enzyme activities. Furthermore, the number of leucocytes staining positively for TGF-β1 increased significantly in the pig intestinal lamina propria 4 d after weaning. These findings strongly suggest that TGF-β plays an important role in the post-weaning adaptation process in the intestine of the pig.
Sequestration of pRb by Cyclin D3 Causes Intranuclear Reorganization of Lamin A/C during Muscle Cell Differentiation
Authors: Mariappan Indumathi , Parnaik Veena K.
Published: February 2005

The A-type lamins that localize in nuclear domains termed lamin speckles are reorganized and antigenically masked specifically during myoblast differentiation. This rearrangement was observed to be linked to the myogenic program as lamin speckles, stained with monoclonal antibody (mAb) LA-2H10, were reorganized in MyoD-transfected fibroblasts induced to transdifferentiate to muscle cells. In C2C12 myoblasts, speckles were reorganized early during differentiation in cyclin D3–expressing cells. Ectopic cyclin D3 induced lamin reorganization in C2C12 myoblasts but not in other cell types. Experiments with adenovirus E1A protein that can bind to and segregate the retinoblastoma protein (pRb) indicated that pRb was essential for the cyclin D3–mediated reorganization of lamin speckles. Cyclin D3–expressing myoblasts displayed site-specific reduction of pRb phosphorylation. Furthermore, disruption of lamin structures by overexpression of lamins inhibited expression of the muscle regulatory factor myogenin. Our results suggest that the reorganization of internal lamins in muscle cells is mediated by key regulators of the muscle differentiation program.
Nuclear Translocation of Integrin Cytoplasmic Domain-associated Protein 1 Stimulates Cellular Proliferation
Authors: Fournier Henri-Noël , Dupé-Manet Sandra , Bouvard Daniel , Luton Frédéric , Degani Simona , Block Marc R. , Retta Saverio Francesco , Albiges-Rizo Corinne
Published: February 2005

Integrin cytoplasmic domain-associated protein 1 (ICAP-1) has been shown to interact specifically with the β1 integrin cytoplasmic domain and to control cell spreading on fibronectin. Interestingly, ICAP-1 also is observed in the nucleus, by immunocytochemical staining, and after biochemical cell fractionation, suggesting that it has additional roles that have yet to be determined. We show that the nucleocytoplasmic shuttling capability of ICAP-1 is dependent on a functional nuclear localization signal. In addition, overexpression of β1 integrin strongly reduced this nuclear localization, suggesting that integrin activity could modulate ICAP-1 shuttling by sequestering it in the cytoplasm. Indeed, the nuclear localization of ICAP-1 is dependent on the stage of cell spreading on fibronectin, and we also show that ICAP-1 expression stimulates cellular proliferation in a fibronectin-dependent manner. This function is dependent on its nuclear localization. Moreover, ICAP-1 is able to activate the c-myc promoter in vitro. Together, these results demonstrate that ICAP-1 shuttles between the nucleus and cytoplasm in a β1 integrin-dependent manner. It could act as a messenger that relays information from sites of integrin-dependent cell adhesion to the nucleus for controlling gene expression and cell proliferation.
In vitro
and
in vivo
biological responses to a novel radiopacifying agent for bone cement
Authors: Wang J.S , Diaz J , Sabokbar A , Athanasou N , Kjellson F , Tanner K.E , McCarthy I.D , Lidgren L
Published: February 2005

Iodixanol (IDX) and iohexol (IHX) have been investigated as possible radiopacification agents for polymethylmethacrylate (PMMA) bone cement, to replace the currently used barium sulphate and zirconia. IDX and IHX are both water-soluble iodine-based contrast media and for the last 20 years have been used extensively in clinical diagnostic procedures such as contrast media enhanced computed tomography, angiography and urography. One of the major reasons to remove the current radiopacifying agents is their well-documented cytotoxicity and their potential to increase bone resorption.

Using
in vitro
bone resorption assays, the effect of PMMA particles plus IDX or IHX to induce osteoclast formation and lacunar resorption on dentine slices has been investigated. These responses have been compared with the
in vitro
response to PMMA particles containing the conventional radiopacifying agents, that is, barium sulphate and zirconia. In parallel, the
in vivo
reaction, in terms of new bone formation, to particles of these materials has been tested using a bone harvest chamber in rabbit tibiae.

In vitro
cell culture showed that PMMA containing IHX resulted in significantly less bone resorption than PMMA containing the conventional opacifiers.
In vivo
testing, however, showed no significant differences between the amounts of new bone formed around cement samples containing the two iodine-based opacifying agents in particulate form, although both led to fewer inflammatory cells than particles of PMMA containing zirconia. Our results suggest that a non-ionic radiopacifier could be considered as an alternative to the conventional radiopacifying agents used in biomaterials in orthopaedic surgery.
Antioxidants, radiation and mutation as revealed by sperm abnormality in barn swallows from Chernobyl
Authors: Møller A. P. , Surai P. , Mousseau T. A.
Published: February 2005

Reduced levels of antioxidants such as carotenoids and vitamins A and E can increase DNA damage caused by free radicals. Exposure to radiation has been proposed to reduce levels of antioxidants that are used for DNA repair and this reduction may be responsible for increased levels of mutation in radioactively contaminated areas. We test this hypothesis using field measures of antioxidants in blood, liver and eggs of the barn swallowHirundo rusticawhile relating these to levels of mutation as reflected by the frequency of abnormal sperm. Antioxidant levels in blood, liver and eggs were reduced in Chernobyl, Ukraine, compared with an uncontaminated control area, and levels of antioxidants correlated negatively with levels of background radiation. The frequency of abnormal sperm was almost an order of magnitude higher in Chernobyl than in the control area and was negatively related to antioxidant levels in blood and liver. This is consistent with the hypothesis of a direct link between radiation and individual levels of antioxidants, suggesting that levels of mutation differ among individuals owing to individual differences in the abundance of antioxidants.
Successful sons or superior daughters: sex–ratio variation in springbok
Authors: Krüger O. , Radford A. N. , Anderson C. , Liversidge R.
Published: February 2005

Mothers would often benefit from producing more offspring of one sex than the other. Although some species show an astonishing ability to skew their sex ratio adaptively, the trends found in many studies on vertebrates have proved inconsistent. Furthermore, evidence for a mechanism by which such a bias is achieved is equivocal at best. Here, we examine sex–ratio variation over 30 years, both at an individual and a population level, in the highly polygynous, size–dimorphic springbok (Antidorcas marsupialis). Many previous studies of similar species have shown that mothers in superior condition preferentially produce sons, whereas those in poorer condition produce more daughters. We found the opposite to be true in springbok, perhaps because daughters provide mothers in superior condition with a more rapid and secure fitness return. This theory was supported by the findings that earlier–conceived offspring tended to be female and that an increased proportion of daughters were produced with increasing rainfall (which was likely to reduce nutritional stress). We also show that selective reabsorption of embryos is unlikely to be the main mechanism by which deviations from an equal sex ratio are achieved. Hence, either differential implantation occurs or females are able to influence the sex of the sperm fertilizing an egg.
Saccharomyces cerevisiae imports the cytosolic pathway for Gln-tRNA synthesis into the mitochondrion
Authors: Rinehart Jesse , Krett Bethany , Rubio Mary Anne T. , Alfonzo Juan D. , Söll Dieter
Published: February 2005

Aminoacyl-tRNA (aa-tRNA) formation, an essential process in protein biosynthesis, is generally achieved by direct attachment of an amino acid to tRNA by the aa-tRNA synthetases. An exception is Gln-tRNA synthesis, which in eukaryotes is catalyzed by glutaminyl-tRNA synthetase (GlnRS), while most bacteria, archaea, and chloroplasts employ the transamidation pathway, in which a tRNA-dependent glutamate modification generates Gln-tRNA. Mitochondrial protein synthesis is carried out normally by mitochondrial enzymes and organelle-encoded tRNAs that are different from their cytoplasmic counterparts. Early work suggested that mitochondria use the transamidation pathway for Gln-tRNA formation. We found no biochemical support for this in Saccharomyces cerevisiae mitochondria, but demonstrated the presence of the cytoplasmic GlnRS in the organelle and its involvement in mitochondrial Gln-tRNA synthesis. In addition, we showed in vivo localization of cytoplasmic tRNAGln in mitochondria and demonstrated its role in mitochondrial translation. We furthermore reconstituted in vitro cytoplasmic tRNAGln import into mitochondria by a novel mechanism. This tRNA import mechanism expands our knowledge of RNA trafficking in the eukaryotic cell. These findings change our view of the evolution of organellar protein synthesis.
Synthesis, crystal structure and molecular conformation of Nα‐Boc‐l‐leucyl‐(Z)‐β‐(3‐pyridyl)‐α,β‐ dehydroalanyl‐l‐leucine methyl ester*
Authors: Yamada K. , Oku H. , Shinoda S.‐S. , Katakai R.
Published: February 2005

Abstract:  A protected tridehydropeptide containing (Z)‐β‐(3‐pyridyl)‐α,β‐dehydroalanine (ΔZ3Pal) residue, Boc‐Leu‐ΔZ3Pal‐Leu‐OMe (1), was synthesized via Erlenmeyer azlactone method. X‐ray crystallographic analysis revealed that the peptide 1 adopts an extended conformation, which is similar to that of a ΔZPhe analog, Boc‐Leu‐ΔZPhe‐Leu‐OMe (2).
Patterns of mixed siliciclastic–carbonate sedimentation adjacent to a large dry‐tropics river on the central Great Barrier Reef shelf, Australia
Authors: ORPIN A. R. , BRUNSKILL G. J. , ZAGORSKIS I. , WOOLFE K. J.
Published: February 2005

The Great Barrier Reef represents the largest modern example of a mixed siliciclastic–carbonate system. The Burdekin River is the largest source of terrigenous sediment to the lagoon and is therefore an ideal location to investigate regional patterns of mixed sedimentation. Sediments become coarser grained and more poorly sorted away from the protection of eastern headlands, with mud accumulation focused in localised ‘hot spots’ in the eastern portion of embayments protected from southeast trade winds. The middle shelf has a variable facies distribution but is dominated by coarse carbonate sand. North of Bowling Green Bay, modern coarse carbonate sand and relict quartzose sand occur. Shore‐normal compositional changes show Ca‐enrichment and Al‐dilution seawards towards the reef, and shore‐parallel trends show Al‐dilution westwards (across bays) along a Ca‐depleted mixing line. Intermediate siliciclastic–carbonate sediment compositions occur on the middle shelf due to the abundance of relict terrigenous sand, a pattern that is less developed on the narrow northern Great Barrier Reef shelf. Rates of sediment deposition from seismic evidence and radiochemical tracers suggest that despite the magnitude of riverine input, 80–90% of the Burdekin‐derived sediment is effectively captured in Bowling Green Bay. Over millennial time‐scales, stratigraphic controls suggest that sediment is being preferentially accreted back to the coast.