bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of echocardiographic and Doppler indexes of left ventricular relaxation in adult hypertensive and normotensive rats
Authors: Slama Michel , Ahn Jwari , Peltier Marcel , Maizel Julien , Chemla Denis , Varagic Jasmina , Susic Dinko , Tribouilloy Christophe , Frohlich Edward D.
Published: April 2005

This study was performed to validate echocardiographic and Doppler techniques for the assessment of left ventricular (LV) diastolic function in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. In 11 Wistar rats and 20 SHR, we compared 51 sets of invasive and Doppler LV diastolic indexes. Noninvasive indexes of LV relaxation were related to the minimal rate of pressure decline (−dP/d tmin), particularly isovolumic relaxation time (IVRT), the Tei index, the early velocity of the mitral annulus ( Em) using Doppler tissue imaging, and early mitral flow propagation velocity using M-mode color ( r = 0.28–0.56 and P < 0.05–0.0001). When the role of systolic load was considered, the correlation between Doppler indexes of LV diastolic function and relaxation rate [(−dP/d tmin)/LV systolic pressure] improved ( r = 0.48–0.86 and P = 0.004–0.0001, respectively). Similarly, Doppler indexes of LV diastolic function and the time constant of isovolumic LV relaxation (τ) correlated well ( r = 0.50–0.84 and P = 0.0002–0.0001, respectively). In addition, eight SHR and eight Wistar rats were compared; their LV end-diastolic diameters were similar, whereas the SHR LV mass was greater. Furthermore, IVRT and Tei index were significantly higher and Em was lower in SHR. Moreover, τ was higher in SHR, demonstrating impaired LV relaxation. In conclusion, LV relaxation can be assessed reliably using echocardiographic and Doppler techniques, and, using these indexes, impaired relaxation was demonstrated in SHR.
Airway hyperresponsiveness induced by cationic proteins in vivo: site of action
Authors: Homma Toshiaki , Bates Jason H. T. , Irvin Charles G.
Published: April 2005

Major basic protein and other native cationic proteins increase airway hyperresponsiveness when administered to the luminal surface of the airways in vitro. To determine whether the same applies in vivo, we assessed airway responsiveness in rats challenged with both aerosolized and intravenously infused methacholine. We partitioned total lung resistance into its airway and tissue components using the alveolar capsule technique. Neither poly-l-lysine nor major basic protein altered baseline mechanics or its dependence on positive end-expiratory pressures ranging from 1 to 13 cmH2O. When methacholine was administered to the lungs as an aerosol, both cationic proteins increased responsiveness as measured by airway resistance, tissue resistance, and tissue elastance. However, responsiveness of all three parameters was unchanged when the methacholine was infused. Together, these findings suggest that cationic proteins alter airway responsiveness in vivo by an effect that is apparently limited to the bronchial epithelium.
Correcting US Imbalances
Authors: Al-Eyd Ali , Barrell Ray , Pomerantz Olga
Published: April 2005

In the January Review discussion of the US current account imbalances, we explored the links between the US current account deficit and exchange rates, and focused on the economic adjustments required to correct the US ‘triple’ deficits. Using NiGEM, we illustrated that a sustained adjustment in the US current account deficit cannot be achieved through a temporary nominal depreciation alone – whether risk or policy driven – but also requires a redressing of the government and household imbalances and a consequent increase in national savings.
Prospects for the UK Economy
Authors: Barrell Ray , Kirby Simon , Metz Robert
Published: April 2005

Output growth in 2004 was 3.1 per cent, and the preliminary estimate for growth of GDP in the first quarter of 2005 was 0.6 per cent, slightly higher than on our early estimate. Relatively robust growth over the recent past suggests to us that the output gap has now closed, as we can see from chart 2. We anticipate that growth will rise further in the second quarter.
Modelling Financial Instability
Authors: Allen Franklin
Published: April 2005

Financial instability can have large adverse effects on an economy. One major cause of instability is asset price bubbles. This paper starts by considering how such bubbles can arise due to the expansion of money and credit. The ways in which subsequent financial instability occurs are then discussed. Banking crises can arise due to panics or as a result of the business cycle. Contagion and financial fragility can cause small disturbances to have large effects. Finally, policy issues are touched upon.
Monetary and Financial Stability: So Close and Yet So Far?
Authors: Borio Claudio
Published: April 2005

This paper argues that changes in the financial and monetary regimes since the early 1980s may have made it more likely that financial factors in general, and the booms and busts in credit and asset prices in particular, act as drivers of economic fluctuations. As a result, the current environment may be more vulnerable to the occasional build-up of financial imbalances, ie. overextensions in (private sector) balance sheets that herald economic weakness and disinflation down the road, as they unwind, raising also the risk of financial strains and possibly even broader financial instability. Achieving simultaneously monetary and financial stability may call for some significant refinements to current policy frameworks, based on closer cooperation between prudential and monetary authorities. These refinements include a strengthening of the macroprudential orientation of regulatory and supervisory frameworks ensuring that monetary frameworks allow enough room for manoeuvre to lean pre-emptively against the build-up of the imbalances.
Courting Customers: Assessing Consumer Racial Profiling and other Marketplace Discrimination
Authors: Harris Anne-Marie G. , Henderson Geraldine R. , Williams Jerome D.
Published: April 2005

Through an examination of 81 federal court decisions made between 1990 and 2002 involving customers’ allegations of race and/or ethnic discrimination, the authors uncover three emergent dimensions of discrimination: (1) the type of alleged discrimination (subtle or overt), (2) the level of service (degradation or denial), and (3) the existence of criminal suspicion in the alleged discriminatory conduct (present or absent). Using a framework that enables the categorization and aggregation of cases with common themes, the authors demonstrate that real and perceived consumer discrimination remains a problem in the U.S. marketplace, and they conclude that further research is necessary for marketers to address the issue effectively.
When Policies and Marketing Systems Explode: An Assessment of Food Marketing in the War-Ravaged Balkans and Implications for Recovery, Sustainable Peace, and Prosperity
Authors: Shultz Clifford J. , Burkink Timothy J. , Grbac Bruno , Renko Nataša
Published: April 2005

The authors examine forces, policy failures, and the ensuing war and devastation of the marketing system of the former Yugoslavia. They provide an overview of the region and discuss food marketing's contributions to recovery. The authors then describe food-marketing institutions that have emerged from destruction and suggest some successful cases and best practices that can be leveraged to sustain peace and prosperity in the war-ravaged Balkans, as well as the broader global community.
What Goes around Comes Around: Understanding Trust–Value Dilemmas of Market Relationships
Authors: Singh Jagdip , Jayanti Rama K. , Kilgore Jean E. , Agarwal Kokil , Gandarvakottai Ramadesikan R.
Published: April 2005

The emerging cultural, societal, and environmental milieu of the twenty-first-century marketplace presents coping challenges for even strong and well-established companies. Few, if any, attempts have been made to examine systematically a firm's symbiotic link with society by focusing on the complexity and interconnectedness of its disparate market relationships. To facilitate a grounded approach to such modeling, the authors use a trust–value framework to analyze market relationships, the interconnections among them, and the trust–value dilemmas that arise in the context of two case studies: (1) the 3M company's decision to pull Scotchgard from the market and (2) the Los Angeles Unified School District versus the Coca-Cola Company regarding the sale of soft drinks on school premises. The authors chronologically assembled and systematically analyzed data from public, secondary, and industry sources, using relationship marketing theory principles to develop the individual case studies. The analyses indicate that the trust–value framework is a useful foundation for theorizing and empirically examining the complexity of a firm's market relationships by revealing interesting trust–value dilemmas and dynamics that connect the disparate relationships. The authors discuss implications for research and practice.
LifeGoals: The Development of a Decision-Making Curriculum for Education
Authors: Reynolds Thomas J.
Published: April 2005

After more than two decades of academic and professional work focusing on the development of psychological theory, research methods, and decision modeling techniques in marketing, the author applies his knowledge to solve what he believes is the single greatest challenge facing the United States—the development of a curriculum and corresponding pedagogy to teach decision-making skills to at-risk children. The initial targets were elementary schoolchildren, but during the developmental process, the author expanded the curriculum to include at-risk young adults and, more recently, MBA students. This chapter began after he retired as professor emeritus (1995) from a school of management and embarked on this new journey into the field of education. 1
Developing a Market Orientation in a Transitional Economy: The Role of Government Regulation and Ownership Structure
Authors: Qu Riliang , Ennew Christine T.
Published: April 2005

In this article, the authors report the findings of an exploratory study that examines the challenges of developing a market orientation in China, the world's largest transitional economy. The findings suggest that though managerial actions are relevant, in transitional economies, environmental factors—most notably, government policies—are a major influence on firms’ aspirations to be market oriented.
Nicking activity on pBR322 DNA of ribosome inactivating proteins from Phytolacca dioica L. leaves
Authors: Aceto Serena , Di Maro Antimo , Conforto Barbara , Siniscalco Gesualdo G. , Parente Augusto , Delli Bovi Pasquale , Gaudio Luciano
Published: April 2005

Ribosome-inactivating proteins isolated fromPhytolacca dioicaL. leaves are rRNA-N-glycosidases, as well as adenine polynucleotide glycosylases. Here we report that some of them cleave supercoiled pBR322 dsDNA, generating relaxed and linear molecules. PD-L1, the glycosylated major form isolated from the winter leaves of adultP.dioicaplants, produces both free 3′-OH and 5′-P termini randomly distributed along the DNA molecule, as suggested by labelling experiments with [α-32P]dCTP and [γ-32P]dATP. Moreover, when the reaction is carried out under low-salt conditions, cleavage is observed mainly at a specific site, located downstream of the ampicillin resistance gene (close to position 3200), ending with the deletion of a fragment of approximately 70 nucleotides. This cleavage pattern is similar to that obtained under the same conditions with mung bean nuclease, a single-strand endonuclease. Furthermore, pBR322 DNA treated with PD-L1 shows reduced transforming activity withE.coliHB101 competent cells in comparison to untreated control plasmid DNA.
Homology modeling and SAR analysis of Schistosoma japonicum cathepsin D (SjCD) with statin inhibitors identify a unique active site steric barrier with potential for the design of specific inhibitors
Authors: Caffrey Conor R. , Placha Lenka , Barinka Cyril , Hradilek Martin , Dostál Jiří , Sajid Mohammed , McKerrow James H. , Majer Pavel , Konvalinka Jan , Vondrášek Jiří
Published: April 2005

Proteases that digest the blood-meal of the parasitic fluke Schistosoma are potential targets for therapy of schistosomiasis, a disease of chronic morbidity in humans. We generated a three-dimensional model of the cathepsin D target protease of Schistosoma japonicum (SjCD) utilizing the crystal structure of human cathepsin D (huCD) in complex with pepstatin as template. A homology model was also generated for the related secreted aspartic protease 2 (SAP2) of the pathogenic yeast, Candida albicans. An initial panel of seven statin inhibitors, originally designed for huCD [Majer et al., Protein Sci. 6 (1997), pp. 1458–1466], was tested against the two pathogen proteases. One inhibitor showed poor reactivity with SjCD. Examination of the SjCD active-site cleft revealed that the poor inhibition was due to a unique steric barrier situated between the S2 and S4 subsites. An in silico screen of 20 potential statin scaffolds with the SjCD model and incorporating the steric barrier constraint was performed. Four inhibitors (SJ1–SJ4) were eventually synthesized and tested with SjCD, bovine CD and SAP2. Of these, SJ2 and SJ3 proved moderately more specific for SjCD over bovine CD, with IC50 values of 15 and 60 nM, respectively. The unique steric barrier identified here provides a structural focus for further development of more specific SjCD inhibitors.
First Homopolymerizable Monomer Containing [C60]Fullerene as a Monoadduct Substituent
Authors: Ungurenasu Cezar , Pinteala Mariana
Published: April 2005

Summary: The hydrosilylation of C60 with 2,4,6,8‐tetramethylcyclotetrasiloxane in the presence of platinum/carbon catalyst produced the cationically polymerizable (C60HsiMeO)4 along with [(C60HsiMeO)3SiMeO]2C60H2 and a polymer consisting of C60 and (SiMeO)4 units. The synthesis and characterization of this first polymerizable tetracyclosiloxane ring system containing C60 as a monoadduct substituent are also reported.

Synthesis and polymerization of 2,4,6,8‐tetramethyl‐2,4,6,8‐tetrafulleryl‐cyclotetrasiloxane.

image

Synthesis and polymerization of 2,4,6,8‐tetramethyl‐2,4,6,8‐tetrafulleryl‐cyclotetrasiloxane.
Analysis of telomeric single‐strand overhang length in human endometrial cancers
Authors: Hashimoto Manabu , Kyo Satoru , Masutomi Kenkichi , Maida Yoshiko , Sakaguchi Junko , Mizumoto Yasunari , Nakamura Mitsuhiro , Hahn William C. , Inoue Masaki
Published: April 2005

The 3′ single‐strand telomeric overhang (3′‐OH) is a key component of telomere structure. Although telomere length has been well analyzed in a variety of human cancers, no information is available on the 3′‐OH length in cancers. In the present study, we examined the 3′‐OH length in normal and malignant endometria using telomere‐oligonucleotide ligation assay. Although 3′‐OH lengths varied among patients, 3′‐OH length observed in endometrial cancers was significantly shorter than that found in samples derived from normal endometria (P
< 0.001: Student's t‐test), suggesting that erosion of 3′‐OH length induces impaired telomeric integrity and genomic instability, leading to carcinogenesis. Interestingly, we found that the most aggressive subtypes of endometrial cancers harbored significantly longer 3′‐OH length than those with non‐aggressive subtypes (P
< 0.001: Sheffe's test), suggesting that cancer cells with long 3′‐OH length have growth advantage due to their stabilized telomere ends. In contrast, we failed to observe an association between overall telomere length and any clinicopathological characteristics of endometrial cancers. These findings suggest that erosion of 3′‐OH length, rather than overall telomere length, play roles in endometrial carcinogenesis. Furthermore, long 3′‐OH may serve as a molecular marker for aggressive phenotype of tumors.
Blocking the cleavage at midportion between γ‐ and ε‐sites remarkably suppresses the generation of amyloid β‐protein
Authors: Sato Toru , Tanimura Yu , Hirotani Naoko , Saido Takaomi C. , Morishima-Kawashima Maho , Ihara Yasuo
Published: April 2005

To examine how γ‐ and ε‐cleavages of β‐amyloid precursor protein (APP) are related, each cleavage site was replaced with a stretch of Trp that cannot be cleaved by γ‐secretase. Replacement of the γ‐ or ε‐site significantly suppressed secretion of amyloid β‐protein (Aβ), and produced longer Aβ or longer APP intracellular domain, respectively. This cleavage at the midportion between γ‐ and ε‐sites was also γ‐secretase‐dependent. Blocking this cleavage with a Trp stretch remarkably suppressed Aβ generation, indicating that the midportion cleavage is required for the generation of Aβ.
Exploring blocker binding to a homology model of the open hERG K+ channel using docking and molecular dynamics methods
Authors: Österberg Fredrik , Åqvist Johan
Published: April 2005

Binding of blockers to the human voltage‐gated hERG potassium channel is studied using a combination of homology modelling, automated docking calculations and molecular dynamics simulations, where binding affinities are evaluated using the linear interaction energy method. A homology model was constructed based on the available crystal structure of the bacterial KvAP channel and the affinities of a series of sertindole analogues predicted using this model. The calculations reproduce the relative binding affinities of these compounds very well and indicate that both polar interactions near the intracellular opening of the selectivity filter as well as hydrophobic complementarity in the region around F656 are important for blocker binding. These results are consistent with recent alanine scanning mutation experiments on the blocking of the hERG channel by other compounds.
Constitutive dimerization of human serotonin 5‐HT4 receptors in living cells
Authors: Berthouze Magali , Ayoub Mohammed , Russo Olivier , Rivail Lucie , Sicsic Sames , Fischmeister Rodolphe , Berque-Bestel Isabelle , Jockers Ralf , Lezoualc‧h Frank
Published: April 2005

Serotonin 5‐HT4 receptor isoforms are G protein‐coupled receptors (GPCRs) with distinct pharmacological properties and may represent a valuable target for the treatment of many human disorders. Here, we have explored the process of dimerization of human 5‐HT4 receptor (h5‐HT4R) by means of co‐immunoprecipitation and bioluminescence resonance energy transfer (BRET). Constitutive h5‐HT4(d)R dimer was observed in living cells and membrane preparation of CHO and HEK293 cells. 5‐HT4R ligands did not influence the constitutive energy transfer of the h5‐HT4(d)R splice variant in intact cells and isolated plasma membranes. In addition, we found that h5‐HT4(d)R and h5‐HT4(g)R which structurally differ in the length of their C‐terminal tails were able to form constitutive heterodimers independently of their activation state. Finally, we found that coexpression of h5‐HT4R and β2‐adrenergic receptor (β2AR) led to their heterodimerization. Given the large number of h5‐HT4R isoforms which are coexpressed in a same tissue, our results points out the complexity by which this 5‐HTR sub‐type mediates its biological effects.
Aβ(31–35) and Aβ(25–35) fragments of amyloid beta‐protein induce cellular death through apoptotic signals: Role of the redox state of methionine‐35
Authors: Clementi M. Elisabetta , Marini Stefano , Coletta Massimo , Orsini Federica , Giardina Bruno , Misiti Francesco
Published: April 2005

Taken together our result indicate that Aβ(31–35) and Aβ(25–35) peptides in non‐aggregated form, i.e., predominantly monomeric, are strongly neurotoxic, having the ability to enter within the cells, determining mitochondrial damage with an evident trigger of apoptotic signals. Such a mechanism of toxicity seems to be dependent by the redox state of methionine‐35.
Functional analysis of transcriptional repressor Otx3/Dmbx1
Authors: Kimura Keita , Miki Takashi , Shibasaki Tadao , Zhang Yan , Ogawa Makoto , Saisho Hiromitsu , Okuno Masaaki , Iwanaga Toshihiko , Seino Susumu
Published: April 2005

Otx3/Dmbx1 is a member of paired class homeodomain transcription factors. In this study, we found that Otx3/Dmbx1 represses the Otx2‐mediated transactivation by forming heterodimer with Otx2 on the P3C (TAATCCGATTA) sequence in vitro. The 156 amino acid region (residues 1–156) of Otx3/Dmbx1 is required for its repressor activity, and interacts directly with Otx2. Co‐localization of Otx3/Dmbx1 and Otx2 in brain sections was confirmed by in situ hybridization. These data suggest that Otx3/Dmbx1 represses Otx2‐mediated transcription in the developing brain. We also identified the consensus binding sequence [TAATCCGATTA and TAATCC(N2‐4)TAATCC] of Otx3/Dmbx1.
Recombinant human αA‐crystallin can protect the enzymatic activity of CpUDG against thermal inactivation
Authors: Zhang Yi , Liu Xipeng , Liu Jianhua
Published: April 2005

α‐Crystallin is one of the major protein components in mammalian lens fiber cells. It is composed of αA and αB subunits that have structural homology to the family of mammalian small heat shock proteins. Horwitz firstly characterized native α‐crystallin as a molecular chaperone in vitro based on its ability to prevent heat‐induced aggregation of lens proteins and enzymes. Andley et al. cloned and expressed human αA‐crystallin in Escherichia coli and confirmed its chaperone activity by suppression of thermal aggregation and singlet oxygen‐induced opacification. Although αA‐crystallin acts as a chaperone protein, there is no report showing on its ability to protect enzymes against thermal inactivation. Here, we present data showing that αA‐crystallin can prevent thermal inactivation of CpUDG that catalyzes uracil removal from DNAs.
Induction of ornithine decarboxylase in T/C‐28a2 chondrocytes by lysophosphatidic acid: Signaling pathway and inhibition of cell proliferation
Authors: Facchini Annalisa , Borzì Rosa Maria , Flamigni Flavio
Published: April 2005

Among several extracellular messengers tested, lysophosphatidic acid (LPA) was able to cause the most marked induction of ornithine decarboxylase (ODC) in serum‐starved human T/C‐28a2 chondrocytes. LPA also induced the activation/phosphorylation of Src, Akt and p44/42 MAPK, and the translocation of PKC‐δ from cytosol to membrane coupled to its tyrosine phosphorylation. Experiments with selective signaling inhibitors indicate that LPA leads to Src activation through Gi protein‐coupled receptors. In turn Src can activate PI3K and PKC‐δ, and all these signaling proteins are required for ODC induction. In conclusion these results show that chondrocytes may be a novel target for LPA action. However, although LPA is considered a mitogen for several cell types and ODC induction is generally correlated to cell growth, LPA was not able to stimulate chondrocyte growth, but rather exerted an anti‐proliferative effect.
Thermodynamics of phosphorylcholine and lysophosphatidylcholine binding to the major protein of bovine seminal plasma, PDC‐109
Authors: Anbazhagan V. , Swamy Musti J.
Published: April 2005

PDC‐109 binds to sperm plasma membranes by specific interaction with choline phospholipids and induces cholesterol efflux, a necessary event before capacitation – and subsequent fertilization – can occur. The binding of phosphorylcholine (PrC) and lysophosphatidylcholine (Lyso‐PC) with PDC‐109 was investigated by monitoring the ligand‐induced changes in the absorption spectrum of PDC‐109. At 20 °C, the association constants (K
a), for PrC and Lyso‐PC were obtained as 81.4 M−1 and 2.02 × 104
M−1, respectively, indicating that the binding of Lyso‐PC to PDC‐109 is 250‐fold stronger than that of PrC. From the temperature dependence of the K
a values, enthalpy of binding (ΔH
0) and entropy of binding (ΔS
0), were obtained as −79.7 and −237.1 J mol−1
K−1 for PrC and −73.0 kJ mol−1 and −167.3 J mol−1
K−1 for Lyso‐PC, respectively. These results demonstrate that although the binding of these two ligands is driven by enthalpic forces, smaller negative entropy of binding associated with Lyso‐PC results in its significantly stronger binding.
Assessment of Sensibility after Nerve Injury and Repair: A Systematic Review of Evidence for Validity, Reliability and Responsiveness of Tests
Authors: JEROSCH-HEROLD C.
Published: April 2005

Recovery of sensibility after peripheral nerve injury and repair needs to be assessed using psychometrically robust measures. In this study the literature was reviewed to identify what tests are available to quantify sensibility and to assess their validity, reliability and responsiveness. The databases Medline, CINAHL, Embase and AMED were searched for studies reporting the psychometric properties of sensibility tests. While there is a plethora of tests and studies reporting the outcomes after peripheral nerve suture only a few of the tests have evidence of validity, reliability and responsiveness. Currently the touch threshold test using monofilaments such as the Weinstein Enhanced Sensory Test (WEST) or Semmes–Weinstein Monofilament Test (SWMT) and the shape–texture identification (STI™) test for tactile gnosis are the only tests which meet criteria for a standardized test and have had their psychometric properties evaluated and quantified.
Photodynamic therapy for the treatment of vertebral metastases in a rat model of human breast carcinoma
Authors: Burch S. , Bisland S. K. , Bogaards A. , Yee A. J. M. , Whyne C. M. , Finkelstein J. A. , Wilson B. C.
Published: April 2005

The feasibility and efficacy of photodynamic therapy (PDT) for the treatment of vertebral metastases using a minimally invasive surgical technique adapted from vertebroplasty was evaluated in a rodent model. Initial validation included photosensitizer (benzoporphyrin‐derivative monoacid‐ring A) drug uptake studies and in vitro confirmation of PDT efficacy. Intracardiac injection of human MT‐1 breast cancer cells was performed in athymic rats. In 63 rats that developed vertebral metastases 21 days postinoculation, single treatment of PDT was performed using a parapedicular approach placing an optical fiber adjacent to targeted vertebrae. Two milligrams per kilogram of photosensitizer drug was administered intravenously followed by 150 mW of 690 nm light illumination at varying drug–light intervals and light energies. Histologic and immunohistochemical analysis was performed assessing treatment effect. Local tumor viability and growth was quantified by bioluminescence imaging pre and 48 h post‐treatment. PDT demonstrated an ablative effect on vertebral metastases (light energies 25–150 J). The effect varied in proportion to light energy with the greatest anti‐tumor effect observed at 150 J using a 3 h drug–light interval. 9/22 rodents in the 3 h drug–light interval developed hindlimb paralysis following treatment, consistent with drug uptake studies demonstrating an increase in spinal cord uptake 3 h following drug administration. The observations of paralysis following treatment highlight the importance of closely defining the therapeutic window of treatment in safety and efficacy. © 2005 Published by Elsevier Ltd. on behalf of Orthopaedic Research Society.
Wintertime spatial characteristics of boundary layer aerosols over peninsular India
Authors: Moorthy K. Krishna , Sunilkumar S. V. , Pillai Preetha S. , Parameswaran K. , Nair Prabha R. , Ahmed Y. Nazeer , Ramgopal K. , Narasimhulu K. , Reddy R. Ramakrishna , Vinoj V. , Satheesh S. K. , Niranjan K. , Rao B. Malleswara , Brahmanandam P. S. , Saha Auromeet , Badarinath K. V. S. , Kiranchand T. R. , Latha K. Madhavi
Published: April 2005

During an intense field campaign for generating a spatial composite of aerosol characteristics over peninsular India, collocated measurements of the mass concentration and size distribution of near‐surface aerosols were made onboard instrumented vehicles along the road network during the dry, winter season (February–March) of 2004. The study regions covered coastal, industrial, urban, village, remote, semiarid, and vegetated forestlands. The results showed (1) comparatively high aerosol (mass) concentrations (exceeding 50 μg m−3), in general, along the coastal regions (east and west) and adjacent to urban locations, and (2) reduced mass concentration (<30 μg m−3) over the semiarid interior continental regions. Fine, accumulation‐mode particles (<1 μm) contribute more than 50% to the total aerosol mass concentration in the coastal regions, which is more conspicuous along the east coast than the west coast, while the interior regions showed abundance (>50% of the total) of coarse‐mode aerosols (>1 μm). The spatial composite of accumulation‐mode share to the total aerosol mass concentration agreed very well with the monthly mean spatial composite of aerosol fine‐mode fraction for February 2004, deduced from Moderate‐Resolution Imaging Spectroradiometer data for the study region, while a point by point comparison yielded a linear association with a slope of 1.09 and correlation coefficient of 0.79 for 76 independent data pairs. Pockets of enhanced aerosol concentration were observed around the industrialized and urban centers along the coast as well as inland. Aerosol size distributions were parameterized using a power law. Spatial variation of the retrieved aerosol size index shows relatively high values (>4) along the coast compared to interior continental regions except at a few locations. Urban locations showed steeper size spectra than the remote locations.
Surface contribution to the anisotropy energy of spherical magnetite particles
Authors: Gilmore Keith , Idzerda Yves U. , Klem Michael T. , Allen Mark , Douglas Trevor , Young Mark
Published: April 2005

The surface contribution to the magneto-crystalline anisotropy energy of spherical magnetite nanoparticles has been investigated. Magnetite particles of three sizes (3.5, 7, and 18nm diameter) were grown inside protein cages. Alternating current magnetic susceptibility measurements revealed the particles to be noninteracting, and allowed a determination of the average anisotropy energy for each sample. Surface atoms were found to increase the volume anisotropy energy density of the particles, and this effect increased sublinearly with particle curvature.
Thermally assisted flux flow and individual vortex pinning in Bi2Sr2Ca2Cu3O10 single crystals grown by the traveling solvent floating zone technique
Authors: Wang X. L. , Li A. H. , Yu S. , Ooi S. , Hirata K. , Lin C. T. , Collings E. W. , Sumption M. D. , Bhatia M. , Ding S. Y. , Dou S. X.
Published: April 2005

Magnetoresisitivity and critical current density Jc as a function of temperature and field are studied for Bi2Sr2Ca2Cu3O10 single crystals grown using the traveling solvent floating zone technique. Below a characteristic field B∗, Jc as a function of field exhibits a field-independent plateau associated with thermally activated pinning of individual vortices. Analysis of resistive transition broadening revealed that thermally activated flux flow is found to be responsible for the resistivity contribution in the vicinity of Tc. The activation energy U0 is 800K in low field, scales as B−1∕6 for B<2T and drops to 200K with B−1∕2 for B>2T.
Magnetic field dependence of Josephson current by applying the external magnetic field perpendicular to the Josephson junction
Authors: Watanabe Norimichi , Nakayama Akiyoshi , Abe Susumu , Aizawa Kunimori
Published: April 2005

The hysteresis of the Josephson current to the external magnetic field Hz perpendicular to the Josephson junction is reported. We have measured the magnetic field Hz dependence of the Josephson current of the Nb∕Al-AlOx∕Nb junction. The Josephson current decreases with oscillating as the magnetic field Hz was increasing. When the magnetic field Hz was applied more than 2800[A∕m], the Josephson current became 0. Even if the magnetic field Hz was decreased from 2800[A∕m] to 0, no Josephson current was observed. The Josephson current exhibited hysteresis to the external magnetic field Hz.
Quantum vibrational state-dependent potentials for classical many-body simulations
Authors: Riga Jeanne M. , Fredj Erick , Martens Craig C.
Published: April 2005

In this paper, we present a method for constructing simple state-dependent many-body potentials for quantum vibrations in a classical bath. The approach is based on an adiabatic separation between high-frequency quantum vibrational modes of the solute and the lower frequency classical motion of the solvent, and on a first-order perturbation theory description of the dependence of the quantum energies on bath configuration. In the simplest realization of the method, the delocalized quantum probability density of the vibrational mode is approximated by a sum of two δ functions, with positions and weights chosen to represent the lowest three moments of the exact distribution. Thus, in the many-body description of the system, each atom describing the quantum vibration is represented by a pair of particles. These quantum particles are held in rigid relative position and interact with the bath via potentials the magnitudes of which are modified by the δ-function weights. The resulting approach allows the classical molecular dynamics of molecules in arbitrary quantum vibrational states to be simulated with a little more effort than a purely classical description. The applicability of the method is illustrated in many-body simulations of the dephasing of vibrational superposition states of I2 in a cryogenic krypton matrix, yielding results in good agreement with experiment.
Effective potential analytic continuation approach for real time quantum correlation functions involving nonlinear operators
Authors: Horikoshi Atsushi , Kinugawa Kenichi
Published: April 2005

We apply the effective potential analytic continuation (EPAC) method to the calculation of real time quantum correlation functions involving operators nonlinear in the position operator q̂. For a harmonic system the EPAC method provides the exact correlation function at all temperature ranges, while the other quantum dynamics methods, the centroid molecular dynamics and the ring polymer molecular dynamics, become worse at lower temperature. For an asymmetric anharmonic system, the EPAC correlation function is in very good agreement with the exact one at t=0. When the time increases from zero, the EPAC method gives good coincidence with the exact result at lower temperature. Finally, we propose a simplified version of the EPAC method to reduce the computational cost required for the calculation of the standard effective potential.
Perspective on the reactions between F
–
and CH
3
CH
2
F: The free energy landscape of the E2 and S
N
2 reaction channels
Authors: Ensing Bernd , Klein Michael L.
Published: April 2005

Recently, we computed the 3D free energy surface of the base-induced elimination reaction between F
–
and CH
3
CH
2
F by using a powerful technique within Car–Parrinello molecular dynamics simulation. Here, the set of three order parameters is expanded to six, which allows the study of the competing elimination and substitution reactions simultaneously. The power of the method is exemplified by the exploration of the six-dimensional free energy landscape, sampling, and mapping out the eight stable states as well as the connecting bottlenecks. The free energy profile and barrier along the E2 and S
N
2 reaction channels are refined by using umbrella sampling. The two mechanisms do not share a common “E2C-like” transition state. Comparison with the zero temperature profiles shows a particularly significant entropy contribution to the S
N
2 channel.
Finding transition states for crystalline solid–solid phase transformations
Authors: Caspersen Kyle J. , Carter Emily A.
Published: April 2005

We present a method to identify transition states and minimum energy paths for martensitic solid–solid phase transformations, thereby allowing quantification of the activation energies of such transformations. Our approach is a generalization of a previous method for identifying transition states for chemical reactions, namely the climbing image-nudged elastic band algorithm, where here the global deformation of the crystalline lattice (volume and shape fluctuations) becomes the reaction coordinate instead of atomic motion. We also introduce an analogue to the Born–Oppenheimer approximation that allows a decoupling of nuclear motion and lattice deformation, where the nuclear positions along the path are determined variationally according to current deformation state. We then apply this technique to characterize the energetics of elemental lithium phase transformations as a function of applied pressure, where we see a validation of the Born–Oppenheimer-like approximation, small energy barriers (expected for martensitic transformations), and a pronounced pressure dependence of various properties characterizing the phase transitions.
Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in polycystic kidney disease
Authors: Tao Yunxia , Kim Jun , Faubel Sarah , Wu Joe C. , Falk Sandor A. , Schrier Robert W. , Edelstein Charles L.
Published: April 2005

We have previously demonstrated an increase in proapoptotic caspase-3 in the kidney of Han:SPRD rats with polycystic kidney disease (PKD). The aim of the present study was to determine the effect of caspase inhibition on tubular cell apoptosis and proliferation, cyst formation, and renal failure in the Han:SPRD rat model of PKD. Heterozygous (Cy/+) and littermate control (+/+) male rats were weaned at 3 weeks of age and then treated with the caspase inhibitor IDN-8050 (10 mg/kg per day) by means of an Alzet (Palo Alto, CA) minipump or vehicle [polyethylene glycol (PEG 300)] for 5 weeks. The two-kidney/total body weight ratio more than doubled in Cy/+ rats compared with +/+ rats. IDN-8050 significantly reduced the kidney enlargement by 44% and the cyst volume density by 29% in Cy/+ rats. Cy/+ rats with PKD have kidney failure as indicated by a significant increase in blood urea nitrogen. IDN-8050 significantly reduced the increase in blood urea nitrogen in the Cy/+ rats. The number of proliferating cell nuclear antigen-positive tubular cells and apoptotic tubular cells in non-cystic and cystic tubules was significantly reduced in IDN-8050-treated Cy/+ rats compared with vehicle-treated Cy/+ rats. On immunoblot, the active form of caspase-3 (20 kDa) was significantly decreased in IDN-8050-treated Cy/+ rats compared with vehicle-treated Cy/+ rats. In summary, in a rat model of PKD, caspase inhibition with IDN-8050 (
i
) decreases apoptosis and proliferation in cystic and noncystic tubules; (
ii
) inhibits renal enlargement and cystogenesis, and (
iii
) attenuates the loss of kidney function.
A unified assembly mode revealed by the structures of tetrameric L27 domain complexes formed by mLin-2/mLin-7 and Patj/Pals1 scaffold proteins
Authors: Feng Wei , Long Jia-fu , Zhang Mingjie
Published: April 2005

Initially identified in
Caenorhabditis elegans
Lin-2 and Lin-7, L27 domain is a protein–protein interaction domain capable of organizing scaffold proteins into supramolecular assemblies by formation of heteromeric L27 domain complexes. L27 domain-mediated protein assemblies have been shown to play essential roles in cellular processes including asymmetric cell division, establishment and maintenance of cell polarity, and clustering of receptors and ion channels. The structural basis of L27 domain heteromeric complex assembly is controversial. We determined the high-resolution solution structure of the prototype L27 domain complex formed by mLin-2 and mLin-7 as well as the solution structure of the L27 domain complex formed by Patj and Pals1. The structures suggest that a tetrameric structure composed of two units of heterodimer is a general assembly mode for cognate pairs of L27 domains. Structural analysis of the L27 domain complex structures further showed that the central four-helix bundles mediating tetramer assembly are highly distinct between different pairs of L27 domain complexes. Biochemical studies revealed that the C-terminal α-helix responsible for the formation of the central helix bundle is a critical specificity determinant for each L27 domain in choosing its binding partner. Our results provide a unified picture for L27 domain-mediated protein–protein interactions.
Structural dynamics of the
lac
repressor–DNA complex revealed by a multiscale simulation
Authors: Villa Elizabeth , Balaeff Alexander , Schulten Klaus
Published: April 2005

A multiscale simulation of a complex between the
lac
repressor protein (LacI) and a 107-bp-long DNA segment is reported. The complex between the repressor and two operator DNA segments is described by all-atom molecular dynamics; the size of the simulated system comprises either 226,000 or 314,000 atoms. The DNA loop connecting the operators is modeled as a continuous elastic ribbon, described mathematically by the nonlinear Kirchhoff differential equations with boundary conditions obtained from the coordinates of the terminal base pairs of each operator. The forces stemming from the looped DNA are included in the molecular dynamics simulations; the loop structure and the forces are continuously recomputed because the protein motions during the simulations shift the operators and the presumed termini of the loop. The simulations reveal the structural dynamics of the LacI–DNA complex in unprecedented detail. The multiple domains of LacI exhibit remarkable structural stability during the simulation, moving much like rigid bodies. LacI is shown to absorb the strain from the looped DNA mainly through its mobile DNA-binding head groups. Even with large fluctuating forces applied, the head groups tilt strongly and keep their grip on the operator DNA, while the remainder of the protein retains its V-shaped structure. A simulated opening of the cleft of LacI by 500-pN forces revealed the interactions responsible for locking LacI in the V-conformation.
Discovery of a unique Ig heavy-chain isotype (IgT) in rainbow trout: Implications for a distinctive B cell developmental pathway in teleost fish
Authors: Hansen John D. , Landis Eric D. , Phillips Ruth B.
Published: April 2005

During the analysis of Ig superfamily members within the available rainbow trout (Oncorhynchus mykiss) EST gene index, we identified a unique Ig heavy-chain (IgH) isotype. cDNAs encoding this isotype are composed of a typical IgH leader sequence and a VDJ rearranged segment followed by four Ig superfamily C-1 domains represented as either membrane-bound or secretory versions. Because teleost fish were previously thought to encode and express only two IgH isotypes (IgM and IgD) for their humoral immune repertoire, we isolated all three cDNA isotypes from a single homozygous trout (OSU-142) to confirm that all three are indeed independent isotypes. Bioinformatic and phylogenetic analysis indicates that this previously undescribed divergent isotype is restricted to bony fish, thus we have named this isotype “IgT” (τ) for teleost fish. Genomic sequence analysis of an OSU-142 bacterial artificial chromosome (BAC) clone positive for all three IgH isotypes revealed that IgT utilizes the standard rainbow trout VHfamilies, but surprisingly, the IgT isotype possesses its own exclusive set of DHand JHelements for the generation of diversity. TheIgTD and J segments and τ constant (C) region genes are located upstream of the D and J elements forIgM, representing a genomicIgHarchitecture that has not been observed in any other vertebrate class. All three isotypes are primarily expressed in the spleen and pronephros (bone marrow equivalent), and ontogenically, expression ofIgTis present 4 d before hatching in developing embryos.
Immunomodulatory oligonucleotides containing a cytosine-phosphate-2′-deoxy-7-deazaguanosine motif as potent Toll-like receptor 9 agonists
Authors: Kandimalla Ekambar R. , Bhagat Lakshmi , Li Yukui , Yu Dong , Wang Daqing , Cong Yan-Ping , Song Sam S. , Tang Jimmy X. , Sullivan Tim , Agrawal Sudhir
Published: April 2005

Bacterial DNA and synthetic oligomers containing CpG dinucleotides activate the immune system through Toll-like receptor (TLR) 9. Here, we compare the immunostimulatory activity of three immunomers with different nucleotide sequences containing a synthetic cytosine-phosphate-2′-deoxy-7-deazaguanosine dinucleotide (CpR), called immunomodulatory oligonucleotides (IMOs), in mouse, human, and monkey systems. IMOs induced IL-12 and IFN-γ secretion more than a control non-CpG IMO in mice. All three IMOs activated HEK293 cells expressing TLR9 but not TLR3, -7, or -8. IMOs induced human B-cell proliferation and enhanced expression of CD86 and CD69 surface markers on B cells. The three IMOs induced CD86 expression on human plasmacytoid dendritic cells, but only IMOs that contained a 5′-terminal TCR nucleotide sequence induced IFN-α secretion. A sequence that forms a duplex structure also was required for IFN-α induction in human peripheral blood mononuclear cell cultures. IMOs induced chemokine and cytokine gene expression in human peripheral blood mononuclear cells. In monkeys, all three IMOs induced transient changes in peripheral blood leukocytes and lymphocytes and activated B and T lymphocytes. All three IMOs induced IFN-αin vivoin monkeys; the IMO sequence that forms a stable secondary structure induced the highest levels of IFN-α. These studies are, to our knowledge, the first comprehensive studies to compare the activity of IMOs containing synthetic stimulatory CpR dinucleotides in mouse, monkey, and human systems. These results suggest that IMOs induce strong and rapid immunostimulation and that the CpR dinucleotide is recognized by TLR9, leading to immune-cell activation and cytokine secretionin vitroandin vivo.
Origin of the long-range attraction between surfactant-coated surfaces
Authors: Meyer Emily E. , Lin Qi , Hassenkam Tue , Oroudjev Emin , Israelachvili Jacob N.
Published: April 2005

We compare the “long-range hydrophobic forces” measured (
i
) in the “symmetric” system between two mica surfaces that had been rendered hydrophobic by the adsorption of a double-chained cationic surfactant, and (
ii
) between one such hydrophobic surface and a hydrophilic surface of bare mica (“asymmetric” case). In both cases, the forces were purely attractive, stronger than van der Waals, and of long-range, as previously reported, with those of the asymmetric, hydrophobic–hydrophilic system being even stronger and of longer range. Atomic force microscopy images of these surfaces show that the monolayers transform into patchy bilayers when the surfaces are immersed in water, and that the resulting surfaces contain large micrometer-sized regions of positive charges (bilayer) and negative charges (bare mica) while remaining overall neutral. The natural alignment of oppositely charged domains as two such surfaces approach would result in a long-range
electrostatic
attraction in water, but the short-range, “truly hydrophobic” interaction is not explained by these results.