bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinematic effects associated with molecular frames in structural isomerization dynamics of clusters
Authors: Yanao Tomohiro , Takatsuka Kazuo
Published: April 2004

Kinematic effects associated with movements of molecular frames, which specify instantaneous orientation of molecules, is investigated in structural isomerization dynamics of a triatomic cluster whose total angular momentum is zero. The principal-axis frame is employed to introduce the so-called principal-axis hyperspherical coordinates, with which the mechanism of structural isomerization dynamics of the cluster is systematically analyzed. A force called “democratic centrifugal force” is extracted from the associated kinematics. This force arises from an intrinsic non-Euclidean metric in the internal space and has an effect of distorting the triatomic cluster to a collapsed shape and of trapping the system around collinear transition states. The latter effect is particularly important in that the kinematics effectively makes a basin at the saddle (transition state) on the potential surface. Based on this framework, we study the effect of the gauge field associated with the Eckart frame in internal space, which has not been carefully examined in the conventional reaction rate theories. Numerical comparison between the dynamics with and without the gauge field has revealed that this field has an effect to suppress the rate of isomerization reaction to a considerable amount. Thus a theory neglecting this effect will significantly overestimate the rate of isomerization. We show the physical origin of this suppressing effect.
Critical fluctuations near the consolute point of n-pentanol-nitromethane. An ultrasonic spectrometry, dynamic light scattering, and shear viscosity study
Authors: Iwanowski I. , Behrends R. , Kaatze U.
Published: April 2004

Ultrasonic attenuation spectra, the shear viscosity, and the mutual diffusion coefficient of the n-pentanol-nitromethane mixture of critical composition have been measured at different temperatures near the critical temperature. The noncritical background contribution, proportional to frequency, to the acoustical attenuation-per-wavelength spectra has been determined and subtracted from the total attenuation to yield the critical contribution. When plotted versus the reduced frequency, with the relaxation rate of order-parameter fluctuations from the shear viscosity and diffusion coefficient measurements, the critical part in the sonic attenuation coefficient displays a scaling function which nicely fits to the data for the critical system 3-methylpentane-nitromethane and also to the empirical scaling function of the Bhattacharjee–Ferrell dynamic scaling theory. The scaled half-attenuation frequency follows from the experimental data as Ω1/2emp=1.8±0.1. The relaxation rate of order-parameter fluctuation shows power-law behavior with the theoretically predicted universal exponent and the extraordinary high amplitude Γo=(187±2)×109 s−1. The amount of the adiabatic coupling constant |g|=0.03, as estimated from the amplitude of the critical contribution to the acoustical spectra, is unusually small.
Polarizability and optical rotation calculated from the approximate coupled cluster singles and doubles CC2 linear response theory using Cholesky decompositions
Authors: Pedersen Thomas Bondo , Sánchez de Merás Alfredo M. J. , Koch Henrik
Published: April 2004

A new implementation of the approximate coupled cluster singles and doubles CC2 linear response model using Cholesky decomposition of the two-electron integrals is presented. Significantly reducing storage demands and computational effort without sacrificing accuracy compared to the conventional model, the algorithm is well suited for large-scale applications. Extensive basis set convergence studies are presented for the static and frequency-dependent electric dipole polarizability of benzene and C60, and for the optical rotation of CNOFH2 and (−)-trans-cyclooctene (TCO). The origin-dependence of the optical rotation is calculated and shown to persist for CC2 even at basis set convergence.
Advantages of polarized two-beam second-harmonic generation in precise characterization of thin films
Authors: Cattaneo Stefano , Vuorimaa Elina , Lemmetyinen Helge , Kauranen Martti
Published: April 2004

Polarized second-harmonic generation using two fundamental beams, instead of one, offers significant advantages for characterizing nonlinear optical thin films. The technique is more precise and allows the internal consistency of the results to be verified. The superiority of the two-beam arrangement over the traditional single-beam arrangement is demonstrated by determining the susceptibility tensors of Langmuir–Blodgett films. We show that, for a well-understood reference sample, the results obtained using two fundamental beams agree qualitatively with those obtained with a single fundamental beam, but are more precise. In a more complicated situation, however, the single-beam technique appears to work well but yields results that are, in fact, incorrect. The two-beam technique, instead, yields clearly inconsistent results, thereby highlighting systematic errors in the experimental arrangement or in the theoretical model used to interpret the results.
Robert Brown's Caladenia revisited, including a revision of its sister genera Cyanicula, Ericksonella and Pheladenia (Caladeniinae: Orchidaceae)
Authors: Hopper Stephen D. , Brown Andrew P.
Published: April 2004

Nomenclatural confusion has been generated regarding the large Australasian terrestrial orchid genus Caladenia following publication from 2001 onwards of three major treatments of Caladeniinae. Here, we review concepts for Caladenia and allied genera in the subtribe, we revise three sister genera of Caladenia (Cyanicula, Ericksonella and Pheladenia), and we present an annotated nomenclatural checklist with many new synonymies and some new combinations. A revised circumscription of ten genera in the Caladeniinae is presented, including both Adenochilus and Eriochilus, which have recently been segregated as monogeneric subtribes by others. We argue for retaining Caladenia in the broad sense, largely reflecting Robert Brown's original concept, differing only in the recognition as genera of Cyanicula, Pheladenia, and Leptoceras, as well as two monotypic genera not known to Brown but later described as species of Caladenia (Praecoxanthus and Ericksonella). Thus Caladenia remains a large Australasian genus of terrestrial orchids with 243 species and six subgenera. This approach maximises nomenclatural stability while ensuring that hypothesised monophyly is upheld in the light of molecular phylogenetics analyses. The valid type for Caladenia is C. carnea, while that for Caladenia sect. Calonema is C. longicauda. The genus Jonesiopsis and generic combination Phlebochilus (Benth.) Szlach. were validly published. These conclusions call into question many recently erected taxa and combinations of other authors. Synonyms of Caladenia include Arachnorchis, Calonemorchis, Drakonorchis, Jonesiopsis, Petalochilus, Phlebochilus and Stegostyla. Pentisia is a synonym of Cyanicula. Calonema (Lindl.) Szlach. and Calonema (Lindl.) D.L. Jones and M.A. Clem. are invalid generic combinations as the name Calonema had already been used for a fungal genus.
New taxa described herein include Ericksonella, Cyanicula subgenus Trilobatae, C. aperta, C. ixioides subsp. candida, × Cyanthera and × C. glossodioides. New combinations include Caladenia subgenus Stegostyla (D.L.
Jones and M.A. Clem.) Hopper and A.P. Br., C. graniticola (Hopper and A.P. Br.) Hopper and A.P. Br., C. saccata (R.S. Rogers) Hopper & A.P. Br., C. orientalis (G.W. Carr) Hopper & A.P. Br., and C. villosissima (G.W. Carr) Hopper & A.P. Br., and Ericksonella saccharata (Reichb.f.) Hopper and A.P.Br.
Regulation of cardiac contractility by Rab4-modulated β2-adrenergic receptor recycling
Authors: Odley Amy , Hahn Harvey S. , Lynch Roy A. , Marreez Yehia , Osinska Hanna , Robbins Jeffrey , Dorn Gerald W.
Published: April 2004

Catecholaminergic activation of myocardial β-adrenergic receptors (βAR) is the principle mechanism regulating cardiac function. Agonists desensitize βAR through G protein-coupled receptor kinase-mediated uncoupling and β-arrestin-mediated internalization. Although inhibition of myocardial G protein-coupled receptor kinase-2 enhances cardiac function and reverses heart failure, pathophysiological effects of modulated βAR internalization/recycling are unknown. We used mutation and transgenic expression of Rab4, which regulates vesicular transport of heptahelical receptors to plasma membranes, to interrogate
in vivo
βAR trafficking and cardiac function. Expression of constitutively active Rab4 Q72L had no effects on cardiac structure or function, but dominant inhibitor Rab4 S27N impaired responsiveness to endogenous and exogenous catecholamines. To relate βAR trafficking to diminished cardiac function, Rab4 mutant mice were crossbred with mice overexpressing human β2AR. In unstimulated β2AR overexpressors, β2AR localized to heavier endosomes and translocated to lighter, caveolin-rich fractions after isoproterenol stimulation. Coexpression of β2AR with activated Rab4 Q72L caused loss of receptors from heavier endosomes while retaining normal inotropy. In contrast, coexpression of β2AR with inhibitory Rab4 S27N mimicked isoproterenol-induced receptor redistribution to caveolae, with diminished cardiac inotropy. Rab4 inhibition alone prevented resensitization after isoproterenol-induced
in vivo
adrenergic desensitization. Confocal and ultrastructural analyses revealed bizarre vesicular structures and abnormal accumulation of β2AR in the sarcoplasm and subsarcollema of Rab4 S27N, but not Q72L, mice. These data provide evidence for constant bidirectional sarcollemal–vesicular βAR trafficking in the
in vivo
heart and show that Rab4-mediated recycling of internalized βAR is necessary for normal cardiac catecholamine responsiveness and resensitization after agonist exposure.
Malondialdehyde adducts in DNA arrest transcription by T7 RNA polymerase and mammalian RNA polymerase II
Authors: Cline Susan D. , Riggins James N. , Tornaletti Silvia , Marnett Lawrence J. , Hanawalt Philip C.
Published: April 2004

Malondialdehyde, a genotoxic byproduct of lipid peroxidation, reacts with guanine in DNA to form pyrimido[1,2-α]purin-10(3
H
)one (M
1
dG), the first endogenous DNA lesion found to be a target of nucleotide excision repair enzymes. A subpathway of nucleotide excision repair, transcription-coupled repair, is thought to occur when RNA polymerase (RNAP) is arrested at damage in transcribed DNA strands and might function for efficient removal of M
1
dG in active genes. Results presented here show that M
1
dG and its stable, exocyclic analog 1,
N
2
-propanodeoxyguanine (PdG), arrest translocation of T7 RNAP and mammalian RNAPII when located in the transcribed strand of a DNA template. M
1
dG paired with thymine is exocyclic and poses a stronger block to transcription than the acyclic
N
2
-(3-oxo-1-propenyl)-dG, formed upon cytosine-catalyzed opening of M
1
dG in duplex DNA. PdG is a complete block to RNAPII regardless of base pairing. The elongation factor TFIIS (SII) induces reversal and RNA transcript cleavage by RNAPII arrested at PdG. Thus, arrested RNAPII complexes may be stable at M
1
dG in cells and may resume transcription once the offending adduct is removed. The conclusion from this work is that malondialdehyde adducts in the transcribed strand of expressed genes are strong blocks to RNAPs and are targets for cellular transcription-coupled repair. If so, then M
1
dG, already known to be highly mutagenic in human cells, also may contribute to apoptosis in the developing tissues of individuals with Cockayne's syndrome, a hereditary disorder characterized by transcription-coupled repair deficiency.
Symposium on Friedel–Crafts catalysts and polymerization
Authors: Plesch P.H
Published: April 2004

On 15 September 1945, Michael Polanyi, F.R.S., Professor of Physical Chemistry at the University of Manchester, convened there a one–day meeting entitled ‘Symposium on Friedel–Crafts Catalysts and Polymerization’. The morning was devoted to Friedel-Crafts catalysts and the afternoon to polymerization.
Recollections of Patrick Blackett 1945-70
1
Authors: Butler C.
Published: April 2004

The author was privileged to work closely with Patrick Blackett from 1945 over a continuous period of 25 years, first at Manchester University and later at Imperial College, London.

In 1945, Blackett returned to Manchester determined to build up his Department of Physics, both undergraduate numbers and the volume of research. He believed passionately that in Britain a satisfactory and effective volume of research in a department could only be achieved if the number of capable undergraduates was much larger than in most pre-war physics departments. Furthermore, he believed the country was in need of more physics graduates. He exploited this belief relentlessly over the 25–year period.

In 1945, Blackett did not have a cut and dried action plan for his department, rather his ideas on how to achieve his purpose developed over time. Early on, however, he became concerned over the small number of professorships available. Pre-war, about 20% of physics staff were professors, but after the war this percentage gradually fell, reaching about 10% by the early 1960s. He took action to stem this trend in his own departments well before 1960.

Over the years Blackett realized he wanted to leave as his legacy a physics department with a wide spread of research expertise in physics and astronomy. If most of the individual research groups in his department were to make the impact he wanted on the world physics scene, then the overall size of the department was inevitably large, compared with the national average.

Without doubt Patrick Blackett made a very significant contribution to the wellbeing and development of physics in Britain, well beyond the bounds of Manchester and Imperial College.
Book reviews
Authors: Shea W.
Published: April 2004

Six book reviews in the January 1999 edition of
Notes and Records
:

Archives of the Scientific Revolution. The formation and exchange of ideas in seventeenth-century Europe
,Michael Hunter (ed.).
Flamsteed's stars, new perspectives on the life and work of the first Astronomer Royal (1646-1719)
, Frances Willmoth (ed.). M. Basso Ricci, L. Cafaraella, A. Meloni and P. Tucci,
Due Secoli di Strumenti Geomagnetici in Italia (1740-1971). Two Centuries of Geomagnetic Instruments in Italy (with a summary in English)
. Frank Smithies,
Cauchy and the creation of Complex Function Theory
.
The correspondence of Charles Darwin, volume 10, 1862
. Frederick Burkhardt, Duncan M. Porter, Joy Harvey and Jonathan R. Topham (eds).
Competence in transition
Authors: Mansfield Bob
Published: April 2004

The former Soviet economies have, for the past 12 years, looked to the advanced economies in the west for help in reforming their systems of vocational education and training. These “transition” economies still bear much of the legacy of the previous system and culture – academic in orientation, firmly supply led and implemented through vocational schools which are in economic crisis. They are offered the western “consensus” – competence‐based training systems and the introduction of common or “core” skills. However, in introducing these methods, approaches and concepts, fundamental flaws appear, flaws that have not been seriously addressed in their countries and cultures of origin. This paper tries to address the problems in dealing with concepts like “competence” and “core skills”, and suggests that we need a coherent, grounded concept of occupational competence to replace the relatively unquestioned “deficiency model” which these concepts represent.
Positioning and branding your organisation
Authors: Knox Simon
Published: April 2004

Opens by exploring the changing relationship between customer value and how it has been traditionally interpreted within the organisation. Business leaders today acknowledge that the traditional 4Ps approach to brand marketing needs to be transformed in order to realise a broader vision of customer value across the organisation. Argues that it is the business leader who should be leading this transformation, as manager of the organisation's brand and its values, as well as challenging the marketing department to redefine its role as brand custodians. Outlines a framework which enables senior management to develop superior customer value through branding and positioning their organisation and to deliver this value through its business processes. Uses practical examples to illustrate the use of this framework and concludes by considering whether or not the traditional marketing department is acting as a barrier when it comes to positioning and branding their organisation.
Contractual and technological approaches for protecting digital works: their relationship with copyright limitations
Authors: Carlos Fernández‐Molina J.
Published: April 2004

To deal with the new circumstances arising in the digital environment, with its particular conditions for the access, distribution and use of intellectual works, three distinct approaches exist: legal (copyright laws are modified to adapt them to the new context), technological (systems designed to control access and use of works), and contractual (through licenses to regulate the conditions of use of the works). The joint use of technological measures and licenses, together with the laws that protect both, are seriously endangering the effectiveness of the limitations to copyright set forth by law to benefit libraries, their users and citizens in general. This represents a strong privatisation of access to information. Using as a point of reference the laws of countries that are on the front lines of this terrain – the USA, the European Union and Australia – some problems created by the new forms of protection of intellectual works are examined.
Can the Web give useful information about commercial uses of scientific research?
Authors: Thelwall Mike
Published: April 2004

Invocations of pure and applied science journals in the Web were analysed, focussing on commercial sites, in order to assess whether the Web can yield useful information about university‐industry knowledge transfer. On a macro level, evidence was found that applied research was more highly invoked on the non‐academic Web than pure research, but only in one of the two fields studied. On a micro level, instances of clear evidence of the transfer of academic knowledge to a commercial setting were sparse. Science research on the Web seems to be invoked mainly for marketing purposes, although high technology companies can invoke published academic research as an organic part of a strategy to prove product effectiveness. It is conjectured that invoking academic research in business Web pages is rarely of clear commercial benefit to a company and that, except in unusual circumstances, benefits from research will be kept hidden to avoid giving intelligence to competitors.
Homogeneity of the Prion Protein Gene in Various European and Asian Pig Breeds
Authors: Lipp O. , Ritzmann M. , Kixmöller M. , Heinritzi K. , Hensel A. , Truyen U.
Published: April 2004

The genetic variability of the prion protein gene influences the susceptibility to infection with transmissible spongiform encephalopathy (TSE) agents in mice, sheep and possibly man. Pigs have been shown to be susceptible to the bovine spongiform encephalopathy (BSE) agent after intracerebral, but not after oral inoculation. In these studies, however, only a very limited number of pigs of a restricted genetic background were used. Therefore, the question arose whether those experiments do reflect the susceptibility of the species pig or rather that of a single possibly resistant pig breed. The prion protein gene of a total of 66 pigs from 12 different breeds (2 × Deutsche Landrasse, 3 × Deutsches Edelschwein, 4 × Leicoma, 4 × Duroc, 11 × Pietrain, 6 × Large White, 9 × Hampshire, 2 × Belgische Landrasse, 8 × Schwäbisch Hällisches Schwein, 6 × Bunte Bentheimer, 7 × Chinesisches Meishan, 4 × Wildschwein (wild boar)) was amplified by PCR and directly sequenced. All sequences were found to be identical and identical to the published sequence (T. Martin, S. Hughes, K. Hughes, and M. Dawson Biochem. Biophys. Acta 1995; 1270: 211).
Artificial hybridization between Pitcairnia flammea and Pitcairnia corcovadensis (Bromeliaceae): analysis of the performance of parents and hybrids
Authors: RÔÇAS GISELLE , KLEIN DENISE E. , DE MATTOS EDUARDO A.
Published: April 2004

The genus Pitcairnia (Bromeliaceae) includes species that hybridize readily in nature and species that occur together, but do not hybridize. In natural populations of P. flammea and P. corcovadensis, floral traits did not reveal morphological intermediates between them. However, it is possible to obtain artificial hybrids. Thus, we aimed to characterize the morphology of F1 hybrids and evaluate the fitness of different hybrids and parental generations. In most of the morphological traits, the F1 hybrids were intermediate to their parents. With regard to the fitness of the F1 hybrids and backcrosses, some traits were intermediate whereas others were parental‐like. In the greenhouse, no post–zygotic barriers for hybrid formation were observed. Due to successful clonal propagation we suggest that hybrids that were eventually produced by a non‐specific pollinator which might persist and spread in nature.
A Continuity of Care Integrated Literature Review, Part 2: Methodological Issues
Authors: Sparbel Kathleen J.H. , Anderson Mary Ann
Published: April 2004

Purpose: In Part 2 of this two‐part series, research designs, methods, and measurement of continuity of care are explored.

Design: Qualitative, integrated literature review of a sample of 38 continuity of care nursing research articles published 1990–1995.

Methods: Ganong's (1987) stages of the integrative literature research review process were followed. A data collection tool was designed and pilot tested, and rules for data analysis and interpretation were established. Research articles were systematically analyzed and reported using descriptive analysis.

Findings: Results showed few nursing models, primarily convenience sampling and nonexperimental cross‐sectional study designs, varied data collection methods, and inadequate instrumentation. Measurement criteria were diverse and influenced by the perspectives of the measurer.

Conclusions: Continuity of patient care was identified as a construct comprised of many related and tangential concepts in need of more sophisticated review. Recommendations for researchers are discussed.
Critical Care Nurses' Perceptions of DNR Status
Authors: Thibault‐Prevost Jocelyne , Jensen Louise A. , Hodgins Marilyn
Published: April 2004

Purpose: To describe the perceptions of nurses regarding do‐not‐resuscitate (DNR) decisions in critical care settings.

Design: A survey assessing knowledge, attitudes, and practices concerning DNR status was distributed to all critical care nurses who were registered with the provincial licensing body in Alberta, Canada, and held positions of staff nurse, educator, or manager.

Methods: Four hundred and five surveys were completed and returned. Descriptive analyses were conducted.

Findings: The term “DNR” was found to be ambiguous. The rationale for DNR orders were also not well articulated in practice. Although nurses believed that patients, families, and nurses should participate in DNR decisions, physicians were most often cited as being responsible for the decision.

Conclusions: Documentation of a comprehensive patient treatment plan and awareness of the rationale for DNR designation are strategies suggested to help achieve desired patient care goals in critical care settings.
Risk Factors for Breast Cancer in Jordanian Women
Authors: Petro‐Nustas Wasileh , Norton Mary E. , Al‐Masarweh Issa
Published: April 2004

Purpose: To investigate risk factors associated with breast cancer in Jordanian women.

Design: Retrospective case‐control study based on data from the Jordanian Cancer Registry in 1996.

Methods: One hundred women with breast cancer (cases) and 100 women without breast cancer (controls) were interviewed in their homes. A questionnaire was developed in Arabic to investigate the risk factors associated with breast cancer in Jordanian women.

Findings: Bivariate analysis indicated significant differences between the cases and controls, including age of menarche and menopause, use of households' pesticides, stressful life events, and direct trauma to the breast. Logistic regression analysis indicated higher odds ratios for breast enlargement, irregular menstruation, use of hair dye, oral contraceptives, and fertility drugs.

Conclusions: Significant differences in correlates of breast cancer were found between the cases and the controls.
Push and Pull Factors in International Nurse Migration
Authors: Kline Donna S.
Published: April 2004

Purpose: To describe the push and pull factors of migration in relation to international recruitment and migration of nurses.

Organizing Construct: Review of literature on nurse migration, examination of effects of donor and receiving countries, and discussion of ethical concerns related to foreign nurse recruitment.

Findings: The primary donor countries are Australia, Canada, the Philippines, South Africa, and the United Kingdom (UK); the primary receiving countries are Australia, Canada, Ireland, the UK, and the United States (US). The effects of migration on donor countries include the loss of skilled personnel and economic investment; receiving countries receive skilled nurses to fill critical shortages with less economic investment. Ethical concerns include the potential for exploitation of foreign nurses.

Conclusions: Nurses migrate to seek better wages and working conditions than they have in their native countries. Given the current conditions, developed countries continue to actively recruit foreign nurses to fill critical shortages. Migration is predicted to continue until developed countries address the underlying causes of nurse shortages and until developing countries address conditions that cause nurses to leave.
Building Capacity Through a Collaborative International Nursing Project
Authors: Ogilvie Linda , Allen Marion , Laryea Joanna , Opare Mary
Published: April 2004

Purpose: To discuss: (a) physical, human, organizational, social, and cultural capital and (b) empowerment as two theoretical foundations for building capacity.

Methods. These theoretical notions are examined in an analysis of a joint project between the Department of Nursing, University of Ghana and the Faculty of Nursing at the University of Alberta, Canada.

Findings: Capacity for the management of international development projects was enhanced at both sites. Building capacity required mutual trust, tolerance of ambiguity, and a willingness to step into the unknown.
Couples' Views of the Effects of Natural Family Planning on Marital Dynamics
Authors: VandeVusse Leona , Hanson Lisa , Fehring Richard J. , Newman Amy , Fox Jaime
Published: April 2004

Purpose: Natural Family Planning (NFP) requires periodic abstinence and partner cooperation to prevent pregnancy. The aim of this study was to learn about the effects of modern NFP methods on marital relationships.

Design: Descriptive survey.

Methods: Questionnaires were mailed to 1,400 randomly selected couples known to use NFP and residing in the United States of America; 334 couples (24%) responded. Content analysis was used to identify meanings and themes. Numeric analyses were used to determine frequencies.

Findings: Nearly two‐thirds of the qualitative comments were positive. Four themes were identified in the positive responses: relationship enhancements, knowledge improvements, spirituality enrichments, and method successes. Three negative themes were identified: strained sexual interactions, worsened relationships, and method problems. Although about onefourth of the comments indicated that NFP presented challenges, the majority (74%) found it beneficial, often resulting in stronger bonds, better communication, and improved knowledge.

Conclusions: NFP had more positive than negative effects and its use warrants further consideration.
The BRRF1 Early Gene of Epstein-Barr Virus Encodes a Transcription Factor That Enhances Induction of Lytic Infection by BRLF1
Authors: Hong Gregory K. , Delecluse Henri-Jacques , Gruffat Henri , Morrison Thomas E. , Feng Wen-Hai , Sergeant Alain , Kenney Shannon C.
Published: April 2004

The switch from the latent to the lytic form of Epstein-Barr virus (EBV) infection is mediated by expression of the viral immediate-early (IE) proteins, BZLF1 (Z) and BRLF1 (R). An EBV early protein, BRRF1 (Na), is encoded by the opposite strand of the BRLF1 intron, but the function of this nuclear protein in the viral life cycle is unknown. Here we demonstrate that Na enhances the R-mediated induction of lytic EBV infection in 293 cells latently infected with a recombinant EBV (R-KO) defective for the expression of both R and Na. Na also enhances R-induced lytic infections in a gastric carcinoma line (AGS) carrying the R-KO virus, although it has no effect in a Burkitt lymphoma line (BL-30) stably infected with the same mutant virus. We show that Na is a transcription factor that increases the ability of R to activate Z expression from the R-KO viral genome in 293 cells and that Na by itself activates the Z promoter (Zp) in EBV-negative cells. Na activation of Zp requires a CRE motif (ZII), and a consensus CRE motif is sufficient to transfer Na responsiveness to the heterologous E1b promoter. Furthermore, we show that Na enhances the transactivator function of a Gal4-c-Jun fusion protein but does not increase the transactivator function of other transcription factors (including ATF-1, ATF-2, and CREB) known to bind CRE motifs. Na expression in cells results in increased levels of a hyperphosphorylated form of c-Jun, suggesting a mechanism by which Na activates c-Jun. Our results indicate that Na is a transcription factor that activates the EBV Zp IE promoter through its effects on c-Jun and suggest that Na cooperates with BRLF1 to induce the lytic form of EBV infection in certain cell types.
Identification of the Nuclear Export Signal and STAT-Binding Domains of the Nipah Virus V Protein Reveals Mechanisms Underlying Interferon Evasion
Authors: Rodriguez Jason J. , Cruz Cristian D. , Horvath Curt M.
Published: April 2004

The V proteins of Nipah virus and Hendra virus have been demonstrated to bind to cellular STAT1 and STAT2 proteins to form high-molecular-weight complexes that inhibit interferon (IFN)-induced antiviral transcription by preventing STAT nuclear accumulation. Analysis of the Nipah virus V protein has revealed a region between amino acids 174 and 192 that functions as a CRM1-dependent nuclear export signal (NES). This peptide is sufficient to complement an export-defective human immunodeficiency virus Rev protein, and deletion and substitution mutagenesis revealed that this peptide is necessary for both V protein shuttling and cytoplasmic retention of STAT1 and STAT2 proteins. However, the NES is not required for V-dependent IFN signaling inhibition. IFN signaling is blocked primarily by interaction between Nipah virus V residues 100 to 160 and STAT1 residues 509 to 712. Interaction with STAT2 requires a larger Nipah virus V segment between amino acids 100 and 300, but deletion of residues 230 to 237 greatly reduced STAT2 coprecipitation. Further, V protein interactions with cellular STAT1 is a prerequisite for STAT2 binding, and sequential immunoprecipitations demonstrate that V, STAT1, and STAT2 can form a tripartite complex. These findings characterize essential regions for
Henipavirus
V proteins that represent potential targets for therapeutic intervention.
Properties of Replication-Competent Vesicular Stomatitis Virus Vectors Expressing Glycoproteins of Filoviruses and Arenaviruses
Authors: Garbutt Michael , Liebscher Ryan , Wahl-Jensen Victoria , Jones Steven , Möller Peggy , Wagner Ralf , Volchkov Viktor , Klenk Hans-Dieter , Feldmann Heinz , Ströher Ute
Published: April 2004

Replication-competent recombinant vesicular stomatitis viruses (rVSVs) expressing the type I transmembrane glycoproteins and selected soluble glycoproteins of several viral hemorrhagic fever agents (Marburg virus, Ebola virus, and Lassa virus) were generated and characterized. All recombinant viruses exhibited rhabdovirus morphology and replicated cytolytically in tissue culture. Unlike the rVSVs with an additional transcription unit expressing the soluble glycoproteins, the viruses carrying the foreign transmembrane glycoproteins in replacement of the VSV glycoprotein were slightly attenuated in growth. Biosynthesis and processing of the foreign glycoproteins were authentic, and the cell tropism was defined by the transmembrane glycoprotein. None of the rVSVs displayed pathogenic potential in animals. The rVSV expressing the Zaire Ebola virus transmembrane glycoprotein mediated protection in mice against a lethal Zaire Ebola virus challenge. Our data suggest that the recombinant VSV can be used to study the role of the viral glycoproteins in virus replication, immune response, and pathogenesis.
Regional Differences in Viral Growth and Central Nervous System Injury Correlate with Apoptosis
Authors: Richardson-Burns Sarah M. , Tyler Kenneth L.
Published: April 2004

Infection of neonatal mice with reovirus T3 Dearing (T3D), the prototypic neurotropic reovirus, causes fatal encephalitis associated with neuronal injury and virus-induced apoptosis throughout the brain. T3D variant K (VarK) is an antigenic variant that has a nearly 1 million-fold reduction in neurovirulence following intracerebral (i.c.) inoculation compared to T3D and a restricted pattern of central nervous system injury with damage limited to the hippocampus, sparing other brain regions. We wished to determine whether the restricted pattern of VarK-induced injury was due to a reduced capacity to replicate in or injure cortical, as opposed to hippocampal, tissue. We found that following i.c. inoculation, VarK grew to similar titers as T3D in the hippocampus but had significantly lower titers in the cortex. Both viruses grew to identical titers and infected the same percentage of cells in mouse primary hippocampal cultures (MHC). In mouse primary cortical cultures (MCC) both the number of infected cells and the viral yield per infected cell were significantly lower for VarK than T3D. VarK-induced apoptosis was limited to the hippocampus in vivo, and in vitro both viruses induced apoptosis equally in MHC but VarK induced significantly less apoptosis than T3D in MCC. Growth of T3D in MCC was reduced to levels comparable to those of VarK following treatment of MCC with caspase inhibitors. Conversely, induction of apoptosis in VarK-infected MCC with fatty acid synthase-activating antibody significantly enhanced viral yield. These results suggest that the decreased neurovirulence of VarK may be due to its failure to efficiently induce apoptosis in cortical neurons.
Moby-Dick and Compassion
Authors: Armstrong Philip
Published: April 2004

Because the notions of "anthropomorphism" and "sentimentality" often are used pejoratively to dismiss research in human-animal studies, there is much to be gained from ongoing and detailed analysis of the changing "structures of feeling" that shape representations and treatments of nonhuman animals. Literary criticism contributes to this project when it pays due attention to differences in historical and cultural contexts. As an example of this approach, a reading of the humanization of cetaceans in Herman Melville's Moby-Dick - and more broadly in nineteenth-century whaling discourse - demonstrates how radically human feelings for nonhuman species are affected by shifting material and ideological conditions.
Functional-Neuroanatomic Correlates of Recollection: Implications for Models of Recognition Memory
Authors: Kahn Itamar , Davachi Lila , Wagner Anthony D.
Published: April 2004

Recognition decisions can be based on familiarity, the sense that an item was encountered previously (item memory), and on recollection, the conscious recovery of contextual information surrounding a previous encounter with the item (e.g., source memory). Recognition with recollection is thought to depend on multiple mechanisms, including prefrontal “control” processes that guide retrieval and recapitulation mechanisms that reactivate posterior neocortical representations that were present at encoding. However, uncertainty remains regarding the precise nature of prefrontal contributions to recollection and the selectivity of recapitulation to veridical recollection. The present event-related functional magnetic resonance imaging study sought to examine whether regions showing “old-new” effects support processes sensitive to recollection success or recollection attempt and whether recapitulation of neocortical representations emerge during veridical recollection as well as during false recognition (i.e., false alarms) or whether false recognition resembles familiarity-based responding. Results revealed that multiple left prefrontal cortical regions were engaged during attempts to recollect previous contextual (source) details, regardless of the nature of the to-be-recollected details and of source recollection outcome (successful vs unsuccessful). Recapitulation effects were observed in regions sensitive to the encoding task, suggesting that veridical recollection entails the reactivation of processes or representations present during encoding. Importantly, in contrast to leading models of recognition memory, false alarms also appeared to be based partially on recollection, as revealed through false recapitulation effects. Implications for neural and cognitive models of recognition are considered.
NMR Studies of electrostatic fields around charged monosaccharides and related molecules
Authors: Glaser Robert , Novoselsky Artem , Shames Alexander , Likhtenshtein Gertz I.
Published: April 2004

A new and simple technique has been developed to experimentally measure electrostatic fields around charged molecules in solution. Using a series of three charged or neutral [4‐hydroxy (or carboxy or amino)‐2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO)] spin probes, the apparent rate constants (k+, ko, and k‐) for a particular nucleus can be calculated as the slope of 1/T1 (i.e., the spin‐lattice relaxation rate) vs. increasing radical concentration. Protons residing within a particular charged region suffer a decrease in their apparent rate constants due to repulsive interactions when the nitroxide spin probe bears the same charge‐type as that of the local electrostatic environment. Accordingly, electrostatic forces of attraction increase the apparent rate constants for these same protons when the nitroxide spin probe bears the opposite charge to that present in the local electrostatic field. The apparent rate constants of the neutral nitroxide spin probe are an indication of the solvent accessibility to that particular site in the molecule being investigated. Ratios of these apparent relaxation rate constants (k+/k‐ > 1 or k‐/k+ > 1, etc.) thus provide a measurement of the sign and magnitude of the local electrostatic fields surrounding a particular proton in the target molecule. Three charged hexosamines [D‐glucosamine·HCl (4), D‐galactosamine·HCl (5), and D‐mannosamine·HCl (6)], a glucuronide metabolite of paracetamol [p‐acetamidophenyl‐ß‐D‐glucuronide sodium salt (7)], and a mononucleotide [thymidine‐3′‐phosphate sodium salt (8)], were investigated in this study. Positively charged environments around protons in the hexosamines are clearly seen by ko/k+ ratios greater than unity, while negatively charged surroundings about protons in the glucuronide and nucleotide are markedly evident from larger than unity k+/k‐ and ko/k‐ ratios. In the case of small charged target molecules such as 6–8, the electrostatic field seems to envelop the entire molecule. In general, a lack of statistically significant differences in the kattraction/krepulsion or kneutral/krepulsion ratios as a function of proton distance from the charged functionality was observed. This finding (with the possible exception of the methyl protons in 7) suggests that the present version of this method is not sensitive enough to map subtle differences in charged environments around small and conformationally flexible or dynamic target molecules.
Layer‐by‐layer deposition of J‐aggregates and polyelectrolytes for electroluminescence applications: A spectroscopic study
Authors: Kirstein Stefan , Bourbon Sebastien , Gao Mingyuan , De Rossi Umberto
Published: April 2004

The self‐assembly method of layer‐by‐layer deposition of oppositely charged polyelectrolytes is used to insert J‐aggregates of the dye tetrachloro‐diethyl‐disulfobutyl‐benzimido‐carbocyanine (TDBC) into thin polymeric films. The J‐aggregates are characterized by a narrow absorption‐ and fluorescence band with its maximum at 590 nm, which is red‐shifted with respect to the monomeric transition at 515 nm. The dyes are either coadsorbed with the polyelectrolytes poly(allylamine hydrochloride (PAH) and poly(styrene sulfonate) (PSS), or alternately deposited with the precursor of poly(phenylene vinylene) (pre‐PPV). The optical properties of the aggregates are not changed significantly by the deposition process. The pre‐PPV/TDBC films are heated under vacuum to convert the PPV to its conjugated form. The resulting films can be used for the fabrication of light‐emitting devices. The optical properties such as fluorescence and electroluminescence are dominated by the J‐aggregates. The excitation energy of PPV is transferred to the dye aggregates with an efficiency of 100%. The electroluminescence is not very stable and shows a very slow turn‐on time. However, the combination of self‐assembled PPV/TDBC layers with a spin‐coated film of PPV results in stable electroluminescence emission under ambient conditions. In this case, light is emitted from both species, the PPV and the J‐aggregates, whereas the ratio of the two intensities strongly depends on temperature.
Multi‐domain binding of cytochrome c peroxidase by cytochrome c: Thermodynamic vs. microscopic binding constants
Authors: Nocek Judith M. , Leesch Valerie W. , Zhou Jian S. , Jiang Min , Hoffman Brian M.
Published: April 2004

We have demonstrated that cytochrome c (Cc) binds to cytochrome c peroxidase (Cc P) with a 2:1 stoichiometry, and that: (i) Cc reacts at two distinct and non‐exclusive surface domains of Cc P; (ii) two molecules of Cc can bind simultaneously to Cc P; and (iii) the ternary complex is more reactive than the binary complex for the heme—heme reaction. The quenching studies, however, provide only stoichiometric (thermodynamic) parameters. They do not directly probe the microscopic properties of the individual domains, and thus do not apportion the reactivity due to 1:1 stoichiometry between the two types of binary complexes: one with Cc bound at the high‐affinity domain and one with Cc bound at a low‐affinity domain. We describe here a method for analyzing the stoichiometric parameters obtained from triplet quenching titrations to partition the quenching of ZnCc by Cc P into contributions from the binary and ternary complexes, and also to give limits on the partition of the quenching into contributions from the low‐ and high‐affinity binding domains. By applying this method to the experimental quenching titration data for the multi‐domain binding of Cc to Cc P, we were able to evaluate, for the first time, the functional relevance of the low‐affinity domain in the binary and ternary complexes at both low and high ionic strength. At low ionic strength, essentially no Cc binds at the low‐affinity domain in a binary complex. However, reactivity at this domain is significant and indeed can be dominant, in the ternary complex, which does form with measureable concentration. At higher, more physiologically‐relevant ionic strengths, very little ternary complex forms, but now the situation is changed, and there is significant reactivity from the 1:1 complex with Cc bound at the low‐affinity domain. In other words, there is substantial reactivity from Cc bound at the weakly binding domain over a wide range of ionic strengths, either in a binary or a ternary complex. Finally, we suggest that at high ionic strength, interactions between the two bound Cc are shielded such that it is easier to bind the second Cc molecule when one domain is occupied already.
Adhesion studies using contact mechanics
Authors: Ulman Abraham , Choi Gun‐Young , Shnidman Yitzhak , Zurawsky Walter
Published: April 2004

We report adhesion studies using the JKR contact mechanics method and poly(dimethylsiloxane) (PDMS) cross‐linked networks. When such networks are extracted, interdigitation of tethered chains into extraction zones at the network‐network interface results in a significant enhancement of adhesion. When these networks come into contact with a silicon oxide surface, an increase in adhesion hysteresis is observed in the order of increasing molecular weight between crosslinks, with a scaling factor of 1/2. Subjecting the system to maximum load for 30 min before unloading results in a scaling factor of 1/3, probably due to molecular weight dependent network relaxation rates. PDMS cross‐link networks form H‐bonds with surface Si–OH groups that result in significant and time‐dependent adhesion increase. Systematic studies of interfacial H‐bonding and its effect on adhesion have been carried out using self‐assembled monolayer (SAM) surfaces. An increase in adhesion strength was observed in the order of increasing acidity of surface OH protons [Au/S(CH2)11OH < Au/S(C6H4)2OH < Au/S(CH2)15COOH < Au/S(CH2)11PO(OH)2]. When surface OH concentration was controlled, the strength of adhesion was found to be proportional to the number of surface OH groups, with nonlinear relationship, probably due to the collective nature of H‐bonding between the PDMS chain and surface OH groups. Isotope effect studies confirmed the formation of interfacial H‐bonding.
Parametric MRI of Water Diffusion in Breast Cancer
Authors: Paran Yael , Adansky‐Boldin Swetlana A. , Margalit Raanan , Degani Hadassa
Published: April 2004

Diffusion MRI studies revealed specific morphological and physiological properties of MCF7 tumors implanted in the mammary gland of immunodeficient mice. These tumors mimic the histological and pathophysiological properties of human breast cancer in patients. The experiments were conducted by (1) applying varying diffusion gradient strengths, Gd, from 0 to 20 G/cm and a short diffusion time (td = 16 ms) in order to minimize the effect of restriction and exchange of water between the intra‐ and extracellular compartments, and (2) applying a strong constant gradient and diffusion times up to 96 ms, revealing water restriction and exchange. The normalized signal intensity was plotted against the diffusion weighting factor b, taking into account interaction with the imaging gradients. The curves were analyzed by applying a bi‐exponential decay function assuming two exchanging water compartments, with fast and slow diffusion coefficients. The amplitudes and decay constants of the two exponents, a fast and a slow one, were related to the fraction and apparent diffusion coefficients of the extra‐ and intracellular water, respectively, considering contributions of restriction and exchange. During tumor progression the distribution of the diffusion parameters for the same experimental protocol varied and became less homogeneous. This was predominantly due to variations in the cellularity and increased necrosis. Upon treatment of the tumors with a new anti‐estrogenic drug, tamoxifen methiodide, the changes in the diffusion parameters indicated increased cell swelling. Hence, this cytostatic response to treatment was detected before actual cell death was apparent. The potential capacity of diffusion MRI is of high clinical relevance and may help improve the noninvasive diagnosis and followup of treatment of this devastating disease.