bluuebunny/crossref_metadata_2025 huggingface dataset:
Irreversible Translation Arrest in the Reperfused Brain
Authors: DeGracia Donald J , Hu Bingren R
Published: August 2006

Irreversible translation arrest occurs in reperfused neurons that will die by delayed neuronal death. It is now recognized that suppression of protein synthesis is a general response of eukaryotic cells to exogenous stressors. Indeed, stress-induced translation arrest can be viewed as a component of cell stress responses, and consists of initiation, maintenance, and termination phases that work in concert with stress-induced transcriptional mechanisms. Within this framework, we review translation arrest in reperfused neurons. This framework provides a basis to recognize that phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is the initiator of translation arrest, and a key marker indicating activation of neuronal stress responses. However, eIF2 alpha phosphorylation is reversible. Other phases of stress-induced translation arrest appear to contribute to irreversible translation arrest specifically in ischemic vulnerable neuron populations. We detail two lines of evidence supporting this view. First, ischemia, as a stress stimulus, induces irreversible co-translational protein misfolding and aggregation after 4 to 6 h of reperfusion, trapping protein synthesis machinery into functionally inactive protein aggregates. Second, ischemia and reperfusion leads to modifications of stress granules (SGs) that sequester functionally inactive 48S preinitiation complexes to maintain translation arrest. At later reperfusion durations, these mechanisms may converge such that SGs become sequestered in protein aggregates. These mechanisms result in elimination of functionally active ribosomes and preclude recovery of protein synthesis in selectively vulnerable neurons. Thus, recognizing translation arrest as a component of endogenous cellular stress response pathways will aid in making sense of the complexities of postischemic translation arrest.
in vivo Presynaptic and Postsynaptic Striatal Dopamine Functions in Idiopathic Normal Pressure Hydrocephalus
Authors: Ouchi Yasuomi , Nakayama Teiji , Kanno Toshihiko , Yoshikawa Etsuji , Shinke Tomomi , Torizuka Tatsuo
Published: August 2006

Differentiation of impaired gait seen in idiopathic normal pressure hydrocephalus (iNPH) from parkinsonian gait is sometimes a great challenge and important for future medication in the clinical setting. To investigate dopaminergic contribution to its pathophysiology, two aspects of the transsynaptic dopamine functions in the striatal region in eight iNPH patients naïve to dopaminergic drugs were examined using positron emission tomography with a presynaptic marker [11C]CFT ([11C]2-β-carbomethoxy-3β-(4-fluorophenyl) tropane) that binds to dopamine transporter and a postsynaptic marker [11C]raclopride that binds to D2 receptor. Quantitative values of binding potentials (BPs) for [11C]CFT and [11C]raclopride were compared between patients and eight age-matched healthy subjects. The BPs and magnetic resonance imaging-based morphometric measures in iNPH were used for correlation analyses between the magnitude of binding of these in vivo markers and clinical severity of the patients. Analysis of variance showed significant reduction in [11C]raclopride binding in the putamen and nucleus accumbens ( P < 0.05, corrected for multiple comparison) and unchanged striatal [11C]CFT binding in iNPH. The dorsal putamen [11C]raclopride binding correlated negatively with gait severity ( r = 0.720, P < 0.05), and the nucleus accumbens [11C]raclopride binding correlated positively with emotional recognition score ( r = 0.727, P < 0.05) in the disease group. No significant relationship was observed between BPs and morphometric measures. The current result of the postsynaptic D2 receptor reduction along with preserved presynaptic activity in the nigrostriatal dopaminergic system reflects a pathophysiology of iNPH. Postsynaptic D2 receptor hypoactivity in the dorsal putamen may predict the severity of gait impairment in iNPH.
Reduction of flatus‐inducing factors in soymilk by immobilized α‐galactosidase
Authors: Kulkarni Dhananjay S. , Kapanoor Shankar S. , Girigouda Kotiguda , Kote Naganagouda V. , Mulimani Veerappa H.
Published: August 2006

α‐Galactosidase from Aspergillus oryzae was immobilized on chitosan beads using glutaraldehyde as a cross‐linking agent. The general properties of free and immobilized enzymes were determined. The optimum pH for the free and immobilized enzymes was 4.8 and 4.6 respectively. The optimum temperature for the free enzyme was 50 °C, whereas that of immobilized enzyme was increased to 56 °C. Kinetic parameters were determined with synthetic substrate (p‐nitrophenyl α‐D‐galactopyranoside) and raffinose. Immobilized enzyme showed a higher Km and a lower Vmax than the free enzyme. The immobilized enzymes were used in batch, repeated and continuous mode. A level of 92% hydrolysis was observed at a flow rate of 60 ml/h. The immobilized enzyme was used repeatedly ten times without any change in the performance of the immobilized enzyme in fluidized‐bed reactor. The results obtained are of considerable interest for industrial purposes.
Identification of TRIO‐GEFD1 chemical inhibitors using the yeast exchange assay
Authors: Blangy Anne , Bouquier Nathalie , Gauthier‐Rouvière Cécile , Schmidt Susanne , Debant Anne , Leonetti Jean‐Paul , Fort Philippe
Published: August 2006

Background information. Rho GTPases are involved in many biological processes and participate in cancer development. Their activation is catalysed by exchange factors [RhoGEFs (Rho GTPase guanine nucleotide‐exchange factor)] of the Dbl family. RhoGEFs display proto‐oncogenic features, thus appearing as candidate targets for anticancer drugs. Dominant‐negative Rho GTPase mutants have been widely used to block RhoGEF signalling. However, these tools suffer from limitations, due to the high number of RhoGEFs and the complex mechanisms that control Rho GTPase activation.

Results. RhoG‐T17N is a poor inhibitor of its exchange factor TRIO‐GEFD1 (first exchange domain of the exchange factor TRIO) in vivo: although it binds to TRIO‐GEFD1, RhoG‐T17N does not block the downstream signalling. Using the yeast exchange assay, we show that in the presence of TRIO‐GEFD1, RhoG‐T17N can bind to its effectors, which illustrates how negative mutants may produce misleading interpretations and emphasizes the need for new types of RhoGEF inhibitors. In that prospect, we adapted the yeast exchange assay method to identify RhoGEF inhibitors. Using this novel approach, we screened a 3500‐chemical‐compound library and identified a potential inhibitor of TRIO‐GEFD1. This molecule inhibited TRIO‐GEFD1 in vitro. Among the chemical analogues of this compound, we identified two molecules with better inhibitory activity. The three TRIO‐GEFD1 inhibitors had no effect on ARHGEF17 and ARNO [ARF (ADP‐ribosylation factor) nucleotide‐binding‐site opener], two exchange factors for RhoA and Arf1 respectively.

Conclusions. The development of RhoGEF inhibitors appears as a valuable tool for the study of Rho GTPase signalling pathways. The yeast exchange assay adaptation we present here is suitable to screen for chemical or peptide libraries and identify candidate inhibitors.
Pulsed lateral epitaxial overgrowth of aluminum nitride on sapphire substrates
Authors: Chen Z. , Qhalid Fareed R. S. , Gaevski M. , Adivarahan V. , Yang J. W. , Khan Asif , Mei J. , Ponce F. A.
Published: August 2006

The authors report on pulsed lateral epitaxial overgrowth of aluminum nitride films on basal plane sapphire substrates. This approach, at temperatures in excess of 1150°C, enhanced the adatom migration, thereby significantly increasing the lateral growth rates. This enabled a full coalescence in wing regions as wide as 4–10μm. Atomic force microscopy and cross-section transmission electron microscopy were used to establish the reduction of threading dislocations in the lateral growth. Cross-sectional monochromatic cathodoluminescence and photoluminescence measurements confirmed the improved optical properties of the laterally overgrown aluminum nitride films.
On the generation of large amplitude spiky solitons by ultralow frequency earthquake emission in the Van Allen radiation belt
Authors: Mofiz U. A.
Published: August 2006

The parametric coupling between earthquake emitted circularly polarized electromagnetic radiation and ponderomotively driven ion-acoustic perturbations in the Van Allen radiation belt is considered. A cubic nonlinear Schrödinger equation for the modulated radiation envelope is derived, and then solved analytically. For ultralow frequency earthquake emissions large amplitude spiky supersonic bright solitons or subsonic dark solitons are found to be generated in the Van Allen radiation belt, detection of which can be a tool for the prediction of a massive earthquake may be followed later.
Joule-heating-enhanced colossal magnetoresistance in La0.8Ca0.2MnO3 films
Authors: Chen Y. F. , Ziese M. , Esquinazi P.
Published: August 2006

The temperature, magnetic field, and current dependence of the magnetotransport properties of a La0.8Ca0.2MnO3 film were studied in a regime of strong Joule heating. In current-voltage curves an abrupt hysteretic transition was observed which is induced by global and nondestructive Joule heating of the manganite film by a large electric current. The apparent magnetoresistance measured at an appropriate temperature/current parameter set is strongly enhanced by a feedback between magnetoresistance and Joule heating.
Concept and demonstration of all organic Gratzel solar cell (dye sensitized solar cell)
Authors: Somani Prakash R. , Somani Savita P. , Umeno M. , Sato A.
Published: August 2006

The authors present the concept of “all organic Gratzel/dye sensitized solar cell” and demonstrate such a device using high Tauc band gap (above 2.5eV) amorphous carbon thin films doped with nitrogen (n type) deposited by microwave assisted surface wave plasma chemical vapor deposition and sensitized with copper-phthalocyanine thin films. Open circuit voltage and short circuit current density obtained are about 0.53V (versus Ag∕AgCl, reference electrode) and 8.52×10−6A∕cm2, respectively. The mechanism of photovoltaic action in such cells may be similar to dye sensitized photoelectrochemical cells using nano-TiO2∕ZnO porous thick films.
Large capacitance in the nanosecond-scale transient response of quantum point contacts
Authors: Naser B. , Ferry D. K. , Heeren J. , Reno J. L. , Bird J. P.
Published: August 2006

The transient electrical response of split-gate quantum point contacts (QPCs) is investigated using ultrashort voltage pulses with rise times as small as 2ns. Our measurements reveal a large (∼1nF) parallel capacitance under conditions where the QPC is formed. The capacitance is independent of the QPC gate geometry, and the amplitude and rise time of the applied transient pulse. Some speculations on the source of this capacitance are offered.
Improved surface morphology of stacked 1.3μm InAs∕GaAs quantum dot active regions by introducing annealing processes
Authors: Yang Tao , Tatebayashi Jun , Nishioka Masao , Arakawa Yasuhiko
Published: August 2006

The authors report a simple but effective way to improve the surface morphology of stacked 1.3μm InAs∕GaAs quantum dot (QD) active regions grown by metal-organic chemical vapor deposition (MOCVD), in which GaAs middle spacer and top separate confining heterostructure (SCH) layers are deposited at a low temperature of 560°C to suppress postgrowth annealing effect that can blueshift emission wavelength of QDs. By introducing annealing processes just after depositing the GaAs spacer layers, the authors demonstrate that the surface morphology of the top GaAs SCH layer can be dramatically improved. For a model structure of five-layer QDs, the surface roughness with the introduced annealing processes (IAPs) is reduced to about 1.3nm (5×5μm2 area), much less than 4.2nm without the IAPs. Furthermore, photoluminescence measurements show that inserting the annealing steps does not induce any changes in emission wavelength. This dramatic improvement in surface morphology results from the improved GaAs spacer surfaces due to the IAPs. The technique reported here has important implications for realizing stacked 1.3μm InAs∕GaAs QD lasers based on MOCVD.
Direct synthesis of single-walled carbon nanotubes bridging metal electrodes by laser-assisted chemical vapor deposition
Authors: Shi J. , Lu Y. F. , Yi K. J. , Lin Y. S. , Liou S. H. , Hou J. B. , Wang X. W.
Published: August 2006

Direct synthesis of single-walled carbon nanotubes (SWNTs) bridging prepatterned Mo electrodes has been achieved using laser-assisted chemical vapor deposition (LCVD). The synthesized SWNTs are found predominantly semiconducting. By controlling the spot size of the focused laser beam, synthesis of SWNTs can be achieved in a localized manner, which is governed by the thermal and optical properties of materials as well as the laser parameters. The synthesis process is fast and can be achieved in both far- and near-infrared laser wavelength regions. LCVD method provides a potential approach to in situ remove SWNTs with specific chiralities during the growth.
Topographies of Home and Citizenship: Arab-American Activists in the United States
Authors: Staeheli Lynn A , Nagel Caroline R
Published: August 2006

Home and citizenship carry contradictory and ambiguous meanings for immigrants as they negotiate lives ‘here’ and ‘there’. We use the concept of topography to analyze the ways in which activists in the Arab-American community draw connections between homes in the United States and in the Middle East. In intensive interviews, we ask activists about how their understanding of home influences their activism and positioning as citizens within the United States. Activists often bring to their work conceptualizations of home and citizenship that are open, and that connect home to broader forces operating at various scales and in more than one place. Rather than pursuing a deterritorialized, transnational citizenship, our respondents forged a politics of home and citizenship whose topography transcended localities and nations, even as they were often rooted in the spaces of both.
Power to the Periphery: Suburban Empowerment in Toulouse, France
Authors: Nicholls Walter J
Published: August 2006

Much of the scholarship on the empowerment of suburbs (‘edge city’, ‘ex-urb’, and so on) focuses on American cases and draws upon social and economic variables to explain the phenomenon. In this paper I aim to broaden the empirical reach of the literature by examining the transformation of several municipalities from rural backwaters into powerful political and economic forces in Toulouse, France. I also aim to broaden existing theoretical approaches by closely examining the state's role in the empowerment of this particular patch of suburbs. In particular, I argue that changes in both local economic and state structures have presented officials across Toulouse, France with a broad range of opportunities. Actors with heightened strategic capacities, like those actors composing the suburbs under investigation, have been better able to acquire the wealth and power needed to become potent territorial forces.
Adeno-associated virus serotype 9 vectors transduce murine alveolar and nasal epithelia and can be readministered
Authors: Limberis Maria P. , Wilson James M.
Published: August 2006

Airway-directed gene transfer has emerged as a promising approach for the treatment of the two genetic diseases of the lung, namely cystic fibrosis and α-1-antitrypsin deficiency. Herein we describe the transduction efficiency of a novel adeno-associated virus (AAV) vector, AAV2/9, across murine nasal and lung airway epithelia. At the peak of gene expression AAV2/9-mediated human α-1-antitrypsin gene expression in serum was ≈60-fold better than that of AAV2/5. We found that AAV2/9-mediated
n
LacZ gene transfer in nasal and lung airways was relatively stable for 9 months, suggesting that a progenitor airway cell population was transduced. Most interestingly, we show that AAV2/9 can be readministered in the presence of high levels of serum-circulating neutralizing antibodies as early as 1 month after initial exposure, with minimal effect on overall reporter gene expression, rendering it a promising gene transfer vector candidate for use in humans.
Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury
Authors: Ziv Yaniv , Avidan Hila , Pluchino Stefano , Martino Gianvito , Schwartz Michal
Published: August 2006

The well regulated activities of microglia and T cells specific to central nervous system (CNS) antigens can contribute to the protection of CNS neural cells and their renewal from adult neural stem/progenitor cells (aNPCs). Here we report that T cell-based vaccination of mice with a myelin-derived peptide, when combined with transplantation of aNPCs into the cerebrospinal fluid (CSF), synergistically promoted functional recovery after spinal cord injury. The synergistic effect was correlated with modulation of the nature and intensity of the local T cell and microglial response, expression of brain-derived neurotrophic factor and noggin protein, and appearance of newly formed neurons from endogenous precursor-cell pools. These results substantiate the contention that the local immune response plays a crucial role in recruitment of aNPCs to the lesion site, and suggest that similar immunological manipulations might also serve as a therapeutic means for controlled migration of stem/progenitor cells to other acutely injured CNS sites.
The last eukaryotic common ancestor (LECA): Acquisition of cytoskeletal motility from aerotolerant spirochetes in the Proterozoic Eon
Authors: Margulis Lynn , Chapman Michael , Guerrero Ricardo , Hall John
Published: August 2006

We develop a symbiogenetic concept of the origin of eukaryotic intracellular motility systems from anaerobic but aerotolerant spirochetes in sulfide-rich environments. The last eukaryotic common ancestors (LECAs) have extant archaeprotist descendants: motile nucleated cells with Embden-Meyerhof glycolysis and substrate-level phosphorylation that lack the α-proteobacterial symbiont that became the mitochondrion. Swimming and regulated O
2
-tolerance via sulfide oxidation already had been acquired by sulfidogenic wall-less archaebacteria (thermoplasmas) after aerotolerant cytoplasmic-tubule-containing spirochetes (eubacteria) attached to them. Increasing stability of sulfide-oxidizing/sulfur-reducing consortia analogous to extant sulfur syntrophies (
Thiodendron
) led to fusion. The eubacteria–archaebacteria symbiosis became permanent as the nucleus evolved by prokaryotic recombination with membrane hypertrophy, analogous to
Gemmata obscuriglobus
and other δ-proteobacteria with membrane-bounded nucleoids. Histone-coated DNA, protein-synthetic RNAs, amino-acylating, and other enzymes were contributed by the sulfidogen whereas most intracellular motility derives from the spirochete. From this redox syntrophy in anoxic and microoxic Proterozoic habitats LECA evolved. The nucleus originated by recombination of eu- and archaebacterial DNA that remained attached to eubacterial motility structures and became the microtubular cytoskeleton, including the mitotic apparatus. Direct LECA descendants include free-living archaeprotists in anoxic environments: archamoebae, metamonads, parabasalids, and some mammalian symbionts with mitosomes. LECA later acquired the fully aerobic Krebs cycle-oxidative phosphorylation-mitochondrial metabolism by integration of the protomitochondrion, a third α-proteobacterial symbiont from which the ancestors to most protoctists, all fungi, plants, and animals evolved. Secondarily anaerobic eukaryotes descended from LECA after integration of this oxygen-respiring eubacterium. Explanatory power and experimental predictions for molecular biology of the LECA concept are stated.
Estrogen receptor (ER)-β isoforms: A key to understanding ER-β signaling
Authors: Leung Yuet-Kin , Mak Paul , Hassan Sazzad , Ho Shuk-Mei
Published: August 2006

Estrogen receptor beta (ER-β) regulates diverse physiological functions in the human body. Current studies are confined to ER-β1, and the functional roles of isoforms 2, 4, and 5 remain unclear. Full-length ER-β4 and -β5 isoforms were obtained from a prostate cell line, and they exhibit differential expression in a wide variety of human tissues/cell lines. Through molecular modeling, we established that only ER-β1 has a full-length helix 11 and a helix 12 that assumes an agonist-directed position. In ER-β2, the shortened C terminus results in a disoriented helix 12 and marked shrinkage in the coactivator binding cleft. ER-β4 and -β5 completely lack helix 12. We further demonstrated that ER-β1 is the only fully functional isoform, whereas ER-β2, -β4, and -β5 do not form homodimers and have no innate activities of their own. However, the isoforms can heterodimerize with ER-β1 and enhance its transactivation in a ligand-dependent manner. ER-β1 tends to form heterodimers with other isoforms under the stimulation of estrogens but not phytoestrogens. Collectively, these data support the premise that (
i
) ER-β1 is the obligatory partner of an ER-β dimer, whereas the other isoforms function as variable dimer partners with enhancer activity, and (
ii
) a single functional helix 12 in a dimer is sufficient for gene transactivation. Thus, ER-β behaves like a noncanonical type-I receptor, and its action may depend on differential amounts of ER-β1 homo- and heterodimers formed upon stimulation by a specific ligand. Our findings have provided previously unrecognized directions for studying ER-β signaling and design of ER-β-based therapies.
Amplification of enantiomeric concentrations under credible prebiotic conditions
Authors: Breslow Ronald , Levine Mindy S.
Published: August 2006

Solutions with as little as 1% enantiomeric excess (ee) of
d
- or
l
-phenylalanine are amplified to 90% ee (a 95/5 ratio) by two successive evaporations to precipitate the racemate. Such a process on the prebiotic earth could lead to a mechanism by which meteoritic chiral α-alkyl amino acids could form solutions with high ee values that were needed for the beginning of biology.
Thomas Edison's Monetary Option
Authors: Hammes David L. , Wills Douglas T.
Published: August 2006

In 1922, Thomas Edison publicly introduced his latest invention—a new type of money, a commodity-backed currency that he believed was the long-term solution to America's monetary woes. “I want to cast the variable out of money. This gold money is not good enough. It's a fiction” he boldly proclaimed (New York Times 1922).
Hayek, The Road to Serfdom, and the British Conservatives
Authors: Shearmur Jeremy
Published: August 2006

Over the years, Friedrich Hayek has received a generous response from some members of the British Conservative Party. One immediately thinks of endorsements of his work by Mrs. Thatcher in the 1970s and '80s.

Those with longer memories—and teeth—might also recall the controversy around Winston Churchill's first election broadcast in 1945, and the response to it by the Labour leader Clement Attlee, the following evening. Churchill spoke of the dangers of planning, and raised the idea that it would, in the end, require the powers of a Gestapo to put the ideal of a planned society into practice. Attlee criticized these ideas, and Hayek as the source of the theoretical conceptions behind them. This led to a fair bit of attention being paid to Hayek by the press, and to his being described as an economic adviser to Churchill. But Hayek himself has downplayed his direct contacts with Churchill (cf. Hayek 1994, pp. 106–107). Indeed, in Hayek on Hayek (Hayek 1994), Hayek indicates that he met Churchill only once. On that occasion he was struck by Churchill's being the worse for drink and then recovering, to Hayek's surprise, to make a first-rate speech.
Schumpeterian Entrepreneurship Revisited: Historical Specificity and the Phases of Capitalist Development
Authors: Ebner Alexander
Published: August 2006

Schumpeter's theory of entrepreneurship and innovation has been repeatedly interpreted in terms of a conceptual dualism, shifting from an early model of personal entrepreneurship in newly founded enterprises to a late model of research and development in large enterprises, responding to changes in the productive organization of capitalism. Due to theoretical inconsistencies, Schumpeter thus seemingly altered his argument on the role of entrepreneurship in economic development (Freeman et al. 1982, pp. 41–42). In countering these allegations, it has been put forward that Schumpeter's instrumental methodology would allow for settling historical experiences and theoretical reasoning on different analytical levels. Accordingly, the substantial validity of the Schumpeterian approach would remain independent from variable historical settings (Frank 1998, pp. 505–506). Adding to these methodological considerations, it has been suggested that the consistency of Schumpeter's argument could be reconstructed in terms of an explanation of capitalist development that resonates Weberian thought on rationalization and bureaucratization (Langlois 1998b, pp. 57–58).
Knut Wicksell and Ludwig von Mises on Money, Interest, and Price Dynamics
Authors: Festré Agnès
Published: August 2006

In the aftermath of the so-called Marginal Revolution of the last end of the nineteenth century, economic analysis split into two branches. The first one was made up of economists who took as the methodological starting-point of their analyses the static or stationary state of a barter economy and considered that this basic framework was likely to be extended in order to account for monetary and financial considerations, as well as dynamics. However, in such a setting, the introduction of money, bank-credit, or any factor of growth did not substantially alter the features that are associated with the rudimentary economy of static real exchange.
Urban pedagogy: a proposal for the twenty-first century
Authors: Dobson Stephen
Published: August 2006

The urban has been studied by students of geography, politics, aesthetics/culture, architects and politicians. Educational researchers in defining the urban as a field of research and practice have looked at schooling and its institutionalized role in cities. A wider discussion of the
very character of urban experience and its relevance for pedagogic reflection and practice is a topic that still has to be explored. There are of course some exceptions, such as the Center for Urban Pedagogy in the US and its interest in environmental experiences in an urban context and researchers
looking at the community–school relationship or the role of the family and locality. This essay makes an argument for urban pedagogy in the twenty-first century. The inspiration for this proposal is taken from psycho-geographers, both classical (the dialectical imagery of Walter Benjamin)
and contemporary (Iain Sinclair) and their emphasis on erfaringspedagogikk (the pedagogy of experience). A number of topics are covered: the movement of pedagogy to informal, less institutionalized arenas, the flâneur, educating the senses (emotions, acoustic, visual/optic, taste,
tactile), signifiers and commodity culture. It is argued that these topics can share a concern with living and learning to live in the urban. Towards the end of the essay, how to realize urban pedagogy is raised as a topic for discussion.
The postmodern university revisited: reframing higher education debates from the 'two cultures' to postmodernity
Authors: Strohl Nicholas M.
Published: August 2006

Current debate on higher education in Britain is focused on its instrumental functions and largely ignores its social and cultural value. This paper considers the 'idea of the university' in an historical perspective and critically examines current policy discourse while identifying
robust alternatives to the utilitarian argument. It proposes, speculatively, the notion of 'cosmopolitanism', as defined by critics of pluralism and postmodernism, as a more meaningful starting point for philosophical and policy discussions.
Characteristics of graduate professional education: expectations and experiences in psychology and law
Authors: Karseth Berit , Solbrekke Tone Dyrdal
Published: August 2006

This paper argues that there are some common characteristics that define what we label graduate professional programmes. By analysing two programmes, law and psychology—as experienced by the students—it becomes obvious that while the programmes educate their students well
in the academic aspects of professional work, they do not prepare students sufficiently for dealing with moral conflicts and complex moral challenges. Although there are substantial differences between the two programmes, they reflect cultural characteristics of the academy with its emphasis
on the authority of disciplinary knowledge. The findings suggest that while there are critical challenges for professional graduate programmes to keep up to date with the academic content, there are also even larger challenges in preparing students more adequately for dealing with practical
and moral issues.
Conducting systematic review in education: a reflexive narrative
Authors: Nind Melanie
Published: August 2006

The evaluation of systematic review as part of the evidence-based or evidence-informed practice movement is a dominant theme in current debates in educational research. This article contributes to the debate by offering a personal, reflexive narrative on the process of doing systematic
review, relating some of the arguments regarding the merits and problems of systematic review to the author's own experience and to parallels in other research approaches. The author highlights areas where systematic review might usefully develop and evolve.
The 'presence' of evaluation theory and practice in educational and social development: toward an inclusive approach
Authors: Saunders Murray
Published: August 2006

This paper outlines a vision of evaluation and its place in social and educational policy and practice. It focuses on the 'presence' of evaluation in theory, organizational learning and internationalization and the 'voice' of participants in the evaluation process drawing on a range
of examples of evaluation practice. It argues for an 'inclusive' evaluation stance from a moral/political standpoint and from the standpoint of sound evaluation design. It offers evaluation as a way of promoting and depicting the effects of social policy on its recipients and concludes by
suggesting the way evaluations can promote 'provisional stabilities' for those experiencing rapid and complex change.
Text similarity: an alternative way to search MEDLINE
Authors: Lewis James , Ossowski Stephan , Hicks Justin , Errami Mounir , Garner Harold R.
Published: August 2006

Motivation: The most widely used literature search techniques, such as those offered by NCBI's PubMed system, require significant effort on the part of the searcher, and inexperienced searchers do not use these systems as effectively as experienced users. Improved literature search engines can save researchers time and effort by making it easier to locate the most important and relevant literature.

Results: We have created and optimized a new, hybrid search system for Medline that takes natural text as input and then delivers results with high precision and recall. The combination of a fast, low-sensitivity weighted keyword-based first pass algorithm to cast a wide net to gather an initial set of literature, followed by a unique sentence-alignment based similarity algorithm to rank order those results was developed that is sensitive, fast and easy to use. Several text similarity search algorithms, both standard and novel, were implemented and tested in order to determine which obtained the best results in information retrieval exercises.

Availability: Literature searching algorithms are implemented in a system called eTBLAST, freely accessible over the web at . A variety of other derivative systems and visualization tools provides the user with an enhanced experience and additional capabilities.

Contact:  Harold.Garner@UTSouthwestern.edu
Systematic component selection for gene-network refinement
Authors: Radde Nicole , Gebert Jutta , Forst Christian V.
Published: August 2006

Motivation: A quantitative description of interactions between cell components is a major challenge in Computational Biology. As a method of choice, differential equations are used for this purpose, because they provide a detailed insight into the dynamic behavior of the system. In most cases, the number of time points of experimental time series is usually too small to estimate the parameters of a model of a whole gene regulatory network based on differential equations, such that one needs to focus on subnetworks consisting of only a few components. For most approaches, the set of components of the subsystem is given in advance and only the structure has to be estimated. However, the set of components that influence the system significantly are not always known in advance, making a method desirable that determines both, the components that are included into the model and the parameters.

Results: We have developed a method that uses gene expression data as well as interaction data between cell components to define a set of genes that we use for our modeling. In a subsequent step, we estimate the parameters of our model of piecewise linear differential equations and evaluate the results simulating the behavior of the system with our model.

We have applied our method to the DNA repair system of Mycobacterium tuberculosis. Our analysis predicts that the gene Rv2719c plays an important role in this system.

Contact:  {radde.gebert}@zpr.uni-koeln.de, chris@lanl.gov
Eigengene-based linear discriminant model for tumor classification using gene expression microarray data
Authors: Shen Ronglai , Ghosh Debashis , Chinnaiyan Arul , Meng Zhaoling
Published: August 2006

Motivation: The nearest shrunken centroids classifier has become a popular algorithm in tumor classification problems using gene expression microarray data. Feature selection is an embedded part of the method to select top-ranking genes based on a univariate distance statistic calculated for each gene individually. The univariate statistics summarize gene expression profiles outside of the gene co-regulation network context, leading to redundant information being included in the selection procedure.

Results: We propose an Eigengene-based Linear Discriminant Analysis (ELDA) to address gene selection in a multivariate framework. The algorithm uses a modified rotated Spectral Decomposition (SpD) technique to select ‘hub’ genes that associate with the most important eigenvectors. Using three benchmark cancer microarray datasets, we show that ELDA selects the most characteristic genes, leading to substantially smaller classifiers than the univariate feature selection based analogues. The resulting de-correlated expression profiles make the gene-wise independence assumption more realistic and applicable for the shrunken centroids classifier and other diagonal linear discriminant type of models. Our algorithm further incorporates a misclassification cost matrix, allowing differential penalization of one type of error over another. In the breast cancer data, we show false negative prognosis can be controlled via a cost-adjusted discriminant function.

Availability: R code for the ELDA algorithm is available from author upon request.

Contact:  zhaoling.meng@sanofi-aventis.com

Supplementary information: Supplementary data are available at Bioinformatics online.
SBML-PET: a Systems Biology Markup Language-based parameter estimation tool
Authors: Zi Zhike , Klipp Edda
Published: August 2006

Summary: The estimation of model parameters from experimental data remains a bottleneck for a major breakthrough in systems biology. We present a Systems Biology Markup Language (SBML) based Parameter Estimation Tool (SBML-PET). The tool is designed to enable parameter estimation for biological models including signaling pathways, gene regulation networks and metabolic pathways. SBML-PET supports import and export of the models in the SBML format. It can estimate the parameters by fitting a variety of experimental data from different experimental conditions. SBML-PET has a unique feature of supporting event definition in the SMBL model. SBML models can also be simulated in SBML-PET. Stochastic Ranking Evolution Strategy (SRES) is incorporated in SBML-PET for parameter estimation jobs. A classic ODE Solver called ODEPACK is used to solve the Ordinary Differential Equation (ODE) system.

Availability:  . The website also contains detailed documentation for SBML-PET.

Contact:  klipp@molgen.mpg.de, zhike_zi@molgen.mpg.de
Pivotal role of Notch signaling in regulation of erythroid maturation and proliferation
Authors: Tachikawa Yoshimichi , Matsushima Takamitsu , Abe Yasunobu , Sakano Seiji , Yamamoto Masahiro , Nishimura Junji , Nawata Hajime , Takayanagi Ryouichi , Muta Koichiro
Published: August 2006

Abstract:  Notch signaling plays an important role in cell fate decisions in developmental systems. To clarify its role in committed hematopoietic progenitor cells, we investigated the effects of Notch signaling in erythroid colony forming cells (ECFCs) generated from peripheral blood. ECFCs express Notch receptors, Notch1 and Notch2, and Notch ligands Delta1, Delta4, and Jagged1. When we assayed the effects of Notch ligands on erythroid maturation by flow cytometry, we found that immobilized Delta1 and immobilized Delta4 in particular inhibited maturation, whereas Jagged1 had no effect. In addition, Delta4 inhibited proliferation without reducing cell viability. Increases in expression levels of the Notch target gene hairy enhancer of split (HES) ‐1 were evident by real‐time PCR after stimulation with immobilized Delta4. The effect of soluble Delta4 on expression of HES‐1 was less pronounced than that seen with the immobilized form, indicating that all surface‐bound ligands are important for effective signal transduction. When ECFCs were cultured in the presence of soluble Delta4 at a low cell concentration, erythroid maturation was slightly inhibited, but at a high concentration, maturation was promoted via competition of soluble Delta4 with endogenous ligands. These results indicate a pivotal role of Notch signaling in regulating erythroid maturation and proliferation, and further suggest that cell–cell interactions modulate growth of erythroid progenitor cells via Notch system.
Induction of remission of relapsed acute myeloid leukemia after unrelated donor cord blood transplantation by concomitant low‐dose cytarabine and calcitriol in adults
Authors: Yamada Kazunari , Mizusawa Masako , Harima Akane , Kajiwara Koichi , Hamaki Tamae , Hoshi Keiko , Kozai Yasuji , Kodo Hideki
Published: August 2006

Abstract:  Low‐dose cytarabine and calcitriol (LDCA + VD3) combination therapy was performed in two adult patients with acute myeloid leukemia (AML) that relapsed within 1 yr after unrelated donor cord blood transplantation (URD CBT) performed in a relapse or non‐remission stage. Concomitant aclarubicin was also administered in one patient. Remission because of recovery of donor cord blood hematopoiesis was obtained in both patients. The treatment was low intensive, and neither adverse effects in terms of digestive symptoms nor hypercalcemia was observed. Activity of daily life was maintained. The patients were followed as outpatients after remission, and the remission duration was approximately 6 months in both patients. Although LDCA + VD3 therapy is minimally intensive chemotherapy, it may prolong the survival time of patients with relapsed AML after URD CBT.
Transcription factor Fli‐1 expression by bone marrow cells in chronic myeloproliferative disorders is independent of an underlying JAK2 (V617F) mutation
Authors: Bock Oliver , Hussein Kais , Neusch Michael , Schlué Jerome , Wiese Birgitt , Kreipe Hans
Published: August 2006

Abstract:  Objectives: Friend leukemia integration‐1 (Fli‐1), a member of the Ets gene family of transcription factors, has been demonstrated to be a target of a leukaemia inducing virus in mice, and is known to be part of a fusion gene in Ewings’ sarcoma in humans. Wild‐type Fli‐1 is involved in lineage commitment of megakaryocytes and myeloid progenitors through induction of Janus kinases (JAKs) following ligand binding to cytokine and growth factor receptors. Proliferation of atypical megakaryocytes is a predominant histopathological feature in Philadelphia chromosome negative chronic myeloproliferative disorders (Ph− CMPD) and a potential aberrant expression of Fli‐1 has not been investigated so far. Methods: Fli‐1 expression was investigated by real‐time RT‐PCR and immunohistochemistry in bone marrow cells derived from Ph− CMPD (n = 80) and non‐neoplastic haematopoiesis (n = 21) following determination of the JAK2 status. Results: Fli‐1 mRNA expression was significantly higher in Essential thrombocythaemia (ET) with JAK2 (V617F) compared with other Ph− CMPD and control (P < 0.001). By immunohistochemistry, Fli‐1 protein could be detected in nuclei of atypical megakaryocytes in Ph− CMPD and, less accentuated, in non‐neoplastic megakaryocytes. Fli‐1 protein expression by myeloid progenitors was considerably heterogenous in Ph− CMPD independent of an underlying JAK2 (V617F) mutation and without notable differences to non‐neoplastic haematopoiesis. Conclusion: Fli‐1 is rather constitutively expressed by bone marrow cells in Ph− CMPD independent of the underlying JAK2 status. The overall stronger labelling for Fli‐1 in megakaryocytes in Ph− CMPD most likely reflects the degree of polyploidisation but aberrant activation of nuclear target genes can not be excluded.
Sivelestat relieves respiratory distress refractory to dexamethasone in all‐trans retinoic acid syndrome: a report of two cases
Authors: Kawasaki Kozo , Akaike Hiroto , Miyauchi Ayaka , Ouchi Kazunobu
Published: August 2006

Abstract:  Treatment with all‐trans retinoic acid (ATRA) improves the prognosis of patients with acute promyelocytic leukemia (APL), but ATRA syndrome may occur as a possible fatal side effect, especially in cases refractory to medication or involving pulmonary hemorrhage. We describe two patients with APL who suffered from intracranial hemorrhage. The first patient was a 16‐yr‐old girl who was treated with ATRA and then developed respiratory distress refractory to treatment with dexamethasone combined with anthracycline‐cytarabine cytoreduction therapy. Treatment with Sivelestat, a small molecule inhibitor of neutrophil elastase, achieved rapid improvement in oxygenation and chest radiograph findings, and the patient has been in complete remission for 24 months. The second patient was a 10‐yr‐old boy in whom pulmonary hemorrhage developed following administration of ATRA, dexamethasone and cytoreduction therapy. Aspiration and administration of Sivelestat improved oxygenation and he remained stable. Hematological improvement was also achieved, but the patient died of brain dysfunction because of cerebral edema accompanied by intracranial bleeding. The two cases suggest that Sivelestat may be effective as an additional agent in the treatment of refractory ATRA syndrome, and, therefore, prospective randomized studies of treatment protocols are warranted.
Serum YKL‐40 concentrations in newly diagnosed multiple myeloma patients and YKL‐40 expression in malignant plasma cells
Authors: Mylin Anne K. , Rasmussen Thomas , Johansen Julia S. , Knudsen Lene M. , Nørgaard Peter H. , Lenhoff Stig , Dahl Inger M. S. , Johnsen Hans E. ,   the Nordic Myeloma Study Group
Published: August 2006

Abstract:  Objectives: A potential role in cancer biology is suggested for YKL‐40 (CHI3L1, HC gp‐39). The purpose of this study was to evaluate the clinical value of serum YKL‐40 (sYKL‐40) in multiple myeloma (MM) and to examine YKL‐40 expression in malignant plasma cells (MM PCs). Methods: sYKL‐40 was measured by enzyme‐linked immunosorbent assay (ELISA) in 82 patients with newly diagnosed MM. YKL‐40 expression in immunophenotypically defined plasma cells was investigated by double‐labelled immunohistochemistry in 21 MM patients and by real‐time reverse transcriptase polymerase chain reaction (RT‐PCR) in cDNA archives generated by global RT‐PCR in seven controls, 14 patients with monoclonal gammopathy of undetermined significance (MGUS), 45 MM patients, nine patients with extramedullary myeloma (exMM), and seven human myeloma cell lines (HMCLs). Results: sYKL‐40 was elevated above a constructed reference range for healthy controls in 29% of the patients investigated. Patients with elevated sYKL‐40 had reduced overall survival and event‐free survival when compared to patients with normal sYKL‐40, but sYKL‐40 level was defeated by β2‐microglobulin in the multivariate analyses. Intramedullary MM PCs lacked significant expression of YKL‐40, but high levels of YKL‐40 expression were seen in extramedullary MM PCs from one exMM patient and in six HMCLs. Further investigations of other bone marrow (BM) cells showed YKL‐40 expression in megakaryocytes, neutrophils and adherent cells from long‐term BM cultures. Conclusions: In newly diagnosed MM‐patients, a sYKL‐40 elevated above the reference range predicts a poor clinical outcome, and YKL‐40 is expressed by other BM cells than MM PCs. At this point, routine measurements of sYKL‐40 are not warranted, but YKL‐40 should be considered as a potential player in the pathophysiology of MM.
Treatment with bortezomib in a patient with heavily pretreated refractory T‐cell lymphoblastic lymphoma
Authors: Mai Wenyuan , Meng Haitao , Jin Jie , Wang Lei
Published: August 2006

Abstract:  T‐cell lymphoblastic lymphomas are highly aggressive non‐Hodgkin's lymphoma (NHL) and account for approximately 3% of all adult NHL histologies, with poor prognosis. We describe a 38‐year‐old patient with T‐cell lymphoblastic lymphoma, who responds to bortezomib and doxorubincin combination, following a failure of conventional chemotherapy. Two months after treatment, the patient showed near complete remission of the lymphadenopathy. These data suggest a possible synergistic effect with bortezomib in combination with doxorubincin and dexamethasone. To our knowledge, this is the first case of T‐cell lymphoblastic lymphoma treated with bortezomib.