bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in the analysis of proteins and peptides by capillary electrophoresis with matrix‐assisted laser desorption/ionization and electrospray‐mass spectrometry detection
Authors: Stutz Hanno
Published: March 2005

High throughput, outstanding certainty in peptide/protein identification, exceptional resolution, and quantitative information are essential pillars in proteome research. Capillary electrophoresis (CE) coupled to mass spectrometry (MS) has proven to meet these requirements. Soft ionization techniques, such as matrix‐assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI), have paved the way for the story of success of CE‐MS in the analysis of biomolecules and both approaches are subject of discussion in this article. Meanwhile, CE‐MS is far away from representing a homogeneous field. Therefore the review will cover a vast area including the coupling of different modes of CE (capillary zone electrophoresis, capillary isoelectric foscusing, capillary electrochromatography, micellar electrokinetic chromatography, nonaqueous capillary electrophoresis) to MS as well as on‐line preconcentration techniques (transient capillary isotachophoresis, solid‐phase extraction, membrane preconcentration) applied to compensate for restricted detection sensitivity. Special attention is given to improvements in interfacing, namely addressing nanospray and coaxial sheath liquid design. Peptide mapping, collision‐induced dissociation with subsequent tandem MS, and amendments in mass accuracy of instruments improve information validity gained from MS data. With 2‐D on‐line coupling of liquid chromatography (LC) and CE a further topic will be discussed. A special section is dedicated to recent attempts in establishing CE‐ESI‐MS in proteomics, in the clinical and diagnostic field, and in the food sector.
Lipopolysaccharide recognition protein, MD‐2, facilitates cellular uptake of E. coli‐derived plasmid DNA in synovium
Authors: Kolka Jacquelyn A. , Vreede Andrew P. , Roessler Blake J.
Published: March 2005

Background

Several cell types are susceptible to transfection in vivo using naked plasmid DNA. The mechanisms involved in mediating in vivo transfection are incompletely known, but evidence suggests that receptor‐mediated endocytosis is important for specific types of cells. In this study we tested the hypothesis that residual Escherichia coli lipopolysaccharide (LPS) forms a non‐covalent complex with expression plasmid DNA, and host‐cell‐derived soluble LPS‐binding proteins bind to the DNA‐LPS complexes in order to facilitate receptor‐mediated endocytosis.

Methods

Cells from the murine synovial lining were used as an in vivo model system and in vivo luciferase imaging was used to quantify levels of transgene expression. Using a series of gene‐deleted mice, the roles of LPS recognition complex proteins, lipopolysaccharide‐binding protein (LBP), CD14 and MD‐2, in the process of in vivo transfection were determined.

Results

Luciferase expression assays revealed that mice lacking LBP or CD14 had increased luciferase expression (p < 0.023 and < 0.165, respectively), while mice deleted of MD‐2 had significant reductions in luciferase expression (p < 0.001). Gene deletion of hyaluronic acid binding protein CD44 was used as a control and had no statistically significant effect on transgene expression in vivo. In muscle tissue, where neither cell surface nor soluble MD‐2 is expressed, no MD‐2 dependence of plasmid transfection was identified, suggesting the role of MD‐2 is tissue or cell type specific. Additionally, depleting mice of macrophages showed that luciferase expression is occurring within fibroblast‐like synoviocytes.

Conclusions

Our data support a physical association between LPS and E. coli‐derived plasmid DNA, and that in vivo transfection of fibroblast‐like synoviocytes is dependent on the soluble form of the LPS‐binding protein MD‐2. Copyright © 2005 John Wiley & Sons, Ltd.
Epidermis promotes dermal fibrosis: role in the pathogenesis of hypertrophic scars
Authors: Bellemare Judith , Roberge Charles J , Bergeron Danielle , Lopez‐Vallé Carlos A. , Roy Michel , Moulin Véronique J
Published: March 2005

Hypertrophic scarring is a pathological process characterized by fibroblastic hyperproliferation and by excessive deposition of extracellular matrix components. It has been hypothesized that abnormalities in epidermal–dermal crosstalk explain this pathology. To test this hypothesis, a tissue‐engineered model of self‐assembled reconstructed skin was used in this study to mimic interactions between dermal and epidermal cells in normal or pathological skin. These skin equivalents were constructed using three dermal cell types: normal wound (Wmyo) or hypertrophic wound (Hmyo) myofibroblasts and normal skin fibroblasts (Fb). Epidermis was reconstructed with normal skin keratinocytes (NK) or hypertrophic scar keratinocytes (HK). In the absence of keratinocytes, Hmyo formed a thicker dermis than Wmyo. When seeded with NK, the dermal thickness of Hmyo (121.2 ± 31.4 µm vs 196.2 ± 27.8 µm) and Fb (43.7 ± 7.1 µm vs 83.6 ± 16.3 µm) dermis was significantly (p < 0.05) reduced, while that of Wmyo (201.5 ± 15.7 µm vs 160.7 ± 21.1 µm) was increased. However, the presence of HK always induced significantly thicker dermis formation than observed with NK (Wmyo: 238.8 ± 25.9 µm; Hmyo: 145.5 ± 22.4 µm; Fb: 74.2 ± 11.2 µm). These results correlated with collagen and MMP‐1 secretion and with cell proliferation, which were increased when keratinocytes were added, except for the collagen secretion of Hmyo and Fb in the presence of NK. The level of dermal apoptosis was not different when epidermis was added to the dermis (<1% in each category). These observations strongly suggest that hypertrophic scar keratinocytes play a role in the development of pathological fibrosis by influencing the behaviour of dermal cells. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Leading Business Improvement: a New Role for Statisticians and Quality Professionals
Authors: Snee Ronald D.
Published: March 2005

Following the successes of Motorola, Allied‐Signal, General Electric and others, many companies are implementing the Six Sigma approach to business improvement. Millions of dollars are being saved in the process. Active leadership by management and others involved is integral to the method and critical to its success. This development provides a unique opportunity for statisticians and quality professionals to be leaders in their organizations. The leadership roles are discussed and it is shown how statisticians and quality professionals can assume leadership roles throughout the deployment process. As a result statisticians and quality professionals can expand their roles as internal trainers and consultants to include being leaders of business improvement. In the process their focus moves from facilitation of technical applications to the implementation of Six Sigma, skill deployment and delivery of bottom line business results. Copyright © 2005 John Wiley & Sons, Ltd.
Modeling institutional change in transition economies
Authors: Kyriazis Nicholas C. , Zouboulakis Michel S.
Published: March 2005

A particular aspect of path dependence and change is discussed here. To understand institutional change in transition economies, a game theoretic model that combines economic changes with changes in the social values system is proposed, in a mechanism where the two changes are interdependent and influence one another in a repeated game. The speed of change in this dynamic model is the result of two rates, the ‘‘learning rate’’, how fast agents are learning to play the new ‘‘capitalist’’ game and the so-called ‘‘going-over rate’’, the mix in every time period of economic agents playing according to the ‘‘old’’ communist values and those playing according to the ‘‘new’’ capitalist values.
Latent structure of depression in a community sample: a taxometric analysis
Authors: SLADE TIM , ANDREWS GAVIN
Published: March 2005

Background. The latent structure of depression was examined using taxometric analysis, a family of statistical procedures designed specifically to test whether a given construct is best conceptualized as a distinct category or a continuous dimension.

Method. Data were derived from the Australian National Survey of Mental Health and Well-Being, a large epidemiological survey that measured the prevalence of the major DSM-IV and ICD-10 mental disorders. Two taxometric procedures, maximum covariance (MAXCOV) and mean above minus below a cut (MAMBAC), were carried out on a sample of 1933 community volunteers. Simulated categorical and dimensional datasets aided in the interpretation of the research data.

Results. The results of the taxometric analyses in the subsample who endorsed at least one symptom of depression were consistent with a dimensional latent structure of depression.

Conclusions. The findings of the current study suggest that depression, as measured in this subsample, is best conceptualized, measured and classified as a continuously distributed syndrome rather than as a discrete diagnostic entity. Incorporation of dimensional measurement into psychiatric classification systems remains a challenge for the future.
The socio-economic status of communities predicts variation in brain serotonergic responsivity
Authors: MANUCK STEPHEN B. , BLEIL MARIA E. , PETERSEN KAREN L. , FLORY JANINE D. , JOHN MANN J. , FERRELL ROBERT E. , MULDOON MATTHEW F.
Published: March 2005

Background. We reported previously that the socio-economic status (SES) of individuals predicts variation in brain serotonergic responsivity, as assessed by neuropharmacological challenge in an adult community sample, and that this association is qualified by allelic variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR). Here we examine whether serotonergic responsivity covaries similarly with the SES of communities, as indexed by US Census data in the same study sample.

Method. Community SES was defined by levels of income, economic disadvantage, housing costs, and educational attainment of census tracts in which 249 locally recruited study participants (54% male) resided. Serotonergic responsivity was assessed as the baseline-adjusted, peak plasma prolactin (Prl) concentration following acute administration of the serotonin-releasing agent, fenfluramine; tissue for DNA extraction and 5-HTTLPR genotyping was available on 131 participants.

Results. Subjects residing in census tracts of lower SES showed a blunted Prl response to fenfluramine (diminished serotonergic responsivity) relative to individuals living in more affluent neighborhoods. When adjusted for personal income and education, SES at the community level continued to predict fenfluramine-stimulated Prl responses and did so independently of 5-HTTLPR genotype.

Conclusions. Area-level indices of relative social and economic disadvantage covary with individual differences in brain serotonergic responsivity, and this association is, in part, independent of individually defined SES. These findings may be relevant to reported effects of low community SES on the prevalence of psychiatric disorders or behaviors associated with dysregulation of central serotonergic function, such as depression, impulsive aggression, and suicide.
A Qualitative Analysis of the Failure of CBT for Chronic Fatigue Conducted by General Practitioners
Authors: Bazelmans Ellen , Huibers Marcus J. H. , Bleijenberg Gijs
Published: March 2005

We assessed the efficacy of cognitive behaviour therapy (CBT) delivered by general practitioners (GPs) to fatigued employees on sick leave. CBT had no substantial effect on clinical outcomes. In the present study, we aim to describe the treatment protocol and present an analysis of the delivery of the intervention. To assess protocol execution, GPs used standardized registration forms in each treatment session. A quality check was performed to assess whether CBT was completed according to protocol. Of the 71 patients starting CBT, 51 patients completed the intervention. There were no striking differences in protocol execution between those who recovered after CBT and those who did not recover. Although there were differences in the performance and delivery of CBT, there was no association between protocol execution and treatment results of individual GPs. Despite the lack of efficacy, the intervention received a positive evaluation from both patients and GPs. CBT completers who recovered did not receive a clearly different treatment than those who did not recover. In addition, successful GPs did not deliver a clearly different treatment than less successful GPs. The lack of efficacy can at least partly be attributed to the inadequacy of the intervention, whether it is the intervention itself or its delivery by GPs.
The Beliefs about Paranoia Scale: Preliminary Validation of a Metacognitive Approach to Conceptualizing Paranoia
Authors: Morrison Anthony P. , Gumley Andrew I. , Schwannauer Matthias , Campbell Michelle , Gleeson Anna , Griffin Elizabeth , Gillan Kate
Published: March 2005

This study reports the development of a self-report measure to assess metacognitive beliefs about paranoia in non-patients. We aimed to test the specific hypotheses that positive beliefs about paranoia would predict frequency of paranoia, and that negative beliefs about paranoia would predict distress associated with delusional ideation. Three-hundred and seventeen non-patient participants were asked to complete questionnaires assessing beliefs about paranoia, paranoia, dimensions of delusional ideation and trait anxiety. The results showed that four empirically distinct subscales were measured by the beliefs about paranoia scale (negative beliefs about paranoia, beliefs about paranoia as a survival strategy, general positive beliefs and normalising beliefs). The scales possessed acceptable internal consistency and were associated with the measures of paranoia, delusional ideation and anxiety. Consistent with predictions, it was found that beliefs about paranoia as a survival strategy were associated with frequency of paranoia, and negative beliefs were associated with distress associated with delusional ideation. These findings suggest that a metacognitive approach to the conceptualization of paranoia as a strategy for managing interpersonal threat may have some utility. The clinical implications of the findings are also discussed.
The Development of Behavioural Coping Skills in a Repetitive and Deliberately Self-Harming Young Woman
Authors: Wheatley Malcolm , Hollin Clive
Published: March 2005

This project reports on the effective delivery of a behavioural coping skills programme with a repetitive deliberately self-harming young woman. A simple single case A-B design was employed to evaluate the intervention due to the applied nature of the project and ethical considerations. An assessment period prior to the intervention phase constituted an extended baseline. Data concerning the primary dependent variable, deliberate self-harm, were collected for a 3-month follow-up period.
Synthesis of Arylmethylenemalononitriles Catalyzed by KF - Al2O3 under Ultrasound
Authors: Li Ji-Tai , Chen Guo-Feng , Wang Shu-Xiang , He Lin , Li Tong-Shuang
Published: March 2005

Knoevenagel condensation of malononitrile with aromatic aldehydes catalyzed by KF–Al2O3 under ultrasound irradiation in anhydrous ethanol results in the formation of arylmethylenemalononitriles in 73–97% yields within 15–60 min.
Ionic Liquids: The Neglected Issues
Authors: Scammells Peter J. , Scott Janet L. , Singer Robert D.
Published: March 2005

There has been an explosion of interest in ionic liquids in the last five years that has resulted in the discovery of a vast number of new ionic liquids with a wide range of interesting applications. Although ionic liquids are invariably described as highly stable green solvents, thorough investigations quantifying their purity, stability, biodegradability, and toxicity have lagged behind the pace of other research in the area. This review addresses these key issues and summarizes the approaches that have been developed for recycling ionic liquids.
General Solution to the Band-Broadening Problem in Polymer Molecular Weight Distributions
Authors: Castro Jeffrey V. , van Berkel Kim Y. , Russell Gregory T. , Gilbert Robert G.
Published: March 2005

A method is developed for overcoming the problem of band broadening (where a sample which is monodisperse in molecular weight elutes over a range of elution volumes) in order to obtain accurate molecular weight distributions of polymers using size exclusion chromatography (SEC). It is proved that the SEC signal from an exponential number distribution (as obtained from free-radical polymerization under certain conditions) has the same functional form at the maximum, irrespective of band broadening. This leads to a method for quantifying the band broadening from any SEC trace, and hence for deconvoluting the trace to obtain the true distribution—by free-radical polymerization one should synthesize ‘standards’ which have exponential distributions and then carry out least-squares fitting to find the corresponding broadening function. The new method opens the way for mechanistic understanding and rate parameters to be obtained from the full detail that has hitherto been inaccessible in molecular weight distributions.
Oligomeric Bax Is a Component of the Putative CytochromecRelease Channel MAC, Mitochondrial Apoptosis-induced Channel
Authors: Dejean Laurent M. , Martinez-Caballero Sonia , Guo Liang , Hughes Cynthia , Teijido Oscar , Ducret Thomas , Ichas François , Korsmeyer Stanley J. , Antonsson Bruno , Jonas Elizabeth A. , Kinnally Kathleen W.
Published: March 2005

Bcl-2 family proteins regulate apoptosis, in part, by controlling formation of the mitochondrial apoptosis-induced channel (MAC), which is a putative cytochrome c release channel induced early in the intrinsic apoptotic pathway. This channel activity was never observed in Bcl-2–overexpressing cells. Furthermore, MAC appears when Bax translocates to mitochondria and cytochrome c is released in cells dying by intrinsic apoptosis. Bax is a component of MAC of staurosporine-treated HeLa cells because MAC activity is immunodepleted by Bax antibodies. MAC is preferentially associated with oligomeric, not monomeric, Bax. The single channel behavior of recombinant oligomeric Bax and MAC is similar. Both channel activities are modified by cytochrome c, consistent with entrance of this protein into the pore. The mean conductance of patches of mitochondria isolated after green fluorescent protein-Bax translocation is significantly higher than those from untreated cells, consistent with onset of MAC activity. In contrast, the mean conductance of patches of mitochondria indicates MAC activity is present in apoptotic cells deficient in Bax but absent in apoptotic cells deficient in both Bax and Bak. These findings indicate Bax is a component of MAC in staurosporine-treated HeLa cells and suggest Bax and Bak are functionally redundant as components of MAC.
Cell Cycle-regulated, Microtubule-independent Organelle Division in Cyanidioschyzon merolae
Authors: Nishida Keiji , Yagisawa Fumi , Kuroiwa Haruko , Nagata Toshiyuki , Kuroiwa Tsuneyoshi
Published: March 2005

Mitochondrial and chloroplast division controls the number and morphology of organelles, but how cells regulate organelle division remains to be clarified. Here, we show that each step of mitochondrial and chloroplast division is closely associated with the cell cycle in Cyanidioschyzon merolae. Electron microscopy revealed direct associations between the spindle pole bodies and mitochondria, suggesting that mitochondrial distribution is physically coupled with mitosis. Interconnected organelles were fractionated under microtubule-stabilizing condition. Immunoblotting analysis revealed that the protein levels required for organelle division increased before microtubule changes upon cell division, indicating that regulation of protein expression for organelle division is distinct from that of cytokinesis. At the mitochondrial division site, dynamin stuck to one of the divided mitochondria and was spatially associated with the tip of a microtubule stretching from the other one. Inhibition of microtubule organization, proteasome activity or DNA synthesis, respectively, induced arrested cells with divided but shrunk mitochondria, with divided and segregated mitochondria, or with incomplete mitochondrial division restrained at the final severance, and repetitive chloroplast division. The results indicated that mitochondrial morphology and segregation but not division depend on microtubules and implied that the division processes of the two organelles are regulated at distinct checkpoints.
TIF1 Represses rDNA Replication Initiation, but Promotes Normal S Phase Progression and Chromosome Transmission inTetrahymena
Authors: Morrison Tara L. , Yakisich J. Sebastian , Cassidy-Hanley Donna , Kapler Geoffrey M.
Published: March 2005

The non-ORC protein, TIF1, recognizes sequences in the Tetrahymena thermophila ribosomal DNA (rDNA) minichromosome that are required for origin activation. We show here that TIF1 represses rDNA origin firing, but is required for proper macronuclear S phase progression and division. TIF1 mutants exhibit an elongated macronuclear S phase and diminished rate of DNA replication. Despite this, replication of the rDNA minichromosome initiates precociously. Because rDNA copy number is unaffected in the polyploid macronucleus, mechanisms that prevent reinitiation appear intact. Although mutants exit macronuclear S with a wild-type DNA content, division of the amitotic macronucleus is both delayed and abnormal. Nuclear defects are also observed in the diploid mitotic micronucleus, as TIF1 mutants lose a significant fraction of their micronuclear DNA. Hence, TIF1 is required for the propagation and subsequent transmission of germline chromosomes. The broad phenotypes associated with a TIF1-deficiency suggest that this origin binding protein is required globally for the proper execution and/or monitoring of key chromosomal events during S phase and possibly at later stages of the cell cycle. We propose that micro- and macronuclear defects result from exiting the respective nuclear S phases with physically compromised chromosomes.
Nietzsche's Moral Perspectivism
Authors: Solomon Robert C.
Published: March 2005

Nietzsche's moral perspectivism is one of the central and best-known themes of his philosophy. I interpret his genealogical argument in On the Genealogy of Moralsas an ad hominem argument, not so much history as moral psychology. In particular, Nietzsche mentions resentment (ressentiment) as a diagnostic tool in moral criticism. But Nietzsche has mixed intentions here. On the one hand, he adopts what I call a “blaming” perspective.” On the other, he urges us to get “beyond judgment.”
“Revelation to US”
Authors: Gatta John
Published: March 2005

By the early nineteenth century, in writings by Bryant, Cooper, and Emerson, one can observe a growing Romantic tendency to imagine Nature in religious terms--as a favored site of worship and a source of revelation largely superseding the Christian scriptures. Both literary artists and Hudson River painters highlighted their impressions of the sacred sublime in American landscapes. And as civilized settlements continued to replace the older freedom of life on the frontier, James Fenimore Cooper dramatized the problematic ethical consequences of this change in his Leatherstocking novels, above all in The Pioneers. Ralph Waldo Emerson’s vision of the nonhuman world as divine “cosmos,” or “beauty” is most memorably presented in his book Nature (1836), which celebrates the intersection between Nature and Civilization he discovered on the “common” space of a village green in Concord, Massachusetts. Emerson’s poem “The Adirondacs,” which describes a camping excursion interrupted by news of laying the first transatlantic telegraph cable, underscores the point that no part of nature could henceforth be wholly removed from human presence or influence.
Imagined Worlds
Authors: Gatta John
Published: March 2005

Every landscape is exotic, from the standpoint of those who stand apart from it or cannot know it fully, so that encounters with strange or forbidding landscapes may have sacred rather than escapist meaning. The exotic terrain of Southern swamps nurtured a distinctive form of religious life for maroon communities of African Americans, a spiritual legacy recalled in W.E.B. Du Bois’s Quest of the Silver Fleece. In Arctic Dreams, Barry Lopez shows how a strange and forbidding place inspires reverence before the sacred mystery of all that the land contains, both visible and invisibly. A comparable reverence toward an elusive, nonhuman, and numinous presence informs the Himalayan quest narrative of Peter Matthiessen in The Snow Leopard. In the Watson trilogy, Matthiessen probes the spiritual ambiguities of American lawlessness and exposes the “desecration of Creation” that human “progress” has brought to Florida’s Everglades.
On Two Non‐Realist Interpretations of Kant's Ethics
Authors: Ameriks Karl
Published: March 2005

Turns to questions about the ultimate nature of the content of Kant’s ethical theory. It criticizes aspects of the very influential constructivist reading of Kant’s ethics, originated by John Rawls and his students and employed in Jerome Schneewind’s important account of the history of modern ethics. There are historical and systematic reasons for allowing a much more positive relation between Kant’s ethical theory and moral realism. As with his theoretical philosophy, Kant’s arguments against the metaphysical tradition can be understood as anything but global and complete and as aimed primarily at very specific forms of dogmatic objectivism or relativism. The second half of the chapter points out some ways in which this realist approach can begin to respond to the most obvious objection to it (raised recently by Charles Larmore, namely that it may not do justice to Kant’s special emphasis on autonomy. It argues that Kant’s notion of autonomy does not in fact have the overly subjective implications that are commonly ascribed to it by its opponents – and that also are often assumed, or even glorified, by many who call themselves followers of Kant.
New Views on Kant's Judgment of Taste
Authors: Ameriks Karl
Published: March 2005

Defends the position of the previous chapter in response to a direct critique of it by Hannah Ginsborg, from the perspective of a subjectivist reading of Kantian taste. The critique provides an opportunity for clarifying ways in which an objectivist reconstruction does not have the kind of unwelcome consequences that it might at first seem to have. There is a way of reading Kant’s argument that shows how taste can be called objective for reasons that are not tied to either the kind of objectivity associated with science or a mere knowledge of causal relations or to the specific kinds of rationalist doctrines that Kant was mainly trying to warn against insofar as he was very reluctant (as he obviously was) explicitly to call his theory an objectivist one.
INTRODUCING THE PUZZLE
Authors: Hawthorne John
Published: March 2005

This chapter introduces the epistemological puzzle to be examined in this volume. In essence, the puzzle consists of a tension between various ordinary claims to know and our apparent incapacity to know whether or not someone will lose a lottery. It discusses why we are inclined to think that lottery propositions are unknowable. These unknowable intuitions are linked to other intuitions concerning our assertoric and deliberative dispositions with regard to lottery propositions. It then discusses the epistemic closure, which is vital to the force of the puzzle.
SKEPTICAL AND MODERATE INVARIANTISM
Authors: Hawthorne John
Published: March 2005

This chapter examines the two kinds of invariantism: sceptical and moderate. The sceptical invariantist claims that the sematic value of the word ‘know’ is such that all or nearly all ordinary positive knowledge ascriptions of the form ‘S knows that p’ are false. The moderate invariantist claims that the semantic value of ‘know’ is such that many of the positive knowledge ascriptions that we make in daily life are true. A moderate invariantist treatment of the puzzle is discussed.
4 The Ethical Task as the Human Task
Authors: Evans C. Stephen
Published: March 2005

Unlike Fear and Trembling, Kierkegaard affixes his name to Concluding Unscientific Postscript, as the ‘editor’, thereby signalling his close affinity to the position outlined by the book’s pseudonym Johannes Climacus. Kierkegaard himself, in The Point of View for My Work as an Author, tells us that he placed his name on the title page as a signal of the similarity of Climacus’s views to his own. Indeed, Climacus provides a formal structure that can be used to illuminate what Kierkegaard says in his own voice in Works of Love and elsewhere. From Climacus in Concluding Unscientific Postscript – and from Kierkegaard himself in Purity of Heart Is to Will One Thing – we have a conception of the ethical life as a life that involves a relationship with God. This knowledge of God, however, is not rooted in God’s revelation in history but is, instead, rooted in the individual’s own conscience.
9 Neighbour‐Love, Natural Loves, and Social Relations
Authors: Evans C. Stephen
Published: March 2005

When Kierkegaard tells us that we must not make ‘distinctions’ in our love, he does not mean that neighbour-love cannot coexist with such natural loves as romantic love and friendship. On the contrary: Kierkegaard believes that neighbour-love teaches us how to love the friend and the beloved as we should. Concrete, local activity is not the only kind of neighbour-love that is possible or appropriate. Broader, cooperative efforts for those whom one may never meet fall within the scope of the divine command to love one’s neighbour as oneself, and this may require political and social action of a type that Kierkegaard himself does not endorse.
‘The Long Hesitation’: Some Reflections on the Romans in Judaea
Authors: Curran John
Published: March 2005

On a day without precise date some time in Judaea in the first century of the common era, an interview of exceptional historical importance took place between a representative of Roman power and a Jewish prophet. What passed between them has left an indelible imprint on history, although religious believers, historians, and theologians have struggled for almost two thousand years to comprehend the legacy. The Roman was Titus Flavius Vespasianus, general of a vast army on its way to Jerusalem, and the Jewish prophet, priest and pharisee was Yosef ben Matthityahu.

The year was AD 67. In the summer of the previous year, the priests of the great temple of the Jewish God in Jerusalem had suspended the sacrifices which had been held twice a day for more than two generations in honour of the emperors of Rome. The suspension marked the formal beginning of a disastrous revolt mounted by the Jews against the empire of Rome in the East. Josephus had been appointed as a commander as soon as the revolt broke out and he had been sent to Galilee, some 50 miles north of Jerusalem, to organize resistance there. After initial success, he had been besieged by Roman forces at Jotapata, 10 miles from Nazareth. And when it became clear to the rebels that they were likely to fall into Roman hands he alleges that they carried out an elaborate mass-suicide, killing their comrades, starting at the lowest levels in the command and working up.
Martelella mediterranea gen. nov., sp. nov., a novel α-proteobacterium isolated from a subterranean saline lake
Authors: Rivas Raúl , Sánchez-Márquez Salud , Mateos Pedro F. , Martínez-Molina Eustoquio , Velázquez Encarna
Published: March 2005

A bacterial strain was isolated from the water of Lake Martel in Mallorca (Spain). The isolate, designated MACL11T, was halotolerant and strictly aerobic. The cells were non-motile, non-spore-forming, Gram-negative short rods. Comparative 16S rRNA gene sequence analysis revealed that MACL11T represents a separate line of descent within the order ‘Rhizobiales’ of the class ‘Alphaproteobacteria’. Strain MACL11T was most closely related to the genera Rhizobium (93·3 % sequence similarity to Rhizobium rhizogenes), Aurantimonas (90·3 % sequence similarity to Aurantimonas coralicida) and Fulvimarina (90·3 % sequence similarity to Fulvimarina pelagi). Chemotaxonomically, strain MACL11T was characterized by the presence of Q-10 as the major respiratory lipoquinone. The major fatty acids detected were C19 : 0 cycloω8c, C18 : 1
ω7c, C16 : 0 and 11-methyl C18 : 1
ω7c. The G+C content of the DNA was 57·4 mol%. Oxidase and catalase activities were present. Growth with many different carbohydrates as the sole carbon source was observed. The data from this polyphasic study suggest that this bacterium belongs to a novel genus of the order ‘Rhizobiales’ and is not associated with any of the known families of this order. It is proposed that isolate MACL11T should be classified in a novel genus and species, Martelella mediterranea gen. nov., sp. nov., with MACL11T (=LMG 22193T=CECT 5861T) as the type strain.
Arabidopsis Has Two Redundant Cullin3 Proteins That Are Essential for Embryo Development and That Interact with RBX1 and BTB Proteins to Form Multisubunit E3 Ubiquitin Ligase Complexes in Vivo
Authors: Figueroa Pablo , Gusmaroli Giuliana , Serino Giovanna , Habashi Jessica , Ma Ligeng , Shen Yunping , Feng Suhua , Bostick Magnolia , Callis Judy , Hellmann Hanjo , Deng Xing Wang
Published: March 2005

Cullin-based E3 ubiquitin ligases play important roles in the regulation of diverse developmental processes and environmental responses in eukaryotic organisms. Recently, it was shown in Schizosaccharomyces pombe, Caenorhabditis elegans, and mammals that Cullin3 (CUL3) directly associates with RBX1 and BTB domain proteins in vivo to form a new family of E3 ligases, with the BTB protein subunit functioning in substrate recognition. Here, we demonstrate that Arabidopsis thaliana has two redundant CUL3 (AtCUL3) genes that are essential for embryo development. Besides supporting anticipated specific AtCUL3 interactions with the RING protein AtRBX1 and representative Arabidopsis proteins containing a BTB domain in vitro, we show that AtCUL3 cofractionates and specifically associates with AtRBX1 and a representative BTB protein in vivo. Similar to the AtCUL1 subunit of the SKP1-CUL1-F-box protein–type E3 ligases, the AtCUL3 subunit of the BTB-containing E3 ligase complexes is subjected to modification and possible regulation by the ubiquitin-like protein Related to Ubiquitin in vivo. Together with the presence of large numbers of BTB proteins with diverse structural features and expression patterns, our data suggest that Arabidopsis has conserved AtCUL3-RBX1-BTB protein E3 ubiquitin ligases to target diverse protein substrates for degradation by the ubiquitin/proteasome pathway.
Role of NAD‐dependent deacetylases SIRT1 and SIRT2 in radiation and cisplatin‐induced cell death in vertebrate cells
Authors: Matsushita Nobuko , Takami Yasunari , Kimura Masayo , Tachiiri Seiji , Ishiai Masamichi , Nakayama Takeo , Takata Minoru
Published: March 2005

Yeast Sir2 is a nicotinamide adenine dinucleotide (NAD)‐dependent histone deacetylase that plays a central role in transcriptional silencing, chromosomal stability, DNA damage response and aging. In mammals, Sir2‐like genes constitute a seven‐member family whose function is largely unknown. To investigate the role of the Sir2 family in vertebrates, we have disrupted Sir2 homologues SIRT1 and SIRT2 in the p53‐deficient chicken cell line DT40. Both SIRT1−/− and SIRT2−/− cells had mild growth defects. Colony survival assays showed moderate and mild sensitivity to cisplatin in SIRT1−/− and SIRT2−/− cells, respectively, while SIRT1−/−, but not SIRT2−/− cells, were sensitive to ionizing radiation (IR). Cells rendered doubly deficient in SIRT1 and SIRT2 exhibited the same levels of IR and cisplatin sensitivity as SIRT1−/− cells. SIRT1−/− cells appeared to be defective neither in DNA double strand break repair nor in G2/M checkpoints, but were more susceptible to cell death induction following IR than wild‐type cells. Furthermore, both SIRT1‐ and SIRT2‐deficient cells were more sensitive to pro‐apoptotic stimuli including cisplatin and staurosporine. Our results indicate that SIRT1 and SIRT2 regulate stress‐induced cell death pathways in a p53‐independent manner.
Lateral cervical epidural catheter placement using nerve stimulation for continuous unilateral upper extremity analgesia following a failed continuous peripheral nerve block
Authors: Prusinkiewicz C. , Lang S. , Tsui B. C. H.
Published: March 2005

This case report describes the application of electrical stimulation (Tsui test) to confirm placement of a cervical epidural catheter for postoperative pain management in a patient with a failed brachial plexus block who underwent upper extremity surgery. An epidural catheter was easily advanced under nerve stimulation guidance to the surgical dermatome C4 level without any resistance from the C7–T1 level. Successful analgesia was achieved with a bolus of 2 mg ml−1 ropivacaine 2 ml and fentanyl 20 µg, followed by a continuous infusion of 2 mg ml−1 ropivacaine with 2 µg ml−1 of fentanyl at a rate of 2 ml h−1. This case reminds the clinician that cervical epidural analgesia may serve as an alternative to a difficult continuous peripheral nerve block. Electrical stimulation may also help to confirm cervical epidural catheter placement at the appropriate dermatome to provide effective analgesia with minimal side‐effects.
Improved analgesia with clonidine when added to local anesthetic during combined spinal‐epidural anesthesia for hip arthroplasty: a double‐blind, randomized and placebo‐controlled study
Authors: Dobrydnjov I. , Axelsson K. , Gupta A. , Lundin A. , Holmström B. , Granath B.
Published: March 2005

Background:  The perioperative effects of intrathecal and epidural clonidine combined with local anesthetic were evaluated in 60 patients undergoing hip arthroplasty.

Methods:  This was a double‐blinded study and the patients were randomized into three groups, with 20 patients in each group. All patients received spinal anesthesia with 17.5 mg of plain bupivacaine with 15 µg of clonidine (Group BC‐RC) or without clonidine (Groups B‐R and B‐RC). Postoperatively, epidural infusion was administered in the following way: Group B‐R – ropivacaine 4 mg h−1; Groups B‐RC and BC‐RC: ropivacaine 4 mg h−1 and clonidine 40 µg h−1. Sensory block was assessed with light touch, pinprick, transcutaneous electrical stimulation at T12 and L2 dermatomes, and perception of thermal stimuli.

Results:  The maximal upper level of sensory block measured by pin‐prick (T6–T7) did not differ between the groups while the partial sensory block for cold and warmth were increased two dermatomes above pin‐prick level in the group with intrathecal clonidine compared to the other two groups (P < 0.05). Duration of anesthesia, analgesia and motor block were longer in Group BC‐RC compared to Groups B‐R and B‐RC (P < 0.02). Postoperatively, both VAS score on movement and PCA‐morphine consumption were higher in Group B‐R than in Groups B‐RC and BC‐RC (P < 0.01). The arterial pressure and heart rate in Groups B‐RC and BC‐RC were significantly lower than in Group B‐R at 10–24 and 15–24 h, respectively, after spinal injection.

Conclusion:  Low‐dose intrathecal clonidine provided a better quality of anesthesia and longer‐lasting analgesia. Epidural clonidine‐ropivacaine infusion resulted in improved postoperative analgesia but was associated with a moderate decrease in blood pressure.
Effect of alfentanil on intracranial pressure during propofol–fentanyl anesthesia for craniotomy. A randomized prospective dose–response study
Authors: Olsen K. S. , Juul N. , Cold G. E.
Published: March 2005

Background:   The effect of alfentanil on intracranial pressure (ICP) in patients with supratentorial cerebral tumors has only been sparsely examined and with somewhat contradictory results.

Methods:  Thirty‐one patients were anesthetized with propofol and fentanyl. After removal of the bone flap a bolus‐dose of alfentanil 10 (group 1), 20 (group 2), or 30 µg kg−1 (group 3) was administered followed by an infusion of 10, 20, or 30 µg·kg−1·h−1 to patients in groups 1, 2, and 3, respectively. A control group received no alfentanil. Subdural ICP, mean arterial blood pressure (MAP), and cerebral perfusion pressure (CPP) were monitored and arterial and jugular bulb blood were sampled before and every minute for 5 min after the bolus administration of alfentanil and again after 5 min of hyperventilation to be able to calculate cerebral arterio‐venous oxygen content difference (AVDO2) and carbon dioxide reactivity (CO2‐reactivity).

Results:  No changes in subdural ICP or AVDO2 from alfentanil in the study period were observed within the groups. However, alfentanil decreased MAP and CPP. The maximum CPP decrease (mean value of each group) was 4 mmHg, 8 mmHg, and 18 mmHg in groups 1, 2, and 3, respectively. There was no difference between groups as regards the CO2‐reactivity.

Conclusion:  We conclude that administration of alfentanil to propofol‐fentanyl anesthetized patients with supratentorial cerebral tumors decreases MAP and CPP in a dose‐related way, but does not influence subdural ICP, AVDO2 or the CO2‐reactivity.
Anterior abdominal wall defects and biliary obstruction
Authors: Teoh L , Wong CKF , Martin H , O'Loughlin EV
Published: March 2005

Abstract:  Three infants with anterior abdominal wall defects (gastroschisis and exomphalos) who presented with obstructive jaundice secondary to biliary obstruction, are described. All three infants had abnormal biliary systems, with mechanical distortion of the biliary tree. Biliary obstruction secondary to structural biliary anomalies should be considered in patients with abdominal wall defects and cholestasis, as prolonged unrelieved biliary obstruction may lead to biliary cirrhosis and portal hypertension.
Whipple's disease presenting as an isolated lesion of the cervical spinal cord
Authors: Schröter A. , Brinkhoff J. , Günthner‐Lengsfeld T. , Suerbaum S , Reiners K. , Messmann H. , Naumann M.
Published: March 2005

Chronic myelitis from Whipple's disease of the spinal cord is extremely rare. The differential diagnosis includes chronic inflammatory lesions, viral or bacterial infections, and tumours of the spinal cord. Here we present a 50‐year‐old man with mild sensory deficits because of a large lesion of the cervical spinal cord who markedly showed improvement during probatory antibiotic therapy. PCR and jejunal biopsy were initially negative and only later confirmed the diagnosis of Whipple's disease. Clinical and neuroradiological criteria are suggested which may be of help in the early diagnosis of spinal Whipple's disease before confirmation by molecular biology or histology.
Prevalence and clinical implications of HFE gene mutations (C282Y and H63D) in patients with chronic hepatitis B and C in Taiwan
Authors: Mah Yone‐Han , Kao Jia‐Horng , Liu Chun‐Jen , Chen Chi‐Ling , Chen Pei‐Jer , Lai Ming‐Yang , Chen Ding‐Shinn
Published: March 2005

Abstract: Background/Aims: The implication of hemochromatosis (HFE) gene mutations in chronic viral hepatitis remains controversial. We therefore studied the prevalence of HFE mutations and their impact on the progression of chronic viral hepatitis in Taiwan.

Patients & methods: H63D and C282Y mutations were screened by using polymerase chain reaction followed by restriction fragment length polymorphism in 152 chronic hepatitis B patients with various stages of liver disease, 87 chronic hepatitis C patients with various stages of liver disease, and 49 healthy controls. The distribution of each allele frequency was then compared among different groups of patients and in various stages of liver disease.

Results: All three groups of patients were C282Y wild type and the majority of H63D mutations were heterozygotes. Although statistically not significant, allele frequencies of H63D mutation in hepatitis B‐related liver cirrhosis (6%) and hepatitis C‐related liver cirrhosis (9.1%) were higher than those in healthy control (2%). After adjustment for age and sex, hepatitis B patients with H63D heterozygosity had a higher likelihood of cirrhosis than those with H63D wild type (odds ratios (OR): 3.2, confidence interval (CI): 0.49–20.5, P=0.22). Similarly, hepatitis C patients with H63D homozygosity had a higher likelihood of cirrhosis compared with those with H63D wild type (OR: 2.35, CI : 0.19–28.5, P=0.52).

Conclusions: Almost all Taiwanese are C282Y wild type. H63D heterozygote and homozygote, occurring in less than 5% of the subjects, tended to be associated with the development of liver cirrhosis, irrespective of viral etiology. Screening for H63D mutation might be considered in patients with chronic viral hepatitis in Taiwan.
Osteoprotegerin and RANKL in alcoholic liver cirrhosis
Authors: Fábrega Emilio , Orive Aitor , García‐Suarez Covadonga , García‐Unzueta Maite , Antonio Amado Jose , Pons‐Romero Fernando
Published: March 2005

Abstract: Background/aims: The mechanisms leading to osteoporosis in alcoholic liver disease remain poorly understood. Recently identified soluble circulating osteoprotegerin (OPG), is the osteoclastogenesis inhibitory factor. It acts as a decoy receptor for osteoclast activating factor, receptor activator of nuclear factor‐κB ligand (RANKL), and impairs osteoclast function. The aim of our study was to investigate the OPG/RANKL system in alcoholic cirrhotic patients and their correlation with biochemical marker of bone turnover.

Patients and methods: Serum OPG, RANKL, osteocalcin (OC), C‐terminal cross‐linking telopeptide of type I collagen (CTX‐I), bone alkaline phosphatase activity (bALP), and urinary hydroxyproline were measured in 30 patients with alcoholic cirrhosis, and in 20 age‐ and sex‐matched healthy controls.

Results: OPG levels were significantly increased in patients with alcoholic cirrhosis compared with healthy subjects (5.9 pmol/l, range 2.7–9.0 vs 4.1 pmol/l, range 1.2–6.6; P<0.001). RANKL levels were significantly higher in patients with cirrhosis (0.48 pmol/l, range 0.01–1.34) than in healthy subjects (0.11 pmol/l, range 0.01–0.90). There was a positive correlation between serum OPG and RANKL (r=0.37; P<0.001), bALP (r=0.66; P<0.001) and urinary hydroxyproline (r=0.51; P<0.05) but not with OC and CTX‐I.

Conclusions: OPG might partly represent a compensating mechanism to the negative balance of bone remodelling in patients with alcoholic cirrhosis.