bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategic Alliance Temporalities and Partner Opportunism*
Authors: Das T. K.
Published: February 2006

The troubling potential for opportunistic behaviour in strategic alliances is acknowledged in both research and practice, and yet the antecedents of such opportunism remain largely unexplored in the literature. In this article we suggest that the inherent temporalities of alliances play significant roles in partner opportunism. We propose a model of potential partner opportunism that assigns antecedent and contingent roles to the temporal horizons of alliances and the temporal orientations of the member firms. We introduce the notion of alliance horizons and suggest that they are constituted by the temporal orientations of the member firms and a number of common alliance formation factors. We also discuss how these alliance horizons in conjunction with the temporal orientations of member firms result in different levels of potential opportunism. Lastly, we develop a number of propositions to facilitate empirical research on the temporal contingencies of partner opportunism and indicate directions for further studies.
QUASI‐NATURALISM AND MORAL REALITY
Authors: Majors Brad
Published: February 2006

In his recent book Moral Reality, Paul Bloomfield has put forward an original set of arguments for moral realism. Central to his treatment is an argument for the reality of moral properties, one which models them on the property of being healthy. The paper is a critical examination of Bloomfield's central line of argument. It is contended that his proposed method of grounding moral realism fails, inasmuch as his Distinction Test criterion for property reality – essentially the claim that a property exists if its existence is required for distinctions that we make and must make – is inadequate. An alternative approach toward properties is suggested, which has the result, inter alia, that Bloomfield's quasi‐naturalistic approach is unnecessary for the defense of moral realism.1
WHY ESSENTIALISM REQUIRES TWO SENSES OF NECESSITY
Authors: McLeod Stephen K.
Published: February 2006

I set up a dilemma, concerning metaphysical modality de re, for the essentialist opponent of a ‘two senses’ view of necessity. I focus specifically on Frank Jackson's two‐dimensional account in his From Metaphysics to Ethics (Oxford: Oxford University Press, 1998). I set out the background to Jackson's conception of conceptual analysis and his rejection of a two senses view. I proceed to outline two purportedly objective (as opposed to epistemic) differences between metaphysical and logical necessity. I conclude that since one of these differences must hold and since each requires the adoption of a two senses view of necessity, essentialism is not consistent with the rejection of a two senses view.1
NATURALISM AND THE TRANSCENDENTAL TURN
Authors: Sacks Mark
Published: February 2006

This paper is to a large extent an exercise in philosophical geography. It traces the way in which a resilient naturalist orientation has derived support, specifically in the analytic tradition, from a central structuring tenet of transcendental idealism. It attempts to bring out the philosophical reasons that drive this Kantian alliance. Attention then turns to the identification of two salient problems that confront this alliance in its most acceptable form. To the extent that a resilient naturalism is desirable, these problems need to be addressed.

While the philosophical issue is brought into focus by attending specifically to developments in the analytic tradition, this is primarily a convenience. The preference for a resilient naturalism and the avoidance of metaphysical excess is not by any means confined to that tradition.
THE UNIVERSE AMONG OTHER THINGS
Authors: Varzi Achille C.
Published: February 2006

Peter Simons has argued that the expression ‘the universe’ is not a genuine singular term: it can name neither a single, completely encompassing individual, nor a collection of individuals. (It is, rather, a semantically plural term standing equally for every existing object.) I offer reasons for resisting Simons's arguments on both scores.
Analysis of Irish Third-Level College Applications Data
Authors: Gormley Isobel Claire , Murphy Thomas Brendan
Published: February 2006

The Irish college admissions system involves prospective students listing up to 10 courses in order of preference on their application. Places in third-level educational institutions are subsequently offered to the applicants on the basis of both their preferences and their final second-level examination results. The college applications system is a large area of public debate in Ireland. Detractors suggest that the process creates artificial demand for ‘high profile’ courses, causing applicants to ignore their vocational callings. Supporters argue that the system is impartial and transparent. The Irish college degree applications data from the year 2000 are analysed by using mixture models based on ranked data models to investigate the types of application behaviour that are exhibited by college applicants. The results of this analysis show that applicants form groups according to both the discipline and the geographical location of their course choices. In addition, there is evidence of the suggested ‘points race’ for high profile courses. Finally, gender emerges as an influential factor when studying course choice behaviour.
Researching into Some Primary School Children's Views About School: Using Personal Construct Psychology in Practice with Children on the Special Needs Register
Authors: MAXWELL TIM
Published: February 2006

This article describes a research project, which collected the views of 13 junior aged children on the special educational needs register of one school about their education. The techniques used for eliciting their views were a series of personal construct psychology (PCP) conversations based on drawings produced by the children of themselves in school. A case study approach was taken within the naturalistic paradigm of ‘constructivist inquiry’. The findings indicated that social activities were of greater importance for the pupils than formal learning experiences. Peer relationships were paramount and these defined the positive or negative experiences the pupils had of school in general. The pupils were able to describe a range of problem solving strategies for resolving peer group difficulties. The implications of the study are also discussed.
Outcome of Medication Overuse Headache after Abrupt in-Patient withdrawal
Authors: Relja G , Granato A , Bratina A , Antonello RM , Zorzon M
Published: February 2006

One hundred and one patients suffering from chronic daily headache (CDH) and medication overuse were treated, in an in-patient setting, with abrupt discontinuation of the medication overused, intravenous hydrating, and intravenous administration of benzodiazepines and ademetionine. The mean time to CDH resolution was 8.8 days. The in-patient withdrawal protocol used was effective, safe and well tolerated. There was a trend for a shorter time to CDH resolution in patients who overused triptans ( P = 0.062). There was no correlation between time to CDH resolution and either the type of initial primary headache or duration of medication abuse, whereas time to CDH resolution was related to daily drug intake ( P = 0.01). In multiple regression analysis, daily drug intake, age and type of medication overused were independent predictors of time to CDH resolution. At 3-months' follow-up, no patient had relapsed and was again overusing symptomatic medications.
Bullying in Schools: A Plea for Measure of Human Rights
Authors: Greene Michael B.
Published: February 2006

Bullying is the most pervasive form of aggression in schools and as such has attracted much international attention. Although the Olweus Bullying Prevention Program has been shown to be moderately effective in reducing bullying behaviors, several obstacles and challenges have been identified. These include securing the full commitment of all key stakeholders in the school to address the problem of bullying, establishing and sustaining a leadership group to maintain bullying prevention efforts in light of changing priorities and mandates, and attending to the different forms of bullying and underlying motivational bases. A human rights framework, consistent with a peace psychology perspective, targets behaviors, or practices that cause harm (mental distress, maltreatment, and exploitation) in children. Infusing a human rights framework into bullying prevention efforts can remedy much of the commonly encountered practical and theoretical obstacles to the effective implementation of such efforts.
Intergroup Contact, Forgiveness, and Experience of “The Troubles” in Northern Ireland
Authors: Hewstone Miles , Cairns Ed , Voci Alberto , Hamberger Juergen , Niens Ulrike
Published: February 2006

Two studies used random sample surveys to test the “contact hypothesis” on intergroup attitudes of Catholics and Protestants in Northern Ireland. In Study 1, archival data from two different surveys in 1989 (N= 310 Catholics, 422 Protestants) and 1991 (N= 319 Catholics, 478 Protestants) showed that contact was positively related to attitudes toward denominational mixing. Study 2 (N= 391 Catholics, 647 Protestants) explored predictors of intergroup forgiveness, and also showed that intergroup contact was positively related to outgroup attitudes, perspective‐taking, and trust (even among those who had a worse experience of sectarian conflict). These studies indicate that research in peace psychology can provide a deeper understanding of the conflict in Northern Ireland and, in due course, contribute to its resolution.
Political Psychology of Nonviolent Democratic Transitions in Southeast Asia
Authors: Montiel Cristina Jayme
Published: February 2006

This research examined social psychological aspects of nonviolent democratic transitions in Southeast Asia at the close of the 20th century. Researchers interviewed prodemocracy activists who participated in the Philippines' People's Power Revolution, Cambodia's Dhammayietra (Buddhist Walk for Peace), and East Timor's peace and liberation movement. Sets of open‐ended vernacular questions were custom‐built to fit each country's unique transition to democracy. In addition, the author used as a data source her personal experiences in the Philippines as a leader of street politics during People's Power. Findings show similar social psychological factors across all three politically‐transformative episodes in Southeast Asia. Shared characteristics include a history of systemic violence, loosening up of the authoritarian regime, violence toward the prodemocracy activists, spiritual orientations of social commitments, networking‐mobilizing skills used to confront an authoritarian state, building a social infrastructure to produce massive force, and conscientizing for active nonviolence.
Realistic Empathy and Active Nonviolence Confront Political Reality
Authors: Schwebel Milton
Published: February 2006

This article employs three concepts to integrate the prior articles in this issue: political reality, realistic empathy, and active nonviolence. People of wealth and power define political reality, making their interests coterminous with national interests. Episodic and structural violence are used to maintain political reality. The prior articles report on diverse means to counter political reality, mitigate the effects of violence and lay the groundwork for peacebuilding. Basic to those means are realistic empathy and active nonviolence.
Price Formation Under Small Numbers Competition: Evidence from Land Auctions in Singapore
Authors: Ooi Joseph T.L. , Sirmans C.F. , Turnbull Geoffrey K.
Published: February 2006

This article examines the price formation process under small numbers competition using data from Singapore land auctions. The theory predicts that bid prices are less than the zero‐profit asset value in these first‐price sealed‐bid auctions. The model also shows that expected sales price increases with the number of bidders both because each bidder has an incentive to offer a higher price and because of a greater likelihood that a high‐value bidder is present. The empirical estimates are consistent with auction theory and show that the standard land attributes are reflected in auction prices as expected.
Diverse Myocardial Extension and Autonomic Innervation on Ligament of Marshall in Humans
Authors: MAKINO MUTSUKI , INOUE SHIN , MATSUYAMA TAKA‐AKI , OGAWA GENYOU , SAKAI TETSUO , KOBAYASHI YOU‐ICHI , KATAGIRI TAKASHI , OTA HIDEKAZU
Published: February 2006

Introduction: The ligament of Marshall (LOM) or the oblique vein of Marshall (VOM) in the left atrium (LA) is one of the origins of nonpulmonary vein ectopies causing atrial fibrillation. The distributions of myocardial bundles (Marshall bundles; MBs) and autonomic nerves adjacent to the LOM have not been completely elucidated.

Methods and Results: Twenty‐eight human hearts were examined postmortem. The inferolateral LA myocardium was dissected en block and cut perpendicularly to the atrioventricular ring. The specimens were sectioned at 1‐mm intervals and stained with hematoxylin and eosin, and Azan‐Mallory. In addition, S‐100 and tyrosine hydroxylase (TH) were employed for the immunohistochemical analysis of the sympathetic and parasympathetic fibers. In 25 cases, MBs were observed. Although the MBs surrounded the VOM at the coronary sinus (CS) juncture, they gradually diminished in density toward the distal venous branch. The connections of the MBs and LA myocardium were frequently observed in the CS juncture and anterior wall of the left pulmonary vein (PV)‐LA junctions. TH‐stained sympathetic nerve fibers were densely distributed around the PV‐LA junctions. On the other hand, non‐TH‐stained parasympathetic ganglions were mainly observed at the CS juncture.

Conclusions: MB‐LA connections were mainly observed at the CS juncture and PV‐LA junctions. The association between sympathetic nerve fibers and MBs was distinct at the PV‐LA junctions. At the CS juncture, the regression of the sympathetic nerve fibers and the increase of parasympathetic ganglions were observed. The diverse arrangement and autonomic innervation of MBs seem to characterize the LOM region in humans.
Esophageal Temperature During Radiofrequency‐Catheter Ablation of Left Atrium: A Three‐Dimensional Computer Modeling Study
Authors: HORNERO FERNANDO , BERJANO ENRIQUE J.
Published: February 2006

Introduction: There is current interest in finding a way to minimize thermal injury in the esophagus during radiofrequency‐catheter ablation of the left atrium. Despite the fact that the esophageal temperature is now being monitored during ablation, the influence of different anatomic and technical factors on the temperature rise remains unknown.

Methods and Results: We implemented a three‐dimensional computational model that included atrial tissue, epicardial fat, esophagus, aorta, and lung, all linked by connective tissue. The finite‐element method was used to calculate the esophageal temperature distribution during a procedure of constant‐temperature ablation with an 8‐mm electrode, under different tissue conditions. Results showed that the distance between electrode and esophagus was the most important anatomic factor in predicting the esophageal temperature rise, the composition of the different tissues being of lesser importance. The measurement of the esophageal temperature in different sites of the lumen offered differences up to 3.7°C, especially for a short electrode–esophagus distance (5 mm). The difference in the convective cooling by circulating blood around electrode and endocardium did not show a significant influence on the esophageal temperature rise.

Conclusion: Computer results suggest that (1) the electrode–esophagus distance is the most important anatomic factor; (2) the incorrect positioning of an esophageal temperature probe could give a low reading for the maximum temperature reached in the esophagus; and (3) the different cooling effect of the circulating blood flow at different atrial sites has little impact on the esophageal temperature rise.
Cardiac Pacing in a Patient with Diaphragm Pacing for Congenital Central Hypoventilation Syndrome (Ondine's Curse)
Authors: KOLB CHRISTOF , EICKEN ANDREAS , ZRENNER BERNHARD , SCHMITT CLAUS
Published: February 2006

Mechanical ventilation support and diaphragm pacing has improved the prognosis of patients with idiopathic congenital central hypoventilation syndrome (CCHS; Ondine's curse). However, severe bradyarrhythmias may occur. This report is about a patient who was supplied with a bilateral diaphragm pacing system at early childhood. At the age of 17 years, he experienced multiple syncopes due to sinus nodal arrest, which was successfully treated by the implantation of a dual chamber pacemaker.
Exploring Triangulation in Infancy: Two Contrasted Cases
Authors: FIVAZ‐DEPEURSINGE ELISABETH , FAVEZ NICOLAS
Published: February 2006

Two contrasted father‐mother‐infant interactions are observed longitudinally during trilogue play. They illustrate the contribution of recent research to the exploration of triangulation in infancy: namely, the infant's capacity to handle triangular interactions and share her affects with her two parents, and the way that this capacity is recruited in functional versus problematic alliances. It is likely that an infant under stress when interacting with one parent will protest at that parent and also at the other. Such is the case when, for example, the father acts intrusively while playing with his baby. The infant is then driven to avert and turns to the mother. The regulation of this dyadic intrusion‐avoidance pattern at family level depends on the family alliance. When coparenting is supportive, the mother validates the infant's bid for help without interfering with the father. Thus, the problematic pattern is contained in the dyad, and the infant's triangular capacities remain in the service of her own developmental goals. But when coparenting is hostile‐competitive, the mother ignores the infant's bid or engages with her in a way that interferes with her play with her father. In this case, the infant's triangular capacities are used to relieve the tension between the parents. The importance of tracing family process back to infancy for family therapy is discussed.
Family Narrative Interaction and Children's Sense of Self
Authors: BOHANEK JENNIFER G. , MARIN KELLY A. , FIVUSH ROBYN , DUKE MARSHALL P.
Published: February 2006

Family narratives about the shared past may be a particularly significant site for preadolescents' emerging sense of self both as an individual and as a member of a unified family. We examined the relations between family narrative interaction style when reminiscing and preadolescents' sense of self. Results indicated three narrative interaction styles that describe the extent to which families discuss or fail to discuss their past in integrated and validating ways. Specifically, conversations with a coordinated perspective incorporated information from all members and were related to higher self‐esteem, especially in girls. Conversations with an individual perspective, in which family members took turns telling their thoughts and feelings about the event without integration among the perspectives, were associated with a more external locus of control, especially in boys. Conversations with an imposed perspective, in which one family member was in charge of the conversation or in which unpleasant exchanges between members occurred, were not associated with either self‐esteem or locus of control. Implications of these narrative interaction styles for children's developing sense of self are discussed.
Using a Metaperspective to Clarify the Structural‐Narrative Debate in Family Therapy
Authors: LEVY JOSHUA
Published: February 2006

The debate in family therapy between structural and narrative therapists often seems irreconcilable. Drawing from work in theoretical sociology that identifies the basic structure of existing social theory, a metaperspective is introduced to clarify a discussion between leading figures in the debate. Disparate views of family interactions are examined in terms of more fundamental disagreements about the center of attention in therapy. Narrative and structural modes of presentation are examined as separate traditions that could not be further apart conceptually. Efforts to identify common ground are discussed in terms of more significant differences that are minimized by drawing out similarities. This analysis provides a framework for standing outside entrenched arguments to see more clearly the unique contributions of each approach.
Risk factors for conjunctival and retinal vessel alterations in sickle cell disease
Authors: Lima Carmen S. P. , Rocha Eduardo M. , Silva Nadia M. , Sonatti Maria F. , Costa Fernando F. , Saad Sara T. O.
Published: February 2006

Purpose:  The aim of this study was to clarify whether the clinical, laboratory and genetic aspects of sickle cell disease (SCD) influence the occurrence of vessel alterations in the conjunctiva and retina.

Methods:  A total of 102 SCD patients underwent biomicroscopical and retinal examination, in addition to evaluations of haemoglobin (Hb) and haematocrit (Ht) levels, fetal haemoglobin (HbF) estimations, serum creatinine and albuminuria levels, glomerular filtration rate (GFR) values, phenotypes, β‐globin gene haplotypes and α‐thalassaemia. The relationship between ocular vessel alterations and clinical, laboratory and genetic features were evaluated using chi‐squared or Fisher tests and logistic regression analysis. In 13 patients on enalapril treatment, a second ophthalmological evaluation was performed after a 12‐month period to evaluate the longitudinal effect of the drug on ocular vessels.

Results:  Conjunctival vessel alteration (CVA) was not influenced by age, gender, HbF estimation, serum creatinine and albuminuria levels, GFR values, β‐globin gene haplotypes or α‐thalassaemia. However, increased frequencies of CVA were found in patients with Hb ≤ 9.0 g/dl, Ht ≤ 26.7% and sickle cell anaemia (SS) phenotype. Retinal vessel alteration (RVA) was identified only in patients aged 17 years or older. Enalapril did not demonstrate ocular vessel amelioration after 12‐months of daily use.

Conclusion:  The results indicate that lower Hb and Ht levels and SS phenotype are risk factors for CVA, and age over 17 years may be risk factors for RVA in SCD patients.
Clinical evaluation of rebound tonometer
Authors: Davies Leon N. , Bartlett Hannah , Mallen Edward A. H. , Wolffsohn James S.
Published: February 2006

Purpose:  To evaluate the reliability and repeatability of intraocular pressure (IOP) measurements using a new rebound tonometer.

Methods:  Intraocular pressure was measured in 42 healthy human eyes of subjects aged 18–30 years (mean ± standard deviation [SD] 21.5 ± 3.2 years) using the ICare Rebound and Goldmann tonometers in two separate sessions.

Results:  Intraocular pressure measurements were found to read slightly, but not significantly, higher with the ICare tonometer compared with the Goldmann instrument in both sessions (first session: mean bias ± SD + 0.50 ± 2.33 mmHg; second session: mean bias ± SD + 0.52 ± 1.92 mmHg). Limits of agreement between repeated readings were ± 5.11 mmHg for measurements taken with the ICare tonometer, compared with ± 3.15 mmHg for measurements taken with the Goldmann method.

Conclusion:  Measurement of IOP in normal, healthy subjects using the ICare rebound tonometer produced a small, statistically insignificant, positive bias when compared with the Goldmann tonometer. Intersessional repeatability of IOP taken with the ICare is poorer than that of IOP taken with the Goldmann tonometer, but is comparable with that of other non‐Goldman‐type tonometers currently available.
Spermatogonial stem cells: characteristics and experimental possibilities
Authors: APONTE PEDRO M. , VAN BRAGT MAAIKE P. A. , DE ROOIJ DIRK G. , VAN PELT ANS M. M.
Published: February 2006

The continuation of the spermatogenic process throughout life relies on a proper regulation of self‐renewal and differentiation of the spermatogonial stem cells. These are single cells situated on the basal membrane of the seminiferous epithelium. Only 0.03% of all germ cells are spermatogonial stem cells. They are the only cell type that can repopulate and restore fertility to congenitally infertile recipient mice following transplantation. Although numerous expression markers have been helpful in isolating and enriching spermatogonial stem cells, such as expression of THY‐1 and GFRα‐1 and absence of c‐kit, no specific marker for this cell type has yet been identified. Much effort has been put into developing a protocol for the maintenance of spermatogonial cellsin vitro. Recently, coculture systems of testicular cells on various feeder cells have made it possible to culture spermatogonial stem cells for a long period of time, as was demonstrated by the transplantation assay. Even expansion of testicular cells, including the spermatogonial stem cells, has been achieved. In these culture systems, hormones and growth factors are investigated for their role in the process of proliferation of spermatogonial stem cells. At the moment the best culture system known still consists of a mixture of testicular cells with about 1.33% spermatogonial stem cells. Recently pure SV40 large T immortalized spermatogonial stem cell lines have been established. These c‐kit‐negative cell lines did not show any differentiationin vitroorin vivo. A telomerase immortalized c‐kit‐positive spermatogonial cell line has been established that was able to differentiatein vitro. Spermatocytes and even spermatids were formed. However, spermatogonial stem cell activity by means of the transplantation assay was not tested for this cell line. Both the primary long‐term cultures and immortalized cell lines have represented a major step forward in investigating the regulation of spermatogonial self‐renewal and differentiation, and will be useful for identifying specific molecular markers.
Human embryonic stem cells and chromosome stability
Authors: HANSON CHARLES , CAISANDER GUNILLA
Published: February 2006

The use of human embryonic stem cells (HESC) in research is increasing exponentially and HESC will certainly be of importance in biological, clinical and toxicological research for many years to come. Once established, HESC lines are expected to be chromosomally stable. However, our own experience of culturing HESC and some published reports indicate that HESC may show chromosomal instability while being cultured continuously in vitro. We conclude that the effects of different culture techniques and long‐term culture on the chromosome stability of HESC still remain to be elucidated and we recommend regular analysis of the chromosome constitution in cell lines using traditional karyotyping, CGH, FISH and PCR. We also recommend freezing of HESC at low passage number and in larger batches after thawing and expansion in order to secure material in case mutations occur in the cell line at a later stage of culture.
The embryonic origins of hematopoietic stem cells: a tale of hemangioblast and hemogenic endothelium
Authors: BOLLEROT KARINE , POUGET CLAIRE , JAFFREDO THIERRY
Published: February 2006

The developmental origin of hematopoietic stem cells has been for decades the subject of great interest. Once thought to emerge from the yolk sac, hematopoietic stem cells have now been shown to originate from the embryonic aorta. Increasing evidence suggests that hematopoietic stem cells are produced from an endothelial intermediate designated by the authors as hemangioblast or hemogenic endothelium. Recently, the allantois in the avian embryo and the placenta in the mouse embryo were shown to be a site of hematopoietic cell production/expansion and thus appear to play a critical role in the formation of the hematopoietic system. In this review we shall give an overview of the data obtained from human, mouse and avian models on the cellular origins of the hematopoietic system and discuss some aspects of the molecular mechanisms controlling hematopoietic cell production.
Stem cell biology and the cellular pathways of carcinogenesis
Authors: GUDJONSSON THORARINN , MAGNUSSON MAGNUS KARL
Published: February 2006

Tissues in the body are maintained by somatic stem cells. This has been demonstrated both in organs with high cell turnover rate, such as the bone marrow, colon and skin, and in organs with low cell turnover rate, such as the brain. To maintain homeostasis in the body it is important to keep tight control over stem cell fate. Stem cells are under strict control from both intrinsic and extrinsic factors and loss of this control has been postulated to be a key step in the carcinogenic process. There is increasing evidence that cancer initiation results from accumulative oncogenic mutations (intrinsic loss of control) in long‐lived stem cells or their immediate progenitor, followed by modification of the surrounding microenvironment (loss of extrinsic control). Decades ago, studies on teratocarcinoma led to the hypothesis that a small subset of self‐renewing cancer stem cells with differentiation potential exists within tumors. These studies showed that teratocarcinomas contain undifferentiated embryonic carcinoma cells that are able to give rise to differentiated cells which belong to all three germ layers. More recent studies have confirmed cancer stem cells in such diverse cancers as leukemia, brain and breast cancer. It is, however, unclear whether cancer stem cells originate from resident stem cells or whether they arise as a result of an acquired gain of self‐renewal capacity in tissue progenitor cells or even more differentiated cells. The characterization of a cancer stem cell profile within diverse cancer types may open up new avenues for cancer treatment. In this review we discuss the concept of cancer stem cells and focus on examples where these cells have been identified.
Cytokine signalling in embryonic stem cells
Authors: KRISTENSEN DAVID MØBJERG , KALISZ MARK , NIELSEN JENS HØIRIIS
Published: February 2006

Cytokines play a central role in maintaining self‐renewal in mouse embryonic stem (ES) cells through a member of the interleukin‐6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK‐STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric complex with LIF and the class I cytokine receptor LIF receptor β. STAT3 has been shown to play a crucial role in self‐renewal in mouse ES cells probably by induction of c‐myc expression. Thus, ablation of STAT3 activation leads to differentiation. However, important connections between STAT3 and other signalling pathways have been documented. In addition, gp130 activation leads to both PI3K and Src activation. The canonical Wnt pathway is sufficient to maintain self‐renewal of both human ES cells and mouse ES cells. It seems quite possible that the main pathway maintaining self‐renewal in ES cells is the Wnt pathway, while the LIF‐JAK‐STAT3 pathway is present in mouse cells as an adaptation for sustaining self‐renewal during embryonic diapause, a condition of delayed implantation in mammals. In keeping with this scenario, the Wnt pathway has been shown to elevate the level of c‐myc. Thus, the two pathways seem to converge on c‐myc as a common target to promote self‐renewal. Whereas LIF does not seem to stimulate self‐renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem cell‐specific factors.
Bone ALP and OC reference standards in adult baboons (Papio hamadryas) by sex and age
Authors: Havill L.M. , Hale L.G. , Newman D.E. , Witte S.M. , Mahaney M.C.
Published: February 2006

Background 
Serum bone‐specific alkaline phosphatase (bone ALP) and intact osteocalcin (OC) are markers of bone formation of interest because of easy measurability and potential utility as identifiers of those at risk for fractures associated with bone metabolism disorders. The baboon (Papio hamadryas) exhibits extensive biological similarities to humans making it particularly well suited to studies of bone maintenance and turnover.

Methods  We measured serum bone ALP and OC in 591 baboons.

Results  We report significant sex and age effects and present reference ranges and percentile distributions for these markers.

Conclusions  This study is the first to characterize normal variation in bone ALP and OC levels in baboons and to assess the age and sex effects on this variation. The results provide much‐needed reference standards to allow researchers to evaluate the status of their animals in cross‐sectional studies and assess the meaning of changes in bone ALP and OC levels in longitudinal studies.
The essential tyrosine‐containing loop conformation and the role of the C‐terminal multi‐helix region in eukaryotic phenylalanine ammonia‐lyases
Authors: Pilbák Sarolta , Tomin Anna , Rétey János , Poppe László
Published: February 2006

Besides the post‐translationally cyclizing catalytic Ala‐Ser‐Gly triad, Tyr110 and its equivalents are of the most conserved residues in the active site of phenylalanine ammonia‐lyase (PAL, EC 4.3.1.5), histidine ammonia‐lyase (HAL, EC 4.3.1.3) and other related enzymes. The Tyr110Phe mutation results in the most pronounced inactivation of PAL indicating the importance of this residue. The recently published X‐ray structures of PAL revealed that the Tyr110‐loop was either missing (forRhodospridium toruloides) or far from the active site (forPetroselinum crispum). In bacterial HAL (∼500 amino acids) and plant and fungal PALs (∼710 amino acids), a core PAL/HAL domain (∼480 amino acids) with ≥ 30% sequence identity along the different species is common. In plant and fungal PAL a ∼100‐residue long C‐terminal multi‐helix domain is present. The ancestor bacterial HAL is thermostable and, in all of its known X‐ray structures, a Tyr83‐loop‐in arrangement has been found. Based on the HAL structures, a Tyr110‐loop‐in conformation of theP. crispumPAL structure was constructed by partial homology modeling, and the static and dynamic behavior of the loop‐in/loop‐out structures were compared. To study the role of the C‐terminal multi‐helix domain, Tyr‐loop‐in/loop‐out model structures of two bacterial PALs (Streptomyces maritimus, 523 amino acids andPhotorhabdus luminescens, 532 amino acids) lacking this C‐terminal domain were also built. Molecular dynamics studies indicated that the Tyr‐loop‐in conformation was more rigid without the C‐terminal multi‐helix domain. On this basis it is hypothesized that a role of this C‐terminal extension is to decrease the lifetime of eukaryotic PAL by destabilization, which might be important for the rapid responses in the regulation of phenylpropanoid biosynthesis.
Stage specific expression of poly(malic acid)‐affiliated genes in the life cycle of Physarum polycephalum
Authors: Pinchai Nadthanan , Lee Bong‐Seop , Holler Eggehard
Published: February 2006

Polymalic acid is receiving interest as a unique biopolymer of the plasmodia of mycetozoa and recently as a biogenic matrix for the synthesis of devices for drug delivery. The acellular slime mold Physarum polycephalum is characterized by two distinctive growth phases: uninucleated amoebae and multinucleated plasmodia. In adverse conditions, plasmodia reversibly transform into spherules. Only plasmodia synthesize poly(malic acid) (PMLA) and PMLA‐hydrolase (polymalatase). We have performed suppression subtractive hybridization (SSH) of cDNA from amoebae and plasmodia to identify plasmodium‐specific genes involved in PMLA metabolism. We found cDNA encoding a plasmodium‐specific, spherulin 3a‐like polypeptide, NKA48 (spherulin 3b), but no evidence for a PMLA‐synthetase encoding transcript. Inhibitory RNA (RNAi)‐induced knockdown of NKA48‐cDNA generated a severe reduction in the level of PMLA suggesting that spherulin 3b functioned in regulating the level of PMLA. Unexpectedly, cDNA of polymalatase was not SSH‐selected, suggesting its presence also in amoebae. Quantitative PCR then revealed low levels of mRNA in amoebae, high levels in plasmodia, and also low levels in spherules, in agreement with the expression under transcriptional regulation in these cells.
An accurate, high‐throughput method for genotyping the −373AnTn polymorphism in the interleukin‐6 promoter
Authors: Khwaja Haris A. , Green Fiona R.
Published: February 2006

Interleukin‐6 (IL‐6) is a pro‐inflammatory cytokine implicated in inflammatory diseases. The four promoter polymorphisms (−174G/C, −373AnTn, −572G/C, −597G/A) have been shown to function as a haplotype in determining IL‐6 gene transcription. Using a capillary‐based electrophoresis system, high‐throughput genotyping for the −373AnTn polymorphism was achieved, thus facilitating IL‐6 promoter haplotype determination.
Polymorphism in the proximal promoter region of the perforin gene and its impact on the course of HIV infection
Authors: McIlroy D. , Meyer L. , Dudoit Y. , Samri A. , Delfraissy J.‐F. , Autran B. , Debré P. , Theodorou I. ,   the SEROCO, IMMUNOCO and ALT study groups
Published: February 2006

Cytotoxic T lymphocytes (CTLs) play an essential role in the control of viral replication during human immunodeficiency virus (HIV) infection. However, the efficacy of the CTL response varies between individuals. We tested the hypothesis that genetic polymorphisms in the lytic effector molecule perforin could influence the progression of HIV infection. The perforin gene was screened for single nucleotide polymorphisms (SNPs) by denaturing high‐performance liquid chromatography (dHPLC). Correlations were sought between perforin genotype, perforin expression and lytic function of CD8+ T lymphocytes from HIV‐positive patients. Association of perforin genotype with disease progression was investigated in 426 seroconverters enrolled in the French SEROCO cohort. AIDS‐free survival curves were constructed using the Kaplan–Meier method and compared using the log‐rank test. Three SNPs were found in the proximal promoter region of the perforin gene: 63G (allelic frequency 0.029), 112G (allelic frequency 0.071) and 1012T (allelic frequency 0.070). The presence of the 1012T genotype correlated with fewer perforin+ cells among circulating CD8+ CTL. However, CTL lines from HIV‐positive individuals heterozygous for the perforin 1012T SNP displayed normal lysis of target cells, and within the SEROCO cohort, patients heterozygous for the 1012T SNP showed normal disease progression. However, 1012T/T homozygotes showed a tendency towards slower disease progression (P = 0.08). In conclusion, polymorphism in the perforin gene is limited, and although the 1012T genotype appears to influence perforin expression, it was not conclusively associated with disease progression in HIV infection.
Drug Resistance of HIV‐1 Protease Against JE‐2147: I47V Mutation Investigated by Molecular Dynamics Simulation
Authors: Bandyopadhyay Pradipta , Meher B. R.
Published: February 2006

Anti‐retroviral therapies for acquired immunodeficiency syndrome (AIDS) patients are at risk because of drug resistance that has been identified with a number of currently marketed drugs. HIV‐1 protease (HIV‐pr), a well‐validated AIDS therapeutic target, undergoes various mutations leading to resistance such existing drugs. However, the molecular basis of drug resistance of HIV‐pr is still not fully understood. JE‐2147, an experimental inhibitor of HIV‐pr, shows a resistance profile different from that of known drugs. Noteworthy, it is less susceptible to several common mutations, but it is still susceptible to a few mutations, including I47V which appears to be specific for JE‐2147. In this work, the molecular details of the effect of I47V mutation is investigated using molecular dynamics simulation. Four simulations of apo and complexed proteins in their wild type (WT) and mutant forms have been performed. It is found that the mobility of the side chain of mutant Val47 in chain B of HIV‐pr about the inhibitor increases significantly relative to WT Ile47 in chain B. This is due to loss of optimized packing of the inhibitor to the residue 47 in chain B of the mutant when compared with WT enzyme. There also are subtle differences in motion involving residues in the flap region, which are more prominent in the apo form.
Water balance and the behaviour of different paving surfaces
Authors: Mansell Martin , Rollet Fabien
Published: February 2006

The concept of water balance is frequently used to describe the main hydrological processes occurring in natural catchments. It can also be applied to urban catchments and in this paper the water balance principle is applied to small‐scale samples of various paving materials. In particular, the relative importance of runoff, evaporation and infiltration is studied. This paper discusses these processes and describes some experimental measurements of water balance on various paving materials and the moisture content distribution within the materials.
A watery form of sustainability
Authors: Cashman A.
Published: February 2006

Regulation has been the most important driver in encouraging the water industry to move towards sustainability, but increasingly the appropriateness and effectiveness of regulation are being questioned. It is argued that, in its present form, sustainability as presented and supported through regulation equates to a form of weak sustainability that privileges the economic and subordinates the environment and societal spheres of sustainability. To overcome this, requires more long‐term perspectives, participatory mechanisms and moves beyond efficiency to intensity of resource use.
The Levels of Selection Debate: Philosophical Issues
Authors: Okasha Samir
Published: February 2006

For a number of years, the debate in evolutionary biology over the ‘levels of selection’ has attracted intense interest from philosophers of science. The main question concerns thelevel of the biological hierarchyat which natural selection occurs. Does selection act on organisms, genes, groups, colonies, demes, species, or some combination of these? According to traditional Darwinian theory the answer is the organism – it is the differential survival and reproduction of individual organisms that drives the evolutionary process. But there are alternative views too, including pluralist views which say that the choice between different levels of selection is often a matter of perspective, not empirical fact.
Contemporary virtue ethics
Authors: Stohr Karen
Published: February 2006

Within contemporary ethics, virtue ethics now seems to be permanently positioned as a major normative theory. Despite its popularity, however, it is often not very clear – even to virtue ethicists – what is included in the term. This article clarifies the territory by setting out some recent developments in virtue ethics. The article also explores the impact of the virtue ethics revival on metaethics and looks at the direction of future debate.
Malebranche's “Vision in God”
Authors: Pessin Andrew
Published: February 2006

Of Malebranche's many famous doctrines, his “Vision in God” (VIG) surely ranks among the most interesting. Inspired by Augustine and Descartes, he argues for it vigorously and gives it a prominent place in his system of thought. And although it won no converts it did win many critics, who, in criticizing, were compelled to clarify their own theories of cognition. Thus VIG is of interest for its own sake, for its role in Malebranche's philosophy, and for its general influence in the early modern period.
The Paradox of Confirmation1
Authors: Fitelson Branden
Published: February 2006

Hempel first introduced the paradox of confirmation in 1937. Since then, a very extensive literature on the paradox has evolved (Vranas 2004). Much of this literature can be seen as responding to Hempel's subsequent discussions and analyses of the paradox (Hempel 1945). Recently, it was noted that Hempel's intuitive (and plausible) resolution of the paradox was inconsistent with his official theory of confirmation (Fitelson and Hawthorne 2006). In this article, we will try to explain how this inconsistency affects the historical dialectic about the paradox and how it illuminates the nature of confirmation. In the end, we will argue that Hempel's intuitions about the paradox of confirmation were (basically) correct, and that it is his theory that should be rejected, in favor of a (broadly) Bayesian account of confirmation.
Time reversed imaging for perturbed media
Authors: Mehta Kurang , Snieder Roel
Published: February 2006

In time reversed imaging a pulse is propagated through a medium, the signal is recorded, and then the time reversed signal is back-propagated through the same medium to refocus the energy at the original location of the source. The refocusing is independent of the medium if the medium is the same during back-propagation. If the speed of back-propagation differs from the speed of forward propagation, the waves refocus at a different location. For a single source and single receiver, the shift is proportional to the distance between the source and the receiver and the speed difference. If several receivers are placed along a circle to form an aperture angle, the shift in the location of the refocused pulse increases with increasing aperture angle for a given source-receiver distance and speed difference. If we analyze the problem using ray theory, an increase in the aperture angle would result in a decrease in the shift of the refocused pulse. The explanation for the shift of the refocused pulse with aperture angle is simple from a wave-front point of view.
Integer versus half-integer angular momentum
Authors: Gatland Ian R.
Published: February 2006

The absence of half-integer orbital angular momentum states is established by considering the realizations of the angular momentum operators in spherical coordinates, θ and φ. The angular momentum raising and lowering operators switch the states between even and odd functions of θ−π∕2. Furthermore, the bottom and top states are both even. Hence there must be an odd number of states. This argument permits integer angular momenta and forbids half-integer angular momenta.
Lock-in detection with DataStudio
Authors: Kraftmakher Yaakov
Published: February 2006

The ScienceWorkshop data acquisition system with DATASTUDIO software is capable of performing lock-in detection of periodic signals. I discuss how DATASTUDIO can be used for teaching this detection technique and doing real experiments. Along with a demonstration of lock-in detection, a determination of the Verdet constant with an ac magnetic field is described.
Quantum mysteries tested: An experiment implementing Hardy’s test of local realism
Authors: Carlson J. A. , Olmstead M. D. , Beck M.
Published: February 2006

We have performed a test of local realism using entangled photons produced by spontaneous parametric downconversion. This experimental test is based on an idea originally proposed by Hardy for a test of local realism without inequalities, although our experiment actually measures an inequality (as any experiment must). We find a more-than-70 standard deviation violation of the predictions of local realism. The experimental effort required for this test is essentially the same as that required for a test of a Bell inequality. However, this test is based on concepts that are easier to understand and more compelling than those behind the original Bell inequality.