bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil transendothelial migration in vitro toStreptococcus pneumoniaeis pneumolysin dependent
Authors: Moreland Jessica G. , Bailey Gail
Published: December 2005

The recruitment of polymorphonuclear leukocytes (PMN) from the vascular space to the alveolar air space is an early event in host defense against pneumococcal pneumonia. Pneumolysin is a virulence factor for Streptococcus pneumoniae, but a specific role for pneumolysin in neutrophil-endothelial cell interactions has not been investigated. Using a Transwell system, we studied in vitro migration of PMNs across a monolayer of human pulmonary microvascular endothelial cells in response to wild-type S. pneumoniae (D39) and a pneumolysin-deficient mutant ( plnA−) incubated on the abluminal surface of the monolayer. S. pneumoniae induction of PMN migration was dose dependent and elicited by ≥105D39. Mutants lacking pneumolysin had dramatically reduced potency for eliciting PMN migration compared with the parent strain (5 × 106plnA−elicits 18.6% PMN migration vs. 55.5% for 5 × 106D39). The disparity between D39 and plnA−persisted in ethanol-fixed bacteria, consistent with the properties of pneumolysin. Neither conditioned medium from D39 nor purified pneumolysin elicited PMN migration to the same extent as the intact D39, suggesting that the role of pneumolysin in eliciting PMN migration requires a more complex interaction between the organism, the endothelium, and the PMN. Both D39 and plnA−adhered to, and translocated across, the endothelium in the abluminal to luminal direction and elicited similar levels of IL-8 production. Neither strain elicited upregulation of the endothelial adhesion molecules ICAM-1, VCAM-1, or E-selectin, and they did not cause translocation of NF-κB to the nucleus. These findings demonstrate a novel role for pneumolysin in pneumococcus-induced PMN recruitment across the pulmonary endothelium.
Differential Log Likelihood for Evaluating and Learning Gaussian Mixtures
Authors: Hulle Marc M. Van
Published: December 2005

We introduce a new unbiased metric for assessing the quality of density estimation based on gaussian mixtures, called differential log likelihood. As an application, we determine the optimal smoothness and the optimal number of kernels in gaussian mixtures. Furthermore, we suggest a learning strategy for gaussian mixture density estimation and compare its performance with log likelihood maximization for a wide range of real-world data sets.
Polychronization: Computation with Spikes
Authors: Izhikevich Eugene M.
Published: December 2005

We present a minimal spiking network that can polychronize, that is, exhibit reproducible time-locked but not synchronous firing patterns with millisecond precision, as in synfire braids. The network consists of cortical spiking neurons with axonal conduction delays and spike-timing-dependent plasticity (STDP); a ready-to-use MATLAB code is included. It exhibits sleeplike oscillations, gamma (40 Hz) rhythms, conversion of firing rates to spike timings, and other interesting regimes. Due to the interplay between the delays and STDP, the spiking neurons spontaneously self-organize into groups and generate patterns of stereotypical polychronous activity. To our surprise, the number of coexisting polychronous groups far exceeds the number of neurons in the network, resulting in an unprecedented memory capacity of the system. We speculate on the significance of polychrony to the theory of neuronal group selection (TNGS, neural Darwinism), cognitive neural computations, binding and gamma rhythm, mechanisms of attention, and consciousness as “attention to memories.”
Magnification Control in Self-Organizing Maps and Neural Gas
Authors: Villmann Thomas , Claussen Jens Christian
Published: December 2005

We consider different ways to control the magnification in self-organizing maps (SOM) and neural gas (NG). Starting from early approaches of magnification control in vector quantization, we then concentrate on different approaches for SOM and NG. We show that three structurally similar approaches can be applied to both algorithms that are localized learning, concave-convex learning, and winner-relaxing learning. Thereby, the approach of concave-convex learning in SOM is extended to a more general description, whereas the concave-convex learning for NG is new. In general, the control mechanisms generate only slightly different behavior comparing both neural algorithms. However, we emphasize that the NG results are valid for any data dimension, whereas in the SOM case, the results hold only for the one-dimensional case.
Genocide and State-Induced Famine: Global Ethics and Western Responsibility for Mass Atrocities in Africa
Authors: Howard-Hassmann Rhoda
Published: December 2005

This article considers Western responsibility for genocide and state-induced famine in Africa. It discusses colonial genocide in South-West Africa and Congo; post-colonial genocide in Rwanda and Darfur; and state-induced famine in Ethiopia and Zimbabwe. The article differentiates core, contributory, and circumstantial responsibility for genocide and famine, arguing that except for the two colonial genocides, African political actors bear core responsibility. Nevertheless, the West is responsible for protecting the human rights of all Africans, regardless of which political actors caused their suffering. The article concludes by discussing empathy and interest as means to persuade Western actors to devote more attention to Africa.
Society and Market in the Era of Globalization
Authors: Pokorný Dušan
Published: December 2005

This chapter considers the meaning of the terms "society" and "market," and the need for markets to be institutionalized and legitimated. Obligatory norms and recommendatory guidelines today come from many sources: from states, from groupings of states, and from worldwide bodies such as the IMF, the WTO, and the World Bank. But when markets create profound inequalities both within and between societies, how do we determine what limits ought to be placed on markets? Since economic institutions are inseparable from culture, this is the "site" where the public will have to decide what is "society," what is the "market," and what will be the relation between them.
Globalization, Markets, and Ethics
Authors: Day Richard
Published: December 2005

This chapter briefly surveys the political and economic issues posed by the debate over globalization and then reformulates them with reference to the problematic relation between markets and ethics in the history of philosophy. Beginning with Aristotle, and then proceeding to Adam Smith, Immanuel Kant, and G.W.F. Hegel, the chapter argues that markets always and everywhere presuppose normative consensus, with the implication that any notion of autonomous globalizing markets is an abstraction that threatens the human right to life and dignity.
Some Consequences of the Three-Dimensional Current and Surface Wave Equations
Authors: Mellor George
Published: December 2005

Three-dimensional, interacting current and surface gravity wave equations have recently been derived and compared with their counterpart vertically integrated equations; they are in the form of sigma-coordinate equations. The purpose of this paper is to examine some of the consequences of these equations including energy transfer between mean energy, wave energy, and turbulence energy, to frame some outstanding research issues, to provide a Cartesian version of the sigma-coordinate equations, and to compare with other formulations of wave–current interaction. In general, the paper is intended to set the stage for the development of numerical coupled surface wave and three-dimensional general circulation models. These models often include a flow-dependent turbulence-based viscosity.
The Effect of Wave Breaking on Surf-Zone Turbulence and Alongshore Currents: A Modeling Study*
Authors: Feddersen Falk , Trowbridge J. H.
Published: December 2005

The effect of breaking-wave-generated turbulence on the mean circulation, turbulence, and bottom stress in the surf zone is poorly understood. A one-dimensional vertical coupled turbulence (k–ɛ) and mean-flow model is developed that incorporates the effect of wave breaking with a time-dependent surface turbulence flux and uses existing (published) model closures. No model parameters are tuned to optimize model–data agreement. The model qualitatively reproduces the mean dissipation and production during the most energetic breaking-wave conditions in 4.5-m water depth off of a sandy beach and slightly underpredicts the mean alongshore current. By modeling a cross-shore transect case example from the Duck94 field experiment, the observed surf-zone dissipation depth scaling and the observed mean alongshore current (although slightly underpredicted) are generally reproduced. Wave breaking significantly reduces the modeled vertical shear, suggesting that surf-zone bottom stress cannot be estimated by fitting a logarithmic current profile to alongshore current observations. Model-inferred drag coefficients follow parameterizations (Manning–Strickler) that depend on the bed roughness and inversely on the water depth, although the inverse depth dependence is likely a proxy for some other effect such as wave breaking. Variations in the bed roughness and the percentage of breaking-wave energy entering the water column have a comparable effect on the mean alongshore current and drag coefficient. However, covarying the wave height, forcing, and dissipation and bed roughness separately results in an alongshore current (drag coefficient) only weakly (strongly) dependent on the bed roughness because of the competing effects of increased turbulence, wave forcing, and orbital wave velocities.
Variability of the Kuroshio Extension Jet, Recirculation Gyre, and Mesoscale Eddies on Decadal Time Scales
Authors: Qiu Bo , Chen Shuiming
Published: December 2005

Twelve years of sea surface height (SSH) data from multiple satellite altimeters are used to investigate the low-frequency changes and the interconnections of the Kuroshio Extension (KE) jet, its southern recirculation gyre, and their mesoscale eddy field. The dominant signal is characterized by the steady weakening of the KE jet/recirculation gyre from 1993 to 1996, followed by a gradual strengthening after 1997. During the weakening period of 1993–96, the KE path migrated southward in general, and this path migration reversed in direction during the strengthening period of the KE jet and recirculation gyre after 1997. By hindcasting the SSH signals using linear vorticity dynamics, it was found that weakening (strengthening) in the KE jet and recirculation gyre is consistent with westward propagation of negative (positive) SSH anomalies generating in the eastern North Pacific and strengthening during their westward propagation. When the KE jet and recirculation gyre were in a weak mode during 1996–2001, the regional eddy kinetic energy level was observed to be higher than when the jet and recirculation gyre were in a strong mode. This negative correlation between the mean flow intensity and the level of regional eddy kinetic energy is found in both the SSH data and the linear vorticity model to result from the migration of the KE jet inflow over the Izu–Ogasawara Ridge. When it is forced southward by the impinging negative SSH anomalies, the KE jet inflow rides over the ridge through a shallow segment, leading to large-amplitude downstream meanders. Impinging of positive SSH anomalies, on the other hand, strengthens the recirculation gyre and forces the inflow northward where it passes through a deep channel, minimizing the path perturbations in the downstream region.
The Shallow and Deep Western Boundary Circulation of the South Atlantic at 5°–11°S
Authors: Schott Friedrich A. , Dengler Marcus , Zantopp Rainer , Stramma Lothar , Fischer Jürgen , Brandt Peter
Published: December 2005

Repeated shipboard observation sections across the boundary flow off northeastern Brazil as well as acoustic Doppler current profiler (ADCP) and current-meter records from a moored boundary array deployed during 2000–04 near 11°S are analyzed here for both the northward warm water flow by the North Brazil Undercurrent (NBUC) above approximately 1100 m and the southward flow of North Atlantic Deep Water (NADW) underneath. At 5°S, the mean from nine sections yields an NBUC transport of 26.5 ± 3.7 Sv (Sv ≡ 106 m3 s−1) along the boundary; at 11°S the mean NBUC transport from five sections is 25.4 ± 7.4 Sv, confirming that the NBUC is already well developed at 11°S. At both latitudes a persistent offshore southward recirculation between 200- and 1100-m depth reduces the net northward warm water flow through the 5°S section (west of 31.5°W) to 22.1 ± 5.3 Sv and through the 11°S section to 21.7 ± 4.1 Sv (west of 32.0°W). The 4-yr-long NBUC transport time series from 11°S yields a seasonal cycle of 2.5 Sv amplitude with its northward maximum in July. Interannual NBUC transport variations are small, varying only by ±1.2 Sv during the four years, with no detectable trend. The southward flow of NADW within the deep western boundary current at 5°S is 25.5 ± 8.3 Sv with an offshore northward recirculation, yielding a nine-section mean of 20.3 ± 10.1 Sv west of 31.5°W. For Antarctic Bottom Water, a net northward flow of 4.4 ± 3.0 Sv is determined at 5°S. For the 11°S section, the moored array data show a pronounced energy maximum at 60–70-day period in the NADW depth range, which was identified in related work as deep eddies translating southward along the boundary. Based on a kinematic eddy model fit to the first half of the moored time series, the mean NADW transfer by the deep eddies at 11°S was estimated to be about 17 Sv. Given the large interannual variability of the deep near-boundary transport time series, which ranged from 14 to 24 Sv, the 11°S mean was considered to be not distinguishable from the mean at 5°S.
Pathways into the Pacific Equatorial Undercurrent: A Trajectory Analysis*
Authors: Goodman Paul J. , Hazeleger Wilco , de Vries Pedro , Cane Mark
Published: December 2005

A time-dependent trajectory algorithm is used to determine the sources of the Pacific Ocean Equatorial Undercurrent (EUC) in a global climate model with ¼° (eddy permitting) resolution and forced with realistic winds. The primary sources and pathways are identified, and the transformation of properties in temperature/salinity space is explored. An estimate for the quantity of recirculation, a notoriously difficult property to estimate from observational data, is given. Over two-thirds of the water in the Pacific EUC at 140°W originates south of the equator; 70% of the EUC is ventilated outside of the Tropics (poleward of 13°S or 10°N): three-quarters of these extratropical trajectories travel through the western boundary currents between their subduction and incorporation into the EUC, and one-fifth of the extratropical trajectories enter and leave the tropical band at least once before entering the EUC.
Tin rich layers on ancient copper based objects
Authors: Giumlia-Mair A.
Published: December 2005

A number of archaeological copper based objects, presenting tin rich layers on the surface, dated to different periods and coming from very different geographical contexts in the Ancient World, are discussed in this paper. The different reasons for the presence of tin rich layers on the surface of ancient items have been discussed before. However, new analyses of archaeological objects now offer data on the early use of tinning, on the use of high tin alloys for distinctive objects in the Bronze Age and of the use of special surface treatments employed in antiquity, which might give new insights into the early history of metallurgy and new elements for the identification of trade routes. A surface treatment, possibly employed in Roman times, is also discussed.
Surfaces of antique marble sculptures in the Uffizi Gallery: Reflection of history and image
Authors: Romualdi A. , Pallecchi P. , Pierelli L. , Tonini G.
Published: December 2005

The Uffizi Gallery owns an extraordinary collection of Roman marble sculptures which are important for the histories of both antique and collectors’ taste. A variety of statuaries, busts, sarcophagi and reliefs, and all parts of the antiquarian collection of the Medici family were restored by famous artists between the 16th and 19th century. Many of these sculptures have been recently restored again. The artworks housed within the museum have been always considered to be protected from physical and chemical degradation, however, from the point of view of conservation, the treatment approach is extremely complex. The surface layer is often the result of a variety of treatments, such as repolishing, addition of ‘tasselli’ (i.e. different stone insertions) and other marble elements. Artificial patination treatments consisting of coloured wax and oil have also been applied at different time throughout the history with the intention of chromatically harmonising the antique parts with the modern additions. Often museum specialists, who are sensitive towards conservation problems concerning outdoor sculptures, have minimised the problems regarding indoor sculptures exposed to thermal variation, dust and pollution deposited on the surfaces from hundreds of daily visitors to the gallery. The surface, considered here image and reflection of the history of each sculpture, is investigated from a morphological point of view, with particular attention to the original tool marks, remains of the original deposition in earth and various types of surface films from ancient and/or recent treatments and applied substances. The aim of the present study is to analyse the geological, chemical and physical compositions of these layers, and to reconstruct the causes of the distributions of these substances on different kinds of sculpted surfaces. If possible, we attempt to reconstruct, at least in part, the archaeological and historical events on each sculpture. The present study evaluates the conservation treatments carried out on several important sculptures through the study of surface stratifications in different categories of marble sculptures (i.e. sarcophagi, statues, etc.).
Brown spot corrosion on historic gold coins and medals
Authors: Griesser M. , Traum R. , Mayerhofer K. E. , Piplits K. , Denk R. , Winter H.
Published: December 2005

In 1998, in the Coin Cabinet of the Kunsthistorisches Museum, Vienna, Austria, brown spot corrosion was detected on about 400 gold coins and medals minted in Central Europe between the late 18th and early 20th century. The cause of the brown spots, their temporal and spatial frequency, the development of the corrosion and the most suitable restoration treatments and storage conditions for these objects has been and is still being studied. For the analysis of the historic coins and medals—as well as a set of test ducats produced in cooperation with the Austrian Mint—different analytical methods, i.e. light microscopy, scanning electron microscopy (SEM), measurement of polarisation curves, and secondary ion mass spectrometry (SIMS) were combined. From these investigations and the study of historical sources it could be shown that the brown spot corrosion is due to the inclusion of silver and/or silver/copper containing particles into the surface of the coins and medals. These inclusions are incorporated during the minting process. Afterwards they corrode to silver and copper sulphides owing to the presence of air pollution and objects releasing sulphur containing compounds (i.e. gypsum casts) nearby the historical objects.
Surface analyses of ‘impasto rosso’ pottery from Southern Etruria and Latium
Authors: Saviano G. , Pilone D. , Felli F. , Drago L.
Published: December 2005

Several fragments of Etruscan and Latial ceramic pottery (from the sixth to eighth centuries BC) were analysed to study both raw materials and structural characteristics of the clay production. The samples come from the Monte Artemisio settlement near Velletri (Latium Vetus) and from Casale del Fosso necropolis at Veio, one of the main Southern Etruria centres. The aim of this paper was to identify techniques used for finishing surfaces and eventually for applying decorations. Scanning electron microscope energy dispersive spectroscopic (SEM-EDS) analyses of different samples were carried out in order to highlight possible differences in mixtures as well as pigment application methods and natural colouring during firing. Mineralogical composition of mixtures was determined by means of X-ray powder diffraction.
Surface alteration and morphological characterisation of pottery specimens from a northern Italian Iron Age site
Authors: Stella C.
Published: December 2005

One hundred and forty-six pottery specimens from Pozzuolo, a northern Italian Iron Age site, have been studied by means of optical devices to establish possible differences or similarities in the ceramic body. Four different clay mixtures have been identified. This suggests different levels of production technology. Special attention is given here to surface structures and to surface alterations of the ceramics.
Role of impact on determination of interfacial toughness measurement by indentation for thermal barrier coating systems
Authors: Ekici B.
Published: December 2005

The measurement of interfacial toughness by an indentation method was proposed several years ago. It has been shown that this method is very simple and reliable for the calculation of interfacial toughness. For this reason, many studies were performed for different substrate and coating combinations. Numerical models also supported these studies. Unfortunately, the success of this method depends on the hardness of the substrate. In most studies, the coating was ceramic and the substrate was steel. The substrate must be hard enough to get a circular crack around the indentation zone. If the substrate is not hard enough, the circular crack cannot be seen. In the light of the experiments performed for different combinations of substrate and coating, the use of the method was restricted to a very narrow range of materials that are mainly used for thermal barrier coating systems. In the present study, this method is used even for a medium hardness substrate. In order to get a circular crack, loading is performed with constant acceleration instead of static loading. The success of the method is shown to be considerably increased.
PSE: A tool for browsing a large amount of MEDLINE/PubMed abstracts with gene names and common words as the keywords
Authors: Yoneya Takashi
Published: December 2005

Background

MEDLINE/PubMed (hereinafter called PubMed) is one of the most important literature databases for the biological and medical sciences, but it is impossible to read all related records due to the sheer size of the repository. We usually have to repeatedly enter keywords in a trial-and-error manner to extract useful records. Software which can reduce such a laborious task is therefore required.

Results

We developed a web-based software, the PubMed Sentence Extractor (PSE), which parses large number of PubMed abstracts, extracts and displays the co-occurrence sentences of gene names and other keywords, and some information from EntrezGene records. The result links to whole abstracts and other resources such as the Online Mendelian Inheritance in Men and Reference Sequence. While PSE executes at the sentence-level when evaluating the existence of keywords, the popular PubMed operates at the record-level. Therefore, the relationship between the two keywords, a gene name and a common word, is more accurately captured by PSE than PubMed. In addition, PSE shows the list of keywords and considers the synonyms and variations on gene names. Through these functions, PSE would reduce the task of searching through records for gene information.

Conclusion

We developed PSE in order to extract useful records efficiently from PubMed. This system has four advantages over a simple PubMed search; the reduction in the amount of collected literatures, the showing of keyword lists, the consideration for synonyms and variations on gene names, and the links to external databases. We believe PSE is helpful in collecting necessary literatures efficiently in order to find research targets. PSE is freely available under the GPL licence as additional files to this manuscript.
All dressed up but nowhere to go? Delayed hospital discharges and older people
Authors: Glasby Jon , Littlechild Rosemary , Pryce Kathryn
Published: December 2005

Objective: Delayed hospital discharges are a key concern in a number of industrialized nations and are the subject of a range of government initiatives in the English National Health Service. The aim of this paper was to review the UK literature on delayed hospital discharges and older people in order to identify and explore the rate and causes of delayed hospital discharges, together with policies and practices that may reduce delayed discharges and improve the experiences of older people.

Methods: Literature review based on searches of major health/social-care databases. Sources which explore the rate and cause of delayed discharges in the UK were included. Relevant documents were categorized using the research hierarchy set out in the National Service Framework for Older People and analysed according to criteria for appraising the quality of qualitative research proposed by Mays et al.

Results: The review identified 21 studies, which suggest very different rates and causes of delayed discharge in different settings. The studies reveal the importance of rehabilitation services to reduce the rate of delayed discharge, the prevalence of delayed discharges caused by internal hospital factors, and the complex and multi-faceted nature of the factors contributing to delayed discharge. Despite this, the studies have a number of methodological flaws and often fail to include a patient perspective or to consider detailed policies and approaches to reduce the number of delayed discharges. There is also a failure to consider the needs of older people with mental health problems or people from minority ethnic communities.

Conclusion: The evidence, as it currently stands, raises a number of issues about current hospital discharge policy, supporting some aspects of the current government agenda in England, but questioning other aspects.
In Vitro Modeling of Paraxial and Lateral Mesoderm Differentiation Reveals Early Reversibility
Authors: Sakurai Hidetoshi , Era Takumi , Jakt Lars Martin , Okada Mitsuhiro , Nakai Shigeru , Nishikawa Satomi , Nishikawa Shin-Ichi
Published: December 2005

Endothelial cells (ECs) are thought to be derived mainly from the vascular endothelial growth factor receptor 2 (VEGFR-2)+ lateral mesoderm during early embryogenesis. In this study, we specified several pathways for EC differentiation using a murine embryonic stem (ES) cell differentiation culture system that is a model for cellular processes during early embryogenesis. Based on the results of in vitro fate analysis, we show that, in the main pathway, committed ECs are differentiated through the VEGFR-2+ platelet-derived growth factor receptor α (PDGFR-α)− single-positive (VSP) population that is derived from the VEGFR-2+PDGFR-α+ double-positive (DP) population. This major differentiation course was also confirmed using DNA microarray analysis. In addition to this main pathway, however, ECs also can be generated from the VEGFR-2−PDGFR-α+ single-positive (PSP) population, which represents the paraxial mesodermal lineage and is also derived from the DP population. Our results strongly suggest that, even after differentiation from the common progenitor DP population into the VSP and PSP populations, these two populations continue spontaneous switching of their surface phenotype, which results in switching of their eventual fates. The rate of this interlineage conversion between VSP and PSP is unexpectedly high. Because of this potential to undergo fate switch, we conclude that ECs can be generated via multiple pathways in in vitro ES cell differentiation.
Psychosocial treatments of suicidal behaviors: A practice‐friendly review
Authors: Comtois Katherine Anne , Linehan Marsha M.
Published: December 2005

Worldwide, almost a million people die by suicide each year. Intentional, nonfatal, self‐inflicted injury, including both suicide attempts and acts without suicide intent, also has very high prevalence. This article provides a practice‐friendly review of controlled studies of psychosocial treatments aiming to prevent suicide, attempted suicide, and nonsuicidal self‐inflicted injuries. Despite relatively small sample sizes for a low‐base‐rate outcome such as self‐inflicted injury, several psychotherapies have been found effective, including cognitive therapy, dialectical behavior therapy, problem‐solving therapy, and interpersonal psychotherapy, as well as outreach interventions, such as sending caring letters. The clinical implications of the review are discussed with the goal of translating the science to service—particularly the importance of outreach and treatment of non‐compliance, the assessment and management of suicide risk, and competency in effective psychotherapies. These are critical steps for clinical psychology and psychotherapists to take in their role in suicide prevention. © 2005 Wiley Periodicals, Inc. J Clin Psychol: In Session 62: 161–170, 2006.
Do SSRIs cause suicide in children? The evidence is underwhelming
Authors: Bostwick John Michael
Published: December 2005

After regulatory agencies in the United Kingdom and United States recommended severe restrictions on antidepressant use in children, many lessons were learned, although one was not that these drugs cause suicide. We learned that pharmaceutical companies selectively released data that reflected positively on their products and that combining suppressed and published data suggested that most of these medications had questionable efficacy. We also learned that the studies lacked uniformity both in which age groups constituted children and which behavior was considered suicidal. Several recent, large nonindustry studies indicated that rates of suicide and suicidal behavior were actually reduced in children who used antidepressants, despite piteous anecdotal tales in the popular press purporting that selective serotonin reuptake inhibitors (SSRIs) caused children to kill themselves. Patients in pharmaceutical trials probably do not represent typical patients in routine clinical practice. Emerging implications are that suicidal behavior—if it does occur—is most likely soon after starting antidepressant use and that prescribers must be both vigilant in educating patients and families about warning signs and available to manage worrisome behavior. © 2005 Wiley Periodicals, Inc. J Clin Psychol: In Session 62: 235–241, 2006.
The case against no‐suicide contracts: The commitment to treatment statement as a practice alternative
Authors: Rudd M. David , Mandrusiak Michael , Joiner Jr. Thomas E.
Published: December 2005

This article reviews the literature on the use of “no‐suicide contracts” in clinical practice, including conceptual discussions, patient and clinician surveys, and a few empirical studies on clinical utility. Our primary conclusion is that no‐suicide contracts suffer from a broad range of conceptual, practical, and empirical problems. Most significantly, they have no empirical support for their effectiveness in the clinical environment. The authors provide and illustrate the commitment to treatment statement as a practice alternative to the no‐suicide contract. © 2005 Wiley Periodicals, Inc. J Clin Psychol: In Session 62: 243–251, 2006.
Human and yeast Hsp110 chaperones exhibit functional differences
Authors: Raviol Holger , Bukau Bernd , Mayer Matthias P.
Published: December 2005

Hsp110 proteins constitute a heterogeneous family of abundant molecular chaperones, related to the Hsp70 proteins and exclusively found in the cytosol of eukaryotic organisms. Hsp110 family members are described as efficient holdases, preventing the aggregation and assisting the refolding of heat‐denatured model substrates in the presence of Hsp70 chaperones and their co‐chaperones. To gain more insights into the mode of action of this protein family we compared two homologues representing two subtypes of Hsp110 proteins, S. cerevisiae Sse1 and H. sapiens Apg‐2, in their structural and functional properties in vitro. In contrast to previous publications both proteins exhibited intrinsic ATPase activities, which only in the case of Sse1 could be stimulated by the Hsp40 co‐chaperone Sis1. Similar to Hsp70 proteins ATP binding and hydrolysis induced conformational rearrangements in both Hsp110 proteins as detected by tryptophane fluorescence. However, nucleotide induced changes in the proteolytic digestion pattern were detected only for Sse1. Sse1 and Apg‐2 thus show significant differences in their biochemical properties, which may relate to differences in their functional roles in vivo.
The identification of a functional interaction between PKC and topoisomerase II
Authors: Mouchel Nathalie A.P. , Jenkins John R.
Published: December 2005

Topoisomerase II plays an essential role in the segregation of chromosomes during cell division. It is also a major component of the nuclear matrix. Proteins that interact with and regulate this essential enzyme are of great interest. To investigate the role of proteins interacting with the N‐terminal domain of the Saccharomyces cerevisiae topoisomerase II, we used a yeast two‐hybrid protein interaction screen. We identified an interaction between the catalytic domain of the yeast protein kinase 1 enzyme (Pkc1) and the N‐terminal domain of the S. cerevisiae topoisomerase II. The S. cerevisiae Pkc1 is the homologue of the mammalian calcium dependent PKC.
Flexor tendon pulley V–Y Plasty: an Alternative to Pulley Venting or Resection
Authors: DONA E. , WALSH W. R.
Published: December 2005

Zone 2 flexor tendon repairs can require “venting” or partial resection of the A2 and/or A4 pulleys. We propose and biomechanically assess a technique used by the authors in which the A2 and A4 pulleys are divided and repaired using a V–Y plasty. Two groups of cadaveric fingers were used, one group for assessing the A2 pulley and the second for assessing the A4 pulley. Prepared fingers were mounted onto custom-made jigs, tested using a servohydraulic testing machine and assessed for load to failure. The loads obtained were 75N (SD = 26N) and 234N (SD = 73N) for the A4 and A2 pulleys, respectively. These loads are well in excess of those one would anticipate during a postoperative active mobilization protocol. Tendon pulley V–Y plasty creates a mechanically sound pulley and maintains sufficient cover of the underlying tendon. This technique provides access to perform a tendon repair and/or permits free tendon gliding post-repair, thus providing an attractive alternative to simply “venting”, or resecting, an otherwise troublesome pulley.
Bacillus thuringiensis subsp. israelensis Cyt1Aa synergizes Cry11Aa toxin by functioning as a membrane-bound receptor
Authors: Pérez Claudia , Fernandez Luisa E. , Sun Jianguang , Folch Jorge Luis , Gill Sarjeet S. , Soberón Mario , Bravo Alejandra
Published: December 2005

Bacillus thuringiensis
subsp.
israelensis
produces crystal proteins, Cry (4Aa, 4Ba, 10Aa, and 11Aa) and Cyt (1Aa and 2Ba) proteins, toxic to mosquito vectors of human diseases. Cyt1Aa overcomes insect resistance to Cry11Aa and Cry4 toxins and synergizes the toxicity of these toxins. However, the molecular mechanism of synergism remains unsolved. Here, we provide evidence that Cyt1Aa functions as a receptor of Cry11Aa. Sequential-binding analysis of Cyt1Aa and Cry11Aa revealed that Cyt1Aa binding to
Aedes aegypti
brush border membrane vesicles enhanced the binding of biotinylated-Cry11Aa. The Cyt1Aa- and Cry11Aa-binding epitopes were mapped by means of the yeast two-hybrid system, peptide arrays, and heterologous competition assays with synthetic peptides. Two exposed regions in Cyt1Aa, loop β6-αE and part of β7, bind Cry11Aa. On the other side, Cry11Aa binds Cyt1Aa proteins by means of domain II-loop α8 and β-4, which are also involved in midgut receptor interaction. Characterization of single-point mutations in Cry11Aa and Cyt1Aa revealed key Cry11Aa (S259 and E266) and Cyt1Aa (K198, E204 and K225) residues involved in the interaction of both proteins and in synergism. Additionally, a Cyt1Aa loop β6-αE mutant (K198A) with enhanced synergism to Cry11Aa was isolated. Data provided here strongly indicates that Cyt1Aa synergizes or suppresses resistance to Cry11Aa toxin by functioning as a membrane-bound receptor.
Bacillus thuringiensis
subsp.
israelensis
is a highly effective pathogenic bacterium because it produces a toxin and also its functional receptor, promoting toxin binding to the target membrane and causing toxicity.
Optical detection of rate-determining ion-modulated conformational changes of the ether-à-go-go K
+
channel voltage sensor
Authors: Bannister John P. A. , Chanda Baron , Bezanilla Francisco , Papazian Diane M.
Published: December 2005

In voltage-dependent ether-à-go-go (eag) K
+
channels, the process of activation is modulated by Mg
2+
and other divalent cations, which bind to a site in the voltage sensor and slow channel opening. Previous analysis of eag ionic and gating currents indicated that Mg
2+
has a much larger effect on ionic than gating current kinetics. From this, we hypothesized that ion binding modulates voltage sensor conformational changes that are poorly represented in gating current recordings. We have now tested this proposal by using a combined electrophysiological and optical approach. We find that a fluorescent probe attached near S4 in the voltage sensor reports on two phases of the activation process. One component of the optical signal corresponds to the main charge-moving conformational changes of the voltage sensor. This is the phase of activation that is well represented in gating current recordings. Another component of the optical signal reflects voltage sensor conformational changes that occur at more hyperpolarized potentials. These transitions, which are rate-determining for activation and highly modulated by Mg
2+
, have not been detected in gating current recordings. Our results demonstrate that the eag voltage sensor undergoes conformational changes that have gone undetected in electrical measurements. These transitions account for the time course of eag activation in the presence and absence of extracellular Mg
2+
.
The spread of attention across modalities and space in a multisensory object
Authors: Busse Laura , Roberts Kenneth C. , Crist Roy E. , Weissman Daniel H. , Woldorff Marty G.
Published: December 2005

Attending to a stimulus is known to enhance the neural responses to that stimulus. Recent experiments on visual attention have shown that this modulation can have object-based characteristics, such that, when certain parts of a visual object are attended, other parts automatically also receive enhanced processing. Here, we investigated whether visual attention can modulate neural responses to other components of a multisensory object defined by synchronous, but spatially disparate, auditory and visual stimuli. The audiovisual integration of such multisensory stimuli typically leads to mislocalization of the sound toward the visual stimulus (ventriloquism illusion). Using event-related potentials and functional MRI, we found that the brain's response to task-irrelevant sounds occurring synchronously with a visual stimulus from a different location was larger when that accompanying visual stimulus was attended versus unattended. The event-related potential effect consisted of sustained, frontally distributed, brain activity that emerged relatively late in processing, an effect resembling attention-related enhancements seen at earlier latencies during intramodal auditory attention. Moreover, the functional MRI data confirmed that the effect included specific enhancement of activity in auditory cortex. These findings indicate that attention to one sensory modality can spread to encompass simultaneous signals from another modality, even when they are task-irrelevant and from a different location. This cross-modal attentional spread appears to reflect an object-based, late selection process wherein spatially discrepant auditory stimulation is grouped with synchronous attended visual input into a multisensory object, resulting in the auditory information being pulled into the attentional spotlight and bestowed with enhanced processing.
Solvent and mutation effects on the nucleation of amyloid β-protein folding
Authors: Cruz Luis , Urbanc Brigita , Borreguero Jose M. , Lazo Noel D. , Teplow David B. , Stanley H. Eugene
Published: December 2005

Experimental evidence suggests that the folding and aggregation of the amyloid β-protein (Aβ) into oligomers is a key pathogenetic event in Alzheimer's disease. Inhibiting the pathologic folding and oligomerization of Aβ could be effective in the prevention and treatment of Alzheimer's disease. Here, using all-atom molecular dynamics simulations in explicit solvent, we probe the initial stages of folding of a decapeptide segment of Aβ,Aβ
21–30
, shown experimentally to nucleate the folding process. In addition, we examine the folding of a homologous decapeptide containing an amino acid substitution linked to hereditary cerebral hemorrhage with amyloidosis–Dutch type, [Gln-22]Aβ
21–30
. We find that: (
i
) when the decapeptide is in water, hydrophobic interactions and transient salt bridges between Lys-28 and either Glu-22 or Asp-23 are important in the formation of a loop in the Val-24–Lys-28 region of the wild-type decapeptide; (
ii
) in the presence of salt ions, salt bridges play a more prominent role in the stabilization of the loop; (
iii
) in water with a reduced density, the decapeptide forms a helix, indicating the sensitivity of folding to different aqueous environments; and (
iv
) the “Dutch” peptide in water, in contrast to the wild-type peptide, fails to form a long-lived Val-24–Lys-28 loop, suggesting that loop stability is a critical factor in determining whether Aβ folds into pathologic structures.
Neurons of the cerebral cortex exhibit precise interspike timing in correspondence to behavior
Authors: Shmiel Tomer , Drori Rotem , Shmiel Oren , Ben-Shaul Yoram , Nadasdy Zoltan , Shemesh Moshe , Teicher Mina , Abeles Moshe
Published: December 2005

We show that times of spikes can be very precise. In the cerebral cortex, where each nerve cell is affected by thousands of others, it is the common belief that the exact time of a spike is random up to an averaged firing rate over tens of milliseconds. In a brain slice, precise time relations of several neurons have been observed. It remained unclear whether this phenomenon can also be observed in brains of behaving animals. Here we show, in behaving monkeys, that time intervals between spikes, measured in correspondence to a specific behavior, may be controlled to within the milliseconds range.
Genome Analysis and Functional Characterization of the E2 and RING-Type E3 Ligase Ubiquitination Enzymes of Arabidopsis
Authors: Kraft Edward , Stone Sophia L. , Ma Lingeng , Su Ning , Gao Ying , Lau On-Sun , Deng Xing-Wang , Callis Judy
Published: December 2005

Attachment of ubiquitin to substrate proteins is catalyzed by the three enzymes E1, E2 (ubiquitin conjugating [UBC]), and E3 (ubiquitin ligase). Forty-one functional proteins with a UBC domain and active-site cysteine are predicted in the Arabidopsis (Arabidopsis thaliana) genome, which includes four that are predicted or shown to function with ubiquitin-like proteins. Only nine were previously characterized biochemically as ubiquitin E2s. We obtained soluble protein for 22 of the 28 uncharacterized UBCs after expression in Escherichia coli and demonstrated that 16 function as ubiquitin E2s. Twelve, plus three previously characterized ubiquitin E2s, were also tested for the ability to catalyze ubiquitination in vitro in the presence of one of 65 really interesting new gene (RING) E3 ligases. UBC22, UBC19-20, and UBC1-6 had variable levels of E3-independent activity. Six UBCs were inactive with all RINGs tested. Closely related UBC8, 10, 11, and 28 were active with the largest number of RING E3s and with all RING types. Expression analysis was performed to determine whether E2s or E3s were expressed in specific organs or under specific environmental conditions. Closely related E2s show unique patterns of expression and most express ubiquitously. Some RING E3s are also ubiquitously expressed; however, others show organ-specific expression. Of all the organs tested, RING mRNAs are most abundant in floral organs. This study demonstrates that E2 diversity includes examples with broad and narrow specificity toward RINGs, and that most ubiquitin E2s are broadly expressed with each having a unique spatial and developmental pattern of expression.
Heterotrimeric G Proteins Facilitate Arabidopsis Resistance to Necrotrophic Pathogens and Are Involved in Jasmonate Signaling
Authors: Trusov Yuri , Rookes James Edward , Chakravorty David , Armour David , Schenk Peer Martin , Botella José Ramón
Published: December 2005

Heterotrimeric G proteinshave been previously linked to plant defense; however a role for the Gβγ dimer in defense signaling has not been described to date. Using available Arabidopsis (Arabidopsis thaliana) mutants lacking functional Gα or Gβ subunits, we show that defense against the necrotrophic pathogens Alternaria brassicicola and Fusarium oxysporum is impaired in Gβ-deficient mutants while Gα-deficient mutants show slightly increased resistance compared to wild-type Columbia ecotype plants. In contrast, responses to virulent (DC3000) and avirulent (JL1065) strains of Pseudomonas syringae appear to be independent of heterotrimeric G proteins. The induction of a number of defense-related genes in Gβ-deficient mutants were severely reduced in response to A. brassicicola infection. In addition, Gβ-deficient mutants exhibit decreased sensitivity to a number of methyl jasmonate-induced responses such as induction of the plant defensin gene PDF1.2, inhibition of root elongation, seed germination, and growth of plants in sublethal concentrations of methyl jasmonate. In all cases, the behavior of the Gα-deficient mutants is coherent with the classic heterotrimeric mechanism of action, indicating that jasmonic acid signaling is influenced by the Gβγ functional subunit but not by Gα. We hypothesize that Gβγ acts as a direct or indirect enhancer of the jasmonate signaling pathway in plants.
ArabidopsisCONSTANS-LIKE3 Is a Positive Regulator of Red Light Signaling and Root Growth
Authors: Datta Sourav , Hettiarachchi G.H.C.M. , Deng Xing-Wang , Holm Magnus
Published: December 2005

CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) is an E3 ubiquitin ligase that represses photomorphogenesis in the dark. Therefore, proteins interacting with COP1 could be important regulators of light-dependent development. Here, we identify CONSTANS-LIKE3 (COL3) as a novel interaction partner of COP1. A green fluorescent protein–COL3 fusion protein colocalizes with COP1 to nuclear speckles when transiently expressed in plant cells. This localization requires the B-box domains in COL3, indicating a novel function of this domain. A loss-of-function col3 mutant has longer hypocotyls in red light and in short days. Unlike constans, the col3 mutant flowers early and shows a reduced number of lateral branches in short days. The mutant also exhibits reduced formation of lateral roots. The col3 mutation partially suppresses the cop1 and deetiolated1 (det1) mutations in the dark, suggesting that COL3 acts downstream of both of these repressors. However, the col3 mutation exerts opposing effects on cop1 and det1 in terms of lateral roots and anthocyanin accumulation, suggesting that COL3 also has activities that are independent of COP1 and DET1. In conclusion, we have identified COL3 as a positive regulator of photomorphogenesis that acts downstream of COP1 but can promote lateral root development independently of COP1 and also function as a daylength-sensitive regulator of shoot branching.