bluuebunny/crossref_metadata_2025 huggingface dataset:
Cathepsin B inactivation attenuates hepatocyte apoptosis and liver damage in steatotic livers after cold ischemia-warm reperfusion injury
Authors: Baskin-Bey E. S. , Canbay A. , Bronk S. F. , Werneburg N. , Guicciardi M. E. , Nyberg S. L. , Gores G. J.
Published: October 2004

Hepatic steatosis predisposes the liver to cold ischemia-warm reperfusion (CI/WR) injury by unclear mechanisms. Because hepatic steatosis has recently been associated with a lysosomal pathway of apoptosis, our aim was to determine whether this cell-death pathway contributes to CI/WR injury of steatotic livers. Wild-type and cathepsin B-knockout ( Ctsb −/−) mice were fed the methionine/choline-deficient (MCD) diet for 2 wk to induce hepatic steatosis. Mouse livers were stored in the University of Wisconsin solution for 24 h at 4°C and reperfused for 1 h at 37°C in vitro. Immunofluorescence analysis of the lysosomal enzymes cathepsin B and D showed a punctated intracellular pattern consistent with lysosomal localization in wild-type mice fed a standard diet after CI/WR injury. In contrast, cathepsin B and D fluorescence became diffuse in livers from wild-type mice fed MCD diet after CI/WR, indicating that lysosomal permeabilization had occurred. Hepatocyte apoptosis was rare in both normal and steatotic livers in the absence of CI/WR injury but increased in wild-type mice fed an MCD diet and subjected to CI/WR injury. In contrast, hepatocyte apoptosis and liver damage were reduced in Ctsb −/− and cathepsin B inhibitor-treated mice fed the MCD diet following CI/WR injury. In conclusion, these findings support a prominent role for the lysosomal pathway of apoptosis in steatotic livers following CI/WR injury.
Temporal Interactions of Air-Puff–Evoked Blinks and Saccadic Eye Movements: Insights Into Motor Preparation
Authors: Gandhi Neeraj J. , Bonadonna Desiree K.
Published: October 2004

Following the initial, sensory response to stimulus presentation, activity in many saccade-related burst neurons along the oculomotor neuraxis is observed as a gradually increasing low-frequency discharge hypothesized to encode both timing and metrics of the impending eye movement. When the activity reaches an activation threshold level, these cells discharge a high-frequency burst, inhibit the pontine omnipause neurons (OPNs) and trigger a high-velocity eye movement known as saccade. We tested whether early cessation of OPN activity, prior to when it ordinarily pauses, acts to effectively lower the threshold and prematurely trigger a movement of modified metrics and/or dynamics. Relying on the observation that OPN discharge ceases during not only saccades but also blinks, air-puffs were delivered to one eye to evoke blinks as monkeys performed standard oculomotor tasks. We observed a linear relationship between blink and saccade onsets when the blink occurred shortly after the cue to initiate the movement but before the average reaction time. Blinks that preceded and overlapped with the cue increased saccade latency. Blinks evoked during the overlap period of the delayed saccade task, when target location is known but a saccade cannot be initiated for correct performance, failed to trigger saccades prematurely. Furthermore, when saccade and blink execution coincided temporally, the peak velocity of the eye movement was attenuated, and its initial velocity was correlated with its latency. Despite the perturbations, saccade accuracy was maintained across all blink times and task types. Collectively, these results support the notion that temporal features of the low-frequency activity encode aspects of a premotor command and imply that inhibition of OPNs alone is not sufficient to trigger saccades.
Reproductive Health in Post-Transition Mongolia: Global Discourses and Local Realities
Authors: Rak Kimberly , Janes Craig
Published: October 2004

Global reproductive health policy is based on assumptions, couched in scientific language, that technological methods of birth control are superior to traditional methods, use of these methods is more modern and "rational" than alternatives, and abortion should not be considered a form of birth control. The authority these assumptions have achieved in global health circles prevents alternative options from being considered. Our research on women's birth control experiences in Mongolia suggests that reproductive health programs based on such global assumptions fail to consider the local cultural contexts of reproductive decision-making address women's needs, and are therefore seriously flawed.
Global Challenges to Equity in Safety and Health at Work: Struggles for Fair Work in Southern Africa
Authors: Loewenson Rene
Published: October 2004

Weaknesses in social protection and risk management systems within workplaces and in the wider public health environment and weak investment in health insurance and health services shift a significant share of the burden of production risks onto worker communities and under-funded public services. Inequality has been constructed by powerful economic and political interests and by weak policies for channelling the benefits of globalization to those most in need. Powerful drivers of inequity are not simply addressed through technical interventions—they demand political and economic action. This paper explores the knowledge and evidence needed to impact public policy and the approaches to building political momentum for that knowledge to be used.
Health Transition and Globalization in the Pacific: Vestiges of Colonialism?
Authors: Finau Sitaleki , Wainiqolo Iris
Published: October 2004

This paper disaggregates the various transitions that led to the so-called health transition in the Pacific. It challenges the notion of unified health transition and looks at changes that shaped the health of Pacificans. It examines the velocity (speed and direction) and the framework with which contemporary discussions of health transition in the Pacific have taken place. This is an effort to look at how health transition is more about power imbalance than about morbidity and mortality. We argue, first, that changes in the health of Pacificans are about power imbalances brought about by globalization, imperialism, and colonialism. We also describe the multiple transitions that need to be taken into account in understanding the health changes among Pacificans. In the end, we suggest a range of alternate ways of viewing the processes of change in the Pacific.
Globalization and Health in the New Millennium
Authors: Harris Richard , Seid Melinda
Published: October 2004

This essay provides an overview of the linkages between globalization and health. It examines many of the global health issues associated with the globalization of economic, political, social, and cultural forces in the world today. The conceptualization and analysis of these linkages between globalization and health and the effects of globalization on population health are discussed from the vantage point of various perspectives. Particular attention is given to the global spread of disease, the diseases of globalization, the health inequities associated with globalization, the effects of globalization on environmental health, and the globalization of health-related technologies.
Globalization and Health Policy in South Africa
Authors: McIntyre Di , Thomas Stephen , Cleary Susan
Published: October 2004

This paper considers influences of globalization on three relevant health policy issues in South Africa, namely, private health sector growth, health professional migration, and pharmaceutical policy. It considers the relative role of key domestic and global actors in health policy development around these issues. While South Africa has not been subject to the overt health policy pressure from international organizations experienced by governments in many other low- and middle-income countries, global influence on South Africa's macroeconomic policy has had a profound, albeit indirect, effect on our health policies. Ultimately, this has constrained South Africa's ability to achieve its national health goals.
The De-Radicalization of Corporate Social Responsibility
Authors: Shamir Ronen
Published: October 2004

This paper situates the field of action known as “corporate social responsibility” within the theoretical context of global capitalism. I posit that corporate social responsibility (CSR) is a field of action that is shaped through the interplay of popular pressures and the response of corporations to such pressures thereof. Specifically, I analyze this field as consisting of a symbolic struggle over the meaning of the term “social responsibility.” I analyze a set of corporate practices relating to CSR and show how they shape the notion of responsibility in ways that diffuse its radical transformative potential. In particular, I look at various corporate strategies designed to prevent the use of law as means for bringing about greater corporate accountability. I also discuss particular agents that mobilize the CSR field. Specifically, I discuss the establishment of corporate-sponsored and corporate-oriented NGOs and analyze the role they play in structuring the CSR field. I designate such organizations as MaNGOs (Market Non-Governmental Organizations) and suggest that such organizations shape notions such as “social responsibility” and “social change” in ways that are amenable to business and employers' concerns.
Inside Shock Music Carnival: Spectacle as Contested Terrain
Authors: Bettez Halnon Karen
Published: October 2004

This paper is based on a four-year concert fieldwork study of some of the most transgressive, shocking, and otherwise explicitly carnivalesque bands increasingly making it into the mainstream (e.g., Eminem, Marilyn Manson, Limp Bizkit, Slipknot, Cradle of Filth, Insane Clown Posse, GWAR, and Mindless Self Indulgence). The dis-alienating attractions of this music for an increasingly heterogeneous fan base are described in rich ethnographic detail, challenging Arnett's earlier work on heavy metal and adolescent alienation. The multi-faceted carnivalesque qualities and symbolic significances of shock music carnival are delineated in a lengthy application of Bakhtin's carnival-grotesque, a festive liminal medium for asserting and expressing human-equalizing realism. The general significance of the paper, as extensions of Kellner and Ritzer's works, is a demonstration of how shock music carnival is not simply spectacle as domination (or the commodification of dissent), but also spectacle as resistance (or a `time outside time' or `second life' in which fans escape and resist a disenchanted and duplicitous world of commercialization, and express everyday rage from living in a “nothing” world of global capital). This paper contributes to cultural Marxism by providing an empirical and ethnographic account of a proto-utopian critique of consumer society.
Being Left in Brooklyn at the Start of the `Post-Industrial' City: Tensions in Political Economy, Race, and Gender in Community Organizing, 1955—1980
Authors: Eisenberg Martin E.
Published: October 2004

This paper is an analytical history of a New York City community organization during a period of economic, racial and ideological turmoil. The organization was committed to integration, provided a wide range of services, and organized residents to address community problems. I examine the role of women in the organization, the organization's opposition to Black Nationalism and its effort to analyze and organize against the austerity resolution to the NYC fiscal crisis. I suggest that a modified model of the organization's political economic perspective and interculturalism may be considered as a possible framework for a broad-based social movement for change.
The Legal Regulation of Information Relations: A Note on the Use of the Internet in the Russian Federation
Authors: Trofimenko Andrei
Published: October 2004

The present note examines the current state of affairs relating to the legal regulation of information in Russia. Special attention is paid to the legal rules and regulations connected to using the Internet. On the basis of an analysis of the legislation in force, a conclusion is drawn that the legislator has (to date) failed to pay sufficient attention to the specifi c features of these relations. In particular, the problem of applicability of the legislation governing mass media to the legal relations relating to the Internet will be considered in this article. Specific criteria are offered, allowing one to make a substantiated conclusion about the applicability of mass media legislation in this special case.
Property Restitution in Eastern Europe: Domestic and International Human Rights Law Responses
Authors: Karadjova Mariana
Published: October 2004

This article presents an overview of how those East European countries that are members of the Council of Europe have approached the problems of restitution as a means of reparation for past injustices. In doing so, attention will be paid to: the entitled persons and the extent of restitution; the underlying motivations vis-à-vis the form of reparation (restitution in kind or compensation), and attitudes towards minority groups and foreigners as part of the restitution process. Emphasis will also be given to the role played by international instruments (the ECHR and its future Protocol 12, the International Covenant on Civil and Political Rights, various UN resolutions, etc), as well as by judicial institutions (the European Court of Human Rights, the UN Human Rights Committee) in the evolution of the restitution process in Eastern Europe in general, and regarding such issues as equality between foreigners and nationals as well as minority and religious groups and the elaboration of an international standard of restitution as reparation for abuses of human rights in particular. The bodies of the ECHR have managed to avoid problems related to restitution and reparations for past injustices by arguing that the right of restitution is not guaranteed by art.1 of Protocol 1 to the the ECHR. But the entry into force of a new Protocol 12 to the Convention will likely result in changes being made in this thought process, at least as regards the position of foreigners. If measures denying restitution, owing to the claimant's nationality, were taken after ratifi cation of Protocol 12, the way should be opened in the future to foreigners (in addition to procedures before the UN Human Rights Committee) to more effectively defend their rights relative to such restorative measures: notably, the possibility of seizing the Strasbourg Court with claims relating to justifi cation for "unequal treatment". The right to remedy the injustices committed to the victims of violations of human rights and international humanitarian law has appeared with increasing frequency on the agenda of the UN Commission on Human Rights. Furthermore, in its recent case law, the UN Human Rights Committee has evidenced a concern over several questions relating to the respect of possessions; it has already opted for the proposition that any discrimination on the basis of nationality in restitution legislation can be deemed to be a violation of the International Covenant on Civil and Political Rights. Lastly, after ratifi cation of Protocol 12, we can expect a link to be forged between the vision of the UN Commission on Human Rights and that of the European Court of Human Rights that may—in the future—lead to the elaboration of a common international mechanism regulating restitution as a means for the reparation of abuses of human rights.
European Norms on the Protection of Human Rights: On the Development of Russian Human Rights Legislation
Authors:   Gorchkova
Published: October 2004

This article examines the problems concerning the observance by the Russian Federation of European conventions, in particular the European Convention on Human Rights and the European Convention for the Prevention of Torture. In recent years, there has been a signifi cant breakthrough in the development of Russian legislation in light of human rights' principles and standards laid down by the Council of Europe. At the same time, the implementation of European standards in the law enforcement area has been carried out at a distinctly slow pace, particularly in relation to the criminal–executive system (where the first tentative steps towards the reform of penitentiary institutions have only been recently taken), the rights of migrants and refugees, the protection of the rights of armed forces personnel, and human rights in Chechnya. This article analyses the problems involved in the legal and judicial protection of human rights in Russia as well as issues concerning the restriction of citizens' rights in special circumstances (such as war or a state of emergency) and the protection of social rights. Lastly, the creation of a unifi ed legal space for human rights in the Russian Federation will also be discussed.
Newton's "Experimental Philosophy"
Authors: Shapiro Alan
Published: October 2004

Newton abjured using the term "experimental philosophy," widely used in Restoration England at the start of his career, until 1712 when he added a passage to the General Scholium of the Principia that briefly expounded his anti-hypothetical methodology. Drafts for query 23 of the second edition of the Opticks (1706) (which became query 31 in the third edition), however, show that he had intended to introduce the term to explain his methodology earlier. Newton introduced the term for polemical purposes to defend his theory of gravity against the criticisms of Cartesians and Leibnizians but, especially in the Principia, against Leibniz himself. "Experimental philosophy" has little directly to do with experiment, but rather more broadly designates empirical science. Newton's manuscripts provide insight into his use of "experimental philosophy" and the formulation of his methodology, especially such key terms as "deduce," "induction," and "phenomena," in the early eighteenth century.
Dot-age: Newton's Mathematical Legacy in the Eighteenth Century
Authors: Guicciardini Niccolò
Published: October 2004

According to the received view, eighteenth-century British mathematicians were responsible for a decline of mathematics in the country of Newton; a decline attributed to chauvinism and a preference for geometrical thinking. This paper challenges this view by first describing the complexity of Newton's mathematical heritage and its reception in the early decades of the eighteenth century. A section devoted to Maclaurin's monumental Treatise of Fluxions (1742) describes its attempt to reach a synthesis of the different strands of Newton's mathematical legacy, and compares it with contemporary Continental work. It is shown that in the middle of the eighteenth century academic Continental mathematicians such as Euler and Lagrange were driven by local cultural assumptions in directions which sensibly diverged from the ones followed by Maclaurin and his fellow countrymen.
Skaergaardite, PdCu, a new platinum-group intermetallic mineral from the Skaergaard intrusion, Greenland
Authors: Rudashevsky N. S. , McDonald A. M. , Cabri L. J. , D. Nielsen T. F. , Stanley C. J. , Kretzer Yu. L. , Rudashevsky V. N.
Published: October 2004

Skaergaardite, PdCu, is a new mineral discovered in the Skaergaard intrusion, Kangerdlugssuaq area, East Greenland. It occurs in a tholeitiic gabbro associated with plagioclase, clinopyroxene, orthopyroxene, ilmenite, titanian magnetite, fayalite and accessory chlorite-group minerals, ferrosaponite, a member of the annite–phlogopite series, hornblende, actinolite, epidote, calcite, ankerite, apatite and baddeleyite. The mineral is found in composite microglobules composed of bornite, chalcocite, digenite, chalcopyrite, with rare cobalt pentlandite, cobaltoan pentlandite, sphalerite, keithconnite, vasilite, zvyagintsevite, (Cu,Pd,Au) and Pt-Fe-Cu-Pd alloys, unnamed PdCu3, (Pd,Cu,Sn), Au3Cu and PdAuCu. Skaergaardite occurs as droplets, equant grains with rounded outlines, subhedral to euhedral crystals and as irregular grains that vary in size from 2 to 75 μm, averaging 22 μm. It is steel grey with a bronze tint, has a black streak, a metallic lustre and is sectile. Neither cleavage nor fracture was observed. The mineral has a micro-indentation hardness of VHN25= 257. It is isotropic, non-pleochroic and exhibits neither discernible internal reflections nor evidence of twinning. Skaergaardite varies from bright creamy white (associated with bornite and chalcopyrite) to bright white (associated with digenite and chalcocite). Reflectance values in air (and in oil) are: 58.65 (47.4) at 470 nm, 62.6 (51.1) at 546 nm, 64.1 (52.8) at 589 nm and 65.25 (53.95) at 650 nm. The average of 311 electron-microprobe analyses gives: Pd 58.94, Pt 1.12, Au 2.23, Cu 29.84, Fe 3.85, Zn 1.46, Sn 1.08, Te 0.28 and Pb 0.39, total 99.19 wt.%, corresponding to (Pd0.967Au0.020Pt0.010)Σ0.997(Cu0.820Fe0.120Zn0.039Sn0.016Te0.004Pb0.003)Σ1.002. The mineral is cubic, space group Pm3m,a= 3.0014(2) Å,V= 27.0378 Å3,Z= 1. Dcalcis 10.64 g/cm3. The six strongest lines in the X-ray powder-diffraction pattern [d in Å (I)(hkl)] are: 2.122(100)(110), 1.5000(20)(200), 1.2254(50)(211), 0.9491(20)(310), 0.8666(10)(222), 0.8021(70)(321). The mineral has the CsCl-type structure. It is believed to be isostructural with wairauite (CoFe), synthetic CuZn (β-brass) and is structurally related to hongshiite (PtCu). Skaergaardite developed from a disordered Pd-Cu-rich metal alloy melt that had exsolved from an earlier Cu-(Fe) sulphide melt. Ordering of Pd and Cu (beginning atT≈ 600°C) results in development of the CsCl structure from a disordered face-centred cubic structure.
The analcime problem and its impact on the geochemistry of ultrapotassic rocks from Serbia
Authors: Prelević D. , Foley S. F. , Cvetković V. , L. Romer R.
Published: October 2004

Tertiary ultrapotassic volcanic rocks from Serbia occasionally display low levels of K2O and K2O/ Na2O. In these rocks, analcime regularly appears as pseudomorphs after pre-existing leucite microphenocrysts. The process ofleucite transformation in Serbian ultrapotassic rocks is very thorough: fresh leucite survives only in ugandites from the Koritnik lava flows as well as in rare inclusions in Cpx. This paper focuses on the impact of ‘analcimization’ on the mineralogy and geochemistry ofthe Serbian ultrapotassic rocks, using the samples where leucite survived as a monitor for the process.

Analcimization has had a great impact on the geochemistry of the rocks, but affects only a restricted number of chemical parameters. These are the falsification of the original K2O/Na2O ratio, the decoupling oflarge-ion lithophile elements resulting in considerable depletion of Rb and K2O, but not ofBa, and sporadic, but extreme enrichment ofCs in some analcime-bearing samples (up to 900 ppm). Analcimization is also recognized by an increase in whole-rock δ18O values of ∼3% compared to fresh rocks, which correlates with the level of whole-rock hydration. Finally, the 87Sr/86Sr enrichment at nearly constant 143Nd/144Nd demonstrated by some rocks can also be explained by the analcimization ofleucite. For samples with variable 87Sr/86Sr from the same lava flow, 87Sr/86Sr values correlate with modal analcime abundance (ex-leucite), loss on ignition of whole-rock and whole-rock δ18O values. The extreme depletion in K and enrichment in Na, together with modification of other geochemical parameters, may have led to the misinterpretation of the origin and geodynamic affiliations of the Serbian ultrapotassic rocks, had the effects of analcimization not been taken into account.
A new graphical presentation and subdivision of potassium micas
Authors: Tischendorf G. , Rieder M. , Förster H.-J. , Gottesmann B. , Guidotti Ch. V.
Published: October 2004

A system based on variation of the octahedrally coordinated cations is proposed for graphical presentation and subdivision of tri- and dioctahedral K micas, which makes use of elemental differences (in a.p.f.u.): (Mg – Li) [= mgli] and (Fetot + Mn + Ti – VIAl) [= feal]. All common true tri- and dioctahedral K micas are shown in a single polygon outlined by seven main compositional points forming its vertices. Sequentially clockwise, starting from Mg3 (phlogopite), these points are: Mg2.5Al0.5, Al2.167□0.833, Al1.75Li1.25, Li2Al (polylithionite), Fe22+Li, and Fe32+ (annite). Trilithionite (Li1.5Al1.5), Li1.5Fe2+Al0.5, Fe22+ Mg, and Mg2Fe2+ are also located on the perimeter of the polygon. IMA-siderophyllite (Fe2+2Al) and muscovite (Al2□) plot inside.

The classification conforms with the IMA-approved mica nomenclature and differentiates among the following mica species according to their position in a diagram consisting of mgli and feal axes plotted orthogonally; trioctahedral: phlogopite, biotite, siderophyllite, annite, zinnwaldite, lepidolite and tainiolite; dioctahedral: muscovite, phengite and celadonite. Potassium micas with [Si] <2.5 a.p.f.u. including IMA-siderophyllite, KFe22+ AlAl2Si2O10(OH)2, and IMA-eastonite, KMg2AlAl2Si2O10(OH)2 seem not to form in nature.

The proposed subdivision has several advantages. All common true, trioctahedral and dioctahedral K micas, whether Li-bearing or Li-free, are shown within one diagram, which is easy to use and gives every mica composition an unambiguously defined name. Mica analyses with Fe2+, Fe3+, Fe2+ + Fe3+, or Fetot can be considered, which is particularly valuable for microprobe analyses. It facilitates easy reconstruction of evolutionary pathways of mica compositions during crystallization, a feature having key importance in petrologically oriented research. Equally important, the subdivision has great potential for understanding many of the crystal-chemistry features of the K micas. In turn this may allow one to recognize and discriminate the extent to which crystal chemistry or bulk composition controls the occurrence of some seemingly possible or hypothetical K mica.
Synthesis and crystal structure of a new microporous silicate with a mixed octahedral-tetrahedral framework: Cs3ScSi8O19
Authors: Kolitsch U. , Tillmanns E.
Published: October 2004

During investigations of the system Sc2O3-Al2O3-TiO2-SiO2, a new, unusual microporous compound, Cs3ScSi8O19, was synthesized as colourless plates from a CsF-MoO3 flux. The crystal structure was determined from single-crystal X-ray diffraction data (Mo-Kα radiation, CCD area detector). The compound is orthorhombic, space group Pnma, with a = 11.286(2), b = 7.033(1), c = 26.714(5) Å, and Z = 4 (R1(F) = 2.6% and wR2all(F2) = 7.3%, using 3066 ‘observed’ reflections with Fo > 4σ(Fo)). The crystal structure of Cs3ScSi8O19 represents a new microporous framework structure type (‘MCV-1’), and the compound is exceptional in being the first representative of a mixed octahedral-tetrahedral framework structure, in which the [TO4]:[MO6] ratio is >6:1. The structure is based on isolated, nearly regular ScO6 octahedra [dav(Sc—O) = 2.112 Å] sharing corners with SiO4 tetrahedra to form an open framework with four-, six- and eight-membered rings; the latter are formed by SiO4 tetrahedra only. Two fully occupied Cs positions are located in large framework voids close to the six-membered rings, whereas four partly occupied and disordered Cs positions are close to very large framework voids bordered by the puckered eight-membered rings. The cavities are linked into channels parallel to [100] and [010]. The structure is compared with that of Cs2TiSi6O15 and related microporous scandium-, REE-, titano- and zirconosilicate minerals and compounds. Cs3ScSi8O19 or derivatives may be important in the context of immobilization of radioactive 137Cs waste, cationic conductivity or catalysis.
Ratios of involved nodes in early breast cancer
Authors: Vinh-Hung Vincent , Verschraegen Claire , Promish Donald I , Cserni Gábor , Van de Steene Jan , Tai Patricia , Vlastos Georges , Voordeckers Mia , Storme Guy , Royce Melanie
Published: October 2004

Introduction

The number of lymph nodes found to be involved in an axillary dissection is among the most powerful prognostic factors in breast cancer, but it is confounded by the number of lymph nodes that have been examined. We investigate an idea that has surfaced recently in the literature (since 1999), namely that the proportion of node-positive lymph nodes (or a function thereof) is a much better predictor of survival than the number of excised and node-positive lymph nodes, alone or together.

Methods

The data were abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results (SEER) program of women diagnosed with nonmetastatic T1–T2 primary breast carcinoma between 1988 and 1997, in whom axillary node dissection was performed. The end-point was death from breast cancer. Cox models based on different expressions of nodal involvement were compared using the Nagelkerke R2 index (R2N). Ratios were modeled as percentage and as log odds of involved nodes. Log odds were estimated in a way that avoids singularities (zero values) by using the empirical logistic transform.

Results

In node-negative cases both the number of nodes excised and the log odds were significant, with hazard ratios of 0.991 (95% confidence interval 0.986–0.997) and 1.150 (1.058–1.249), respectively, but without improving R2N. In node-positive cases the hazard ratios were 1.003–1.088 for the number of involved nodes, 0.966–1.005 for the number of excised nodes, 1.015–1.017 for the percentage, and 1.344–1.381 for the log odds. R2N improved from 0.067 (no nodal covariate) to 0.102 (models based on counts only) and to 0.108 (models based on ratios).

Discussion

Ratios are simple optimal predictors, in that they provide at least the same prognostic value as the more traditional staging based on counting of involved nodes, without replacing them with a needlessly complicated alternative. They can be viewed as a per patient standardization in which the number of involved nodes is standardized to the number of nodes excised. In an extension to the study, ratios were validated in a comparison with categorized staging measures using blinded data from the San Jose–Monterey cancer registry. A ratio based prognostic index was also derived. It improved the Nottingham Prognostic Index without compromising on simplicity.
Signaling through BMP type 1 receptors is required for development of interneuron cell types in the dorsal spinal cord
Authors: Wine-Lee Lara , Ahn Kyung J. , Richardson Rory D. , Mishina Yuji , Lyons Karen M. , Crenshaw E. Bryan
Published: October 2004

During spinal cord development, distinct classes of interneurons arise at stereotypical locations along the dorsoventral axis. In this paper, we demonstrate that signaling through bone morphogenetic protein (BMP) type 1 receptors is required for the formation of two populations of commissural neurons, DI1 and DI2, that arise within the dorsal neural tube. We have generated a double knockout of both BMP type 1 receptors, Bmpr1a and Bmpr1b, in the neural tube. These double knockout mice demonstrate a complete loss of D1 progenitor cells, as evidenced by loss of Math1expression, and the subsequent failure to form differentiated DI1 interneurons. Furthermore, the DI2 interneuron population is profoundly reduced. The loss of these populations of cells results in a dorsal shift of the dorsal cell populations, DI3 and DI4. Other dorsal interneuron populations, DI5 and DI6, and ventral neurons appear unaffected by the loss of BMP signaling. The Bmpr double knockout animals demonstrate a reduction in the expression of Wnt and Id family members, suggesting that BMP signaling regulates expression of these factors in spinal cord development. These results provide genetic evidence that BMP signaling is crucial for the development of dorsal neuronal cell types.
Muscle reconstitution by muscle satellite cell descendants with stem cell-like properties
Authors: Hashimoto Naohiro , Murase Takeshi , Kondo Syunzo , Okuda Asuko , Inagawa-Ogashiwa Masayo
Published: October 2004

Recent studies have demonstrated that a distinct subpopulation with stem cell-like characteristics in myoblast culture is responsible for new muscle fiber formation after intramuscular transplantation. The identification and isolation of stem-like cells would have significant implications for successful myogenic cell transfer therapy in human muscle disorders. Using a clonal culture system for mouse muscle satellite cells, we have identified two cell types, designated `round cells' and `thick cells', in clones derived from single muscle satellite cells that have been taken from either slow or fast muscle. Clonal analysis of satellite cells revealed that the round cells are immediate descendants of quiescent satellite cells in adult muscle. In single-myofiber culture, round cells first formed colonies and then generated progeny, thick cells, that underwent both myogenic and osteogenic terminal differentiation under the appropriate culture conditions. Thick cells, but not round cells, responded to terminal differentiation-inducing signals. Round cells express Pax7, a specific marker of satellite cells, at high levels. Myogenic cell transfer experiments showed that round cells reconstitute myofibers more efficiently than thick cells. Furthermore, round cells restored dystrophin in myofibers of mdx nude mice, even when as few as 5000 cells were transferred into the gastrocnemius muscle. These results suggest that round cells are satellite-cell descendants with stem cell-like characteristics and represent a useful source of donor cells to improve muscle regeneration.
Phosphatidylserine receptor is required for the engulfment of dead apoptotic cells and for normal embryonic development in zebrafish
Authors: Hong Jiann-Ruey , Lin Gen-Hwa , Lin Cliff Ji-Fan , Wang Wan-ping , Lee Chien-Chung , Lin Tai-Lang , Wu Jen-Leih
Published: October 2004

During development, the role of the phosphatidylserine receptor (PSR) in the removal of apoptotic cells that have died is poorly understood. We have investigated this role of PSR in developing zebrafish. Programmed cell death began during the shield stage, with dead cells being engulfed by a neighboring cell that showed a normal-looking nucleus and the nuclear condensation multi-micronuclei of an apoptotic cell. The zebrafish PSR engulfing receptor was cloned (zfpsr), and its nucleotide sequence was compared with corresponding sequences in Drosophila melanogaster (76% identity),human (74%), mouse (72%) and Caenorhabditis elegans (60%). The PSR receptor contained a jmjC domain (residues 143-206) that is a member of the cupin metalloenzyme superfamily, but in this case serves an as yet unknown function(s). psr knockdown by a PSR morpholino oligonucleotide led to accumulation of a large number of dead apoptotic cells in whole early embryo. These cells interfered with embryonic cell migration. In addition, normal development of the somite, brain, heart and notochord was sequentially disrupted up to 24 hours post-fertilization. Development could be rescued in defective embryos by injecting psr mRNA. These results are consistent with a PSR-dependent system in zebrafish embryos that engulfs apoptotic cells mediated by PSR-phagocytes during development, with the system assuming an important role in the normal development of tissues such as the brain, heart,notochord and somite.
accordion, a zebrafish behavioral mutant, has a muscle relaxation defect due to a mutation in the ATPase Ca2+ pump SERCA1
Authors: Hirata Hiromi , Saint-Amant Louis , Waterbury Julie , Cui Wilson , Zhou Weibin , Li Qin , Goldman Daniel , Granato Michael , Kuwada John Y.
Published: October 2004

When wild-type zebrafish embryos are touched at 24 hours post-fertilization(hpf), they typically perform two rapid alternating coils of the tail. By contrast, accordion (acc) mutants fail to coil their tails normally but contract the bilateral trunk muscles simultaneously to shorten the trunk, resulting in a pronounced dorsal bend. Electrophysiological recordings from muscles showed that the output from the central nervous system is normal in mutants, suggesting a defect in muscles is responsible. In fact,relaxation in acc muscle is significantly slower than normal. In vivo imaging of muscle Ca2+ transients revealed that cytosolic Ca2+ decay was significantly slower in acc muscle. Thus,it appears that the mutant behavior is caused by a muscle relaxation defect due to the impairment of Ca2+ re-uptake. Indeed, accmutants carry a mutation in atp2a1 gene that encodes the sarco(endo)plasmic reticulum Ca2+-ATPase 1 (SERCA1), a Ca2+ pump found in the muscle sarcoplasmic reticulum (SR) that is responsible for pumping Ca2+ from the cytosol back to the SR. As SERCA1 mutations in humans lead to Brody disease, an exercise-induced muscle relaxation disorder, zebrafish accordion mutants could be a useful animal model for this condition.
Developmental potential of defined neural progenitors derived from mouse embryonic stem cells
Authors: Plachta Nicolas , Bibel Miriam , Tucker Kerry Lee , Barde Yves-Alain
Published: October 2004

The developmental potential of a uniform population of neural progenitors was tested by implanting them into chick embryos. These cells were generated from retinoic acid-treated mouse embryonic stem (ES) cells, and were used to replace a segment of the neural tube. At the time of implantation, the progenitors expressed markers defining them as Pax6-positive radial glial (RG)cells, which have recently been shown to generate most pyramidal neurons in the developing cerebral cortex. Six days after implantation, the progenitors generated large numbers of neurons in the spinal cord, and differentiated into interneurons and motoneurons at appropriate locations. They also colonized the host dorsal root ganglia (DRG) and differentiated into neurons, but, unlike stem cell-derived motoneurons, they failed to elongate axons out of the DRG. In addition, they neither expressed the DRG marker Brn3a nor the Trk neurotrophin receptors. Control experiments with untreated ES cells indicated that when colonizing the DRG, these cells did elongate axons and expressed Brn3a, as well as Trk receptors. Our results thus indicate that ES cell-derived progenitors with RG characteristics generate neurons in the spinal cord and the DRG. They are able to respond appropriately to local cues in the spinal cord, but not in the DRG, indicating that they are restricted in their developmental potential.
Mice expressing a dominant-negative Ret mutation phenocopy human Hirschsprung disease and delineate a direct role of Ret in spermatogenesis
Authors: Jain Sanjay , Naughton Cathy K. , Yang Mao , Strickland Amy , Vij Kiran , Encinas Mario , Golden Judy , Gupta Akshay , Heuckeroth Robert , Johnson Eugene M. , Milbrandt Jeffrey
Published: October 2004

The Ret receptor tyrosine kinase mediates physiological signals of glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) and is essential for postnatal survival in mice. It is implicated in a number of human diseases and developmental abnormalities. Here, we describe our analyses of mice expressing a Ret mutant (RetDN) with diminished kinase activity that inhibits wild-type Ret activity, including its activation of AKT. All RetDN/+ mice died by 1 month of age and had distal intestinal aganglionosis reminiscent of Hirschsprung disease (HSCR) in humans. The RetDN/+ proximal small intestine also had severe hypoganglionosis and reduction in nerve fiber density, suggesting a potential mechanism for the continued gastric dysmotility in postsurgical HSCR patients. Unlike Ret-null mice, which have abnormalities in the parasympathetic and sympathetic nervous systems, the RetDN/+ mice only had defects in the parasympathetic nervous system. A small proportion of RetDN/+ mice had renal agenesis, and the remainder had hypoplastic kidneys and developed tubulocystic abnormalities postnatally. Postnatal analyses of the testes revealed a decreased number of germ cells, degenerating seminiferous tubules,maturation arrest and apoptosis, indicating a crucial role for Ret in early spermatogenesis.
No hemoglobin but NO: the icefish (Chionodraco hamatus) heart as a paradigm
Authors: Pellegrino D. , Palmerini C. A. , Tota B.
Published: October 2004

The role of nitric oxide (NO) in cardio-vascular homeostasis is now known to include allosteric redox modulation of cell respiration. An interesting animal for the study of this wide-ranging influence of NO is the cold-adapted Antarctic icefish Chionodraco hamatus, which is characterised by evolutionary loss of hemoglobin and multiple cardio-circulatory and subcellular compensations for efficient oxygen delivery. Using an isolated,perfused working heart preparation of C. hamatus, we show that both endogenous (l-arginine) and exogenous (SIN-1 in presence of SOD)NO-donors as well as the guanylate cyclase (GC) donor 8Br-cGMP elicit positive inotropism, while both nitric oxide synthase (NOS) and sGC inhibitors, i.e. l-NIO and ODQ, respectively, induce significant negative inotropic effects. These results therefore demonstrate that under basal working conditions the icefish heart is under the tonic influence of a NO-cGMP-mediated positive inotropism. We also show that the working heart,which has intracardiac NOS (shown by NADPH-diaphorase activity and immunolocalization), can produce and release NO, as measured by nitrite appearance in the cardiac effluent. These results indicate the presence of a functional NOS system in the icefish heart, possibly serving a paracrine/autocrine regulatory role.
Voluntary running in deer mice: speed, distance, energy costs and temperature effects
Authors: Chappell Mark A. , Garland Theodore , Rezende Enrico L. , Gomes Fernando R.
Published: October 2004

The energetics of terrestrial locomotion are of considerable interest to ecologists and physiologists, but nearly all of our current knowledge comes from animals undergoing forced exercise. To explore patterns of energy use and behavior during voluntary exercise, we developed methods allowing nearly continuous measurements of metabolic rates in freely behaving small mammals,with high temporal resolution over periods of several days. We used this approach to examine relationships between ambient temperature(Ta), locomotor behavior and energy costs in the deer mouse, a small mammal that routinely encounters a large range of temperatures in its natural habitat. We tested for individual consistency in running behavior and metabolic traits, and determined how locomotor costs vary with speed and Ta. Because of the importance of thermoregulatory costs in small mammals, we checked for substitution of exercise heat for thermostatic heat production at Ta below the thermal neutral zone and determined the fraction of the daily energy budget comprising exercise costs.

Locomotor behavior was highly variable among individuals but had high repeatability, at least over short intervals. We found few temperature-related changes in speed or distance run, but Ta strongly affected energy costs. Partial substitution of exercise heat for thermogenic heat occurred at low Ta. This reduced energy expenditure during low-temperature running by 23–37%, but running costs comprised a fairly minor fraction of the energy budget, so the daily energy savings viasubstitution were much smaller. Deer mice did not adjust running speed to maximize metabolic economy, as they seldom used the high speeds that provide the lowest cost of transport. The highest voluntary speeds (4–5 km h-1) were almost always below the predicted maximal aerobic speed,and were much less than the species' maximal sprint speed. Maximum voluntarily attained rates of oxygen consumption(V̇O2) were highest at low Ta, but rarely approached maximal V̇O2 during forced treadmill exercise. Mean respiratory exchange ratios coincident with maximal voluntary V̇O2increased slightly as Ta declined, but were always below 1.0 (another indication that metabolic rate was less than the aerobic maximum). Individuals with high running performance (cumulative distance and running time) had high resting metabolism, which suggests a cost of having high capacity or propensity for activity.
Motor units are recruited in a task-dependent fashion during locomotion
Authors: Wakeling James M.
Published: October 2004

Muscle fibres have a range of contractile properties from fast to slow. Traditional understanding of muscle fibre recruitment suggests that the slower fibres within a mixed muscle are used for all contractions including those at rapid speeds. However, mechanical arguments predict that some locomotor tasks are best performed by solely the faster fibres. Motor recruitment patterns can be indicated by the spectral properties of the myoelectric signals. High- and low-frequency myoelectric spectra that have similar spectral power indicate the activity of faster and slower motor units, respectively. In this study,the myoelectric signals in humans were measured from nine muscles of the leg during walking and running at 1.5, 3 and 4.5 m s–1. The myoelectric spectra for 20 points in each stride were calculated using wavelet techniques, and the spectral properties quantified using principal component analysis. Bursts of muscle activity were characterized by hysteresis in the myoelectric frequencies, with different frequencies occurring at different times, indicating time-varying shifts in the motor recruitment patterns. This hysteresis occurred at all locomotor speeds tested. It is likely that the different types of motor unit are recruited in a task-dependent fashion during locomotion.
The energetic cost of variations in wing span and wing asymmetry in the zebra finch Taeniopygia guttata
Authors: Hambly C. , Harper E. J. , Speakman J. R.
Published: October 2004

Asymmetry is a difference in the sizes of bilaterally paired structures. Wing asymmetry may have an effect on the kinematics of flight, with knock-on effects for the energetic cost of flying. In this study the 13C-labelled bicarbonate technique was used to measure the energy expended during the flight of zebra finches Taeniopygia guttata,prior to and after experimental manipulation to generate asymmetry and a change in wing span by trimming the primary feathers. In addition,simultaneous high-speed video footage enabled differences in flight kinematics such as flight speed, wing amplitude, up- and downstroke duration and wing beat frequency to be examined. In 10 individuals, the primary feathers on the right wing were trimmed first, by 0.5 cm, and then by an additional 0.5 cm in six of these individuals. In a separate `control' group (N=7),approximately 0.25 cm was trimmed off the primary feathers of both wings, to produce the same reduction in wing span as 0.5 cm trimmed from one wing, while maintaining symmetry. When birds were manipulated to become asymmetric they maintained flight speed. They also increased the left wing amplitude and decreased the right up- and downstroke durations to counteract the changes in wing shape, which meant that they had an increase in wing beat frequency. When the wing area was reduced while maintaining symmetry, birds flew with slower flight speed. In this case wing amplitude did not change and wing upstroke slightly decreased, causing an increased wing beat frequency. The mean flight cost in the pre-manipulated birds was 1.90±0.1 W. There was a slight increase in flight cost with both of the asymmetry manipulations (0.5 cm,increase of 0.04 W; 1.0 cm, increase of 0.12 W), neither of which reached statistical significance. There was, however, a significantly increased flight cost when the wing span was reduced without causing asymmetry (increase of 0.45 W; paired t-test T=2.3, P=0.03).