bluuebunny/crossref_metadata_2025 huggingface dataset:
Divided Government and U.S.Trade Policy: Much Ado About Nothing?
Authors: Karol David
Published: July 2002

Scholars assert that divided government impedes the liberalization of U.S. trade policy. They claim that presidents favor freer trade and will use the negotiating authority Congress delegates to them to reach agreements lowering trade barriers. Since presidents gain more support from their congressional co-partisans, less liberalization ensues under divided government. This theory rests on the premise that party is unrelated to congressional trade policy preferences beyond legislators' tendencies to support their presidential co-partisans. Yet before 1970 congressional Democrats were relatively free trading regardless of the president's party affiliation. Since then, the same has been true of Republicans. Divided government facilitates the trade policies of presidents from the protectionist party since they win more support from their “opposition” in this area. Divided government does impede the efforts of presidents from the free-trading party to liberalize. I conclude that divided government has no consistent effect on trade policy outcomes.
Perceptions and alliances in Europe, 1865–1940
Authors: Christensen Thomas J.
Published: July 2002

While some structural realists and their liberal and institutionalist critics continue to fight a high-profile battle about the fundamental nature of international politics, a quieter discussion is progressing about how to integrate various aspects of realist thinking into a more coherent approach to security politics. The goal of this discussion is to marry the two major strands of contemporary realist thought: balance-of-power theory and security dilemma theory. Recent works advocate combining structural variables, such as the number of great actors in the system and the distribution of capabilities among them, with security dilemma variables, such as the comparative efficacy of offensive versus defensive doctrines given available weaponry and military training.
Agricultural Policy Reform and the Uruguay Round: Synergistic Linkage in a Two-Level Game?
Authors: Paarlberg Robert
Published: July 2002

Domestic agricultural subsidy policies in the United States and in the European Union (EU) underwent substantial liberal reforms between 1990 and 1996. In the United States in 1990, Congress reduced acreage on which farmers could receive income-support payments (deficiency payments) by 15 percent under a budget reconciliation act. In the EU in 1991–92, the Common Agricultural Policy (CAP) was dramatically modified under a set of reforms (the MacSharry reforms) that reduced internal cereal price guarantees by 29 percent over three years and obliged larger EU farmers to leave 15 percent of their arable land idle as a further check on excess production. Then in 1995–96, the U.S. Congress passed the Federal Agricultural Improvement and Reform (FAIR) Act, a sweeping measure that eliminated for at least seven years all deficiency payments to farmers as well as all annual land-idling programs. U.S. Senator Richard Lugar, chair of the Senate Agriculture Committee, asserted that this new law would “change agricultural policy [in the United States] more fundamentally than any law in sixty years.”
Rationalizing Politics: The Emerging Synthesis of International, American, and Comparative Politics
Authors: Milner Helen V.
Published: July 2002

International relations has often been treated as a separate discipline distinct from the other major fields in political science, namely American and comparative politics. A main reason for this distinction has been the claim that politics in the international system is radically different from politics domestically. The degree of divergence between international relations (IR) and the rest of political science has waxed and waned over the years; however, in the past decade it seems to have lessened. This process has occurred mainly in the “rationalist research paradigm,” and there it has both substantive and methodological components. Scholars in this paradigm have increasingly appreciated that politics in the international realm is not so different from that internal to states, and vice versa. This rationalist institutionalist research agenda thus challenges two of the main assumptions in IR theory. Moreover, scholars across the three fields now tend to employ the same methods. The last decade has seen increasing cross-fertilization of the fields around the importance of institutional analysis. Such analysis implies a particular concern with the mechanisms of collective choice in situations of strategic interaction. Some of the new tools in American and comparative politics allow the complex, strategic interactions among domestic and international agents to be understood in a more systematic and cumulative way.
From the Artificial to the Art: A Short Introduction to a Theory and Its Applications
Authors: Negrotti Massimo
Published: July 2002

The author presents the idea that all human attempts to reproduce natural objects (“exemplars”) or their functions—that is, to build artificial objects or processes—unavoidably result in a transfiguration of the exemplars. After introducing the main concepts of a theory of the artificial, the author extends the theory to communication and the arts, both of which provide compelling examples of the generation of artificial objects or processes. The author conceives of art as a paradoxical communication process by which transfiguration does not represent a failure of the reproduction process but, rather, the true objective of the artist.
Incremental Processing and Acceptability
Authors: Morrill Glyn
Published: July 2002

We describe a left-to-right incremental procedure for the processing of Lambek categorial grammar by proof net construction. A simple metric of complexity, the profile in time of the number of unresolved valencies, correctly predicts a wide variety of performance phenomena including garden pathing, the unacceptability of center embedding, preference for lower attachment, left-to-right quantifier scope preference, and heavy noun phrase shift.
Attractor Networks for Shape Recognition
Authors: Amit Yali , Mascaro Massimo
Published: July 2002

We describe a system of thousands of binary perceptrons with coarse-oriented edges as input that is able to recognize shapes, even in a context with hundreds of classes. The perceptrons have randomized feed-forward connections from the input layer and form a recurrent network among themselves. Each class is represented by a prelearned attractor (serving as an associative hook) in the recurrent net corresponding to a randomly selected subpopulation of the perceptrons. In training, first the attractor of the correct class is activated among the perceptrons; then the visual stimulus is presented at the input layer. The feedforward connections are modified using field-dependent Hebbian learning with positive synapses, which we show to be stable with respect to large variations in feature statistics and coding levels and allows the use of the same threshold on all perceptrons. Recognition is based on only the visual stimuli. These activate the recurrent network, which is then driven by the dynamics to a sustained attractor state, concentrated in the correct class subset and providing a form of working memory. We believe this architecture is more transparent than standard feedforward two-layer networks and has stronger biological analogies.
A Comparison of the Accuracy of an Electromagnetic and a Hybrid Ultrasound-Inertia Position Tracking System
Authors: Kindratenko Volodymyr
Published: July 2002

Results of a comparison study of the tracking accuracy of two commercially available wide-range position tracking systems suitable for CAVEs are presented. An experiment was conducted with Flock of Birds and IS-900 tracking systems installed in the same CAVE environment to compare their accuracy. Another experiment was performed with a newly deployed IS-900 to investigate the impact of different ultrasound emitter configurations on the accuracy of the location tracking. The results show that the IS-900 has a much better accuracy over a larger range of operation than does the Flock of Birds; however, it is sensitive to the optimality of the ultrasound emitters configuration.
The Educational Value of an Information-Rich Virtual Environment
Authors: Bowman Doug A. , Hodges Larry F. , Allison Don , Wineman Jean
Published: July 2002

Information-rich virtual environments consist not only of three-dimensional graphics and other spatial data but also information of an abstract or symbolic nature that is related to the space. An environment of this type can stimulate learning and comprehension, because it provides a tight coupling between symbolic and experiential information. In our virtual zoo exhibit, students can explore an accurate model of the gorilla habitat at Zoo Atlanta and access information related to the design of the exhibit. This paper discusses the design of the application and the interaction techniques used to obtain information. We also present the results of a formal evaluation. Although no statistically significant differences were found, results indicate that students who used the virtual environment had higher test scores than those who only attended a lecture on the material. Trends suggest that the virtual experience allowed students to learn information directly and also equipped them to better learn and understand material from a traditional lecture.
Emergence of Multicellular Organisms with Dynamic Differentiation and Spatial Pattern
Authors: Furusawa Chikara , Kaneko Kunihiko
Published: July 2002

The origin of multicellular organisms and the mechanism of development in cell societies are studied by choosing a model with intracellular biochemical dynamics allowing for oscillations, cell–cell interaction through diffusive chemicals on a two-dimensional grid, and state-dependent cell adhesion. Cells differentiate due to a dynamical instability, as described by our “isologous diversification” theory. A fixed spatial pattern of differentiated cells emerges, where spatial information is sustained by cell–cell interactions. This pattern is robust against perturbations. With an adequate cell adhesion force, active cells are released that form the seed of a new generation of multicellular organisms, accompanied by death of the original multicellular unit as a halting state. It is shown that the emergence of multicellular organisms with differentiation, regulation, and life cycle is not an accidental event, but a natural consequence in a system of replicating cells with growth.
FORESTRY EXPERTISE AND NATIONAL NARRATIVES: SOME CONSEQUENCES FOR OLD-GROWTH CONFLICTS IN FINLAND
Authors: Berglund Eeva
Published: July 2002

Environmentalists, especially old-growth activists, often rely on expert discourses which effectively disempower those whose livelihoods depend on forest products. They are often said to do this by fetishising nature as the other. In Finland, which is perhaps the world's most forestry-dependent country, old-growth activism opposing the forest products industry and sustained-yield forestry clearly expresses both desires to seek connection with sublime nature, but also to control and manage nature in an expert idiom much like that of the forestry profession itself. To help explain the prominence of expert discourses the paper charts the historical emergence of Finland as a nation-state, made economically dependent on timber products, but also characterised by a national culture emphasising forest-nature as something quintessentially Finnish. These two national narratives helped seal a national "forest consensus" which is now, however, being challenged with the very language that created it in the first place.
Intraspecific taxonomy and nomenclature of the Danube crested newt, Triturus dobrogicus
Authors: Borkin Leo , Litvinchuk Spartak
Published: July 2002

The Pannonian and Danube Delta populations of Triturus dobrogicus are well separated morphologically from each other. We recognize two subspecies of the Danube crested newt. The nominotypic subspecies inhabits the Danube Delta. Triturus dobrogicus macrosomus (Boulenger, 1908), comb. and stat. nov., occurs in the remaining part of the species' range.
MATING AND AGGRESSIVE BEHAVIOUR IN DENDROBATID FROGS FROM CORCOVADO NATIONAL PARK, COSTA RICA: A COMPARATIVE STUDY
Authors: Summers Kyle
Published: July 2002

1. Mating and aggressive behaviour was observed in four species of dendrobatid frogs in Corcovado National Park, Costa Rica: Colostethus nubicola, Colostethus talamancae, Phyllobates vittatus and Dendrobates granuliferus. 2. Males of both species of Colostethus were more likely to respond to call playbacks than male P. vittatus or D. granuliferus. Male D. granuliferus were less likely to be found calling than males of the other species. Conspecific male-male aggression was observed in P. vittatus, but not in the other species. 3. Females were more active during courtship in P. vittatus. Female-female aggression was observed on one occasion in P. vittatus. Females were more likely to reject males than the reverse in all species. 4. These observations suggest that sexual conflict occurs in P. vittatus, but not in C. nubicola or C. talamancae.
ORIENTATION BEHAVIOUR IN STICKLEBACKS: MODIFIED BY EXPERIENCE OR POPULATION SPECIFIC?
Authors: Girvan Joanna , Braithwaite Victoria
Published: July 2002

To investigate the mechanisms underlying preferred spatial information use in Three-spined sticklebacks we reared fish derived from contrasting habitats (pond and river populations) under a range of conditions. The rearing conditions were designed to determine whether the spatial information used by sticklebacks is population specific, whether it is learned or whether it is produced by an interaction between these two factors. Fish reared under different conditions were trained to solve two experimental tasks to determine what spatial information they preferred to use. The results indicate that the fish learned spatial cues relevant to the environment that they were raised in but there was also evidence of a gene by environment interaction that influenced which spatial cues were learned.
Rhigonematida from New Britain diplopods. 2. The genera Rhigonema Cobb, 1898 and Zalophora Hunt, 1994 (Rhigonematoidea: Rhigonematidae) with descriptions of three new species
Authors: Hunt David , Moore Dave
Published: July 2002

Three new species from the genera Rhigonema and Zalophora are described and illustrated from two unidentified species of spirobolid diplopod from New Britain. The species proposed are Rhigonema licinacanthum sp. n., Zalophora deinostoma sp. n. and Z. nemophila sp. n. A second population of R. tribonophorum Hunt, 1995 is described and the original description supplemented, caudal rugosities being recorded in the male for the first time in the genus. SEM micrographs supplement the descriptions. The bionomics of Zalophora are discussed and evidence presented to show that, unlike the other members of the Rhigonematida, Zalophora species are predators on the other nematode inhabitants of the diplopod gut. It is postulated that this trophic specialism may explain such unusual aspects as the occurrence of only one adult female Zalophora per diplopod host, the low prevalence of juveniles and the apparent absence of males. Rhigonematida de Nouvelle-Bretagne. 2. Les genres Rhigonema Cobb, 1898 et Zalophora Hunt, 1994 (Rhigonematoidea: Rhigonematidae) et description de trois nouvelles especes - Trois nouvelles especes des genres Rhigonema et Zalophora sont decrites et illustrees provenant de deux especes non identifiees de diplopodes spirobolides originaires de Nouvelle-Bretagne. Ces especes sont Rhigonema licinacanthum sp. n., Zalophora deinostoma sp. n. et Z. nemophila sp. n. Une seconde population de R. tribonophorum Hunt, 1995 est decrite et illustree et la description originale est completee, des rugosites caudales ayant ete observees chez le male pour la premiere fois dans le genre. Des photos au microscope electronique a balayage completent les descriptions. L'ecologie du genre Zalophora est discutee et une preuve certaine est presentee selon laquelle, a la difference des autres membres des Rhigonematida, les especes de Zalophora sont predatrices des autres nematodes presents dans les intestins des diplopodes. Il est postule que cette specialisation trophique pourrait expliquer certaines caracteristiques inhabituelles tels la presence d'une seule femelle adulte de Zalophora par diplopode, la faible frequence des juveniles et l'apparente absence des males.
Criconematidae (Nematoda: Tylenchida) from the New Zealand region: genera Ogma Southern, 1914 and Blandicephalanema Mehta & Raski, 1971
Authors: Wouts Wilhelmus , Yeates Gregor , Loof Pieter
Published: July 2002

Seven Ogma species new to science are described from native vegetation in New
Zealand. O. campbelli n. sp. and O. sexcostatum n. sp. have six, Ogma
polyandra n. sp., O. subantarcticum n. sp., O. semicrenatum n. sp., O.
paucispinatum n. sp. and O. crenulatum n. sp. have eight or more rows of
palmate scales. O. sexcostatum differs from O. campbelli by its shorter body
(0.36 vs 0.49 mm), greater number of body annules (60-69 vs 50-57) and
shorter spines on the ventral side of the post-vulval area. O.
subantarcticum and O. polyandra both have a fringe of appendages on the lip
annules but differ in body diameter (64 vs 47 mu m), number of spines per
body scale (more than seven vs less than eight) and stylet length (102 vs 92
mu m). O. semicrenatum has no appendages on the first lip annule. O.
paucispinatum differs from the previous species by having less than five
(generally three) appendages on the scales. O. crenulatum differs from O.
subantarcticum and O. semicrenatum, the species with about five appendages,
by the weakly crenate or smooth edge of both the first and the second lip
annule. Blandicephalanema is represented by B. serratum Mehta & Raski,
1971, B. pilatum Mehta & Raski, 1971 and B. bossi Reay, 1987.
Criconematidae (Nematoda: Tylenchida) de Nouvelle Zelande: genres Ogma
Southern, 1914 et Blandicephalanema Mehta & Raski, 1971 - Sept nouvelles
especes pour la science associees a la vegetation indigene sont decrites de
Nouvelle Zelande, Ogma campbelli n. sp. et O. sexcostatum n. sp. montrant
six rangees d'ecailles palmees, O. polyandra n. sp., O. subantarcticum n.
sp., O. semicrenatum n. sp., O. paucispinatum n. sp. et O. crenulatum n. sp.
en montrant huit ou plus. O. sexcostatum se difference d'O. campbelli par le
corps plus court (0.36 vs 0.49 mm), le plus grand nombre d'anneaux du corps
(60-69 vs 50-57) et les epines plus courtes sur la face ventrale de la
region post vulvaire. O. subantarcticum et O. polyandra portent tous deux
une frange d'appendices sur les anneaux labiaux mais se differencient par le
diametre du corps (64 vs 47 mu m), le nombre d'epines par ecaille (moins de
sept vs plus de huit) et la longueur du stylet (102 vs 92 mu m). O.
semicrenatum ne porte pas d'appendice sur l'anneau labial. O. paucispinatum
se differencie des precedentes especes en ayant moins de cinq (generalement
trois) appendices sur les ecailles. O. crenulatum se differencie d'O.
subantarcticum et O. semicrenatum, especes avec environ cinq appendices, par
le bord legerement crenele ou lisse du premier et du second anneau labial.
Blandicephalanema est represente par B. serratum Mehta & Raski, 1971, B.
pilatum Mehta & Raski, 1971 et B. bossi Reay, 1987.
Synthesis of a regularly interstratified 2:1 margarite and beidellite (34 Å phase)
Authors: Matsuda T.
Published: July 2002

Regularly interstratified mica-smectites and chlorite-smectites have been synthesized by Ueda & Sudo (1966), Frank-Kamenetskij et al. (1972), Matsuda & Henmi (1973, 1974) and by Eberl (1978). Only a few studies have been carded out, however, on regularly interstratified minerals whose spacings exceed 30 Å (Lazarenko & Korolev, 1970; Sato & Kizaki, 1972).
Crystal structure of Ba8[Al3O10][AlO4], a novel mixed-anion Ba aluminate related to kilchoanite
Authors: Kahlenberg V.
Published: July 2002

Crystal growth experiments in the system BaO–Al2O3 yielded single crystals of a new Ba oxo-aluminate with composition Ba4Al2O7. The title compound is orthorhombic, with cell parameters a = 11.3126(5), b = 11.7045(9), c = 27.1850(14) Å, space group Cmca. The structure was solved by direct methods followed by difference Fourier synthesis from X-ray single crystal diffraction data (R1 = 0.048 for 1213 independent observed reflections and 135 parameters). The main building units of tetrabarium aluminate are Al3O10 trimers and isolated AlO4 tetrahedra. Seven crystallographically different Ba sites crosslink between the tetrahedral groups and are co-ordinated by six to nine oxygen ligands. The structure is closely related to the mineral kilchoanite (Ca6[SiO4][Si3O10]) and the first representative of an unbranched oligo-aluminate with triple tetrahedra.
Mineral chemistry of the Mull-Morvern Tertiary lava succession, western Scotland
Authors: Kerr Andrew C.
Published: July 2002

The 1800 m thick preserved remnant of the Tertiary lava succession of Mull and Morvern consists of three basic mantle-derived magma types, with compositions varying from tholeiitic to mildly alkalic, and from picritic basalts to trachytes. This results in a similarly wide range in mineral compositions. Contrary to the suggestions of previous workers the mineral chemistry of the lava succession (in conjunction with published major and trace element chemistry) is strongly supportive of a fractional crystallisation origin for the more evolved lavas.

Resorped and regrown (with more basic material) plagioclase phenocrysts found in the more-evolved are indicative of magma mixing processes involving replenishment of an evolving magma chamber with more-basic magma. Lavas containing 15–20 vol.% plagioclase phenocrysts probably represent eruptions from the top of a magma chamber where flotation cumulates of plagioclase had developed. Fragmental phenocrysts found in some highly plagioclase phyric lavas (from near the top of the
preserved lava succession) suggest that the eruption of lavas may have been explosive.
The crystal structure of szenicsite, Cu3MoO4(OH)4
Authors: Burns Peter C.
Published: July 2002

The crystal structure of szenicsite, Cu3MoO4(OH)4, orthorhombic, a = 8.5201(8), b = 12.545(1), c = 6.0794(6) Å, V = 649.8(2) Å3, space group Pnnm, Z = 4, has been solved by direct methods and refined by least-squares techniques to an agreement index (R) of 3.34% and a goodness-of-fit (S) of 1.11 for 686 unique observed [|F| ⩾ 4σF] reflections collected using graphite-monochromated Mo-Kα X-radiation and a CCD area detector. The structure contains three unique Cu2+ positions that are each coordinated by six anions in distorted octahedral arrangements; the distortions of the octahedra are due to the Jahn-Teller effect associated with a d9 metal in an octahedral ligand-field. The single unique Mo6+ position is tetrahedrally coordinated by four O2− anions. The Cu2+ϕ6 (ϕ: unspecified ligand) octahedra share trans edges to form rutile-like chains, three of which join by the sharing of octahedral edges to form triple chains that are parallel to [001]. The MoO4 tetrahedra are linked to either side of the triple chain of Cu2+ϕ6 octahedra by the sharing of two vertices per tetrahedron, and the resulting chains are cross-linked through tetrahedral-octahedral vertex sharing to form a framework structure. The structure of szenicsite is closely related to that of antlerite, Cu3SO4(OH)4, which contains similar triple chains of edge-sharing Cu2+ϕ6 octahedra.
Cell proliferation through forced engagement of c-Kit and Flt-3
Authors: Otto Kevin G. , Jin Liqing , Spencer David M. , Blau C. Anthony
Published: July 2002

To investigate the potential for functional interactions between heterologous receptors, the cytoplasmic domains of 2 different receptors (c-Kit and Flt-3) were coexpressed in the interleukin-3–dependent cell line Ba/F3. The receptor signaling domains were presented in the context of fusion proteins, with c-Kit linked to the FK506 binding protein (FKBP12) and Flt-3 linked to the FRB domain of the FKBP12–rapamycin-associated protein. The fusions were brought into apposition with the use of chemical inducers of dimerization (CIDs). Two classes of CID were employed. FK1012 and its synthetic analogue AP1510 bring together 2 copies of the FKBP12 domain, thereby inducing homodimerization of the c-KitFKBP12fusion. A second type of CID, rapamycin, brings together one FKBP12 domain and one FRB domain, resulting in heterodimerization of the c-KitFKBP12 and Flt-3FRB fusions. Ba/F3 cell growth was promoted not only by FK1012- or AP1510-induced homodimerization of the c-KitFKBP12 fusion (as reported previously), but also by rapamycin-induced c-KitFKBP12–Flt-3FRB heterodimerization. These findings demonstrate the potential for a direct functional interaction between c-Kit and Flt-3.
Autocrine interleukin-6 production and highly malignant multiple myeloma: relation with resistance to drug-induced apoptosis
Authors: Frassanito Maria Antonia , Cusmai Antonio , Iodice Giuseppe , Dammacco Franco
Published: July 2002

In this study, flow cytometry was used to evaluate interleukin-6 (IL-6) production by bone marrow mononuclear cells from 47 patients with multiple myeloma (MM) in different clinical stages and 15 patients with monoclonal gammopathy of undetermined significance. In patients with MM, autocrine IL-6 production paralleled the clinical disease stage. The largest proportion of syndecan-1+/IL-6+ cells was detected in patients with resistant relapse or primary refractory disease, suggesting that tumor progression involves expansion of myeloma cells producing IL-6. The authors assessed autocrine IL-6 production and in vitro proliferation and apoptosis of myeloma cells in 6 myeloma cell clones (MCCs) and in 2 myeloma cell lines, namely IM-9 and U-266-1970, which showed different sensitivities to the addition of exogenous IL-6. Autocrine IL-6 production was observed in IL-6–independent MCC-2, MCC-3, and MCC-5 cloned from patients with aggressive disease and in the IM-9 cell line. In contrast, IL-6–dependent MCC-1, MCC-4, and MCC-6 were syndecan-1+ and IL-6−. Blocking experiments with anti–IL-6 monoclonal antibody from clone AH65, which binds IL-6–IL-6Rα complexes, prevented cell proliferation of IL-6+ MCCs. Flow cytometry evaluations after propidium iodide staining revealed different susceptibilities of MCCs to cell death. IL-6–producing MCCs showed minimal spontaneous and dexamethasone-induced apoptosis, whereas a regular amplitude of apoptosis occurred in the IL-6− MCCs. These data provide evidence that autocrine IL-6 reflects a highly malignant phenotype of myeloma cells. In fact, autocrine IL-6 production and deregulated apoptosis may induce expansion of selective IL-6+ myeloma cells resistant to spontaneous and drug-induced cell death.
Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency
Authors: Rubocki Ronald J. , Parsa Jennifer R. , Hershfield Michael S. , Sanger Warren G. , Pirruccello Samuel J. , Santisteban Ines , Gordon Bruce G. , Strandjord Sarah E. , Warkentin Phyllis I. , Coccia Peter F.
Published: July 2002

Bone marrow transplantation (BMT) for severe combined immunodeficiency (SCID) with human leukocyte antigen (HLA)-identical sibling donors but no pretransplantation cytoreduction results in T-lymphocyte engraftment and correction of immune dysfunction but not in full hematopoietic engraftment. A case of a 17-month-old girl with adenosine deaminase (ADA) deficiency SCID in whom full hematopoietic engraftment developed after BMT from her HLA-identical sister is reported. No myeloablative or immunosuppressive therapy or graft-versus-host disease (GVHD) prophylaxis was given. Mild acute and chronic GVHD developed, her B- and T-cell functions became reconstituted, and she is well almost 11 years after BMT. After BMT, repeated studies demonstrated: (1) Loss of a recipient-specific chromosomal marker in peripheral blood leukocytes (PBLs) and bone marrow, (2) conversion of recipient red blood cell antigens to donor type, (3) conversion of recipient T-cell, B-cell, and granulocyte lineages to donor origin by DNA analysis, and (4) increased ADA activity and metabolic correction in red blood cells and PBLs.
Interleukin 9 promotes influx and local maturation of eosinophils
Authors: Louahed Jamila , Zhou Yuhong , Maloy W. Lee , Rani Pyapalli U. , Weiss Christine , Tomer Yaniv , Vink Anne , Renauld Jean-Christophe , Van Snick Jacques , Nicolaides Nicholas C. , Levitt Roy C. , Haczku Angela
Published: July 2002

The interleukin 9 (IL-9) pathway has recently been associated with the asthmatic phenotype including an eosinophilic tissue inflammation. The mechanism by which IL-9 affects eosinophils (eos) is not known. To investigate whether this cytokine has a direct activity on the development of eos and eosinophilic inflammation, a model of thioglycolate-induced peritoneal inflammation was used in IL-9 transgenic (TG5) and background strain (FVB) mice. In this model, a transient eosinophilic infiltration in the peritoneal cavity was observed in FVB mice 12 to 24 hours after thioglycolate injection that coincided with peak IL-5 and IL-9 release. In contrast, TG5 mice developed a massive eosinophilia that persisted at high levels (81% of total cells) even 72 hours after thioglycolate injection. Release of eosinophilic major basic protein (MBP), IL-4, and IL-5 to the peritoneal cavity of these mice was significantly increased when compared with the control FVB strain. To study the mechanism by which IL-9 exerts its effect on eos, bone marrow or peritoneal cells were cultured in the presence of IL-5, IL-9, or their combination in vitro. IL-5 alone was able to generate significant numbers of eos in TG5 but not FVB mice, whereas a combination of IL-5 and IL-9 induced marked eosinophilia in both strains indicating a synergism between these 2 cytokines. These data suggest that IL-9 may promote and sustain eosinophilic inflammation via IL-5–driven eos maturation of precursors.
New insights into the thrombopoietic status of patients on dialysis through the evaluation of megakaryocytopoiesis in bone marrow and of endogenous thrombopoietin levels
Authors: Ando Minoru , Iwamoto Yuhsuke , Suda Akio , Tsuchiya Ken , Nihei Hiroshi
Published: July 2002

The thrombopoietic status of patients with uremia remains unclear. This issue was addressed with particular reference to marrow megakaryocytopoiesis and endogenous thrombopoietin (TPO) levels. A study was conducted in 114 patients on hemodialysis, 43 patients on continuous ambulatory peritoneal dialysis, and 48 age-matched controls. Reticulated platelets, a marker of marrow megakaryocytopoiesis, were measured by flow cytometry. Serum TPO levels, platelet-associated IgG (PAIgG) levels, and hepatitis C virus (HCV) antibody titers were also measured by enzyme-linked immunosorbent assay. Circulating and reticulated platelet counts were significantly lower in the patients on dialysis than in the controls. Thrombocytopenia (less than 150 × 109/L) was most frequent in the HCV-positive hemodialysis patients, who had a higher incidences and higher PAIgG titers. The following results were obtained in the HCV-negative dialysis patients: (1) platelet counts chronologically decreased with years on hemodialysis; (2) platelet counts were associated with the reticulated platelet counts; (3) serum TPO levels were significantly elevated in the dialysis patients, responding to the decrease of reticulated platelets; (4) hematocrits had a positive correlation with serum TPO levels, and serum TPO levels were significantly higher in the patients on hemodialysis who did not require recombinant human erythropoietin therapy than in the other patients. In conclusion, thrombocytopenia is a frequent finding in patients on dialysis. The failure of megakaryocyte production could be the principal cause of the platelet reduction, and the peripheral destruction and sequestration of platelets may be concomitantly involved. Elevation of serum TPO may in part serve as an aid to erythropoiesis in dialysis patients.
The diversity of rearranged immunoglobulin heavy chain variable region genes in peripheral blood B cells of preterm infants is restricted by short third complementarity-determining regions but not by limited gene segment usage
Authors: Zemlin Michael , Bauer Karl , Hummel Michael , Pfeiffer Sabine , Devers Simone , Zemlin Cosima , Stein Harald , Versmold Hans T.
Published: July 2002

The immunoglobulin diversity is restricted in fetal liver B cells. This study examined whether peripheral blood B cells of extremely preterm infants show similar restrictions (overrepresentation of some gene segments, short third complementarity-determining regions [CDR3]). DNA of rearranged immunoglobulin heavy chain genes was amplified by polymerase chain reaction, cloned, and sequenced. A total of 417 sequences were analyzed from 6 preterm infants (25-28 weeks of gestation), 6 term infants, and 6 adults. Gene segments from the entire VHand DH gene locus were rearranged in preterm infants, even though the DH7-27 segment was overrepresented (17% of rearrangements) compared to term infants (7%) and adults (2%). CDR3 was shorter in preterm infants (40 ± 10 nucleotides) than in term infants (44 ± 12) and adults (48 ± 14) (P < .001) due to shorter N regions. Somatic mutations were exclusively found in term neonates and adults (mutational frequency 0.8% and 1.8%). We conclude that preterm infants have no limitations in gene segment usage, whereas the diversity of CDR3 is restricted throughout gestation.
Interleukin-7 restores immunity in athymic T-cell–depleted hosts
Authors: Fry Terry J. , Christensen Barbara L. , Komschlies Kristin L. , Gress Ronald E. , Mackall Crystal L.
Published: July 2002

Thymic-deficient hosts rely primarily on antigen-driven expansion to restore the peripheral T-cell compartment following T-cell depletion (TCD). The degree to which this thymic-independent pathway can restore immune competence remains poorly understood but has important implications for a number of clinical conditions including stem cell transplantation and human immunodeficiency virus (HIV) infection. A model of HY-mediated skin graft rejection by athymic, TCD mice was used to show that restoration of naive and recall responses via peripheral expansion requires transfer of only 25 × 106 lymph node (LN) cells representing approximately 10% of the T-cell repertoire. Consitutive expression of bcl-2 in the expanding inocula restored recall responses to HY at a substantially lower LN cell dose (1 × 106), which is normally insufficient to induce HY-mediated graft rejection in athymic hosts. Interestingly, bcl-2 had no effect on primary responses. Interleukin-7 (IL-7) potently enhanced thymic-independent peripheral expansion and led to HY graft rejection using an LN cell dose of 1 × 106 in both primary and recall models. The restoration of immune competence by IL-7 appeared to be mediated through a combination of programmed cell death inhibition, improved costimulation, and modulation of antigen-presenting cell (APC) function. These results show that immune competence for even stringent antigens such as HY can be restored in the absence of thymic function and identify IL-7 as a potent modulator of thymic-independent T-cell regeneration.
Targeted disruption of the murine Fanconi anemia gene,Fancg/Xrcc9
Authors: Yang Yi , Kuang Yanan , De Oca Rocio Montes , Hays Tobias , Moreau Lisa , Lu Naifang , Seed Brian , D'Andrea Alan D.
Published: July 2002

Fanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder characterized by cellular sensitivity to mitomycin C and ionizing radiation. Six FA genes (corresponding to subtypes A, C, D2, E, F, and G) have been cloned, and the encoded FA proteins interact in a common cellular pathway. To further understand the in vivo role of one of these human genes (FANCG), we generated a targeted disruption of murine Fancg and bred mice homozygous for the targeted allele. Similar to the phenotype of the previously described Fancc−/− andFanca−/− mice, theFancg−/− mice had normal viability and no gross developmental abnormalities. Primary splenic lymphocytes, bone marrow progenitor cells, and murine embryo fibroblasts from theFancg−/− mice demonstrated spontaneous chromosome breakage and increased sensitivity to mitomycin C and, to a lesser extent, ionizing radiation. Fancg−/−lymphocytes had a defect in the FA pathway, based on their failure to activate the monoubiquitination of the downstream Fancd2protein in response to IR. Finally,Fancg−/− mice had decreased fertility and abnormal gonadal histology. In conclusion, disruption of theFancg gene confirms the role of Fancg in the FA pathway. The Fancg−/− mouse may be useful as an animal model for future gene therapy and cancer susceptibility studies.
Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial
Authors: Goldstone Anthony H. , Burnett Alan K. , Wheatley Keith , Smith Alastair G. , Hutchinson R. Michael , Clark Richard E.
Published: July 2002

In an attempt to improve induction chemotherapy for older patients with acute myeloid leukemia (AML),1314 patients were randomized to 1 of 3 induction treatments for 2 courses of DAT (daunorubicin, cytarabine, and thioguanine) 3 + 10, ADE (daunorubicin, cytarabine, and etoposide) 10 + 3 + 5, or MAC (mitoxantrone-cytarabine). The remission rate in the DAT arm was significantly better than ADE (62% vs 50%; P = .002) or MAC (62% vs 55%;P = .04). This benefit was seen in patients younger and older than 70 years. There were no differences between the induction schedules with respect to overall survival at 5 years (12% vs 8% vs 10%). A total of 226 patients were randomized to receive granulocyte colony-stimulating factor (G-CSF) or placebo as supportive care from day 8 after the end of treatment course 1. The remission rate or survival were not improved by G-CSF, although the median number of days to recover neutrophils to 1.0 × 109/L was reduced by 5 days. Patients who entered remission (n = 371) were randomized to stop after a third course (DAT 2 + 7) or after 6 courses, ie, a subsequent COAP (cyclophosphamide, vincristine, cytarabine, and prednisolone), DAT 2 + 5, and COAP. The relapse risk (81% vs 73%), disease-free survival (16% vs 23%), and overall survival at 5 years (23% vs 22%) did not differ between the 3-course or 6-course arms. In addition to a treatment duration randomization, 362 patients were randomized to receive 12-month maintenance treatment with low-dose interferon, but no benefit was seen with respect to relapse risk, disease-free survival, or overall survival.
The zebrafish klf gene family
Authors: Oates Andrew C. , Pratt Stephen J. , Vail Brenda , Yan Yi-lin , Ho Robert K. , Johnson Stephen L. , Postlethwait John H. , Zon Leonard I.
Published: July 2002

The Krüppel-like factor(KLF) family of genes encodes transcriptional regulatory proteins that play roles in differentiation of a diverse set of cells in mammals. For instance, the founding memberKLF1 (also known as EKLF) is required for normal globin production in mammals. Five new KLF genes have been isolated from the zebrafish, Danio rerio, and the structure of their products, their genetic map positions, and their expression during development of the zebrafish have been characterized. Three genes closely related to mammalian KLF2 andKLF4 were found, as was an ortholog of mammalianKLF12. A fifth gene, apparently missing from the genome of mammals and closely related to KLF1 and KLF2,was also identified. Analysis demonstrated the existence of novel conserved domains in the N-termini of these proteins. Developmental expression patterns suggest potential roles for these zebrafish genes in diverse processes, including hematopoiesis, blood vessel function, and fin and epidermal development. The studies imply a high degree of functional conservation of the zebrafish genes with their mammalian homologs. These findings further the understanding of theKLF genes in vertebrate development and indicate an ancient role in hematopoiesis for the Krüppel-like factorgene family.
Immunotherapy using heat-shock protein preparations of leukemia cells after syngeneic bone marrow transplantation in mice
Authors: Sato Kazuya , Torimoto Yoshihiro , Tamura Yasuaki , Shindo Motohiro , Shinzaki Hitoshi , Hirai Katsuyuki , Kohgo Yutaka
Published: July 2002

Heat-shock proteins (HSPs) act as molecular chaperones binding endogenous antigenic peptides and transporting them to major histocompatibility complexes. HSPs chaperone a broad repertoire of endogenous peptides including tumor antigens. For the immunotherapy of tumors, a strategy using HSPs may be more advantageous than other procedures because the identification of each tumor-specific antigen is not necessary. In this study, the efficacy of immunotherapy against minimal residual leukemia cells using HSP preparations was evaluated. HSP70 and GP96 were purified from syngeneic leukemia cell line A20 and immunized into BALB/c mice during the reconstitution period of the immune system after syngeneic bone marrow transplantation. In this procedure, all mice not immunized were dead within 60 days of A20 inoculation, whereas the survival times of HSP-immunized mice were significantly prolonged. In addition, the depletion of either CD4+ or CD8+ T lymphocyte significantly abrogated this efficacy, indicating that both CD4+ and CD8+ T lymphocytes were required for tumor cell rejection. Moreover, the vaccination of HSPs elicited a specific response of potent CD8+ T lymphocytes cytotoxic against A20 in vitro. These observations suggest that immunization of the complex of HSPs and peptides derived from leukemia cells leads to immune responses. These immune responses are sufficient to reject minimal amounts of leukemia cells for relatively immunocompromised mice after syngeneic bone marrow transplantation.
Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry
Authors: McKenna Robert W. , Washington LaBaron T. , Aquino Deborah B. , Picker Louis J. , Kroft Steven H.
Published: July 2002

Bone marrow hematogones (B-lymphocyte precursors) may cause problems in diagnosis because of their morphologic and immunophenotypic similarities to neoplastic lymphoblasts. The purposes of this prospective, multiparametric flow cytometry study were to quantify hematogones across age groups and a spectrum of clinical conditions, to identify factors that affect the relative quantity of hematogones, and to compare their immunophenotype with that of neoplastic lymphoblasts. A total of 662 consecutive marrow specimens were analyzed for hematogones using one of two 4-color antibody combinations; hematogones were identified in 528 (79.8%). There was a significant decline in hematogones with increasing age (P < .001), but a broad range was found at all ages and many adults had a relatively high number. Specimens processed by density gradient had a higher mean percent hematogones than those processed by erythrocyte lysis (P < .001). There was a direct decline in hematogones with increasing marrow involvement with neoplastic cells. A total of 8% of the 662 specimens contained 5% or more hematogones: 24.6% of specimens from patients aged less than 16 years and 6.3% from those 16 and older (P < .000 01). Increased hematogones were observed most often in patients with lymphoma, marrow regenerative states, immune cytopenias, and acquired immunodeficiency syndrome. Hematogones always exhibited a typical complex spectrum of antigen expression that defines the normal antigenic evolution of B-cell precursors and lacked aberrant expression. In contrast, lymphoblasts in 49 cases of precursor B-ALL showed maturation arrest and exhibited 1 to 11 immunophenotypic aberrancies. Four-color flow cytometry with optimal combinations of antibodies consistently distinguishes between hematogones and neoplastic lymphoblasts.
Slow, programmed maturation of the immunoglobulin HCDR3 repertoire during the third trimester of fetal life
Authors: Schroeder Harry W. , Zhang Liming , Philips Joseph B.
Published: July 2002

The mean distribution of lengths in the third complementarity-determining region of the heavy chain (HCDR3) serves as a measure of the development of the antibody repertoire during ontogeny. To determine the timing and pattern of HCDR3 length maturation during the third trimester of pregnancy, the mean distribution of HCDR3 lengths among variable-diversity-joining-constant–μ (VDJCμ) transcripts from the cord blood was analyzed from 138 infants of 23 to 40 weeks' gestation, including 3 sets of twins, 2 of which were of dizygotic origin. HCDR3 maturation begins at the start of the third trimester; follows a slow, continuous expansion over a 5-month period; and is unaffected by race or sex. The range and mean distribution of lengths may vary in dizygotic twins, indicating individual rates of development. The mean HCDR3 length distribution in 10 premature infants with documented bacterial sepsis was then followed for 2 to 12 weeks after their first positive blood culture. HCDR3 spectrotype analysis demonstrated oligoclonal B-cell activation and expansion after sepsis, but maturation of the repertoire was not accelerated even by the systemic exposure to external antigen represented by bacteremia. Antibody repertoire development appears to be endogenously controlled and adheres to an individualized developmental progression that probably contributes to the relative immaturity of the neonatal immune response.
Erythropoietin receptor-dependent erythroid colony-forming unit development: capacities of Y343 and phosphotyrosine-null receptor forms
Authors: Miller Chris P. , Heilman Destin W. , Wojchowski Don M.
Published: July 2002

Red cell development depends on the binding of erythropoietin (EPO) to receptors expressed by erythroid colony-forming units (CFUe) and the subsequent activation of receptor-bound Janus kinase (Jak2). Jak2 then mediates the phosphorylation of receptor tyrosine sites and the recruitment of 25 or more Src homology 2 domain-encoding proteins and associated factors. Previous studies have shown that an EPO receptor form containing Jak2-binding domains plus a single phosphotyrosine343 (PY343)–STAT5-binding site provides all signals needed for erythroid cell development. However, roles for PY343 and STAT5 remain controversial, and findings regarding PY-null receptor activities and erythropoiesis in STAT5-deficient mice are disparate. To study activities of a PY-null EPO receptor in primary cells while avoiding compensatory mechanisms, a form retaining domains for Jak2 binding and activation, but lacking all cytoplasmic tyrosine sites, was expressed in transgenic mice from aGATA1 gene-derived vector as a human epidermal growth factor receptor- murine EPO receptor chimera (EE-T-Y343F). The bio-signaling capacities of this receptor form were investigated in CFUe from thiamphenicol-treated mice. Interestingly, this PY-null EPO receptor form supported CFUe development (in the absence of detectable STAT5 activation) at efficiencies within 3-fold of those levels mediated by either an EE-T-Y343 form or the endogenous EPO receptor. However, EE-T-Y343F–dependent Ter119+ erythroblast maturation was attenuated. In tests of cosignaling with c-Kit, EE-T-Y343F nonetheless retained full capacity to synergize with c-Kit in promoting erythroid progenitor cell proliferation. Thus, EPO receptor PY-dependent events can assist late erythropoiesis but may be nonessential for EPO receptor–c-Kit synergy.