bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Translational Research Working Group Developmental Pathways: Introduction and Overview
Authors: Hawk Ernest T. , Matrisian Lynn M. , Nelson William G. , Dorfman Gary S. , Stevens Lisa , Kwok Jennifer , Viner Jaye , Hautala Judith , Grad Oren ,   for the Translational Research Working Group
Published: July 2008

Abstract
The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of the National Cancer Institute's investment in translational research and envision its future in an inclusive, representative, and transparent manner. To clarify the challenges facing translational research and facilitate its deliberations, the TRWG conceptualized translational research as a set of developmental processes or pathways focused on various clinical goals. Drawing on the collective knowledge of the TRWG members, six pathways were derived, with two addressing the development of tools designed to characterize an individual's cancer-related health status (biospecimen-based and image-based assessment modalities) and four addressing the development of interventions intended to change cancer-related health status (drugs or biological agents, immune response modifiers, interventive devices, and life-style alterations). The pathways, which share a number of common structural elements, are graphically represented by schematic flowcharts that capture relevant contingencies, decision points, and interdependencies. They are conceived not as comprehensive descriptions of the corresponding real-world processes but as tools designed to serve specific purposes including research program management and research project management, coordination of research efforts, and professional and lay education and communication. Further development of the pathways is encouraged, as is application of the pathway concept to translational research on other diseases.
Quelques Observations D'Un Orientaliste Sur La Thèse De Pirenne 1)
Authors: Ashtor E. 
Published: July 2008

AbstractLa thèse de Pirenne qui a suscité des discussions si animées a été négligée pendant de longues années par les orientalistes de métier. Autant que nous sachions l'exposé brillant de notre collègue Cl. Cahen sur" Quelques problèmes concernant l'expansion économique musulmane au Haut Moyen Age"2) est la première contribution qu'y aient faite les historiens de l'Orient musulman. Le but du présent article serait d'amplifier les arguments avancés par Cahen, d'en apporter de nouveaux et, cela s'entend, de donner ça et là d'autres interprétations des textes. Nous voudrions dans ce modeste essai attirer l'attention des collègues "occidentalistes" sur ce qu'on pourrait inférer des sources orientales, arabes et en d'autres langues, en ce qui concerne le problème des échanges commerciaux entre l'Orient musulman et l'Occident chrétien, au Ville, au IXe et dans la première moitié du Xe siècle 3).
Spanien Og De Forenede Nationer
Authors: De Erice José Sebastian 
Published: July 2008

AbstractØjeblikket turde være inde til at søge at skaffe sig et Overblik over, hvad der foregik i de forenede Nationer ved disses Behandling af det saakaldte »spanske Sporgsmaal«. Til bedre Forstaaelse heraf vil det vaere nyttigt kort at erindre, dels om de oprindelige Direktiver for Organisationen, dels om hvad der gik forud for den ejendommelige Holdning, den gennem 4 Aar indtog overfor vort Land
Norske Dommer Angående Folkerett Og Tnternasjonal Privatrett i aRene I953 Og I954
Authors: Hambro Edvard 
Published: July 2008

AbstractDen forholdsvis sparsomme norske rettspraksis pÅ det internasjonale felt er blitt beriket ved noen ganske interessante høyesterettsdommer i de siste par År De folkerettslige dommer er i sitt innhold mindre interessante enn de dommer som angÅr internasjonal privatrett, ikke fordi de forhold som er gjenstand for dommene i og for seg har mindre betydning, men fordi de grunnleggende teoretiske forhold som til en viss grad ble behandlet i prosedyren ikke blev avgjort av høyesterett, mens derimot de store farskapssaker av 24 september 1953 i virkeligheten betyr et oppgjør med tidligere praksis og derfor er blitt meget omstendelige
The glycoprotein Ib-IX-V complex contributes to tissue factor–independent thrombin generation by recombinant factor VIIa on the activated platelet surface
Authors: Weeterings Cees , de Groot Philip G. , Adelmeijer Jelle , Lisman Ton 
Published: July 2008

AbstractSeveral lines of evidence suggest that recombinant factor VIIa (rFVIIa) is able to activate factor X on an activated platelet, in a tissue factor-independent manner. We hypothesized that, besides the anionic surface, a receptor on the activated platelet surface is involved in this process. Here, we showed that, in an ELISA setup, a purified extracellular fragment of GPIbα bound to immobilized rFVIIa. Surface plasmon resonance established a affinity constant (Kd) of approximately 20 nM for this interaction. In addition, CHO cells transfected with the GPIb-IX-V complex could adhere to immobilized rFVIIa, whereas wild-type CHO cells could not. Furthermore, platelets sti-mulated with a combination of collagen and thrombin adhered to immobilized rFVIIa under static conditions. Platelet adhesion was inhibited by treatment with O-sialoglycoprotein endopeptidase, which specifically cleaves GPIbα from the platelet surface. In addition, rFVIIa-mediated thrombin generation on the activated platelet surface was inhibited by cleaving GPIbα from its surface. In summary, 3 lines of evidence showed that rFVIIa interacts with the GPIb-IX-V complex, and this interaction enhanced tissue factor-independent thrombin generation mediated by rFVIIa on the activated platelet surface. The rFVIIa-GPIbα interaction could contribute to cessation of bleeding after administration of rFVIIa to patients with bleeding disorders.
A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial)
Authors: Mead Graham M. , Barrans Sharon L. , Qian Wendi , Walewski Jan , Radford John A. , Wolf Max , Clawson Simon M. , Stenning Sally P. , Yule Claire L. , Jack Andrew S. 
Published: July 2008

AbstractThis prospective study aimed to develop reproducible diagnostic criteria for sporadic Burkitt lymphoma (BL), applicable to routine practice, and to evaluate the efficacy of dose-modified (dm) CODOX-M/IVAC in patients diagnosed using these criteria. The study was open to patients with an aggressive B-cell lymphoma with an MKI67 fraction approaching 100%. Immunophenotype and fluorescent in situ hybridization (FISH) were used to separate BL from other aggressive B-cell lymphomas. BL was characterized by the presence of a cMYC rearrangement as a sole cytogenetic abnormality occurring in patients with a germinal center phenotype with absence of BCL-2 expression and abnormal TP53 expression. A total of 128 patients were eligible for the study, of whom 58 were considered to have BL and 70 to have diffuse large B-cell lymphoma (DLBCL). There were 110 clinically fit patients who received dmCODOX-M (methotrexate, dose 3 g/m2) with or without IVAC according to risk group. The 2-year progression-free survival was 64% (95% confidence interval [CI] 51%-77%) for BL, 55% (95% CI 42%-66%) for DLBCL, 85% (95% CI 73%-97%) for low risk, and 49% (95% CI 38%-60%) for high-risk patients. The observed differences in outcome and other clinical features validate the proposed diagnostic criteria. Compared with the previous trial LY06 with full-dose methotrexate (6.7 g/m2), there was a reduction in toxicity with comparable outcomes. This study was registered at www.clinicaltrials.gov as NCT00040690.
EVI1activation in blast crisis CML due to juxtaposition to the rare 17q22 partner region as part of a 4-way variant translocation t(9;22)
Authors: De Weer An , Poppe Bruce , Cauwelier Barbara , Carlier Andre , Dierick Jan , Verhasselt Bruno , Philippé Jan , Van Roy Nadine , Speleman Frank 
Published: July 2008

Abstract

Background
Variant translocations t(9;22) occur in 5 to 10% of newly diagnosed CMLs and additional genetic changes are present in 60–80% of patients in blast crisis (BC). Here, we report on a CML patient in blast crisis presenting with a four-way variant t(9;22) rearrangement involving the EVI1 locus.

Methods
Dual-colour Fluorescence In Situ Hybridisation was performed to unravel the different cytogenetic aberrations. Expression levels of EVI1 and BCR/ABL1 were investigated using real-time quantitative RT-PCR.

Results
In this paper we identified a patient with a complex 4-way t(3;9;17;22) which, in addition to BCR/ABL1 gene fusion, also resulted in EVI1 rearrangement and overexpression.

Conclusion
This report illustrates how a variant t(9;22) translocation can specifically target a second oncogene most likely contributing to the more aggressive phenotype of the disease. Molecular analysis of such variants is thus warranted to understand the phenotypic consequences and to open the way for combined molecular therapies in order to tackle the secondary oncogenic effect which is unresponsive to imatinib treatment.
The effect on the extracellular matrix of the deep fascia in response to leg lengthening
Authors: Wang Hai-Qiang , Li Xin-Kui , Wu Zi-Xiang , Wei Yi-Yong , Luo Zhuo-Jing 
Published: July 2008

AbstractBackgroundWhereas the alterations of diverse tissues in cellular and molecular levels have been investigated during leg lengthening via microscopy and biochemical studies, little is known about the response of deep fascia. This study aims to investigate the changes of the extracellular matrix in deep fascia in response to leg lengthening.MethodsAnimal model of leg lengthening was established in New Zealand white rabbits. Distraction was initiated at a rate of 1 mm/day and 2 mm/day in two steps, and preceded until increases of 10% and 20% in the initial length of tibia had been achieved. Alcian blue stain and picrosirius-polarization method were used for the study of the extracellular matrix of deep fascia samples. Leica DM LA image analysis system was used to investigate the quantitative changes of collagen type I and III.ResultsAlcian blue stain showed that glycosaminoglycans of fascia of each group were composed of chondroitin sulphate and heparin sulphate, but not of keratan sulphate. Under the polarization microscopy, the fascia consisted mainly of collagen type I. After leg lengthening, the percentage of collagen type III increased. The most similar collagen composition of the fascia to that of the normal fascia was detected at a 20% increase in tibia length achieved via a distraction rate of 1 mm/d.ConclusionThe changes in collagen distribution and composition occur in deep fascia during leg lengthening. Although different lengthening schemes resulted in varied matrix changes, the most comparable collagen composition to be demonstrated under the scheme of a distraction rate of 1 mm/day and 20% increase in tibia length. Efficient fascia regeneration is initiated only in certain combinations of the leg load parameters including appropriate intensity and duration time, e.g., either low density distraction that persist a relatively short time or high distraction rates.
Modulation of microtubule assembly by the HIV-1 Tat protein is strongly dependent on zinc binding to Tat
Authors: Egelé Caroline , Barbier Pascale , Didier Pascal , Piémont Etienne , Allegro Diane , Chaloin Olivier , Muller Sylviane , Peyrot Vincent , Mély Yves 
Published: July 2008

Abstract

Background
During HIV-1 infection, the Tat protein plays a key role by transactivating the transcription of the HIV-1 proviral DNA. In addition, Tat induces apoptosis of non-infected T lymphocytes, leading to a massive loss of immune competence. This apoptosis is notably mediated by the interaction of Tat with microtubules, which are dynamic components essential for cell structure and division. Tat binds two Zn2+ ions through its conserved cysteine-rich region in vitro, but the role of zinc in the structure and properties of Tat is still controversial.

Results
To investigate the role of zinc, we first characterized Tat apo- and holo-forms by fluorescence correlation spectroscopy and time-resolved fluorescence spectroscopy. Both of the Tat forms are monomeric and poorly folded but differ by local conformational changes in the vicinity of the cysteine-rich region. The interaction of the two Tat forms with tubulin dimers and microtubules was monitored by analytical ultracentrifugation, turbidity measurements and electron microscopy. At 20°C, both of the Tat forms bind tubulin dimers, but only the holo-Tat was found to form discrete complexes. At 37°C, both forms promoted the nucleation and increased the elongation rates of tubulin assembly. However, only the holo-Tat increased the amount of microtubules, decreased the tubulin critical concentration, and stabilized the microtubules. In contrast, apo-Tat induced a large amount of tubulin aggregates.

Conclusion
Our data suggest that holo-Tat corresponds to the active form, responsible for the Tat-mediated apoptosis.
A broad spectrum, one-step reverse-transcription PCR amplification of the neuraminidase gene from multiple subtypes of influenza A virus
Authors: Alvarez Alejandra Castillo , Brunck Marion EG , Boyd Victoria , Lai Richard , Virtue Elena , Chen Wenbin , Bletchly Cheryl , Heine Hans G , Barnard Ross 
Published: July 2008

Abstract

Background
The emergence of high pathogenicity strains of Influenza A virus in a variety of human and animal hosts, with wide geographic distribution, has highlighted the importance of rapid identification and subtyping of the virus for outbreak management and treatment. Type A virus can be classified into subtypes according to the viral envelope glycoproteins, hemagglutinin and neuraminidase. Here we review the existing specificity and amplification of published primers to subtype neuraminidase genes and describe a new broad spectrum primer pair that can detect all 9 neuraminidase subtypes.

Results
Bioinformatic analysis of 3,337 full-length influenza A neuraminidase segments in the NCBI database revealed semi-conserved regions not previously targeted by primers. Two degenerate primers with M13 tags, NA8F-M13 and NA10R-M13 were designed from these regions and used to generate a 253 bp cDNA product. One-step RT-PCR testing was successful in 31/32 (97%) cases using a touchdown protocol with RNA from over 32 different cultured influenza A virus strains representing the 9 neuraminidase subtypes. Frozen blinded clinical nasopharyngeal aspirates were also assayed and were mostly of subtype N2. The region amplified was direct sequenced and then used in database searches to confirm the identity of the template RNA. The RT-PCR fragment generated includes one of the mutation sites related to oseltamivir resistance, H274Y.

Conclusion
Our one-step RT-PCR assay followed by sequencing is a rapid, accurate, and specific method for detection and subtyping of different neuraminidase subtypes from a range of host species and from different geographical locations.
The Last Universal Common Ancestor: emergence, constitution and genetic legacy of an elusive forerunner
Authors: Glansdorff Nicolas , Xu Ying , Labedan Bernard 
Published: July 2008

AbstractBackgroundSince the reclassification of all life forms in three Domains (Archaea, Bacteria, Eukarya), the identity of their alleged forerunner (Last Universal Common Ancestor or LUCA) has been the subject of extensive controversies: progenote or already complex organism, prokaryote or protoeukaryote, thermophile or mesophile, product of a protracted progression from simple replicators to complex cells or born in the cradle of "catalytically closed" entities? We present a critical survey of the topic and suggest a scenario.ResultsLUCA does not appear to have been a simple, primitive, hyperthermophilic prokaryote but rather a complex community of protoeukaryotes with a RNA genome, adapted to a broad range of moderate temperatures, genetically redundant, morphologically and metabolically diverse. LUCA's genetic redundancy predicts loss of paralogous gene copies in divergent lineages to be a significant source of phylogenetic anomalies, i.e. instances where a protein tree departs from the SSU-rRNA genealogy; consequently, horizontal gene transfer may not have the rampant character assumed by many. Examining membrane lipids suggest LUCA hadsn1,2ester fatty acid lipids from which Archaea emerged from the outset as thermophilic by "thermoreduction," with a new type of membrane, composed ofsn2,3ether isoprenoid lipids; this occurred without major enzymatic reconversion. Bacteria emerged by reductive evolution from LUCA and some lineages further acquired extreme thermophily by convergent evolution. This scenario is compatible with the hypothesis that the RNA to DNA transition resulted from different viral invasions as proposed by Forterre. Beyond the controversy opposing "replication first" to metabolism first", the predictive arguments of theories on "catalytic closure" or "compositional heredity" heavily weigh in favour of LUCA's ancestors having emerged as complex, self-replicating entities from which a genetic code arose under natural selection.ConclusionLife was born complex and the LUCA displayed that heritage. It had the "body "of a mesophilic eukaryote well before maturing by endosymbiosis into an organism adapted to an atmosphere rich in oxygen. Abundant indications suggest reductive evolution of this complex and heterogeneous entity towards the "prokaryotic" Domains Archaea and Bacteria. The word "prokaryote" should be abandoned because epistemologically unsound.ReviewersThis article was reviewed by Anthony Poole, Patrick Forterre, and Nicolas Galtier.
Accumulation of GC donor splice signals in mammals
Authors: Churbanov Alexander , Winters-Hilt Stephen , Koonin Eugene V , Rogozin Igor B 
Published: July 2008

Abstract

Abstract
The GT dinucleotide in the first two intron positions is the most conserved element of the U2 donor splice signals. However, in a small fraction of donor sites, GT is replaced by GC. A substantial enrichment of GC in donor sites of alternatively spliced genes has been observed previously in human, nematode and Arabidopsis, suggesting that GC signals are important for regulation of alternative splicing. We used parsimony analysis to reconstruct evolution of donor splice sites and inferred 298 GT > GC conversion events compared to 40 GC > GT conversion events in primate and rodent genomes. Thus, there was substantive accumulation of GC donor splice sites during the evolution of mammals. Accumulation of GC sites might have been driven by selection for alternative splicing.

Reviewers
This article was reviewed by Jerzy Jurka and Anton Nekrutenko. For the full reviews, please go to the Reviewers' Reports section.
Characterization of seed nuclei in glucagon aggregation using light scattering methods and field-flow fractionation
Authors: Hoppe Cindy C , Nguyen Lida T , Kirsch Lee E , Wiencek John M 
Published: July 2008

Abstract

Background
Glucagon is a peptide hormone with many uses as a therapeutic agent, including the emergency treatment of hypoglycemia. Physical instability of glucagon in solution leads to problems with the manufacture, formulation, and delivery of this pharmaceutical product. Glucagon has been shown to aggregate and form fibrils and gels in vitro. Small oligomeric precursors serve to initiate and nucleate the aggregation process. In this study, these initial aggregates, or seed nuclei, are characterized in bulk solution using light scattering methods and field-flow fractionation.

Results
High molecular weight aggregates of glucagon were detected in otherwise monomeric solutions using light scattering techniques. These aggregates were detected upon initial mixing of glucagon powder in dilute HCl and NaOH. In the pharmaceutically relevant case of acidic glucagon, the removal of aggregates by filtration significantly slowed the aggregation process. Field-flow fractionation was used to separate aggregates from monomeric glucagon and determine relative mass. The molar mass of the large aggregates was shown to grow appreciably over time as the glucagon solutions gelled.

Conclusion
The results of this study indicate that initial glucagon solutions are predominantly monomeric, but contain small quantities of large aggregates. These results suggest that the initial aggregates are seed nuclei, or intermediates which catalyze the aggregation process, even at low concentrations.
At-TAX: a whole genome tiling array resource for developmental expression analysis and transcript identification in Arabidopsis thaliana
Authors: Laubinger Sascha , Zeller Georg , Henz Stefan R , Sachsenberg Timo , Widmer Christian K , Naouar Naïra , Vuylsteke Marnik , Schölkopf Bernhard , Rätsch Gunnar , Weigel Detlef 
Published: July 2008

AbstractGene expression maps for model organisms, including Arabidopsis thaliana, have typically been created using gene-centric expression arrays. Here, we describe a comprehensive expression atlas, Arabidopsis thaliana Tiling Array Express (At-TAX), which is based on whole-genome tiling arrays. We demonstrate that tiling arrays are accurate tools for gene expression analysis and identified more than 1,000 unannotated transcribed regions. Visualizations of gene expression estimates, transcribed regions, and tiling probe measurements are accessible online at the At-TAX homepage.
Induction of human CD4+ regulatory T cells by mycophenolic acid-treated dendritic cells
Authors: Lagaraine Christine , Lemoine Roxane , Baron Christophe , Nivet Hubert , Velge-Roussel Florence , Lebranchu Yvon 
Published: July 2008

AbstractDepending on their degree of maturation, costimulatory molecule expression, and cytokine secretion, dendritic cells (DC) can induce immunity or tolerance. DC treated with mycophenolic acid during their maturation (MPA-DC) have a regulatory phenotype and may therefore provide a new approach to induce allograft tolerance. Purified CD4+ T cells stimulated in a human in vitro model of mixed culture by allogeneic MPA-DC displayed much weaker proliferation than T cells activated by mature DC and were anergic. This hyporesponsiveness was alloantigen-specific. Interestingly, T cells stimulated by MPA-DC during long-term coculture in four 7-day cycles displayed potent, suppressive activity, as revealed by marked inhibition of the proliferation of naive and preactivated control T cells. These regulatory T cells (Tregs) appeared to have antigen specificity and were contact-dependent. Tregs induced by MPA-DC were CD25+glucocorticoid-induced TNFR+CTLA-4+CD95+, secreted IL-5 and large amounts of IL-10 and TGF-β, and displayed enhanced forkhead box p3 expression. These results obtained in vitro demonstrate that human MPA-DC can induce allospecific Tregs that may be exploited in cell therapy to induce allograft tolerance.