bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diplomatic Cultures: Comparing Russia and the West in Terms of a 'Modern Model of Diplomacy'
Authors: Zonova Tatiana 
Published: June 2007

AbstractDiplomacy is an international institution, although national and regional diplomatic services keep their own intrinsic identity. Existing differences occasionally interfere with mutual understanding as an essential requirement for overcoming today's instability. Comparative analysis of Western and Russian diplomacy enables deeper insight into some essential reasons for existing differences. The modern model of diplomacy was formed because of the Renaissance, which was characterized by a process of secularization. In Russia this process was delayed by the Byzantine tradition of 'symphony'. From Tsar Peter's era, however, a gradual rapprochement can be observed between the two systems of diplomacy — Western and Russian. However, within new parameters, the ghost of Byzantium appeared now and again. Even under Soviet-imposed atheism, diplomacy was viewed as a tool for a new Messianic universalism (as it was in pre-Petrine times), expressed in terms of 'proletarian internationalism'. New and dramatic events placed an urgent need for a qualitatively new type of diplomacy on the agenda: the European experience, with its emphasis on a solid juridical basis, rationalism and human rights; and the Russian experience, with its universalism that is attentive to existential problems and traditional values. Diplomacy of the future should be based on a synthesis of both European and Russian historical experiences.
Security through Disarmament: The Story of the Weapons of Mass Destruction Commission
Authors: Rydell Randy 
Published: June 2007

AbstractThe world has been trying to eliminate weapons of mass destruction (WMD) — nuclear, biological and chemical arms — for over half a century. Yet many such weapons remain, and progress in nuclear disarmament has been especially disappointing. The chronic failure to achieve agreed WMD disarmament mandates has prompted the creation of several independent international commissions to find some solutions. The WMD Commission created by Sweden in late 2003 was the latest such venture, and its 2006 report has received international acclaim. Chaired by Hans Blix, the Commission covered disarmament, non-proliferation and counter-terrorism issues, and did so from a variety of policy dimensions, from unilateral action through fully multilateral cooperation. Written by a member of the Commission's secretariat staff, this article tells the story of the Commission: how it conducted its work, what it proposed and what impacts it has had — and may yet have — in revitalizing WMD disarmament efforts.
Generation of FGF reporter transgenic zebrafish and their utility in chemical screens
Authors: Molina Gabriela A , Watkins Simon C , Tsang Michael 
Published: June 2007

Abstract

Background
Fibroblast Growth Factors (FGFs) represent a large family of secreted proteins that are required for proper development and physiological processes. Mutations in mouse and zebrafish FGFs result in abnormal embryogenesis and lethality. A key to understanding the precise role for these factors is to determine their spatial and temporal activity during embryogenesis.

Results
Expression of Dual Specificity Phosphatase 6 (dusp6, also known as Mkp3) is controlled by FGF signalling throughout development. The Dusp6 promoter was isolated from zebrafish and used to drive expression of destabilized green fluorescent protein (d2EGFP) in transgenic embryos (Tg(Dusp6:d2EGFP)). Expression of d2EGFP is initiated as early as 4 hours post-fertilization (hpf) within the future dorsal region of the embryo, where fgf3 and fgf8 are initially expressed. At later stages, d2EGFP is detected within structures that correlate with the expression of Fgf ligands and their receptors. This includes the mid-hindbrain boundary (MHB), pharyngeal endoderm, otic vesicle, hindbrain, and Kupffer's vesicle. The expression of d2EGFP is under the control of FGF signalling as treatment with FGF Receptor (FGFR) inhibitors results in the suppression of d2EGFP expression. In a pilot screen of commercially available small molecules we have evaluated the effectiveness of the transgenic lines to identify specific FGF inhibitors within the class of indolinones. These compounds were counter screened with the transgenic line Tg(Fli1:EGFP)

y1, that serves as an indirect read-out for Vascular Endothelial Growth Factor (VEGF) signalling in order to determine the specificity between related receptor tyrosine kinases (RTKs). From these assays it is possible to determine the specificity of these indolinones towards specific RTK signalling pathways. This has enabled the identification of compounds that can block specifically the VEGFR or the FGFR signalling pathway.

Conclusion
The generation of transgenic reporter zebrafish lines has allowed direct visualization of FGF signalling within the developing embryo. These FGF reporter transgenic lines provide a tool to screen for specific compounds that can distinguish between two conserved members of the RTK family.
Uptake and metabolism of ciclesonide and retention of desisobutyryl-ciclesonide for up to 24 hours in rabbit nasal mucosa
Authors: Sato Hideyuki , Nave Ruediger , Nonaka Takashi , Yoshihisa Nishibe , Atsuhiro Nagano , Mochizuki Tsutomu , Takahama Shigehiro , Kondo Shiro , Wingertzahn Mark 
Published: June 2007

Abstract

Background
The nasal tissue uptake and metabolism of ciclesonide, a new-generation corticosteroid under investigation for treatment of allergic rhinitis, to its active metabolite, desisobutyryl-ciclesonide (des-CIC), was evaluated when administered to rabbits in a hypotonic versus an isotonic ciclesonide suspension. Nasal mucosa extracts from normal Japanese white rabbits were evaluated by high-performance liquid chromatography with tandem mass spectrometry detection after a single 143-μg dose of ciclesonide. Retention and formation of fatty acid conjugates of des-CIC were also measured in nasal mucosa extracts postadministration of a hypotonic ciclesonide suspension (143-μg single dose).

Results
Versus an isotonic suspension, the hypotonic suspension achieved higher concentrations of des-CIC (5.6-fold, 11.4-fold, and 13.4-fold; p < 0.05 for all) and ciclesonide (25.3-fold, 34.2-fold [p = not significant], and 16-fold [p < 0.05]) at 30, 120, and 240 min postadministration. Additionally, when administered via a hypotonic suspension, des-CIC was retained up to 24 h postadministration (45.46 pmol/g tissue). Highest concentration of major fatty acid ester conjugate, des-CIC-oleate, was detected in nasal mucosa at 8 h postadministration.

Conclusion
These data suggest that a hypotonic ciclesonide suspension provides higher intracellular concentrations of des-CIC up to 24 h, thereby providing a rationale for investigation of ciclesonide as a convenient once-daily nasal spray for treatment of allergic rhinitis.
Imported Crimean-Congo hemorrhagic fever cases in Istanbul
Authors: Midilli Kenan , Gargılı Ayşen , Ergonul Onder , Şengöz Gönül , Ozturk Recep , Bakar Mehmet , Jongejan Frans 
Published: June 2007

Abstract
We described a series of imported cases of Crimean-Congo Hemorrhagic Fever (CCHF) in Istanbul and investigated the genetic diversity of the virus. All the suspected cases of CCHF, who were applied to the health centers in Istanbul, were screened for CCHF virus (CCHFv) infection by using semi-nested Polymerase Chain Reaction (PCR) following RT-PCR. Simultaneous blood samples were also sent to the national reference laboratory in Ankara for serologic investigation. In 10 out of 91 patients, CCHFv was detected by PCR, and among 9 out of 10, anti-CCHFv IgM antibodies were also positive. Clinical features were characterized by fever, myalgia, and hemorrhage. The levels of liver enzymes, creatinine phosphokinase, and lactate dehydrogenase were elevated, and bleeding markers were prolonged. All the cases were treated with ribavirin. There was no fatal case. All the strains clustered within the same group as other Europe/Turkey isolates.
Reconstruction of the kinetochore: a prelude to meiosis
Authors: Asakawa Haruhiko , Haraguchi Tokuko , Hiraoka Yasushi 
Published: June 2007

Abstract
In eukaryotic organisms, chromosomes are spatially organized within the nucleus. Such nuclear architecture provides a physical framework for the genetic activities of chromosomes, and changes its functional organization as the cell moves through the phases of the cell cycle. The fission yeast Schizosaccharomyces pombe provides a striking example of nuclear reorganization during the transition from mitosis to meiosis. In this organism, centromeres remain clustered at the spindle-pole body (SPB; a centrosome-equivalent structure in fungi) during mitotic interphase. In contrast, during meiotic prophase, centromeres dissociate from the SPB and telomeres cluster to the SPB. Recent studies revealed that this repositioning of chromosomes is regulated by mating pheromone signaling. Some centromere proteins disappear from the centromere in response to mating pheromone, leading to dissociation of centromeres from the SPB. Interestingly, mating pheromone signaling is also required for monopolar orientation of the kinetochore which is crucial for proper segregation of sister chromatids during meiosis. When meiosis is induced in the absence of mating pheromone signaling, aberrant chromosome behaviors are observed: the centromere proteins remain at the centromere; the centromere remains associated with the SPB; and sister chromatids segregate precociously in the first meiotic division. These aberrant chromosome behaviors are all normalized by activating the mating pheromone signaling pathway. Thus, action of mating pheromone on the centromere is important for coherent behavior of chromosomes in meiosis. Here we discuss repositioning and reconstruction of the centromere during the transition from mitosis to meiosis, and highlight its significance for proper progression of meiosis.
Risk factors for breast cancer characterized by the estrogen receptor alpha A908G (K303R) mutation
Authors: Conway Kathleen , Parrish Eloise , Edmiston Sharon N , Tolbert Dawn , Tse Chiu-Kit , Moorman Patricia , Newman Beth , Millikan Robert C 
Published: June 2007

Abstract
Introduction
Estrogen is important in the development of breast cancer, and its biological effects are mediated primarily through the two estrogen receptors alpha and beta. A point mutation in the estrogen receptor alpha gene, ESR1, referred to as A908G or K303R, was originally identified in breast hyperplasias and was reported to be hypersensitive to estrogen. We recently detected this mutation at a low frequency of 6% in invasive breast tumors of the Carolina Breast Cancer Study (CBCS).

Methods
In this report, we evaluated risk factors for invasive breast cancer classified according to the presence or absence of the ESR1 A908G mutation in the CBCS, a population-based case-control study of breast cancer among younger and older white and African-American women in North Carolina. Of the 653 breast tumors evaluated, 37 were ESR1 A908G mutation-positive and 616 were mutation-negative.

Results
ESR1 A908G mutation-positive breast cancer was significantly associated with a first-degree family history of breast cancer (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.15 to 6.28), whereas mutation-negative breast cancer was not. Comparison of the two case subgroups supported this finding (OR = 2.65, 95% CI = 1.15 to 6.09). There was also the suggestion that longer duration of oral contraceptive (OC) use (OR = 3.73, 95% CI = 1.16 to 12.03; Ptrend = 0.02 for use of more than 10 years) and recent use of OCs (OR = 3.63, 95% CI = 0.80 to 16.45; Ptrend = 0.10 for use within 10 years) were associated with ESR1 A908G mutation-positive breast cancer; however, ORs for comparison of the two case subgroups were not statistically significant. Hormone replacement therapy use was inversely correlated with mutation-negative breast cancer, but the effect on mutation-positive cancer was unclear due to the small number of postmenopausal cases whose tumors carried the mutation. Mutation-negative breast cancer was associated with several reproductive factors, including younger age at menarche (OR = 1.46, 95% CI = 1.09 to 1.94) and greater total estimated years of ovarian function (OR = 1.82, 95% CI = 1.21 to 2.74).

Conclusion
These preliminary results suggest that OCs may interact with the ESR1 A908G mutant receptor to drive the development of some breast tumors.
Red blood cell transfusions and the risk of acute respiratory distress syndrome among the critically ill: a cohort study
Authors: Zilberberg Marya D , Carter Chureen , Lefebvre Patrick , Raut Monika , Vekeman Francis , Duh Mei Sheng , Shorr Andrew F 
Published: June 2007

Abstract
Introduction
Recent data indicate that transfusion of packed red blood cells (pRBCs) may increase the risk for the development of acute respiratory distress syndrome (ARDS) in critically ill patients. Uncertainty remains regarding the strength of this relationship.

Methods
To quantify the association between transfusions and intensive care unit (ICU)-onset ARDS, we performed a cohort study within Crit, a multicenter, prospective, observational study of transfusion practice in the ICU which enrolled 4,892 critically ill patients in 284 ICUs in the United States. Diagnostic criteria for ARDS were prospectively defined, and we focused on subjects without ARDS at admission. The development of ARDS in the ICU served as the primary endpoint.

Results
Among the 4,730 patients without ARDS at admission, 246 (5.2%) developed ARDS in the ICU. At baseline, ARDS cases were younger, more likely to be in a surgical ICU, and more likely to be admitted with pneumonia or sepsis than controls without ARDS. Cases also were more likely to have a serum creatinine of greater than 2.0 mg/dl (23% versus 18%) and a serum albumin of less than or equal to 2.3 g/dl (54% versus 30%) and were more severely ill upon ICU admission as measured by either the APACHE II (Acute Physiology and Chronic Health Evaluation II) or SOFA (Sequential Organ Failure Assessment) score (p < 0.05 for all). Sixty-seven percent and 42% of cases and controls, respectively, had exposure to pRBC transfusions (p < 0.05), and the unadjusted odds ratio (OR) of developing ARDS in transfused patients was 2.74 (95% confidence interval [CI], 2.09 to 3.59; p < 0.0001) compared to those never transfused. After age, baseline severity of illness, admitting diagnosis, and process-of-care factors were adjusted for, the independent relationship between pRBC transfusions and ICU-onset ARDS remained significant (adjusted OR, 2.80; 95% CI, 1.90 to 4.12; p < 0.0001).

Conclusion
Development of ARDS after ICU admission is common, occurring in approximately 5% of critically ill patients. Transfusion of pRBCs is independently associated with the development of ARDS in the ICU.
A functional map of NFκB signaling identifies novel modulators and multiple system controls
Authors: Halsey Thomas A , Yang Longlong , Walker John R , Hogenesch John B , Thomas Russell S 
Published: June 2007

Abstract
Background
The network of signaling pathways that leads to activation of the NFκB transcription factors is a branched structure with different inputs and cross-coupling with other signaling pathways. How these signals are integrated to produce specific, yet diverse responses is not clearly understood. To identify the components and structural features of the NFκB network, a series of cell-based, genomic screens was performed using a library of approximately 14,500 full-length genes.

Results
A total of 154 positive and 88 negative modulators of NFκB signaling were identified. Using a series of dominant-negative constructs and functional assays, these modulators were mapped to the known NFκB signaling cascade. Most of the positive modulators acted upstream of the IκB kinase complex, supporting previous observations that the IκB kinases represent the primary point of convergence in the network. A number of negative modulators were localized downstream of the IκB kinase β (IKBKB) subunit, suggesting that they form an additional layer of negative control within the system. The expression of the modulators at the RNA level was distributed disproportionately across tissues, providing flexibility in network structure, and the number of positive and negative modulators present in a given tissue was highly correlated, suggesting that positive and negative regulation is balanced at the tissue level.

Conclusion
The relative locations of the modulators are consistent with an hourglass structure for the NFκB network that is characteristic of robust systems. The tissue distribution of the modulators and downstream location of the negative modulators serve as layers of control within the system that allow differential responses to different stimuli.
Fibrinogen is localized on dark zone follicular dendritic cells in vivo and enhances the proliferation and survival of a centroblastic cell line in vitro
Authors: Lefevre Eric A , Hein Wayne R , Stamataki Zania , Brackenbury Louise S , Supple Emma A , Hunt Lawrence G , Monaghan Paul , Borhis Gwenoline , Richard Yolande , Charleston Bryan 
Published: June 2007

AbstractFollicular dendritic cells (FDC) in the germinal centers (GC) of secondary lymphoid organs increase the survival and proliferation of antigen-stimulated B cells and are pivotal for the affinity maturation of an antibody response and for maintenance of B cell immunological memory. The dark zone (DZ) and the light zone (LZ) constitute distinct areas of the GC containing different subtypes of FDC as identified by their morphology and phenotype. Until now, most available FDC-specific reagents identify LZ FDC, and there are no reagents recognizing DZ FDC specifically. Here, we report a new mAb, D46, which stains FDC specifically in the DZ of bovine and ovine GC within the secondary follicles. We identify its ligand as bovine fibrinogen, and using commercially available anti-human fibrinogen antibodies, show that this inflammatory protein is also present on DZ FDC of human GC within palatine tonsils. In vitro, the addition of exogenous fibrinogen stimulates the proliferation and survival of BCR-stimulated L3055 cells, which constitute a clonal population of centroblastic cells and retain important features of normal GC B cells. Together, our results suggest that fibrinogen localized on DZ FDC could support the extensive proliferation and survival of GC B cells within the DZ in vivo.
Distinct approaches to investigate the importance of the murine 4-1BB–4-1BBL interaction in the antibody response toStreptococcus pneumoniae
Authors: Moens Leen , Jeurissen Axel , Mittler Robert S , Wuyts Greet , Michiels George , Boon Louis , Ceuppens Jan L , Bossuyt Xavier 
Published: June 2007

AbstractProtection against infection with Streptococcus pneumoniae is based mainly on the generation of antibodies to the pneumococcal capsular polysaccharides (caps-PS). Although caps-PS are considered thymus-independent antigens, there is a growing body of evidence that T lymphocytes and costimulatory molecules are involved in the regulation of the antibody response to caps-PS. We investigated whether the interaction between 4-1BB and 4-1BB ligand (4-1BBL) is involved in the modulation of the antibody response to caps-PS after immunization with Pneumovax® or with intact heat-killed S. pneumoniae. Treatment with agonistic anti-4-1BB mAb, which mimics engagement of 4-1BB by 4-1BBL, had no effect on the IgG and IgM immune response to caps-PS (Serotype 3) after immunization with Pneumovax or with S. pneumoniae Serotype 3. However, anti-4-1BB treatment strongly inhibited the IgG response to pneumococcal surface protein A (PspA). By contrast, the IgG anti-caps-PS (Serotype 3) antibody response was reduced strongly in 4-1BBL−/− mice immunized with S. pneumoniae Serotype 3. The IgG anti-PspA antibody response in the 4-1BB−/− mice was comparable with the immune response in the wild-type mice. We conclude that distinct pathways are involved in the humoral antibody response to pneumococcal antigens, depending on the nature of the antigen and the context in which the different antigens are presented. The 4-1BB–4-1BBL interaction is not involved in the antibody response to soluble caps-PS. The influence of the 4-1BB–4-1BBL interaction in the immune reaction to S. pneumoniae Serotype 3 depends on the experimental system used.
Association between a C/T Polymorphism in Exon 33 of the Thyroglobulin Gene Is Associated with Relapse of Graves’ Hyperthyroidism after Antithyroid Withdrawal in Taiwanese
Authors: Hsiao Jeng-Yueh , Hsieh Ming-Chia , Tien Kai-Jen , Hsu Shih-Chie , Shin Shyi-Jang , Lin Shiu-Ru 
Published: June 2007

Abstract
Context: Graves’ disease (GD) is an autoimmune disorder with genetic predisposition. The thyroglobulin (Tg) is a major autoantigen for GD. The human Tg gene polymorphism has specific features that make it important in GD.
Objective: This study investigated whether Tg single nucleotide polymorphisms (SNPs) relate to GD development in a Taiwanese population.
Design and Setting: This was a case-control association study.
Patients and Main Outcome Measures: We enrolled 215 Taiwanese patients with GD and 141 controls from the Endocrine Clinic of Kaohsiung Medical University Chung-Ho Memorial Hospital. This study investigated the association between gene polymorphism and relapse of hyperthyroidism after medication was discontinued in three GD patient groups and a control group. We also compared clinical and laboratory data obtained from patients with the three different genotypes with the three different Tg SNPs (E10SNP158, E12SNP, and E33SNP).
Results: We found a significant increase in the T/T genotype of E33SNP compared with the control group (P &lt; 0.001). We also found the E33SNP C/C genotype of the Tg gene was strongly associated with a subgroup of GD patients who were also characterized as having a higher relapse rate, significantly higher levels of persisting TSH-receptor antibody at the end of treatment, a higher frequency in smoking, and a higher incidence of ophthalmopathy (P &lt; 0.05).
Conclusions: This study showed that Taiwanese patients with the C/C genotype of E33SNP, smoking, ophthalmopathy, and positive TSH-receptor antibodies at the end of the treatment were more likely to have a relapse of Graves’ hyperthyroidism after antithyroid medication is withdrawn.