bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody profiles for the diagnosis of antiphospholipid syndrome
Authors: Biasiolo Alessandra , Pegoraro Cinzia , Cucchini Umberto , Noventa Franco , Iliceto Sabino , Pengo Vittorio 
Published: May 2005

SummaryAmong the so called‘antiphospholipid antibodies’, the presence of Lupus Anticoagulant (LA) is associated with thrombosis-related events and defines the antiphospholipid syndrome. The role of anti-cardiolipin (aCL) antibodies and anti-human β2-glycoprotein I (aβ2GPI) antibodies is less striking. Since the problem of standardization for these tests is far from resolved, we evaluated whether the combination of results (antiphospholipid laboratory profiles) could help to better classify these patients. Over a 6-year period, 618 consecutive subjects (55% of whom had previous documented thrombosis-related events) were referred to our clinic for Antiphospholipid antibody detection. LA was detected according to internationally accepted recommendations. ACL and aβ2GPI antibodies were detected by Enzyme-Linked-Immunosorbent Assay (ELISA). Patients’ records were reviewed for the presence of previous thromboembolic events or obstetric complications according to Sapporo’s clinical criteria for the diagnosis of antiphospholipid syndrome (APS) and each patient underwent a physical examination. When individual tests were considered in a multivariate analysis which took into account age, gender, the presence of SLE or other autoimmune diseases and established risk factors for venous and arterial thromboembolism, LA (Odds Ratio 4.4, Confidence Interval 1.5–13.3) and aβ2GPI antibodies (Odds Ratio 2.9, Confidence Interval 1.1–7.5) but not aCL antibodies (Odds Ratio 1.2, Confidence Interval 0.5–2.7) were found to be independent risk factors for thrombosis-related events. When antiphospholipid antibody profiles instead of individual test positivity were analyzed in the above mentioned model, triple positivity resulted a strong independent risk factor (Odds Ratio 33.3, Confidence Interval 7.0–157.6), retaining its significance when the association with venous or arterial thromboembolism was considered. Double positivity with negative LA was close to significance for thrombosis-related events (Odds Ratio 2.2, Confidence Interval1.0–5.2, p=0.056) and highly significant risk factor for obstetric complications (Odds Ratio 10.8, Confidence Interval 2.9–40.8). Other combinations did not reach statistical significance. The mean level of IgG aβ2GPI antibodies was statistically higher in triple positive profile and might account for positive LA. As compared to a single test, the analysis of a complete antiphospholipid antibody profile can better determine patients at risk.
Thrombin activates the p21-activated kinase in pulmonary artery smooth muscle cells
Authors: BelAiba Rachida , Hess John , Kietzmann Thomas , Görlach Agnes 
Published: May 2005

SummaryThe p21-activated serine/threonine kinases (PAK) play an important role in a variety of cellular functions. However, their role in the smooth muscle response to thrombin, which is activated upon vascular injury and promotes vascular remodelling processes, is not resolved. Here we investigated the role of PAK in thrombin signalling and regulation of tissue factor (TF), the activator of the extrinsic coagulation cascade, in pulmonary artery smooth muscle cells (PASMC), the main cell type responsible for vascular remodelling in pulmonary hypertension. PAK was rapidly phosphorylated in response to thrombin. Thrombin and active PAKT423E phosphorylated p38 MAP kinase (p38MAPK), ERK1/2, phosphatidylinositol-dependent kinase-1 (PDK1) and protein kinase B/Akt (PKB) whereas kinase-deficient PAK1 prevented activation of these kinases by thrombin. In addition, kinase-deficient MKK3 inhibited activation of PDK1 and PKB by thrombin. Further, thrombin and active PAK1 induced TF expression and promoter activity while kinase-deficient PAK1 diminished thrombin-induced TF upregulation. Moreover, kinase-deficient MKK3, PDK1 and PKB inhibited thrombin- and PAK-dependent TF expression and promoter activity. Together these findings show that PAK is a critical element of thrombin signalling in PASMC which is involved in the regulation of TF expression by sequentially activating MKK3/p38MAPK, PDK1 and PKB. Thus, PAK may play an important role in promoting vascular remodelling processes in pulmonary hypertension.
Recombinant factor VIIa
Authors: Zaffanello Marco , Veneri Dino , Franchini Massimo 
Published: May 2005

SummaryRecombinant activated factor VII (rFVIIa, Novo Seven®) has been successfully used to treat bleeding episodes in patients with antibodies against coagulation factors VIII and IX. In recent years, rFVIIa has also been employed for the management of uncontrolled bleeding in a number of congenital and acquired haemos-
tatic abnormalities. Based on a literature search, this review examines the current knowledge on therapy with rFVIIa, from the now well-standardized uses to the newer and less well-characterised clinical applications.
Characterisation of blood coagulation factor XIT475I
Authors: Lal Kalpana , Imanaka Yasufumi , Kemball-Cook Geoffrey , Bolton-Maggs Paula , Tuddenham Edward , McVey John 
Published: May 2005

SummaryPCR-SSCP and DNA sequence analysis of a factor XI (FXI) deficient patient (FXI:C 39 U/dL; FXI:Ag 27 U/dL) identified a C to T transition in exon 12 of the FXI gene (F11 c.1521C>T) that predicts the substitution of Thr475 by Ile (FXIT475I) within the serine protease domain of FXI. This mutation destroys a consensus sequence for N-linked glycosylation, N473-Y-T475, known to be utilized in vivo. The FXIT475I variant was generated by site-directed mutagenesis, together with other variants that could help explain the phenotype, and recombinant FXI variants were expressed in Chinese hamster ovary cells. FXI:Ag expression was analysed by Western blot analysis, ELISA and immunocyto-chemical staining. Wild-type FXI:Ag was secreted at high levels, however the mutant (FXIT475I) was secreted very poorly. Substitution of Thr475 by Ala, Pro, Lys or Arg (all of which abolish the glycosylation consensus sequence) also severely reduced the level of secreted FXI:Ag suggesting that glycosylation at Asn473 is required for folding or secretion. Concordant with this hypothesis the conservative substitution of Thr475 by Ser (which preserves the glycosylation consensus sequence) had no effect on FXI secretion. Thr/Ser475 is highly conserved in serine protease domains but the glycosylation site (Asn473) is not. Surprisingly, substitution of Asn473 by Ala (which removes the N-linked glycosylation site) had no effect on the levels of FXI:Ag secreted. In conclusion, although the FXI-T475I mutation destroys an N-linked glycosylation consensus sequence, the cause of failure to secrete FXI is not the loss of a glycosylation site but rather a direct effect of the substitution of this highly conserved residue.
Interannual Variability of the Altimetry-Derived Eddy Field and Surface Circulation in the Extratropical North Atlantic Ocean in 1993–2001
Authors: Volkov Denis L. 
Published: May 2005

Abstract
The distribution of surface eddy kinetic energy (EKE) depicts main oceanic surface circulation features. The interannual variability of EKE and associated geostrophic velocity anomalies in the North Atlantic Ocean were analyzed to describe the variations in oceanic currents between 1993 and 2002. The sea level anomaly maps of the combined TOPEX/Poseidon + ERS-1/2 and TOPEX/Poseidon-alone satellite altimetry data were used to derive EKE. The study focused on the areas of the Gulf Stream extension (GS), North Atlantic Current (NAC), Azores Current (AC), and the northeastern (Rockall Channel and Iceland Basin) and northwestern (Irminger Basin and Labrador Sea) North Atlantic. The interannual variability of the altimetry-derived EKE field in the GS extension area reflected the meridional displacements of the GS core described in earlier studies. The interannual change of EKE in the AC was characterized by high values in 1993–95 followed by lower EKE in subsequent years. The interannual variability of EKE in the NAC area west of the Mid-Atlantic Ridge exhibited an out-of-phase change between the band centered at ∼47°N and two bands on either side centered at ∼43° and ∼50°N. In the Rockall Channel the geostrophic velocity anomalies indicated an intensified northeastward flow in 1993–95 followed by a relaxation in 1996–2000. The EKE band associated with the NAC branch in the Iceland Basin was found to be extended farther west after 1996, possibly following the North Atlantic Oscillation (NAO)-induced shift of the subpolar front. A rise of EKE was observed in the Irminger Basin from 1995 to 1999. This rise may have been associated with large anticyclonic geostrophic velocity anomalies, which indicated significant weakening of the cyclonic circulation in the Irminger Basin after 1996, and/or with possibly intensified eddy generation mechanisms due to the NAO-induced approach of the subpolar front. The interannual change of EKE in the Labrador Sea did not appear to always follow the atmospheric forcing expressed by NAO. Therefore other eddy generation mechanisms in the Labrador Sea can be important.
Mechanisms of Decadal Variability of the Wind-Driven Ocean Circulation
Authors: Hogg Andrew Mc C. , Killworth Peter D. , Blundell Jeffrey R. , Dewar William K. 
Published: May 2005

Abstract
Eddy-resolving quasigeostrophic simulations of wind-driven circulation in a large ocean basin are presented. The results show that strong modes of low-frequency variability arise in many parameter regimes and that the strength of these modes depends upon the presence of inertial recirculations in the flow field. The inertial recirculations arise through advection of anomalous potential vorticity by the western boundary current and are barotropized by the effect of baroclinic eddies in the flow. The mechanism of low-frequency oscillations is explored with reference to previous studies, and it is found that the observed mode can be linked to the gyre mode but is strongly modified by the effect of eddies.
Characterizing Transport between the Surface Mixed Layer and the Ocean Interior with a Forward and Adjoint Global Ocean Transport Model
Authors: Primeau François 
Published: May 2005

Abstract
The theory of first-passage time distribution functions and its extension to last-passage time distribution functions are applied to the problem of tracking the movement of water masses to and from the surface mixed layer in a global ocean general circulation model. The first-passage time distribution function is used to determine in a probabilistic sense when and where a fluid element will make its first contact with the surface as a function of its position in the ocean interior. The last-passage time distribution is used to determine when and where a fluid element made its last contact with the surface. A computationally efficient method is presented for recursively computing the first few moments of the first- and last-passage time distributions by directly inverting the forward and adjoint transport operator. This approach allows integrated transport information to be obtained directly from the differential form of the transport operator without the need to perform lengthy multitracer time integration of the transport equations. The method, which relies on the stationarity of the transport operator, is applied to the time-averaged transport operator obtained from a three-dimensional global ocean simulation performed with an OGCM. With this approach, the author (i) computes surface maps showing the fraction of the total ocean volume per unit area that ventilates at each point on the surface of the ocean, (ii) partitions interior water masses based on their formation region at the surface, and (iii) computes the three-dimensional spatial distribution of the mean and standard deviation of the age distribution of water.
Convection above the Labrador Continental Slope
Authors: Cuny Jérôme , Rhines Peter B. , Schott Friedrich , Lazier John 
Published: May 2005

Abstract
The Labrador Sea is one of the few regions of the World Ocean where deep convection takes place. Several moorings across the Labrador continental slope just north of Hamilton Bank show that convection does take place within the Labrador Current. Mixing above the lower Labrador slope is facilitated by the onshore along-isopycnal intrusions of low-potential-vorticity eddies that weaken the stratification, combined with baroclinic instability that sustains slanted mixing while restratifying the water column through horizontal fluxes. Above the shelf break, the Irminger seawater core is displaced onshore while the stratification weakens with the increase in isopycnal slope. The change in stratification is partially due to the onshore shift of the “classical” Labrador Current, baroclinic instability, and possibly slantwise convection.
Expressivism, Deflationism and Correspondence
Authors: Marino Patricia 
Published: May 2005

AbstractOn an expressivist view, ethical claims are not fact stating; instead they serve the alternative function of expressing our feelings, attitudes and values. On a deflationary view, truth is not a property with a nature to be analyzed, but merely a grammatical device to aid us in endorsing sentences. Views on the relationship between expressivism and deflationism vary widely: they are compatible; they are incompatible; they are a natural pair; they doom one another. Here I explain some of these views, extract some necessary distinctions, and put these to use for understanding expressivism. I argue that contrary to the opinions of some, deflationism doesn’t help with problems of objectivity, knowledge and reasoning in ethics. I suggest alternative expressivist treatments of these problems, and show how expressivism as a metaethical view must have consequences for our ethical lives and beliefs. In particular it must affect the way we deal with ethical consistency—when norms or beliefs conflict—and ethical incompleteness—when ethical questions have no right answer.
Virtue for Pluralists
Authors: Sabl Andrew 
Published: May 2005

AbstractLiberal or democratic virtue theories have successfully spread the idea that liberal democracies cannot flourish unless their citizens have certain qualities of mind and character. Such theories cannot agree, however, on what those qualities are. This article attempts to explain and solve this problem. It proposes distinguishing between core virtues, necessary for the actual survival of liberal democracies, and ideal virtues, which promote “progress” according to a given conception of what liberal democracies ought to be about and which values they should most embody. Beyond this, it portrays the relevant virtues as pluralistic (not everyone need have the same ones) and episodic (different virtues are relevant at different times and under different circumstances). It then applies this framework to some key issues of political action and motivation: acts of loyalty and dissent express different aspects of a common response to moral pluralism, and the virtues of citizens differ fundamentally in origin and nature from those of professional politicians. Finally, it suggests more briefly that questions of civil religion, patriotic mobilization in times of war, civic courage, and selfish versus altruistic motives for public action can profit from being seen in this new way.
GPVI and α2β1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow
Authors: Sarratt Kendra L. , Chen Hong , Zutter Mary M. , Santoro Samuel A. , Hammer Daniel A. , Kahn Mark L. 
Published: May 2005

AbstractThe roles of the 2 major platelet-collagen receptors, glycoprotein VI (GPVI) and integrin α2β1, have been intensely investigated using a variety of methods over the past decade. In the present study, we have used pharmacologic and genetic approaches to study human and mouse platelet adhesion to collagen under flow conditions. Our studies demonstrate that both GPVI and integrin α2β1 play significant roles for platelet adhesion to collagen under flow and that the loss of both receptors completely ablates this response. Intracellular signaling mediated by the cytoplasmic adaptor Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) but not by the transmembrane adaptor linker for activation of T cells (LAT) is critical for platelet adhesion to collagen under flow. In addition, reduced GPVI receptor density results in severe defects in platelet adhesion to collagen under flow. Defective adhesion to collagen under flow is associated with prolonged tail-bleeding times in mice lacking one or both collagen receptors. These studies establish platelet-collagen responses under physiologic flow as the consequence of a close partnership between 2 structurally distinct receptors and suggest that both receptors play significant hemostatic roles in vivo.
A SCID-hu in vivo model of human Waldenström macroglobulinemia
Authors: Tassone Pierfrancesco , Neri Paola , Kutok Jeffery L. , Tournilhac Olivier , Santos Daniel Ditzel , Hatjiharissi Evdoxia , Munshi Vidit , Venuta Salvatore , Anderson Kenneth C. , Treon Steven P. , Munshi Nikhil C. 
Published: May 2005

AbstractThe preclinical evaluation of investigational agents for Waldenström macroglobulinemia (WM) has been limited by the lack of in vivo models that enable the use of explanted patient cells. We describe here a novel in vivo model of human WM in severe combined immunodeficient (SCID) mice implanted with human fetal bone chips (SCID-hu mice) into which WM cells from patient bone marrow are engrafted directly into the human bone marrow (huBM) microenvironment. WM cells in SCID-hu mice produced human monoclonal paraprotein (immunoglobulin M [IgM] and/or κ or λ chain) detectable in mice sera. Immunohistochemical analysis of human bone retrieved from SCID-hu mice showed infiltration with CD20+, IgM+, and monotypic light chain+ lymphoplasmacytic cells. Mast cells were observed to be associated with the infiltrate in these sections. Treatment of SCID-hu mice bearing WM with rituximab induced tumor regression, associated with a decrease in serum paraprotein. This model, therefore, recapitulates the in vivo biology of WM and allows the study of novel investigational drugs targeting WM cells in the huBM milieu. (Blood. 2005;106:1341-1345)
Altered NKG2D function in NK cells induced by chronic exposure to NKG2D ligand–expressing tumor cells
Authors: Coudert Jérôme D. , Zimmer Jacques , Tomasello Elena , Cebecauer Marek , Colonna Marco , Vivier Eric , Held Werner 
Published: May 2005

AbstractNKG2D is an activation receptor that allows natural killer (NK) cells to detect diseased host cells. The engagement of NKG2D with corresponding ligand results in surface modulation of the receptor and reduced function upon subsequent receptor engagement. However, it is not clear whether in addition to modulation the NKG2D receptor complex and/or its signaling capacity is preserved. We show here that the prolonged encounter with tumor cell-bound, but not soluble, ligand can completely uncouple the NKG2D receptor from the intracellular mobilization of calcium and the exertion of cell-mediated cytolysis. However, cytolytic effector function is intact since NKG2D ligand-exposed NK cells can be activated via the Ly49D receptor. While NKG2D-dependent cytotoxicity is impaired, prolonged ligand exposure results in constitutive interferon γ (IFNγ) production, suggesting sustained signaling. The functional changes are associated with a reduced presence of the relevant signal transducing adaptors DNAX-activating protein of 10 kDa (DAP-10) and killer cell activating receptor-associated protein/DNAX-activating protein of 12 kDa (KARAP/DAP-12). That is likely the consequence of constitutive NKG2D engagement and signaling, since NKG2D function and adaptor expression is restored to normal when the stimulating tumor cells are removed. Thus, the chronic exposure to tumor cells expressing NKG2D ligand alters NKG2D signaling and may facilitate the evasion of tumor cells from NK cell reactions. (Blood. 2005;106:1711-1717)
Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes
Authors: Abadie Valérie , Badell Edgar , Douillard Patrice , Ensergueix Danielle , Leenen Pieter J. M. , Tanguy Myriam , Fiette Laurence , Saeland Sem , Gicquel Brigitte , Winter Nathalie 
Published: May 2005

AbstractThe early innate response after Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination is poorly characterized but probably decisive for subsequent protective immunity against tuberculosis. Therefore, we vaccinated mice with fluorescent BCG strains in the ear dorsum, as a surrogate of intradermal vaccination in humans. During the first 3 days, we tracked BCG host cells migrating out of the dermis to the auricular draining lymph nodes (ADLNs). Resident skin dendritic cells (DCs) or macrophages did not play a predominant role in early BCG capture and transport to ADLNs. The main BCG host cells rapidly recruited both in the dermis and ADLNs were neutrophils. Fluorescent green or red BCG strains injected into nonoverlapping sites were essentially sheltered by distinct neutrophils in the ADLN capsule, indicating that neutrophils had captured bacilli in peripheral tissue and transported them to the lymphoid organ. Strikingly, we observed BCG-infected neutrophils in the lumen of lymphatic vessels by confocal microscopy on ear dermis. Fluorescence-labeled neutrophils injected into the ears accumulated exclusively into the ipsilateral ADLN capsule after BCG vaccination. Thus, we provide in vivo evidence that neutrophils, like DCs or inflammatory monocytes, migrate via afferent lymphatics to lymphoid tissue and can shuttle live microorganisms. (Blood. 2005;106: 1843-1850)
Pigs in sequence space: A 0.66X coverage pig genome survey based on shotgun sequencing
Authors: Wernersson Rasmus , Schierup Mikkel H , Jørgensen Frank G , Gorodkin Jan , Panitz Frank , Stærfeldt Hans-Henrik , Christensen Ole F , Mailund Thomas , Hornshøj Henrik , Klein Ami , Wang Jun , Liu Bin , Hu Songnian , Dong Wei , Li Wei , Wong Gane KS , Yu Jun , Wang Jian , Bendixen Christian , Fredholm Merete , Brunak Søren , Yang Huanming , Bolund Lars 
Published: May 2005

Abstract
Background
Comparative whole genome analysis of Mammalia can benefit from the addition of more species. The pig is an obvious choice due to its economic and medical importance as well as its evolutionary position in the artiodactyls.

Results
We have generated ~3.84 million shotgun sequences (0.66X coverage) from the pig genome. The data are hereby released (NCBI Trace repository with center name "SDJVP", and project name "Sino-Danish Pig Genome Project") together with an initial evolutionary analysis.
The non-repetitive fraction of the sequences was aligned to the UCSC human-mouse alignment and the resulting three-species alignments were annotated using the human genome annotation. Ultra-conserved elements and miRNAs were identified. The results show that for each of these types of orthologous data, pig is much closer to human than mouse is. Purifying selection has been more efficient in pig compared to human, but not as efficient as in mouse, and pig seems to have an isochore structure most similar to the structure in human.

Conclusion
The addition of the pig to the set of species sequenced at low coverage adds to the understanding of selective pressures that have acted on the human genome by bisecting the evolutionary branch between human and mouse with the mouse branch being approximately 3 times as long as the human branch. Additionally, the joint alignment of the shot-gun sequences to the human-mouse alignment offers the investigator a rapid way to defining specific regions for analysis and resequencing.