bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fusion proteins comprising annexin V and Kunitz protease inhibitors are highly potent thrombogenic site-directed anticoagulants
Authors: Chen Hsiu-Hui , Vicente Cristina P. , He Li , Tollefsen Douglas M. , Wun Tze-Chein 
Published: January 2005

AbstractThe anionic phospholipid, phosphatidyl-l-serine (PS), is sequestered in the inner layer of the plasma membrane in normal cells. Upon injury, activation, and apoptosis, PS becomes exposed on the surfaces of cells and sheds microparticles, which are procoagulant. Coagulation is initiated by formation of a tissue factor/factor VIIa complex on PS-exposed membranes and propagated through the assembly of intrinsic tenase (factor VIIIa/factor IXa), prothrombinase (factor Va/factor Xa), and factor XIa complexes on PS-exposed activated platelets. We constructed a novel series of recombinant anticoagulant fusion proteins by linking annexin V (ANV), a PS-binding protein, to the Kunitz-type protease inhibitor (KPI) domain of tick anticoagulant protein, an aprotinin mutant (6L15), amyloid β-protein precursor, or tissue factor pathway inhibitor. The resulting ANV-KPI fusion proteins were 6- to 86-fold more active than recombinant tissue factor pathway inhibitor and tick anticoagulant protein in an in vitro tissue factor–initiated clotting assay. The in vivo antithrombotic activities of the most active constructs were 3- to 10-fold higher than that of ANV in a mouse arterial thrombosis model. ANV-KPI fusion proteins represent a new class of anticoagulants that specifically target the anionic membrane-associated coagulation enzyme complexes present at sites of thrombogenesis and are potentially useful as antithrombotic agents.
Tie2Cre-mediated gene ablation defines the stem-cell leukemia gene (SCL/tal1)–dependent window during hematopoietic stem-cell development
Authors: Schlaeger Thorsten M. , Mikkola Hanna K. A. , Gekas Christos , Helgadottir Hildur B. , Orkin Stuart H. 
Published: January 2005

AbstractThe stem-cell leukemia gene (SCL/tal1) is essential for the formation of all blood lineages. SCL is first expressed in mesodermal cells that give rise to embryonic blood cells, and continues to be expressed in fetal and adult hematopoietic stem cells (HSCs). However, SCL is not required for the maintenance of established long-term repopulating (LTR) HSCs in the adult. The time point at which HSC development becomes SCL independent has not been defined. Tyrosine kinase with immunoglobulin and epidermal growth factor homology domains–2 (Tie2) expression appears in hemogenic and vasculogenic sites shortly after SCL. We therefore used the Tie2Cre mouse to inactivate SCL early during embryonic and fetal hematopoiesis. Tie2Cre completely inactivated SCL in yolk sac, the aortagonad-mesonephros (AGM) region, and fetal liver hematopoietic cells and circulating blood cells. However, the fetal liver was colonized by functional LTR-HSCs. Yet SCL remained crucial for proper differentiation of both primitive and definitive red cells and megakaryocytes. These results indicate that the SCL-dependent phase of HSC development ends before Tie2Cre-mediated gene ablation becomes effective.
Graph-representation of oxidative folding pathways
Authors: Ágoston Vilmos , Cemazar Masa , Kaján László , Pongor Sándor 
Published: January 2005

Abstract
Background
The process of oxidative folding combines the formation of native disulfide bond with conformational folding resulting in the native three-dimensional fold. Oxidative folding pathways can be described in terms of disulfide intermediate species (DIS) which can also be isolated and characterized. Each DIS corresponds to a family of folding states (conformations) that the given DIS can adopt in three dimensions.

Results
The oxidative folding space can be represented as a network of DIS states interconnected by disulfide interchange reactions that can either create/abolish or rearrange disulfide bridges. We propose a simple 3D representation wherein the states having the same number of disulfide bridges are placed on separate planes. In this representation, the shuffling transitions are within the planes, and the redox edges connect adjacent planes. In a number of experimentally studied cases (bovine pancreatic trypsin inhibitor, insulin-like growth factor and epidermal growth factor), the observed intermediates appear as part of contiguous oxidative folding pathways.

Conclusions
Such networks can be used to visualize folding pathways in terms of the experimentally observed intermediates. A simple visualization template written for the Tulip package http://www.tulip-software.org/ can be obtained from V.A.
Inter-species horizontal transfer resulting in core-genome and niche-adaptive variation within Helicobacter pylori
Authors: Saunders Nigel J , Boonmee Prawit , Peden John F , Jarvis Stephen A 
Published: January 2005

Abstract
Background
Horizontal gene transfer is central to evolution in most bacterial species. The detection of exchanged regions is often based upon analysis of compositional characteristics and their comparison to the organism as a whole. In this study we describe a new methodology combining aspects of established signature analysis with textual analysis approaches. This approach has been used to analyze the two available genome sequences of H. pylori.

Results
This gene-by-gene analysis reveals a wide range of genes related to both virulence behaviour and the strain differences that have been relatively recently acquired from other sequence backgrounds. These frequently involve single genes or small numbers of genes that are not associated with transposases or bacteriophage genes, nor with inverted repeats typically used as markers for horizontal transfer. In addition, clear examples of horizontal exchange in genes associated with 'core' metabolic functions were identified, supported by differences between the sequenced strains, including: ftsK, xerD and polA. In some cases it was possible to determine which strain represented the 'parent' and 'altered' states for insertion-deletion events. Different signature component lengths showed different sensitivities for the detection of some horizontally transferred genes, which may reflect different amelioration rates of sequence components.

Conclusion
New implementations of signature analysis that can be applied on a gene-by-gene basis for the identification of horizontally acquired sequences are described. These findings highlight the central role of the availability of homologous substrates in evolution mediated by horizontal exchange, and suggest that some components of the supposedly stable 'core genome' may actually be favoured targets for integration of foreign sequences because of their degree of conservation.
Synaptogenesis and outer segment formation are perturbed in the neural retina of Crx mutant mice
Authors: Morrow Eric M , Furukawa Takahisa , Raviola Elio , Cepko Constance L 
Published: January 2005

Abstract
Background
In Leber's congenital amaurosis (LCA), affected individuals are blind, or nearly so, from birth. This early onset suggests abnormal development of the neural retina. Mutations in genes that affect the development and/or function of photoreceptor cells have been found to be responsible in some families. These examples include mutations in the photoreceptor transcription factor, Crx.

Results
A Crx mutant strain of mice was created to serve as a model for LCA and to provide more insight into Crx's function. In this study, an ultrastructural analysis of the developing retina in Crx mutant mice was performed. Outer segment morphogenesis was found to be blocked at the elongation stage, leading to a failure in production of the phototransduction apparatus. Further, Crx-/- photoreceptors demonstrated severely abnormal synaptic endings in the outer plexiform layer.

Conclusions
This is the first report of a synaptogenesis defect in an animal model for LCA. These data confirm the essential role this gene plays in multiple aspects of photoreceptor development and extend our understanding of the basic pathology of LCA.
Managing change in the nursing handover from traditional to bedside handover – a case study from Mauritius
Authors: Kassean Hemant K , Jagoo Zaheda B 
Published: January 2005

Abstract
Background
The shift handover forms an important part of the communication process that takes place twice within the nurses' working day in the gynaecological ward. This paper addresses the topic of implementing a new system of bedside handover, which puts patients central to the whole process of managing care and also addresses some of the shortcomings of the traditional handover system.

Methods
A force field analysis in terms of the driving forces had shown that there was dissatisfaction with the traditional method of handover which had led to an increase in the number of critical incidents and complaints from patients, relatives and doctors. The restraining forces identified were a fear of accountability, lack of confidence and that this change would lead to more work. A 3 – step planned change model consisting of unfreezing, moving and refreezing was used to guide us through the change process. Resistance to change was managed by creating a climate of open communication where stakeholders were allowed to voice opinions, share concerns, insights, and ideas thereby actively participating in decision making.

Results
An evaluation had shown that this process was successfully implemented to the satisfaction of patients, and staff in general.

Conclusion
This successful change should encourage other nurses to become more proactive in identifying areas for change management in order to improve our health care system.
The role of 'confounding by indication' in assessing the effect of quality of care on disease outcomes in general practice: results of a case-control study
Authors: de Koning Johan S , Klazinga Niek S , Koudstaal Peter J , Prins Ad , Borsboom Gerard JJM , Mackenbach Johan P 
Published: January 2005

Abstract
Background
In quality of care research, limited information is found on the relationship between quality of care and disease outcomes. This case-control study was conducted with the aim to assess the effect of guideline adherence for stroke prevention on the occurrence of stroke in general practice. We report on the problems related to a variant of confounding by indication, that may be common in quality of care studies.

Methods
Stroke patients (cases) and controls were recruited from the general practitioner's (GP) patient register, and an expert panel assessed the quality of care of cases and controls using guideline-based review criteria.

Results
A total of 86 patients was assessed. Compared to patients without shortcomings in preventive care, patients who received sub-optimal care appeared to have a lower risk of experiencing a stroke (OR 0.60; 95% CI 0.24 to 1.53). This result was partly explained by the presence of risk factors (6.1 per cases, 4.4 per control), as reflected by the finding that the OR came much closer to 1.00 after adjustment for the number of risk factors (OR 0.82; 95% CI 0.29 to 2.30). Patients with more risk factors for stroke had a lower risk of sub-optimal care (OR for the number of risk factors present 0.76; 95% CI 0.61 to 0.94). This finding represents a variant of 'confounding by indication', which could not be fully adjusted for due to incomplete information on risk factors for stroke.

Conclusions
At present, inaccurate recording of patient and risk factor information by GPs seriously limits the potential use of a case-control method to assess the effect of guideline adherence on disease outcome in general practice. We conclude that studies on the effect of quality of care on disease outcomes, like other observational studies of intended treatment effect, should be designed and performed such that confounding by indication is minimized.
Clash of kingdoms or why Drosophila larvae positively respond to fungal competitors
Authors: Rohlfs Marko 
Published: January 2005

Abstract
Background
Competition with filamentous fungi has been demonstrated to be an important cause of mortality for the vast group of insects that depend on ephemeral resources (e.g. fruit, dung, carrion). Recent data suggest that the well-known aggregation of Drosophila larvae across decaying fruit yields a competitive advantage over mould, by which the larvae achieve a higher survival probability in larger groups compared with smaller ones. Feeding and locomotor behaviour of larger larval groups is assumed to cause disruption of fungal hyphae, leading to suppression of fungal growth, which in turn improves the chances of larval survival to the adult stage. Given the relationship between larval density, mould suppression and larval survival, the present study has tested whether fungal-infected food patches elicit communal foraging behaviour on mould-infected sites by which larvae might hamper mould growth more efficiently.

Results
Based on laboratory experiments in which Drosophila larvae were offered the choice between fungal-infected and uninfected food patches, larvae significantly aggregated on patches containing young fungal colonies. Grouping behaviour was also visible when larvae were offered only fungal-infected or only uninfected patches; however, larval aggregation was less strong under these conditions than in a heterogeneous environment (infected and uninfected patches).

Conclusion
Because filamentous fungi can be deadly competitors for insect larvae on ephemeral resources, social attraction of Drosophila larvae to fungal-infected sites leading to suppression of mould growth may reflect an adaptive behavioural response that increases insect larval fitness and can thus be discussed as an anti-competitor behaviour. These observations support the hypothesis that adverse environmental conditions operate in favour of social behaviour. In a search for the underlying mechanisms of communal behaviour in Drosophila, this study highlights the necessity of investigating the role of inter-kingdom competition as a potential driving force in the evolution of spatial behaviour in insects.
Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors That Do Not Express the Epidermal Growth Factor Receptor by Immunohistochemistry
Authors: Chung Ki Young , Shia Jinru , Kemeny Nancy E. , Shah Manish , Schwartz Gary K. , Tse Archie , Hamilton Audrey , Pan Dorothy , Schrag Deborah , Schwartz Lawrence , Klimstra David S. , Fridman Daniel , Kelsen David P. , Saltz Leonard B. 
Published: January 2005

Purpose To establish evidence of activity, or lack thereof, of cetuximab-based therapy in patients with refractory colorectal cancer with tumors that do not demonstrate epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC). Patients and Methods Pharmacy computer records were reviewed to identify all patients who received cetuximab at Memorial Sloan-Kettering Cancer Center in a nonstudy setting during the first 3 months of cetuximab's commercial availability. Medical records of these patients were then reviewed to identify colorectal cancer patients who had experienced failure with a prior irinotecan-based regimen and who had a pathology report indicating an EGFR-negative tumor by IHC. Pathology slides from these patients were reviewed by a reference pathologist to confirm EGFR negativity, and computed tomography scans during cetuximab-based therapy were reviewed by a reference radiologist. Response rates were reported using WHO criteria. Results Sixteen chemotherapy-refractory, EGFR-negative colorectal cancer patients who received cetuximab in a nonstudy setting were identified. Fourteen of these patients received cetuximab plus irinotecan, and two received cetuximab monotherapy. In the 16 patients, four major objective responses were seen (response rate, 25%; 95% CI, 4% to 46%). Conclusion Colorectal cancer patients with EGFR-negative tumors have the potential to respond to cetuximab-based therapies. EGFR analysis by current IHC techniques does not seem to have predictive value, and selection or exclusion of patients for cetuximab therapy on the basis of currently available EGFR IHC does not seem warranted.
Suppression of ps20 Expression in the Rat Uterus by Tamoxifen and Estrogens
Authors: Hung Huynh 
Published: January 2005

Abstract
Using differential display methodology, we isolated a tamoxifen-regulated cDNA. This cDNA was identical to the ps20 cDNA isolated from urogenital sinus mesenchymal cells. ps20 expression was detected in various female rat tissues, with the highest expression in lung and heart. ps20 transcripts were low during estrus and proestrus, but high during the diestrous stage of the estrous cycle coincident with estrogen-induced uterine cell proliferation. Treatment of ovary-intact or ovariectomized rats with estrogens or tamoxifen resulted in increased uterine weight and decreased ps20 expression. Uterine involution associated with ovariectomy or antiestrogen treatment led to up-regulation of ps20. Antibody against rat ps20 recognized the native rat ps20 in conditioned medium of primary rat uterine cells and stable ps20-transfected MCF-7 cells with molecular masses of approximately 24, 27, and 29 kDa. In primary rat uterine cells, ps20 secretion was enhanced by ICI 182,780, but was inhibited by estrogens and tamoxifen. Immunohistochemistry revealed that ps20 was localized to smooth muscle and luminal epithelial cells as well as the glandular population of uterine tissue. Conditioned medium derived from ps20-transfected MCF-7 cells, but not Escherichia coli recombinant ps20, exhibited mild growth suppression on PC-3 cells. The data indicate that ps20 expression is negatively regulated by estrogens and tamoxifen and suggest that ps20 may function as a mediator of local growth.
Regulation of T Cell-Mediated Hepatic Inflammation by Adiponectin and Leptin
Authors: Sennello Joseph A. , Fayad Raja , Morris Alison M. , Eckel Robert H. , Asilmaz Esra , Montez Jason , Friedman Jeffrey M. , Dinarello Charles A. , Fantuzzi Giamila 
Published: January 2005

AbstractConcanavalin A-induced hepatotoxicity was compared in lipodystrophic aP2-nSREBP-1c transgenic mice (LD mice) lacking adipose tissue, obese leptin-deficient ob/ob mice, and lean wild-type (WT) mice. Serum leptin and adiponectin were low in LD mice, whereas ob/ob mice had undetectable leptin, but high adiponectin. Protection from hepatotoxicity was observed in ob/ob, but not in LD mice, despite low cytokine levels and reduced T cell activation and hepatic natural killer T cells in both groups. Administration of adiponectin protected LD mice from hepatotoxicity without altering cytokine levels. In contrast, administration of leptin heightened disease susceptibility by restoring cytokine production. Neutralization of TNFα protected LD mice from liver damage. Increased in vivo susceptibility to the hepatotoxic effect of TNFα was observed in LD mice. In vitro, adiponectin protected primary hepatocytes from TNFα-induced death, whereas leptin had no protective effect. In conclusion, although leptin increases susceptibility to hepatotoxicity by regulating cytokine production and T cell activation, adiponectin protects hepatocytes from TNFα-induced death.
Quantitative estimation of the effects of bile salt surfactant systems on insulin stability and permeability in the rat intestine using a mass balance model
Authors: Lane Majella E , O'Driscoll Caitriona M , Corrigan Owen I 
Published: January 2005

AbstractThe oral delivery of peptides and proteins is compromised by chemical and proteolytic instability as well as by permeability limitations. The aim of this study was to delineate the relative contributions of simple bile salt and bile salt:fatty acid mixed micellar systems to protein stability vs permeability enhancement in the rat intestine. Insulin disappearance from the rat intestine was evaluated when administered in simple micellar systems of sodium cholate (NaC), sodium taurocholate (NaTC) and sodium glycocholate (NaGC), and in mixed micellar systems of these bile salts and linoleic acid (LA). In-vitro stability studies were used to evaluate the extent of insulin degradation in the different micellar systems. After correction for insulin degradation in all systems a mass balance model was used to estimate the fractions of insulin absorbed for all systems. Mass balance estimates for the extent of insulin absorption in control perfusion systems were consistent with previously reported predictions of the model for ileal insulin absorption. Mass balance estimates for NaGC suggested no significant effects on the fraction of insulin absorbed relative to control. However, insulin absorption was estimated to occur to a significantly greater extent for NaTC simple micellar systems and was coincident with increased permeability of the hydrophilic marker molecule PEG 4000. The mass balance model estimated higher fractions of insulin absorbed for all mixed micellar systems in line with enhanced plasma insulin levels and higher PEG 4000 permeabilities for these systems.
Angioleiomyoma of the Cavernous Sinus: Case Report
Authors: Figueiredo Eberval Gadelha , Gomes Marcos , Vellutini Eduardo , Rosemberg Sérgio , Marino Raul 
Published: January 2005

Abstract

OBJECTIVE AND IMPORTANCE:
Angioleiomyomas (ALMs) are relatively rare, benign, vascular soft tissue tumors that occur most frequently in the extremities of middle-aged individuals. To date, only two cases of intracranial ALMs have been described, both with little emphasis on the clinical, surgical, and radiological aspects. Neither of these reported cases of ALM involved the cavernous sinus. Furthermore, there is no previous intracranial ALM magnetic resonance imaging scan described in the literature. This report presents the first case of cavernous sinus ALM, emphasizing the clinical, radiological, and surgical aspects.

CLINICAL PRESENTATION:
A 52-year-old man had a 2-year history of horizontal diplopia and frontal headache. Facial numbness and impaired visual acuity in the previous 6 months were also reported. Physical examination revealed paralysis of right Cranial Nerves III, IV, and VI. A decrease in optical acuity was also noted. Computed tomographic and magnetic resonance imaging scans demonstrated a mass lesion located in the right cavernous sinus, which enhanced homogeneously with administration of intravenous contrast medium.

INTERVENTION:
A total resection was performed via a right frontotemporal craniotomy and a pretemporal approach with peeling of the middle fossa. The postoperative course was uneventful. Histological examination identified the ALM, with no recurrence noted during follow-up.

CONCLUSION:
It is unknown why intracranial ALMs have not been reported more frequently in the literature. Although ALMs are a rare occurrence, misinterpretation of this lesion may also have contributed to the lack of reported cases. Before surgery, ALMs can be distinguished from meningiomas and schwannomas but not from hemangiomas. The prognosis of intracranial ALM is good, as suggested in this case as well as the two previously reported cases.
Zielorientierte Requirements Engineering Methoden zur Entwicklung von Agentensystemen (Goal oriented Requirements Engineering Methods for Developing Agent Systems)
Authors: Heine Christian 
Published: January 2005

Abstract
Nach grundlegender Definition des Agentenbegriffs, wird unter Fokussierung auf eine wesentliche Eigenschaft von Softwareagenten — proaktives, zielorientiertes Verhalten und die sich daraus ableitenden Anforderungen näher beleuchtet. Ausgehend von einer Erläuterung der Problemstellung des zielorientierten Requirements Engineering wird im vorliegenden Papier eine Aufarbeitung der bisherigen Forschungsaktivitäten vorgenommen und ein systematischer Vergleich bestehender zielorientierter Requirements Engineering Methoden erarbeitet.