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Endostatin is a Mr 20,000 COOH-terminal fragment of collagen XVIII that inhibits the growth of several primary tumors. We report here the cloning and expression of mouse endostatin in both prokaryotic and eukaryotic expression systems. Soluble recombinant protein expressed in yeast (15–20 mg/L) inhibited the proliferation and migration of endothelial cells in response to stimulation by basic fibroblast growth factor. A rabbit polyclonal antibody was raised that showed positive immunoreactivity to the recombinant protein expressed from both systems. Importantly, the biological activity of the mouse recombinant protein could be neutralized by this antiserum in both endothelial proliferation and chorioallantoic membrane assays. Systemic administration of endostatin at 10 mg/kg suppressed the growth of renal cell cancer in a nude mouse model. The inhibition of tumor growth with soluble yeast-produced protein was comparable to that obtained with non-refolded precipitated protein expressed from bacteria. In addition, two closely related COOH-terminal deletion mutants of endostatin were also tested and showed strikingly differing activity. Collectively, these findings demonstrate the expression of a biologically active form of mouse endostatin in yeast, define a role for the molecule in inhibiting endothelial cell migration, extend its antitumor effects to renal cell carcinoma, and provide a formal proof (via the neutralizing antiserum experiments and the mutant data) that endostatin (and not a possible contaminant) acts as an antiangiogenic agent. Finally, the high level expression of mouse endostatin in yeast serves as an endotoxin free, soluble source of protein for fundamental studies on the mechanisms of tumor growth suppression by angiogenesis inhibitors.

Endostatin is a Mr 20,000 COOH-terminal fragment of collagen XVIII that inhibits the growth of several primary tumors. We report here the cloning and expression of mouse endostatin in both prokaryotic and eukaryotic expression systems. Soluble recombinant protein expressed in yeast (15–20 mg/L) inhibited the proliferation and migration of endothelial cells in response to stimulation by basic fibroblast growth factor. A rabbit polyclonal antibody was raised that showed positive immunoreactivity to the recombinant protein expressed from both systems. Importantly, the biological activity of the mouse recombinant protein could be neutralized by this antiserum in both endothelial proliferation and chorioallantoic membrane assays. Systemic administration of endostatin at 10 mg/kg suppressed the growth of renal cell cancer in a nude mouse model. The inhibition of tumor growth with soluble yeast-produced protein was comparable to that obtained with non-refolded precipitated protein expressed from bacteria. In addition, two closely related COOH-terminal deletion mutants of endostatin were also tested and showed strikingly differing activity. Collectively, these findings demonstrate the expression of a biologically active form of mouse endostatin in yeast, define a role for the molecule in inhibiting endothelial cell migration, extend its antitumor effects to renal cell carcinoma, and provide a formal proof (via the neutralizing antiserum experiments and the mutant data) that endostatin (and not a possible contaminant) acts as an antiangiogenic agent. Finally, the high level expression of mouse endostatin in yeast serves as an endotoxin free, soluble source of protein for fundamental studies on the mechanisms of tumor growth suppression by angiogenesis inhibitors.

Background: Interactions with professional caregivers affect the quality of support and life of people with intellectual disabilities and contribute to the occurrence of challenging behaviour. The present literature review provides an overview of factors facilitating or hindering meaningful staff-client interactions in people with borderline to profound intellectual disabilities and challenging behaviour. Method: Database searches, reference list and citation screening, and expert consultations were undertaken. A thematic synthesis of 28 studies was performed. Results: Factors were identified at the client (i.e. behaviour, emotions and (dis)abilities), staff (i.e. interactive principles, knowledge, psychological resources, attributions, attitudes and (coping with) emotions) and context levels (i.e. group size, team and organization). Conclusions: The present overview provides insights into factors that facilitate or hinder meaningful staff-client interactions with people with intellectual disabilities and challenging behaviour. The results support the need to combine client, staff and contextual factors when considering staff-client interactions in research and practice.

Livia Guadagnoli,1 Madison Simons,2 Josie McGarva,2 Tiffany H Taft,2 Miranda AL van Tilburg3– 5 1Department of Chronic Diseases, Metabolism, and Ageing, Laboratory for Brain-Gut Axis Studies (LABGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium; 2Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 3Joan C Edwards School of Medicine, Department of Internal Medicine, Marshall University, Huntington, WV, USA; 4Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA; 5School of Social Work, University of Washington, Seattle, WA, USACorrespondence: Miranda AL van Tilburg, Email miranda_van_tilburg@med.unc.eduAbstract: Gastroesophageal reflux disease (GERD) is a common gastrointestinal illness with symptoms of heartburn, chest pain, and regurgitation. Management of GERD can involve medication use, lifestyle modification (eg, dietary modification), and surgical intervention depending on the individual patient and disease severity. Poor adherence to medication and recommended lifestyle changes may result in increased symptom severity and decreased quality of life. This paper aimed to systematically review the literature on lifestyle modification for the management of GERD. Fourteen articles were included based on search criteria. Following review and analysis, three types of lifestyle modifications were present in the literature and include medication use, dietary recommendations, and sleep recommendations. Despite being a pharmacological treatment, medication adherence was included in the review, as health behavior change can be used to improve adherence. Overall, the factors associated with adherence to modifications varied in terms of impact and directionality, depending on the type of lifestyle modification. Symptom severity emerged as important across all lifestyle modifications, and is associated with increased adherence to medication use, but decreased adherence to dietary guidelines. While patient–provider communication appeared to improve patient knowledge, it is unclear if increased knowledge translates to improved adherence. The review also demonstrated a lack of clear and standardized guidelines across lifestyle modifications, which may have an influence on adherence and adherence reporting. Future research in GERD treatment adherence would benefit from the use of validated measures to assess adherence. Specific recommendations to improving patient adherence are discussed.Keywords: GERD, nutrition, sleep, medication, compliance

The mechanical properties of glacier beds play a fundamental role in regulating the sensitivity of glaciers to environmental forcing across a wide range of timescales. Glaciers are commonly underlain by deformable till whose mechanical properties and influence on ice flow are not well understood but are critical for reliable projections of future glacier states. Using synoptic-scale observations of glacier motion in different seasons to constrain numerical ice flow models, we study the mechanics of the bed beneath Hofsjökull, a land-terminating ice cap in central Iceland. Our results indicate that the bed deforms plastically and weakens following incipient summertime surface melt. Combining the inferred basal shear traction fields with a Coulomb-plastic bed model, we estimate the spatially distributed effective basal water pressure and show that changes in basal water pressure and glacier accelerations are non-local and non-linear. These results motivate an idealized physical model relating mean basal water pressure and basal slip rate wherein the sensitivity of glacier flow to changes in basal water pressure is inversely related to the ice surface slope.

Our understanding of the earthquake process requires detailed insights into how the tectonic stresses are accumulated and released on seismogenic faults. We derive the full vector displacement field due to the Bam, Iran, earthquake of moment magnitude 6.5 using radar data from the Envisat satellite of the European Space Agency. Analysis of surface deformation indicates that most of the seismic moment release along the 20-km-long strike-slip rupture occurred at a shallow depth of 4 - 5 km, yet the rupture did not break the surface. The Bam event may therefore represent an end-member case of the 'shallow slip deficit' model, which postulates that coseismic slip in the uppermost crust is systematically less than that at seismogenic depths ( 4 - 10 km). The InSAR-derived surface displacement data from the Bam and other large shallow earthquakes suggest that the uppermost section of the seismogenic crust around young and developing faults may undergo a distributed failure in the interseismic period, thereby accumulating little elastic strain.

Critical educational research offers the researcher a position and an ethos of comfort. Even the declared recognition of the relativity of principles, norms or criteria so characteristic of much critical research does not prevent it from looking immediately for a way out of this uncomfortable situation i.e. to keep to the idea that comfort (for the researcher) is needed and desirable. However, we suggest that this uncomfortable condition is constitutive for critical educational research and may be even for education as such. Therefore the article can be considered as a genealogical analysis of this comfortable critical research, in which we show how the birth of the milieu of the modern school goes together with the instauration of two forms of a comfortable research "ethos": a research ethos rooted in a pastoral milieu and a research ethos rooted in a bureaucratic milieu. In the last section of the article we indicate that another "experimental" ethos of research is possible, including the acceptance of discomfort. This is the ethos of a critical researcher as an inhabitant of a coming research community and as being exposed to the present.