Erfahrungswissenschaft und Expertenblick -Eine Forschungsmethode inspiriert von der biologisch-dynamischen Landwirtschaft

Experiential science is based on the unique knowledge gathered by experienced practitioners. Both the reflective evaluation of case studies and expert judgement processes and the use of pattern recognition are core elements of experiential scien-tific methodology. Development of experiential knowledge and insights are thus pri-marily based on experts’ actions and the reflections on those actions. The methodol-ogy has been created based on intensive cooperation between single farmers or farmer groups and scientists/advisors. Experiential knowledge is not only holistic, but also adequate. As in formal science, experienced practitioners develop valid knowl-edge and in new, unknown situations they have a capability to integrate their diagno-sis (“knowing what”) and suitable actions, necessary at a specific time (“knowing that”)

Building a comprehensive mentoring academy for schools of health.

Formal mentoring programs are increasingly recognized as critical for faculty career development. We describe a mentoring academy (MA) developed for faculty across tracks (i.e., researchers, clinicians, educators) within a "school of health" encompassing schools of medicine and nursing. The program is anchored dually in a clinical and translational science center and a school of health. The structure includes the involvement of departmental and center mentoring directors to achieve widespread uptake and oversight. A fundamental resource provided by the MA includes providing workshops to enhance mentoring skills. Initiatives for junior faculty emphasize establishing and maintaining strong mentoring relationships and implementing individual development plans (IDPs) for career planning. We present self-report data on competency improvement from mentor workshops and data on resources and barriers identified by junior faculty (n = 222) in their IDPs. Mentors reported statistically significantly improved mentoring competency after workshop participation. Junior faculty most frequently identified mentors (61%) and collaborators (23%) as resources for goal attainment. Top barriers included insufficient time and time-management issues (57%), funding limitations (18%), work-life balance issues (18%), including inadequate time for self-care and career development activities. Our MA can serve as a model and roadmap for providing resources to faculty across traditional tracks within medical schools

Initial results of in vivo non-invasive cancer imaging in the human breast using near-infrared photoacoustics

Near-infrared photoacoustic images of regions-of-interest in 4 of the 5 cases of patients with symptomatic breasts reveal higher intensity regions which we attribute to vascular distribution associated with cancer. Of the 2 cases presented here, one is especially significant where benign indicators dominate in conventional radiological images, while photoacoustic images reveal vascular features suggestive of malignancy, which is corroborated by histopathology. The results show that photoacoustic imaging may have potential in visualizing certain breast cancers based on intrinsic optical absorption contrast. A future role for the approach could be in supplementing conventional breast imaging to assist detection and/or diagnosis.\ud \u

S-matrix approach to quantum gases in the unitary limit II: the three-dimensional case

A new analytic treatment of three-dimensional homogeneous Bose and Fermi gases in the unitary limit of negative infinite scattering length is presented, based on the S-matrix approach to statistical mechanics we recently developed. The unitary limit occurs at a fixed point of the renormalization group with dynamical exponent z=2 where the S-matrix equals -1. For fermions we find T_c /T_F is approximately 0.1. For bosons we present evidence that the gas does not collapse, but rather has a critical point that is a strongly interacting form of Bose-Einstein condensation. This bosonic critical point occurs at n lambda^3 approximately 1.3 where n is the density and lambda the thermal wavelength, which is lower than the ideal gas value of 2.61.Comment: 26 pages, 16 figure

Peribiliary glands are key in regeneration of the human biliary epithelium after severe bile duct injury

Peribiliary glands (PBG) are a source of stem/progenitor cells organized in a cellular network encircling large bile ducts. Severe cholangiopathy with loss of luminal biliary epithelium has been proposed to activate PBG, resulting in cell proliferation and differentiation to restore biliary epithelial integrity. However, formal evidence for this concept in human livers is lacking. We, therefore, developed a novel ex vivo model using precision-cut slices of extrahepatic human bile ducts obtained from discarded donor livers, providing an intact anatomical organization of cell structures, to study spatiotemporal differentiation and migration of PBG cells after severe biliary injury. Post-ischemic bile duct slices were incubated in oxygenated culture medium for up to a week. At baseline, severe tissue injury was evident with loss of luminal epithelial lining and mural stroma necrosis. In contrast, PBG remained relatively well preserved and different reactions of PBG were noted, including PBG dilatation, cell proliferation and maturation. Proliferation of PBG cells increased after 24 h of oxygenated incubation, reaching a peak after 72 h. Proliferation of PBG cells was paralleled by a reduction in PBG apoptosis and differentiation from a primitive and pluripotent (Nanog+/Sox9+) to a mature (CFTR+/secretin receptor+) and activated phenotype (increased expression of HIF-1α, Glut-1, and VEGF-A). Migration of proliferating PBG cells in our ex vivo model was unorganized, but resulted in generation of epithelial monolayers at stromal surfaces. CONCLUSION: Human PBG contain biliary progenitor cells and are able to respond to bile duct epithelial loss with proliferation, differentiation, and maturation to restore epithelial integrity. The ex vivo spatiotemporal behaviour of human PBG cells provides evidence for a pivotal role of PBG in biliary regeneration after severe injury. This article is protected by copyright. All rights reserved

Prolonged and tunable residence time using reversible covalent kinase inhibitors.

Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrated biochemical residence times spanning from minutes to 7 d. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK for more than 18 h after clearance from the circulation. The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating the generalizability of the approach. Targeting of noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates 'residence time by design', the ability to modulate and improve the duration of target engagement in vivo

Why rational argument fails the genetic modification (GM) debate

AbstractGenetic modification (GM) of crops provides a methodology for the agricultural improvements needed to deliver global food security. However, public opposition to GM-food is great. The debate has tended to risk communication, but here we show through study of a large nationally representative sample of British adults that public acceptance of GM-food has social, cultural and affective contexts. Regression models showed that metaphysical beliefs about the sanctity of food and an emotional dislike of GM-food were primary negative determinants, while belief in the value of science and favourable evaluation of the benefits-to-risks of GM-food were secondary positive determinants. Although institutional trust, general knowledge of the GM-food debate and belief in the eco-friendliness of GM-food were all associated with acceptance, their influence was minor. While a belief in the sanctity of food had a direct inverse effect on GM acceptance, belief in the value of science was largely mediated through favourable perception of benefits-to-risks. Furthermore, segmentation analysis demonstrated that anxiety about GM-food had social and cultural antecedents, with white men being least anxious and older vegetarian women being most anxious. Rational argument alone about the risks and benefits of GM-food is unlikely to change public perceptions of GM-technology

The centromeric/nucleolar chromatin protein ZFP-37 may function to specify neuronal nuclear domains

Murine ZFP-37 is a member of the large family of C2H2 type zinc finger proteins. It is characterized by a truncated NH2-terminal Kruppel-associated box and is thought to play a role in transcriptional regulation. During development Zfp-37 mRNA is most abundant in the developing central nervous system, and in the adult mouse expression is restricted largely to testis and brain. Here we show that at the protein level ZFP-37 is detected readily in neurons of the adult central nervous system but hardly in testis. In brain ZFP-37 is associated with nucleoli and appears to contact heterochromatin. Mouse and human ZFP-37 have a basic histone H1-like linker domain, located between KRAB and zinc finger regions, which binds double-stranded DNA. Thus we suggest that ZFP-37 is a structural protein of the neuronal nucleus which plays a role in the maintenance of specialized chromatin domains

Anchoring of proteins to lactic acid bacteria

The anchoring of proteins to the cell surface of lactic acid bacteria (LAB) using genetic techniques is an exciting and emerging research area that holds great promise for a wide variety of biotechnological applications. This paper reviews five different types of anchoring domains that have been explored for their efficiency in attaching hybrid proteins to the cell membrane or cell wall of LAB. The most exploited anchoring regions are those with the LPXTG box that bind the proteins in a covalent way to the cell wall. In recent years, two new modes of cell wall protein anchoring have been studied and these may provide new approaches in surface display. The important progress that is being made with cell surface display of chimaeric proteins in the areas of vaccine development and enzyme- or whole-cell immobilisation is highlighted.