Glycophenotype of prostatic carcinomas.

The factors that affect the progression of prostatic carcinoma are poorly understood, but it is known that carbohydrate antigens on the tumour cell surface play a role in the transforming and metastatic processes. The present report aimed to perform a comparative, lectin-histochemical study of benign and carcinomatous prostates, using a battery of lectins, in combination with monoclonal antibodies against Lewis antigens, and a semi quantitative study, to investigate the changes in glycosylation patterns that occur in prostatic carcinoma. Blocks from 27 necropsy cases of prostatic carcinoma were sectioned and stained with H+E, fifteen biotinylated lectins chosen to probe for a wide range of oligosaccharide sequences within several categories of glycoprotein glycans, using a lectin-biotin avidin-peroxidase method, and monoclonal antibodies against Lewisa, sialyl Lewisa and sialyl Lewisx antigens. The glycophenotype of prostatic carcinoma differed from that of the noncancerous prostate in revealing more intense staining with the following lectins (AAA, UEA-1, DBA, WFA, VVA, HPA, BSA-1B4, MPA, ECA, AHA, and CTA), while the binding patterns of (GNA and NPA) were almost similar in both prostatic carcinoma and the noncancerous prostate. Lewis antigens are found to be expressed in prostatic carcinomas but not in the noncancerous prostate. The observations of this study suggest that the gylcophenotype of transformed prostatic cells was modified. It showed a moderate increase in, and changing patterns of, fucosylation and galactosylation, increased branching of side chains and sharp rise in 2 deoxy, 2 acetamido galactosylation and masking process by sialylation, especially by Îą2-3 and Îą2-6 linkages. All these changes in the glycosylation pattern of the transformed prostatic cells were observed on O-glycans, no changes were observed on N-glycans

Kinetic and Thermodynamic Approaches for the Efficient Formation of Mechanical Bonds

Among the growing collection of molecular systems under consideration for nanoscale device applications, mechanically interlocked compounds derived from electrochemically switchable bistable [2]rotaxanes and [2]catenanes show great promise. These systems demonstrate dynamic, relative movements between their components, such as shuttling and circumrotation, enabling them to serve as stimuli-responsive switches operated via reversible, electrochemical oxidation−reduction rather than through the addition of chemical reagents. Investigations into these systems have been intense for a number of years, yet limitations associated with their synthesis have hindered incorporation of their mechanical bonds into more complex architectures and functional materials. We have recently addressed this challenge by developing new template-directed synthetic protocols, operating under both kinetic and thermodynamic control, for the preparation of bistable rotaxanes and catenanes. These methodologies are compatible with the molecular recognition between the π-electron-accepting cyclobis(paraquat-p-phenylene) (CBPQT4+) host and complementary π-electron-donating guests. The procedures that operate under kinetic control rely on mild chemical transformations to attach bulky stoppering groups or perform macrocyclizations without disrupting the host−guest binding of the rotaxane or catenane precursors. Alternatively, the protocols that operate under thermodynamic control utilize a reversible ring-opening reaction of the CBPQT4+ ring, providing a pathway for two cyclic starting materials to thread one another to form more thermodynamically stable catenaned products. These complementary pathways generate bistable rotaxanes and catenanes in high yields, simplify mechanical bond formation in these systems, and eliminate the requirement that the mechanical bonds be introduced into the molecular structure in the final step of the synthesis. These new methods have already been put into practice to prepare previously unavailable rotaxane architectures and novel complex materials. Furthermore, the potential for utilizing mechanically interlocked architectures as device components capable of information storage, the delivery of therapeutic agents, or other desirable functions has increased significantly as a result of the development of these improved synthetic protocols

History in the Making: Outreach and Collaboration between Special Collections and Makerspaces

Makerspaces present unique possibilities for creative partnerships within libraries, including the opportunity for interdisciplinary use of emerging technologies with archival objects and primary sources. One example of this type of interdisciplinary collaboration is the fabrication of cultural heritage replicas via 3D scanning and printing of historical university objects in academic libraries. Two departments in the University of Idaho Library, Special Collections and Archives (SPEC) and the Making, Innovating, and Learning Laboratory (MILL), partnered on such a project as a way to broaden maker competencies across library departments, leverage interdisciplinary connections between emerging technologies and historic archives, and create innovative outreach opportunities. Since many academic libraries house both special collections and makerspaces, this article outlines a path towards creative collaboration while creating an in-library maker community of practice and suggests opportunities for outreach and engagement that are widely applicable to library professionals

A Push-Button Molecular Switch

The preparation, characterization, and switching mechanism of a unique single-station mechanically switchable hetero[2]catenane are reported. The facile synthesis utilizing a “threading-followed-by-clipping” protocol features Cu^(2+)-catalyzed Eglinton coupling as a mild and efficient route to the tetrathiafulvalene-based catenane in high yield. The resulting mechanically interlocked molecule operates as a perfect molecular switch, most readily described as a “push-button” switch, whereby two discrete and fully occupied translational states are toggled electrochemically at incredibly high rates. This mechanical switching was probed using a wide variety of experimental techniques as well as quantum-mechanical investigations. The fundamental distinctions between this single-station [2]catenane and other more traditional bi- and multistation molecular switches are significant

Revitalising audit and feedback to improve patient care

Healthcare systems face challenges in tackling variations in patient care and outcomes. Audit and feedback aim to improve patient care by reviewing clinical performance against explicit standards and directing action towards areas not meeting those standards. It is a widely used foundational component of quality improvement, included in around 60 national clinical audit programmes in the United Kingdom. Ironically, there is currently a gap between what audit and feedback can achieve and what they actually deliver, whether led locally or nationally. Several national audits have been successful in driving improvement and reducing variations in care, such as for stroke and lung cancer, but progress is also slower than hoped for in other aspects of care (table 1). Audit and feedback have a chequered past.6 Clinicians might feel threatened rather than supported by top-down feedback and rightly question whether rewards outweigh efforts invested in poorly designed audit. Healthcare organisations have limited resources to support and act on audit and feedback. Dysfunctional clinical and managerial relationships undermine effective responses to feedback, particularly when it is not clearly part of an integrated approach to quality assurance and improvement. Unsurprisingly, the full potential of audit and feedback has not been realised

Bioreactor mechanically guided 3D mesenchymal stem cell chondrogenesis using a biocompatible novel thermo-reversible methylcellulose-based hydrogel

Autologous chondrocyte implantation for cartilage repair represents a challenge because strongly limited by chondrocytes' poor expansion capacity in vitro. Mesenchymal stem cells (MSCs) can differentiate into chondrocytes, while mechanical loading has been proposed as alternative strategy to induce chondrogenesis excluding the use of exogenous factors. Moreover, MSC supporting material selection is fundamental to allow for an active interaction with cells. Here, we tested a novel thermo-reversible hydrogel composed of 8% w/v methylcellulose (MC) in a 0.05 M Na 2 SO 4 solution. MC hydrogel was obtained by dispersion technique and its thermo-reversibility, mechanical properties, degradation and swelling were investigated, demonstrating a solution-gelation transition between 34 and 37 °C and a low bulk degradation (<20%) after 1 month. The lack of any hydrogel-derived immunoreaction was demonstrated in vivo by mice subcutaneous implantation. To induce in vitro chondrogenesis, MSCs were seeded into MC solution retained within a porous polyurethane (PU) matrix. PU-MC composites were subjected to a combination of compression and shear forces for 21 days in a custom made bioreactor. Mechanical stimulation led to a significant increase in chondrogenic gene expression, while histological analysis detected sulphated glycosaminoglycans and collagen II only in loaded specimens, confirming MC hydrogel suitability to support load induced MSCs chondrogenesis