Engaging Outside Counsel in Transactional Law Clinics

This article examines the plurality of objectives and methods by which transactional law clinics collaborate with outside attorneys to competently represent their organizational clients on a wide range of legal issues. Some transactional law clinics rely on outside counsel as informal legal advisors or consultants; others collaborate with outside counsel for the development of community projects or referral of legal work; many transactional law clinics engage outside counsel as “local counsel” when assisting a client in other jurisdictions or internationally; still others engage outside counsel more formally to assist in student supervision of client work. For some, the idea of a clinic working with outside counsel poses a credible threat to clinical pedagogy, clinical faculty status, and the permanent integration of clinics into the law school curriculum. To others, collaborating with outside counsel is a part of everyday client representation, and may be necessary for ethical and professional responsibility reasons. While identifying and discussing the import of these concerns, this article asserts the benefits of collaborating with outside attorneys for law school clinical programs and proposes a framework for deciding whether and how to collaborate with outside attorneys. Specifically, this article sets forth a deliberate and systematic decision-making process for the clinical law professor’s use. The decision-making process proposed is context-specific and dependent on the objectives of the clinical law professor. This article further recommends proactive steps that a clinical law professor can take to facilitate the clinical law professor’s objectives if she decides to engage outside counsel, such as entering into a Memorandum of Understanding to solidify roles and responsibilities of all parties involved in the collaboration. While this article examines collaboration with outside counsel primarily through the lens of transactional law based clinical programs, our discussion provides helpful guidance to law school clinical programs generally

The mechanism of glycosphingolipid degradation revealed by a GALC-SapA complex structure.

Sphingolipids are essential components of cellular membranes and defects in their synthesis or degradation cause severe human diseases. The efficient degradation of sphingolipids in the lysosome requires lipid-binding saposin proteins and hydrolytic enzymes. The glycosphingolipid galactocerebroside is the primary lipid component of the myelin sheath and is degraded by the hydrolase β-galactocerebrosidase (GALC). This enzyme requires the saposin SapA for lipid processing and defects in either of these proteins causes a severe neurodegenerative disorder, Krabbe disease. Here we present the structure of a glycosphingolipid-processing complex, revealing how SapA and GALC form a heterotetramer with an open channel connecting the enzyme active site to the SapA hydrophobic cavity. This structure defines how a soluble hydrolase can cleave the polar glycosyl headgroups of these essential lipids from their hydrophobic ceramide tails. Furthermore, the molecular details of this interaction provide an illustration for how specificity of saposin binding to hydrolases is encoded

Coping with methodological dilemmas; about establishing the effectiveness of interventions in routine medical practice

BACKGROUND: The aim of this paper is to show how researchers balance between scientific rigour and localisation in conducting pragmatic trial research. Our case is the Quattro Study, a pragmatic trial on the effectiveness of multidisciplinary patient care teams used in primary health care centres in deprived neighbourhoods of two major cities in the Netherlands for intensified secondary prevention of cardiovascular diseases. METHODS: For this study an ethnographic design was used. We observed and interviewed the researchers and the practice nurses. All gathered research documents, transcribed observations and interviews were analysed thematically. RESULTS: Conducting a pragmatic trial is a continuous balancing act between meeting methodological demands and implementing a complex intervention in routine primary health care. As an effect, the research design had to be adjusted pragmatically several times and the intervention that was meant to be tailor-made became a rather stringent procedure. CONCLUSION: A pragmatic trial research is a dynamic process that, in order to be able to assess the validity and reliability of any effects of interventions must also have a continuous process of methodological and practical reflection. Ethnographic analysis, as we show, is therefore of complementary value

A simeprevir-inducible molecular switch for the control of cell and gene therapies

Abstract Chemical inducer of dimerization (CID) modules can be used effectively as molecular switches to control biological processes, and thus there is significant interest within the synthetic biology community in identifying novel CID systems. To date, CID modules have been used primarily in engineering cells for in vitro applications. To broaden their utility to the clinical setting, including the potential to control cell and gene therapies, the identification of novel CID modules should consider factors such as the safety and pharmacokinetic profile of the small molecule inducer, and the orthogonality and immunogenicity of the protein components. Here we describe a CID module based on the orally available, approved, small molecule simeprevir and its target, the NS3/4A protease from hepatitis C virus. We demonstrate the utility of this CID module as a molecular switch to control biological processes such as gene expression and apoptosis in vitro, and show that the CID system can be used to rapidly induce apoptosis in tumor cells in a xenograft mouse model, leading to complete tumor regression