Transcript: Workshop on the Future of the Legal Course Book

Most every law school right now is thinking about its curriculum. The Carnegie Report certainly was a big factor in spurring that, although curricular reform is something that law schools, of course, are always engaged in. It moves at a glacial pace sometimes. One of the things that really struck us here at Seattle University, as everyone started to talk about Carnegie and started to talk about curricular reform, is that it was, frankly, a bit of old news to us. Seattle University School of Law has always prided itself on being at the forefront of legal education in many ways, and one of them is that we’ve always had an incredibly robust clinic, legal writing programs, and trial advocacy programs. The idea that we need to be more focused on the whole person, not only cognitive learning but the other dimensions of learning, was something that we’ve been working at for some time. It certainly has struck me, during all those conversations, that one of the things missing was the question of what materials we were going to use to do this teaching. As we all recognize, what happens in the classroom is a chemical sort of reaction, where the mix is based on the students, on the professor, and the materials, including the format in which those materials are presented. To take these conversations to the next level, this is a topic that we really needed to address, and so it is most fitting, I think, that it is here.

Human apoB contributes to increased serum total apo(a) level in LPA transgenic mice

Background The Lp(a) lipoprotein (Lp(a)) consists of the polymorphic glycoprotein apolipoprotein(a) (apo(a)), which is attached by a disulfide bond to apolipoprotein B (apoB). Apo(a), which has high homology with plasminogen, is present only in primates and hedgehogs. However, transgenic mice and rabbits with high serum apo(a) levels exist. Liver is the main site for apo(a) synthesis, but the site of removal is uncertain. To examine differences between transgenic mice expressing the LPA gene and mice capable of forming Lp(a) particles, LPA -YAC transgenic mice and hAPOB transgenic mice were crossed and their offspring examined. Results Comparison of LPA -YAC with LPA -YAC/hAPOB transgenic mice showed that LPA -YAC/hAPOB transgenic mice have higher serum total apo(a) and total cholesterol level than mice lacking the hAPOB gene. However, hepatic apo(a) mRNA level was higher in LPA -YAC transgenic mice than in LPA -YAC/hAPOB transgenic mice. Feeding of a high-cholesterol/high-fat diet to male LPA -YAC transgenic mice with or without the hAPOB gene resulted in reduced serum total apo(a) and hepatic apo(a) mRNA level. Conclusion In conclusion, the higher serum total apo(a) level in LPA -YAC/hAPOB transgenic mice than in LPA -YAC transgenic mice is not caused by increased apo(a) synthesis. Lower hepatic apo(a) mRNA level in LPA -YAC/hAPOB than in LPA -YAC transgenic mice may suggest that the increase in total apo(a) level is a result of apo(a) accumulation in serum. Furthermore, observed higher serum total cholesterol level in LPA -YAC/hAPOB transgenic mice than either in wild type or LPA -YAC transgenic mice may further suggest that human APOB transgenicity is a factor that contributes to increased serum total apo(a) and cholesterol levels. Our results on reduced serum total apo(a) and hepatic apo(a) mRNA levels in HCHF fed male LPA -YAC transgenic mice confirm earlier findings in females, and show that there are no sex difference in mechanisms for lowering apo(a) level in response to HCHF feeding

Criminal Justice Through Management: From Police, Prosecutors, Courts, and Prisons to a Modern Administrative Agency

96 pagesIn 1941, responding to a wide-ranging effort to enact legislation that would constrain the operation of New Deal agencies, Franklin Roosevelt commissioned the Attorney General to produce a report on the role and importance of administrative governance. The report stated, “If administrative agencies did not exist in the Federal Government, Congress would be limited to a technique of legislation primarily designed to correct evils after they have arisen rather than to prevent them from arising. The criminal law, of course, operates in this after-the-event fashion.” This familiar distinction would appear to leave our criminal law system mired in the premodern mindset this Report’s casual “of course” implies. It suggests that we continue to conceive of the system by which we combat crime as after-the-fact punishment of individual wrongdoers. Following the quoted language, the Attorney General’s Report continued: “Congress declares a given act to be a crime. The mere declaration may act as a deterrent. But if it fails to do so the courts can only punish the wrong-doer; they cannot wipe out or make good the wrong.” Actually, it is generally recognized that punishing people after they have committed crimes is a second-best response. The preferable approach—and here we can add a more convincing “of course”—is to do what the Attorney General said that administrative agencies do in their assigned areas, prevent crime from occurring in the first place. Not only do we know this, but it has generally been the purpose of the Western World’s criminal justice systems since their inception

Large-scale discovery of enhancers from human heart tissue.

Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified ∼6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their in vivo enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart

Impact of the SPOP Mutant Subtype on the Interpretation of Clinical Parameters in Prostate Cancer.

Purpose: Molecular characterization of prostate cancer, including The Cancer Genome Atlas, has revealed distinct subtypes with underlying genomic alterations. One of these core subtypes, SPOP (speckle-type POZ protein) mutant prostate cancer, has previously only been identifiable via DNA sequencing, which has made the impact on prognosis and routinely used risk stratification parameters unclear. Methods: We have developed a novel gene expression signature, classifier (Subclass Predictor Based on Transcriptional Data), and decision tree to predict the SPOP mutant subclass from RNA gene expression data and classify common prostate cancer molecular subtypes. We then validated and further interrogated the association of prostate cancer molecular subtypes with pathologic and clinical outcomes in retrospective and prospective cohorts of 8,158 patients. Results: The subclass predictor based on transcriptional data model showed high sensitivity and specificity in multiple cohorts across both RNA sequencing and microarray gene expression platforms. We predicted approximately 8% to 9% of cases to be SPOP mutant from both retrospective and prospective cohorts. We found that the SPOP mutant subclass was associated with lower frequency of positive margins, extraprostatic extension, and seminal vesicle invasion at prostatectomy; however, SPOP mutant cancers were associated with higher pretreatment serum prostate-specific antigen (PSA). The association between SPOP mutant status and higher PSA level was validated in three independent cohorts. Despite high pretreatment PSA, the SPOP mutant subtype was associated with a favorable prognosis with improved metastasis-free survival, particularly in patients with high-risk preoperative PSA levels. Conclusion: Using a novel gene expression model and a decision tree algorithm to define prostate cancer molecular subclasses, we found that the SPOP mutant subclass is associated with higher preoperative PSA, less adverse pathologic features, and favorable prognosis. These findings suggest a paradigm in which the interpretation of common risk stratification parameters, particularly PSA, may be influenced by the underlying molecular subtype of prostate cancer