On deterrence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68170/2/10.1177_002200276100500312.pd

The Library in Literature

Senior Project submitted to The Division of Languages and Literature of Bard College

Pop, Lock, and Bach it/ The Places I\u27ve Been

Senior Project submitted to The Division of Arts of Bard College

The Size of a Murine Heavy Chain Variable Region Gene Family: Implications for the Magnitude and Evolution of the VH Locus in Mouse

The problem of how much antibody diversity is encoded in the germline as variable region genes has long been of interest to immunologists. We have measured the size of the J558 VH family in the BALB/c mouse by a probe excess titration method, and found that the family contains approximately 1000 members. As a control for systematic error, we used the same method to measure the number of class I MHC genes in BALB/c. We found that the third domain of the class I Dd gene detects 36-40 class I genes. Dot blots and genome blots with copy number controls give results consistent with a J558 family size of 500-1000 VH genes. We note that each band evident on genomic blots of DNA from several mouse strains contains multiple VH genes, and that a significant fraction of these bands are polymorphic among the mouse strains tested. We discuss the implications of this result for both the size and evolution of the VH locus in mouse.</p

THE ART OF MUSIC IN GB-Lbl Add. MS 4911: A CASE FOR ROBERT CARVOR AS THE ANONYMOUS SCOT

GB-Lbl Add. MS 4911, the sole source of an anonymous music treatise, The Art of Music, is among the few manuscripts to have survived the Scottish Reformation. In answer to the puzzle of its authorship, masters of song schools in Edinburgh or Aberdeen have been proposed. A new reading of the text places the date of its creation between 1559 and 1567 and leads to a revised profile of the author, which, as is demonstrated here, the Scottish composer Robert Carvor (1487/8 – c. 1568) uniquely matches. Further supporting Carvor as the author of the treatise is its inclusion of a section of Carvor’s Missa L’homme armé and of a caricature strikingly similar to one found in the Carvor Choirbook (GB-En MS Adv. 5.1.15), where Carvor’s compositions bear his signature. An Appendix includes the first English translation of the rules of faburden, which are unique to The Art of Music (f.94r-f.112r)

Functional cis-regulatory genomics for systems biology

Gene expression is controlled by interactions between trans-regulatory factors and cis-regulatory DNA sequences, and these interactions constitute the essential functional linkages of gene regulatory networks (GRNs). Validation of GRN models requires experimental cis-regulatory tests of predicted linkages to authenticate their identities and proposed functions. However, cis-regulatory analysis is, at present, at a severe bottleneck in genomic system biology because of the demanding experimental methodologies currently in use for discovering cis-regulatory modules (CRMs), in the genome, and for measuring their activities. Here we demonstrate a high-throughput approach to both discovery and quantitative characterization of CRMs. The unique aspect is use of DNA sequence tags to “barcode” CRM expression constructs, which can then be mixed, injected together into sea urchin eggs, and subsequently deconvolved. This method has increased the rate of cis-regulatory analysis by >100-fold compared with conventional one-by-one reporter assays. The utility of the DNA-tag reporters was demonstrated by the rapid discovery of 81 active CRMs from 37 previously unexplored sea urchin genes. We then obtained simultaneous high-resolution temporal characterization of the regulatory activities of more than 80 CRMs. On average 2–3 CRMs were discovered per gene. Comparison of endogenous gene expression profiles with those of the CRMs recovered from each gene showed that, for most cases, at least one CRM is active in each phase of endogenous expression, suggesting that CRM recovery was comprehensive. This approach will qualitatively alter the practice of GRN construction as well as validation, and will impact many additional areas of regulatory system biology

Information processing at the foxa node of the sea urchin endomesoderm specification network

The foxa regulatory gene is of central importance for endoderm specification across Bilateria, and this gene lies at an essential node of the well-characterized sea urchin endomesoderm gene regulatory network (GRN). Here we experimentally dissect the cis-regulatory system that controls the complex pattern of foxa expression in these embryos. Four separate cis-regulatory modules (CRMs) cooperate to control foxa expression in different spatial domains of the endomesoderm, and at different times. A detailed mutational analysis revealed the inputs to each of these cis-regulatory modules. The complex and dynamic expression of foxa is regulated by a combination of repressors, a permissive switch, and multiple activators. A mathematical kinetic model was applied to study the dynamic response of foxa cis-regulatory modules to transient inputs. This study shed light on the mesoderm–endoderm fate decision and provides a functional explanation, in terms of the genomic regulatory code, for the spatial and temporal expression of a key developmental control gene

Phenylbutyrate inhibits the invasive properties of prostate and breast cancer cell lines in the sea urchin embryo basement membrane invasion assay

Histone deacetylase inhibitors, such as phenylbutyrate, are currently undergoing clinical trials as potential anticancer agents. Phenylbutyrate can induce cell differentiation and apoptosis in a number of cancer cell types and can act in synergy with ionizing radiation and chemotherapy to induce apoptosis. We used the sea urchin embryo basement membrane invasion assay to show that phenylbutyrate potently inhibited the invasive properties of both prostate and breast cancer cells at clinically achievable doses. This inhibition was dose-dependent and persisted for at least 24 hr after the drug was removed. These results suggest that in addition to activating apoptosis in cancer cells, phenylbutyrate may be used in prevention of metastatic disease. © 2002 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34396/1/10609_ftp.pd

Market Share Growth and Stock Returns

We find a negative relationship between market share growth and subsequent stock returns, three- and four-factor alphas. We report the potential explanatory role of market share growth in explaining subsequent average monthly stock returns. High (Low) market share growth firms report good (poor) operating performance and positive (negative) SUEs in the quarter in which market share growth is measured and investors overact to that good (bad) news. However, high (low) market share growth firms experience decrease (increase) in operating performance and SUEs in the subsequent quarters resulting in corrections in investors’ expectations and subsequent lower (higher) stock returns