The Apple E-Book Agreement and Ruinous Competition: Are E-Goods Different for Antitrust Purposes?

Publishers have spent the last decade and a half struggling against falling prices for digital goods. The recent antitrust case against Apple and the major publishers highlights collusive price fixing as a potential method for resisting depreciation. This Article examines the myriad ways in which digital distribution puts downward pressure on prices, and seeks to determine whether or not collusive price fixing would serve as an appropriate response to such pressure given the goals of the copyright grant. Considering retailer bargaining power, increased access to substitutes, the loss of traditional price discrimination methods, the effects of vertical integration in digital publishing, and the increasing competitiveness of the public domain, I conclude that the resultant downward price pressure might in fact significantly hamper the commodity distribution of digital goods. I remain unconvinced, however, that price fixing is an appropriate solution. The copyright grant affords rights holders commercial opportunities beyond simple commodity distribution. These other methods for commercializing e-goods suggest to me that current pricing trends are not indicative of market failure, but rather of a changing marketplace

Movements, Moments, and the Eroding Antitrust Consensus

Timothy Wu, The Curse of Bigness: Antitrust in the New Gilded Age (Columbia Global Reports, 2018). $14.99. Timothy Wu’s book, The Curse of Bigness, offers a brief history on and critical perspective of antitrust law’s development over the last century, calling for a return to a Brandeisian approach to the law. In this review-essay, I use Wu’s text as a starting point to explore antitrust law’s current political moment. Tracing the dynamics at play in this debate and Wu’s role in it, I note areas underexplored in Wu’s text regarding the interplay of antitrust law with other forms of industrial regulation, highlighting in particular current difficulties in copyright law as one of the underlying tensions driving popular discontent with the major technology firms or “tech trusts.” I consider the continuing influence of Robert Bork’s The Antitrust Paradox, now more than forty years old, and how the current reform movement might execute a shift as lasting and substantial as the one Bork spearheaded with his book

A Demonstration of Procrustes: A System to Automatically Deploy Data-Based Information Systems over the World Wide Web

Procrustes automatically deploys any ODBC data-based Information over the World Wide Web. No knowledge of HTML, SQL, or ODBC protocols is required on the part of the person publishing the database. Users are provided with a graphical Boolean query capability requiring minimal database knowledge

The Role of Tau in Neurodegenerative Diseases and Its Potential as a Therapeutic Target

The abnormal deposition of proteins in and around neurons is a common pathological feature of many neurodegenerative diseases. Among these pathological proteins, the microtubule-associated protein tau forms intraneuronal filaments in a spectrum of neurological disorders. The discovery that dominant mutations in the MAPT gene encoding tau are associated with familial frontotemporal dementia strongly supports abnormal tau protein as directly involved in disease pathogenesis. This and other evidence suggest that tau is a worthwhile target for the prevention or treatment of tau-associated neurodegenerative diseases, collectively called tauopathies. However, it is critical to understand the normal biological roles of tau, the specific molecular events that induce tau to become neurotoxic, the biochemical nature of pathogenic tau, the means by which pathogenic tau exerts neurotoxicity, and how tau pathology propagates. Based on known differences between normal and abnormal tau, a number of approaches have been taken toward the discovery of potential therapeutics. Key questions still remain open, such as the nature of the connection between the amyloid-β protein of Alzheimer's disease and tau pathology. Answers to these questions should help better understand the nature of tauopathies and may also reveal new therapeutic targets and strategies

Targeting mRNA for Alzheimer's and Related Dementias

Brain deposition of the amyloid beta-protein (Aβ) and tau are characteristic features in Alzheimer's disease (AD). Mutations in the Aβ precursor protein (APP) and a protease involved in Aβ production from APP strongly argue for a pathogenic role of Aβ in AD, while mutations in tau are associated with related disorders collectively called frontotemporal lobar degeneration (FTLD). Despite intense effort, therapeutic strategies that target Aβ or tau have not yet yielded medications, suggesting that alternative approaches should be pursued. In recent years, our laboratory has studied the role of mRNA in AD and FTLD, specifically those encoding tau and the Aβ-producing protease BACE1. As many FTLD-causing tau mutations destabilize a hairpin structure that regulates RNA splicing, we have targeted this structure with small molecules, antisense oligonucleotides, and small molecule-antisense conjugates. We have also discovered that microRNA interaction with the 3′-untranslated region of tau regulates tau expression. Regarding BACE1, we found that alternative splicing leads to inactive splice isoforms and antisense oligonucleotides shift splicing toward these inactive isoforms to decrease Aβ production. In addition, a G-quadruplex structure in the BACE1 mRNA plays a role in splice regulation. The prospects for targeting tau and BACE1 mRNAs as therapeutic strategies will be discussed

Hydrometeorological investigations on a small valley glacier in the Sawtooth Range, Ellesmere Island, Northwest Territories

Hydrometeorological techniques were employed during the summer of 1993 to study a small (4.7km2) valley glacier in the Sawtooth Range, Fosheim Peninsula, Ellesmere Island, Northwest Territories. The annual 1992-93 mass balance for Quviagivaa Glacier (unofficial name), and for the adjacent Nirukittuq Glacier (unofficial name) was -532mm and -530mm water equivalent respectively. The equilibrium line altitude was above the upper limit of the glaciers due to the exceptional warmth of the summer. Slight marginal shrinking in the areal extent of Quviagivaa Glacier since 1959 suggests that strongly negative mass balances such as those recorded in 1993 are not indicative of the last 46 years. In order to determine the main factors influencing ablation and runoff on the glacier, statistical analyses were performed using daily runoff values, ablation data, and several hydrometeorological elements. Accumulated hourly temperature (melting degree hours) had the highest correlated with ablation. The best prediction of average daily discharge was achieved using a multiple regression of discharge with air temperature, wind speed, shortwave incoming radiation, and net radiation hours. Superimposed ice formed on 95% of the surface of Quviagivaa Glacier during the melt season, and reached thicknesses of 30cm at the glacier terminus. A strong correlation was found between snow depth and superimposed ice formation. On average, 67% of the snowpack water equivalent formed superimposed ice. The net accumulation of superimposed ice occurred on \u3c10% of the area of Quviagivaa Glacier, but evidence suggests that in 1992 this percentage was closer to 65%. It is likely that the primary form of net accumulation for the glaciers of the Sawtooth Range is superimposed ice

Dysfunctional γ-Secretase in Familial Alzheimer’s Disease

This is a post-peer-review, pre-copyedit version of an article published in Neurochemical Research. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11064-018-2511-1.Genetics strongly implicate the amyloid β-peptide (Aβ) in the pathogenesis of Alzheimer’s disease. Dominant missense mutation in the presenilins and the amyloid precursor protein (APP) cause early-onset familial Alzheimer’s disease (FAD). As presenilin is the catalytic component of the γ-secretase protease complex that produces Aβ from APP, mutation of the enzyme or substrate that produce Aβ leads to FAD. However, the mechanism by which presenilin mutations cause FAD has been controversial, with gain of function and loss of function offered as binary choices. This overview will instead present the case that presenilins are dysfunctional in FAD. γ-Secretase is a multi-functional enzyme that proteolyzes the APP transmembrane domain in a complex and processive manner. Reduction in a specific function—the carboxypeptidase trimming of initially formed long Aβ peptides containing most of the transmembrane domain to shorter secreted forms—is an emerging common feature of FAD-mutant γ-secretase complexes