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\"Through a series of articles spanning over 15 years of research, Paul D. Kaplan, who developed the methodologies behind the Morningstar Rating and the Morningstar Style Box tackles the issues investors face when they attempt to put the concepts of asset allocation into practice, among them: How should the asset classes be defined? Should equities be divided into asset classes based on investment style, geography, or other factors? Should asset classes be represented by market-cap-weighted indexes or should other principles, such as fundamental weights, be used? How do actively managed funds fit into asset-class mixes? Kaplan also interviews the intellectuals who have greatly influenced the evolution of asset allocation, including Harry Markowitz, Roger Ibbotson, and the late Benoit Mandelbrot. Throughout the book, Kaplan offers his own opinions and analysis. He includes three appendices that put theory into action with technical details for new asset-allocation frameworks, including the next generation of portfolio construction, which Kaplan dubs 'Markowitz 2.0.'\"-- Provided by publisher.

In his best-selling travel memoir, The Innocents Abroad, Mark Twain punningly refers to the black man who introduces him to Venetian Renaissance painting as a \"contraband guide,\" a term coined to describe fugitive slaves who assisted Union armies during the Civil War. By means of this and similar case studies, Paul H. D. Kaplan documents the ways in which American cultural encounters with Europe and its venerable artistic traditions influenced nineteenth-century concepts of race in the United States. Americans of the Civil War era were struck by the presence of people of color in European art and society, and American artists and authors, both black and white, adapted and transformed European visual material to respond to the particular struggles over the identity of African Americans. Taking up the work of both well- and lesser-known artists and writers—such as the travel writings of Mark Twain and William Dean Howells, the paintings of German American Emanuel Leutze, the epistolary exchange between John Ruskin and Charles Eliot Norton, newspaper essays written by Frederick Douglass and William J. Wilson, and the sculpture of freed slave Eugène Warburg—Kaplan lays bare how racial attitudes expressed in mid-nineteenth-century American art were deeply inflected by European traditions. By highlighting the contributions people of black African descent made to the fine arts in the United States during this period, along with the ways in which they were represented, Contraband Guides provides a fresh perspective on the theme of race in Civil War–era American art. It will appeal to art historians, to specialists in African American studies and American studies, and to general readers interested in American art and African American history.

We have developed 22 mouse IgG1 monoclonal antibodies (mAbs) against Bacteroides fragilis zinc metalloprotease toxins 1 and 2 (BFT1 and BFT2). Mice were immunized with recombinant BFT1 or BFT2 proteins with metalloprotease activity. Eight of the mAbs bind specifically to BFT1. One mAb, 2H6, binds specifically to BFT2. The remaining 13 mAbs bind to both BFT1 and BFT2. The eight BFT1-specific mAbs recognize at least five different epitopes on the toxin. Four of the BFT1-specific mAbs neutralized rBFT1 metalloprotease activity. Only one of these four mAbs, 1D9, neutralizes the cytotoxic effect of BFT1. Here, we describe the development of enzyme-linked immunosorbent assays (ELISAs) to detect BFT1 or BFT2 toxin in an isotype-specific manner. The sandwich ELISAs have a detection limit of 20 to 40 ng/ml when purified recombinant BFT protein is diluted into PBS. The sandwich ELISA can be used to distinguish and quantify levels of rBFT1 and rBFT2 in stool. This ELISA can be an important tool to investigate the association between BFT expression by enterotoxigenic B. fragilis and diseases such as diarrhea, inflammatory bowel disease and colorectal cancer.

Background ALZ-801 is an orally available, valine-conjugated prodrug of tramiprosate. Tramiprosate, the active agent, is a small-molecule β-amyloid (Aβ) anti-oligomer and aggregation inhibitor that was evaluated extensively in preclinical and clinical investigations for the treatment of Alzheimer’s disease (AD). Tramiprosate has been found to inhibit β-amyloid oligomer formation by a multi-ligand enveloping mechanism of action that stabilizes Aβ42 monomers, resulting in the inhibition of formation of oligomers and subsequent aggregation. Although promising as an AD treatment, tramiprosate exhibited two limiting deficiencies: high intersubject pharmacokinetic (PK) variability likely due to extensive gastrointestinal metabolism, and mild-to-moderate incidence of nausea and vomiting. To address these, we developed an optimized prodrug, ALZ-801, which retains the favorable efficacy attributes of tramiprosate while improving oral PK variability and gastrointestinal tolerability. In this study, we summarize the phase I bridging program to evaluate the safety, tolerability and PK for ALZ-801 after single and multiple rising dose administration in healthy volunteers. Methods Randomized, placebo-controlled, phase I studies in 127 healthy male and female adult and elderly volunteers included [ 1 ] a single ascending dose (SAD) study; [ 2 ] a 14-day multiple ascending dose (MAD) study; and [ 3 ] a single-dose tablet food-effect study. This program was conducted with both a loose-filled capsule and an immediate-release tablet formulation, under both fasted and fed conditions. Safety and tolerability were assessed, and plasma and urine were collected for liquid chromatography-mass spectrometry (LC-MS) determination and non-compartmental PK analysis. In addition, we defined the target dose of ALZ-801 that delivers a steady-state plasma area under the curve (AUC) exposure of tramiprosate equivalent to that studied in the tramiprosate phase III study. Results ALZ-801 was well tolerated and there were no severe or serious adverse events (AEs) or laboratory findings. The most common AEs were transient mild nausea and some instances of vomiting, which were not dose-related and showed development of tolerance after continued use. ALZ-801 produced dose-dependent maximum plasma concentration ( C max ) and AUC exposures of tramiprosate, which were equivalent to that after oral tramiprosate, but with a substantially reduced intersubject variability and a longer elimination half-life. Administration of ALZ-801 with food markedly reduced the incidence of gastrointestinal symptoms compared with the fasted state, without affecting plasma tramiprosate exposure. An immediate-release tablet formulation of ALZ-801 displayed plasma exposure and low variability similar to the loose-filled capsule. ALZ-801 also showed excellent dose-proportionality without accumulation or decrease in plasma exposure of tramiprosate over 14 days. Based on these data, 265 mg of ALZ-801 twice daily was found to achieve a steady-state AUC exposure of tramiprosate equivalent to 150 mg twice daily of oral tramiprosate in the previous phase III trials. Conclusions ALZ-801, when administered in capsule and tablet forms, showed excellent oral safety and tolerability in healthy adults and elderly volunteers, with significantly improved PK characteristics over oral tramiprosate. A clinical dose of ALZ-801 (265 mg twice daily) was established that achieves the AUC exposure of 150 mg of tramiprosate twice daily, which showed positive cognitive and functional improvements in apolipoprotein E4/4 homozygous AD patients. These bridging data support the phase III development of ALZ-801in patients with AD.

\"Due to the graphic nature of this program, viewer discretion is advised.\" Most of us have encountered this warning while watching television at some point. It is typically attached to a brand of reality crime TV that Paul Kaplan and Daniel LaChance call \"crimesploitation\": spectacles designed to entertain mass audiences by exhibiting \"real\" criminal behavior and its consequences. This book examines their enduring popularity in American culture. Analyzing the structure and content of several popular crimesploitation shows, including Cops, Dog: The Bounty Hunter, and To Catch a Predator, as well as newer examples like Making a Murderer and Don't F**K with Cats, Kaplan and LaChance highlight the troubling nature of the genre: though it presents itself as ethical and righteous, its entertainment value hinges upon suffering. Viewers can imagine themselves as deviant and ungovernable like the criminals in the show, thereby escaping a law-abiding lifestyle. Alternatively, they can identify with law enforcement officials, exercising violence, control, and \"justice\" on criminal others. Crimesploitation offers a sobering look at the depictions of criminals, policing, and punishment in modern America.

In his best-selling travel memoir, The Innocents Abroad , Mark Twain punningly refers to the black man who introduces him to Venetian Renaissance painting as a \"contraband guide,\" a term coined to describe fugitive slaves who assisted Union armies during the Civil War. By means of this and similar case studies, Paul H. D. Kaplan documents the ways in which American cultural encounters with Europe and its venerable artistic traditions influenced nineteenth-century concepts of race in the United States. Americans of the Civil War era were struck by the presence of people of color in European art and society, and American artists and authors, both black and white, adapted and transformed European visual material to respond to the particular struggles over the identity of African Americans. Taking up the work of both well- and lesser-known artists and writers-such as the travel writings of Mark Twain and William Dean Howells, the paintings of German American Emanuel Leutze, the epistolary exchange between John Ruskin and Charles Eliot Norton, newspaper essays written by Frederick Douglass and William J. Wilson, and the sculpture of freed slave Eugène Warburg-Kaplan lays bare how racial attitudes expressed in mid-nineteenth-century American art were deeply inflected by European traditions. By highlighting the contributions people of black African descent made to the fine arts in the United States during this period, along with the ways in which they were represented, Contraband Guides provides a fresh perspective on the theme of race in Civil War-era American art. It will appeal to art historians, to specialists in African American studies and American studies, and to general readers interested in American art and African American history.

In 1994, Larry Siegel and I published an article in this journal in response to an article that claimed that (1) mean-variance optimization (MVO), a vital part of modern portfolio theory (MPT) as developed by Harry Markowitz, is flawed, and (2) postmodern portfolio theory (PMPT) is a superior method for constructing portfolios, thus making MVO obsolete. Although we defended MVO and pointed out the limitations of PMPT, in retrospect, I believe the most important point that we made was that portfolio theory should be more broadly understood to mean any portfolio construction model that presents the investor with a trade-off between reward (however defined) and risk (however defined). Hence, MVO and PMPT are both special cases of portfolio theory. Years later, Sam Savage and I developed such a general framework, in which the user of our model can select a measure of reward and a measure of risk and have a wide choice of return distribution models. This framework, which we dubbed Markowitz 2.0 , I believe is a logical progression from MVO, which we dubbed Markowitz 1.0 .

Paul Kaplan reviews Ghosts Over the Boiler: Voices from Alabama’s Death Row edited by Katie Owens-Murphy 

These research notes explore the idea of comparing executions in the United States (US) to executions undertaken by the Islamic State of Iraq and Syria (ISIS). Is it possible that America’s ostensibly rational, formal, and “clinical” death penalty is more painful for its victims than ISIS victims? I investigate this question by considering the suffering caused by the death penalty in the US, making some informed speculations about ISIS executions, discussing execution in two influential Islamic nations, and observing some ironies these topic raise about the rule of law and capital punishment. My goal with these notes is to spur interest in comparative research on state violence and the death penalty.

In 2014, the authors introduced gamma, a new metric designed to quantify the value of more intelligent financial planning decisions, with a focus on the potential benefits of working with a financial advisor. This article revisits gamma, but with a relatively narrow scope: to quantify the potential benefits of implementing a gamma-efficient portfolio strategy for an investor; that is, to measure the gamma of investing decisions. We do this using a framework of seven questions an investor should consider during the portfolio construction process. This framework is far more comprehensive than simply selecting a few mutual funds. Based on our empirical tests and existing research, we estimate that the \"average\" investor is likely to benefit significantly from working with a financial advisor, so long as the advisor provides comprehensive, high-quality portfolio services for a reasonable fee. The potential benefits associated with making better portfolio decisions will vary considerably by investor.