Republics and empires provides transnational perspectives
on the significance of Italy to American art and visual culture and
the impact of the United States on Italian art and popular culture.
...Covering the period from the Risorgimento to the Cold War,
it reveals the complexity of the visual discourses that bound two
relatively new nations together. It also gives substantial
attention to literary and critical texts that addressed the
evolving cultural relationship between Italy and the United States.
While American art history has tended to privilege French, British
and German ties, these chapters highlight a rich body of
contemporary research by Italian and American scholars that moves
beyond a discussion of influence as a one-way directive towards a
deeper understanding of cultural transactions that profoundly
affected the artistic expression of both nations.
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.
We report the results of a long-term follow-up of subjects in a phase 1 study of AAV2-hAADC (adeno-associated virus type 2-human aromatic L-amino acid decarboxylase) gene therapy for the treatment of ...Parkinson's disease (PD). Ten patients with moderately advanced PD received bilateral putaminal infusions of either a low or a high dose of AAV2-hAADC vector. An annual positron emission tomography (PET) imaging with (18)Ffluoro-L-m-tyrosine tracer was used for evaluation of AADC expression, and a standard clinical rating scale Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess effect. Our previous analysis of the 6-month data suggested that this treatment was acutely safe and well tolerated. We found that the elevated PET signal observed in the first 12 months persisted over 4 years in both dose groups. A significantly increased PET value compared with the presurgery baseline was maintained over the 4-year monitoring period. The UPDRS in all patients off medication for 12 hr improved in the first 12 months, but displayed a slow deterioration in subsequent years. This analysis demonstrates that apparent efficacy continues through later years with an acceptable safety profile. These data indicate stable transgene expression over 4 years after vector delivery and continued safety, but emphasize the need for a controlled efficacy trial and the use of a higher vector dose.
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.
Knauer referenced Burckhardt in conjunction with her discussion of the two Black African oarsmen in Vittore Carpaccio's Hunting on the Lagoon (circa 1492–1494; figure 1), but did not offer any ...discussion of either Burckhardt's brief speculation about Othello or the Renaissance source that had prompted it.2 The text in which Burckhardt had found mention of a Black African commander was Alessandro Benedetti's Diaria de bello carolino (Diary of the Caroline War), which was first published (almost certainly in Venice, and probably by Aldus Manutius) either in 1496 or shortly thereafter.3 The relevant passage reads: "Finally, since it was not without gratitude in the smallest matters, the Senate presented to the wife of Johannis Aethiops John the Ethiopian, now a widow, 72 ducats each year from the treasury and a home forever. Sanuto, whose narrative of the opening phase of the Italian wars was not published until 1873—which explains why it escaped the attention of Burckhardt in his 1869 note—gives a similar account in a section titled "Remuneration made by the Venetian state to many deserving persons for the operations at the Taro": "To the wife of one Zuan Bianco John White who was a commander contestabele, who died at the aforementioned event Fornovo, who was a most valiant or capable Black African saracino valentissimo, was given a house in the citadel of Verona, where she might live, and six ducats a month for life. Photo: The Picture Art Collection. Six ducats a month (seventy-two a year) in addition to free housing for life would have provided a comfortable existence for the widow and children, and this level of remuneration was provided to the families of several other slain military captains in this era.
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.
We present measurements of the stress response of packings formed from a wide range of particle shapes. Besides spheres these include convex shapes such as the Platonic solids, truncated tetrahedra, ...and triangular bipyramids, as well as more complex, non-convex geometries such as hexapods with various arm lengths, dolos, and tetrahedral frames. All particles were 3D-printed in hard resin. Well-defined initial packing states were established through preconditioning by cyclic loading under given confinement pressure. Starting from such initial states, stress-strain relationships for axial compression were obtained at four different confining pressures for each particle type. While confining pressure has the largest overall effect on the mechanical response, we find that particle shape controls the details of the stress-strain curves and can be used to tune packing stiffness and yielding. By correlating the experimentally measured values for the effective Young's modulus under compression, yield stress and energy loss during cyclic loading, we identify trends among the various shapes that allow for designing a packing's aggregate behavior.
Packings of 3d-printed particles are used to establish relationships between shape of the constituents and aggregate mechanical properties (stiffness, yield stress, and energy loss) under compression.
Due to the religious restrictions on imagery introduced by the Reformation, depictions of the Black African incarnation of Saint Maurice were sharply reduced and transformed in the German-speaking ...lands after 1530. This essay looks in detail at developments in several Saxon cities and also in the Baltic cities of Tallinn (Reval) and Riga. In Magdeburg and Halle, the focus is on secularized images of Maurice, while in Halle a little-known but vast painting replaced the Black Maurice with other Black characters more closely tied to the Bible. In the Baltic cities, the Black Maurice was in a complicated relationship with the heraldry of the Black Heads merchant guilds; only in the last few centuries has a secular version of the Black Maurice fully reappeared.
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 .
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