The majority of theranostic prodrugs reported so far relay information through a fluorogenic response generated upon release of the active chemotherapeutic agent. A chemiluminescence detection mode ...offers significant advantages over fluorescence, mainly due to the superior signal‐to‐noise ratio of chemiluminescence. Here we report the design and synthesis of the first theranostic prodrug monitored by a chemiluminescence diagnostic mode. As a representative model, we prepared a prodrug from the chemotherapeutic monomethyl auristatin E, which was modified for activation by β‐galactosidase. The activation of the prodrug in the presence of β‐galactosidase is accompanied by emission of a green photon. Light emission intensities, which increase with increasing concentration of the prodrug, were linearly correlated with a decrease in the viability of a human cell line that stably expresses β‐galactosidase. We obtained sharp intravital chemiluminescent images of endogenous enzymatic activity in β‐galactosidase‐overexpressing tumor‐bearing mice. The exceptional sensitivity achieved with the chemiluminescence diagnostic mode should allow the exploitation of theranostic prodrugs for personalized cancer treatment.
Ray of light: A chemiluminescence detection mode offers significant advantages over fluorescence, mainly due to a superior signal‐to‐noise ratio. A theranostic prodrug that is monitored through a chemiluminescence diagnostic mode was designed. As a representative example, a prodrug was prepared from the chemotherapeutic monomethyl auristatin E, which was modified for activation by β‐galactosidase.
Blue Studios DuPlessis, Rachel Blau
2006, 2010-11-18
eBook
Feminist issues in avant garde poetry.   In her now-classic The Pink Guitar , Rachel Blau DuPlessis examined a number of modern and contemporary poets and artists to explore the possibility of ...finding a language that would question deeply held assumptions about gender. In the 12 essays and introduction that constitute Blue Studios , DuPlessis continues that task, examining the work of experimental poets and the innovative forms they have fashioned to challenge commonplace assumptions about gender and cultural authority.   The essays in “Attitudes and Practices” deal with two questions: what a feminist reading of cultural texts involves, and the nature of the essay itself as a mode of knowing: how poetry can be discursive and how the essay can be poetic. The goal of “Marble Paper,” with its studies of William Wordsworth, Ezra Pound, and Charles Olson is to suggest terms for a “feminist history of poetry.”  
The heterogeneity of pancreatic ductal adenocarcinoma (PDAC) suggests that successful treatment might rely on simultaneous targeting of multiple genes, which can be achieved by RNA interference-based ...therapeutic strategies. Here we show a potent combination of microRNA and siRNA delivered by an efficient nanocarrier to PDAC tumors. Using proteomic-microRNA profiles and survival data of PDAC patients from TCGA, we found a novel signature for prolonged survival. Accordingly, we used a microRNA-mimic to increase miR-34a together with siRNA to silence PLK1 oncogene. For in vivo dual-targeting of this combination, we developed a biodegradable amphiphilic polyglutamate amine polymeric nanocarrier (APA). APA-miRNA-siRNA polyplexes systemically administered to orthotopically inoculated PDAC-bearing mice showed no toxicity and accumulated at the tumor, resulting in an enhanced antitumor effect due to inhibition of MYC oncogene, a common target of both miR-34a and PLK1. Taken together, our findings warrant this unique combined polyplex's potential as a novel nanotherapeutic for PDAC.
This interview with poet, essayist, literary critic, and collagist Rachel Blau DuPlessis was conducted via email correspondence between June 11 and August 29, 2020. Author of over a dozen volumes of ...poetry and half a dozen books in modernist studies, poetics, and feminist criticism, DuPlessis reflects broadly on her career in this interview. She discusses the ongoing role of feminism in her writing and thought, the forms of the fold and the fragment, the relationship between her poetry and criticism, her work in and on the long poem, and her post‐
poetry, including her (at the time) most recent book,
(2020). The interview concludes with a conversation about the relationship between poetry and theorizing practices and a meditation on writing during a global pandemic.
Poet George Oppen (1908–1984) and artist and writer Mary Oppen (1908–1990) were striking, exemplary, and somewhat mysterious cultural figures of the last decades of the twentieth century. To a ...younger group of artists, George Oppen functioned as a mentor, an irritant, and a supporter. Together, because of their intense and unique union, the Oppens provided a model of the companionate artistic life. In this book the poets, editors, writers, composers, and teachers who knew the couple consider their encounters and relationships with George and Mary Oppen. Set at a politically crucial time in US history, from the Cold War through the Vietnam War and the women's movement, the essays show how people tried to integrate art and politics in the spirit of the Oppens' own debates and choices.
Recent years have seen tremendous progress in the design and study of molecular imaging geared towards biological and biomedical applications. The expression or activity of specific enzymes including ...proteases can be monitored by cutting edge molecular imaging techniques. Cathepsin B plays key roles in tumor progression via controlled degradation of extracellular matrix. Consequently, this protease has been attracting significant attention in cancer research, and many imaging probes targeting its activity have been developed. Here, we describe the design, synthesis and evaluation of two novel near infrared (NIR) fluorescent probes for detection of cathepsin B activity with different turn-ON mechanisms. One probe is based on an ICT activation mechanism of a donor-two-acceptor π-electron dye system, while the other is based on the FRET mechanism obtained by a fluorescent dye and a quencher. The two probes exhibit significant fluorescent turn-ON response upon cleavage by cathepsin B. The NIR fluorescence of the ICT probe in its OFF state was significantly lower than that of the FRET-based probe. This effect results in a higher signal-to-noise ratio and consequently increased sensitivity and better image contrast.
What ispatriarchal poetry? How can it be both attractive and tempting and yet be so hegemonic that it is invisible? How does it combine various mixes of masculinity, femininity, effeminacy, and ...eroticism? At once passionate and dispassionate, Rachel Blau DuPlessis meticulously outlines key moments of choice and debate about masculinity among writers as disparate as Ezra Pound, T. S. Eliot, Louis Zukofsky, Charles Olson, Robert Creeley, and Allen Ginsberg, choices that construct consequential models for institutions of poetic practice.
As DuPlessis writes, "There are no genderless subjects in any relationship structuring literary culture: not in production, dissemination, or reception; not in objects, discourses, or practices; not in reading experiences or in interpretations." And, as she reveals in careful and enthralling detail, for the poets at the center of this book, questions of masculinity loomed large and were continuously articulated in their self-creation as writers, in literary bonding, and in its deployment.
These gender-laden choices, debates, and contradictions all have a striking influence today. In this empathic yet critical historical polemic, DuPlessis reveals the outcomes of these many investments in the radical reconstruction of masculinity, in their strains, incompleteness, tensions-and failures. At the heart of modernist maleness and poetic practices are contradictions and urgencies, gender ideas both progressive and defensive.In a striking book on male behavior in poetic dyads, the third book in a feminist critical trilogy, DuPlessis tracks the poetic debates and arguments about gender that continuously affirm patriarchal poetry.
Introns are key regulators of eukaryotic gene expression and present a potentially powerful tool for the design of synthetic eukaryotic gene expression systems. However, intronic control over gene ...expression is governed by a multitude of complex, incompletely understood, regulatory mechanisms. Despite this lack of detailed mechanistic understanding, here we show how a relatively simple model enables accurate and predictable tuning of synthetic gene expression system in yeast using several predictive intron features such as transcript folding and sequence motifs. Using only natural Saccharomyces cerevisiae introns as regulators, we demonstrate fine and accurate control over gene expression spanning a 100 fold expression range. These results broaden the engineering toolbox of synthetic gene expression systems and provide a framework in which precise and robust tuning of gene expression is accomplished.
Epidermal sensors for remote healthcare and performance monitoring require the ability to operate under the effects of bodily motion, heat, and perspiration. Here, the use of purpose‐synthesized ...polymer‐based dry electrodes and graphene‐based strain gauges to obtain measurements of swallowed volume under typical conditions of exercise is evaluated. The electrodes, composed of the common conductive polymer poly(3,4 ethylenedioxythiophene) (PEDOT) electrostatically bound to poly(styrenesulfonate)‐b‐poly(poly(ethylene glycol) methyl ether acrylate) (PSS‐b‐PPEGMEA), collect surface electromyography (sEMG) signals on the submental muscle group, under the chin. Simultaneously, the deformation of the surface of the skin is measured using strain gauges comprising single‐layer graphene supporting subcontinuous coverage of gold and a highly plasticized composite containing PEDOT:PSS. Together, these materials permit high stretchability, high resolution, and resistance to sweat. A custom printed circuit board (PCB) allows this multicomponent system to acquire strain and sEMG data wirelessly. This sensor platform is tested on the swallowing activity of a cohort of 10 subjects while walking or cycling on a stationary bike. Using a machine learning (ML) model, it is possible to predict swallowed volume with absolute errors of 36% for walking and 43% for cycling.
A wearable sensor platform for detecting swallow volume during exercise is studied. Participants wear a stretchable organic sensor set and perform exercises during which they swallow various volumes of water. The data are collected, transmitted to a cellphone, and used to train a machine learning algorithm. The sensors show promising durability and sensitivity, while the algorithm has reasonable accuracy, especially at higher swallow volumes.
Frequent sensor-assisted monitoring of changes in swallowing function may help improve detection of radiation-associated dysphagia before it becomes permanent. While our group has prototyped an ...epidermal strain/surface electromyography sensor that can detect minute changes in swallowing muscle movement, it is unknown whether patients with head and neck cancer would be willing to wear such a device at home after radiation for several months.
We iteratively assessed patients' design preferences and perceived barriers to long-term use of the prototype sensor.
In study 1 (questionnaire only), survivors of pharyngeal cancer who were 3-5 years post treatment and part of a larger prospective study were asked their design preferences for a hypothetical throat sensor and rated their willingness to use the sensor at home during the first year after radiation. In studies 2 and 3 (iterative user testing), patients with and survivors of head and neck cancer attending visits at MD Anderson's Head and Neck Cancer Center were recruited for two rounds of on-throat testing with prototype sensors while completing a series of swallowing tasks. Afterward, participants were asked about their willingness to use the sensor during the first year post radiation. In study 2, patients also rated the sensor's ease of use and comfort, whereas in study 3, preferences were elicited regarding haptic feedback.
The majority of respondents in study 1 (116/138, 84%) were willing to wear the sensor 9 months after radiation, and participant willingness rates were similar in studies 2 (10/14, 71.4%) and 3 (12/14, 85.7%). The most prevalent reasons for participants' unwillingness to wear the sensor were 9 months being excessive, unwanted increase in responsibility, and feeling self-conscious. Across all three studies, the sensor's ability to detect developing dysphagia increased willingness the most compared to its appearance and ability to increase adherence to preventive speech pathology exercises. Direct haptic signaling was also rated highly, especially to indicate correct sensor placement and swallowing exercise performance.
Patients and survivors were receptive to the idea of wearing a personalized risk sensor for an extended period during the first year after radiation, although this may have been limited to well-educated non-Hispanic participants. A significant minority of patients expressed concern with various aspects of the sensor's burden and its appearance.
ClinicalTrials.gov NCT03010150; https://clinicaltrials.gov/study/NCT03010150.
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