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Main Street movies : the history of local film in the United States
Prior to the advent of the home movie camer and the ubiquitousness of the camera phone, there was the local film. This cultural phenomenon, produced across the country from the 1890s to the 1950s, gave ordinary people a chance to be on the silver screen without leaving their hometowns. Through these movies, residents could see themselves in the same theaters where they saw major Hollywood motion pictures. Traveing filmmakers plied their trade in small towns and cities, where these films were received by locals as being part of the larger cinema experience. With access to the rare film clips under discussion, Main Street Movies documents the diversity and longevity of local film production and examines how itinerant filmmakers responded to industry changes to keep sponsors and audiences satisfied. From town-pride films in the 1910s to Hollywood knockoffs in the 1930s, local films captured not just images of local people and places but also ideas about the function and meaning of cinema that continue to resonate today.
Book
The native ORAI channel trio underlies the diversity of Ca2+ signaling events
The essential role of ORAI1 channels in receptor-evoked Ca
2+
signaling is well understood, yet little is known about the physiological activation of the ORAI channel trio natively expressed in all cells. The roles of ORAI2 and ORAI3 have remained obscure. We show that ORAI2 and ORAI3 channels play a critical role in mediating the regenerative Ca
2+
oscillations induced by physiological receptor activation, yet ORAI1 is dispensable in generation of oscillations. We reveal that ORAI2 and ORAI3 channels multimerize with ORAI1 to expand the range of sensitivity of receptor-activated Ca
2+
signals, reflecting their enhanced basal STIM1-binding and heightened Ca
2+
-dependent inactivation. This broadened bandwidth of Ca
2+
influx is translated by cells into differential activation of NFAT1 and NFAT4 isoforms. Our results uncover a long-sought role for ORAI2 and ORAI3, revealing an intricate control mechanism whereby heteromerization of ORAI channels mediates graded Ca
2+
signals that extend the agonist-sensitivity to fine-tune transcriptional control.
The essential role of ORAI1 channels in receptor-evoked Ca
2+
signaling is well understood, but the roles of ORAI2 and ORAI3 remained obscure. Here authors show that ORAI2 and ORAI3 channels multimerize with ORAI1 to expand the range of sensitivity of receptor-activated Ca
2+
signals, reflecting their enhanced basal STIM1-binding and heightened Ca
2+
-dependent inactivation.
Journal Article
Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions
Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process that produced 24 kilograms of prexasertib monolactate monohydrate suitable for use in human clinical trials. Eight continuous unit operations were conducted to produce the target at roughly 3 kilograms per day using small continuous reactors, extractors, evaporators, crystallizers, and filters in laboratory fume hoods. Success was enabled by advances in chemistry, engineering, analytical science, process modeling, and equipment design. Substantial technical and business drivers were identified, which merited the continuous process. The continuous process afforded improved performance and safety relative to batch processes and also improved containment of a highly potent compound.
Journal Article
Main Street movies : the history of local film in the United States
1. The scholarship in this book is a unique and ground-breaking perspective on film culture in small-town America 2. It is a strong project by an up and coming scholar who is very engaged in his field. 3. The book provides rich archival evidence, and multimedia is hosted in enhanced e-book edition as well as online for our print readers via our partnership with the IU Online Media Archives.
eBook
Analyzing social networks using R
This approachable book introduces network research in R, walking you through every step of doing social network analysis. Drawing together research design, data collection and data analysis, it explains the core concepts of network analysis in a non-technical way. The book balances an easy to follow explanation of the theoretical and statistical foundations underpinning network analysis with practical guidance on key steps like data management, preparation and visualisation.
Book
Polarized Political Communication, Oppositional Media Hostility, and Selective Exposure
Previous research has consistently documented a hostile media effect in which people see bias in balanced reporting on political controversies. In the contemporary fragmented media environment, partisan news outlets intentionally report political news from ideological perspectives, raising the possibility that ideologically biased news may cause viewers to become increasingly suspicious of and antagonistic toward news media—which we call oppositional media hostility. However, the fragmented media environment also gives television viewers ample opportunities to tune out news outlets with which they disagree as well as the news altogether, and this should moderate oppositional media hostility. We investigate the effects of partisan news shows on media perceptions across six laboratory-based experiments. We find that counterattitudinal news programming is more likely to induce hostile media perceptions than proattitudinal programming, but that the presence of choice blunts oppositional media hostility. We explore possible mechanisms that underlie the moderating effects of selective exposure.
Journal Article
STIM1 is a core trigger of airway smooth muscle remodeling and hyperresponsiveness in asthma
Airway remodeling and airway hyperresponsiveness are central drivers of asthma severity. Airway remodeling is a structural change involving the dedifferentiation of airway smooth muscle (ASM) cells from a quiescent to a proliferative and secretory phenotype. Here, we show up-regulation of the endoplasmic reticulum Ca2+ sensor stromal-interacting molecule 1 (STIM1) in ASM of asthmatic mice. STIM1 is required for metabolic and transcriptional reprogramming that supports airway remodeling, including ASM proliferation, migration, secretion of cytokines and extracellular matrix, enhanced mitochondrial mass, and increased oxidative phosphorylation and glycolytic flux. Mechanistically, STIM1-mediated Ca2+ influx is critical for the activation of nuclear factor of activated T cells 4 and subsequent interleukin-6 secretion and transcription of pro-remodeling transcription factors, growth factors, surface receptors, and asthma-associated proteins. STIM1 drives airway hyperresponsiveness in asthmatic mice through enhanced frequency and amplitude of ASM cytosolic Ca2+ oscillations. Our data advocates for ASM STIM1 as a target for asthma therapy.
Journal Article