859 research outputs found
Crossing boundaries: Male consumption of Korean TV dramas and negotiation of gender relations in modern day Hong Kong
The gendered nature of modernity in the European Enlightenment tradition has naturalized and institutionalized an essentialist, binary system of masculinity and femininity. A similarly hierarchicalized, binary system of gender role relationships also underlies the Confucianist social order in East Asian cultural traditions. Our recent study of some educated, Chinese, heterosexual men's consumption of Korean TV dramas in the late/post-industrial (but not post-capitalist) society of Hong Kong, however, shows that while the binary gender boundaries are increasingly being destabilized and crossed over in their everyday lived experiences, these boundaries are also simultaneously being nostalgically hung onto by some of the men in their pleasurable consumption of Korean dramas. The implications of their consumption practices are discussed in terms of the dilemmas faced by some Hong Kong men when they are confronted with the increasing destabilization of the gender role boundaries and how they use Korean dramas to negotiate new gender relations in modern day Hong Kong society.postprin
VCP-dependent muscle degeneration is linked to defects in a dynamic tubular lysosomal network in vivo.
Lysosomes are classically viewed as vesicular structures to which cargos are delivered for degradation. Here, we identify a network of dynamic, tubular lysosomes that extends throughout Drosophila muscle, in vivo. Live imaging reveals that autophagosomes merge with tubular lysosomes and that lysosomal membranes undergo extension, retraction, fusion and fission. The dynamics and integrity of this tubular lysosomal network requires VCP, an AAA-ATPase that, when mutated, causes degenerative diseases of muscle, bone and neurons. We show that human VCP rescues the defects caused by loss of Drosophila VCP and overexpression of disease relevant VCP transgenes dismantles tubular lysosomes, linking tubular lysosome dysfunction to human VCP-related diseases. Finally, disruption of tubular lysosomes correlates with impaired autophagosome-lysosome fusion, increased cytoplasmic poly-ubiquitin aggregates, lipofuscin material, damaged mitochondria and impaired muscle function. We propose that VCP sustains sarcoplasmic proteostasis, in part, by controlling the integrity of a dynamic tubular lysosomal network
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MCTP is an ER-resident calcium sensor that stabilizes synaptic transmission and homeostatic plasticity.
Presynaptic homeostatic plasticity (PHP) controls synaptic transmission in organisms from Drosophila to human and is hypothesized to be relevant to the cause of human disease. However, the underlying molecular mechanisms of PHP are just emerging and direct disease associations remain obscure. In a forward genetic screen for mutations that block PHP we identified mctp (Multiple C2 Domain Proteins with Two Transmembrane Regions). Here we show that MCTP localizes to the membranes of the endoplasmic reticulum (ER) that elaborate throughout the soma, dendrites, axon and presynaptic terminal. Then, we demonstrate that MCTP functions downstream of presynaptic calcium influx with separable activities to stabilize baseline transmission, short-term release dynamics and PHP. Notably, PHP specifically requires the calcium coordinating residues in each of the three C2 domains of MCTP. Thus, we propose MCTP as a novel, ER-localized calcium sensor and a source of calcium-dependent feedback for the homeostatic stabilization of neurotransmission
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A postsynaptic PI3K-cII dependent signaling controller for presynaptic homeostatic plasticity.
Presynaptic homeostatic plasticity stabilizes information transfer at synaptic connections in organisms ranging from insect to human. By analogy with principles of engineering and control theory, the molecular implementation of PHP is thought to require postsynaptic signaling modules that encode homeostatic sensors, a set point, and a controller that regulates transsynaptic negative feedback. The molecular basis for these postsynaptic, homeostatic signaling elements remains unknown. Here, an electrophysiology-based screen of the Drosophila kinome and phosphatome defines a postsynaptic signaling platform that includes a required function for PI3K-cII, PI3K-cIII and the small GTPase Rab11 during the rapid and sustained expression of PHP. We present evidence that PI3K-cII localizes to Golgi-derived, clathrin-positive vesicles and is necessary to generate an endosomal pool of PI(3)P that recruits Rab11 to recycling endosomal membranes. A morphologically distinct subdivision of this platform concentrates postsynaptically where we propose it functions as a homeostatic controller for retrograde, trans-synaptic signaling
Freight Sequencing to Improve Hub Operations in the Less-Than-Truckload Freight Transportation Industry
In less-than-truckload freight transportation, hub operations affect the service levels that carriers are able to provide their customers. This paper focuses on improving the efficiency of hub operations by reducing freight handling time and cost. Specifically, the freight sequencing problem (FSP) is investigated to determine the freight unloading and loading sequence that minimizes the time for dock workers to transfer shipments from origin trailers to destination trailers. The FSP is modeled as a Rural Postman Problem (RPP) and three algorithms are compared: trailer-at-atime, nearest neighbor, and balance-and-connect. Using five industrial data sets, the results demonstrate the effectiveness, advantages, and disadvantages of the approaches
Biased diversity metrics revealed by bacterial 16S pyrotags derived from different primer sets.
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Evolving from Student to Teacher: Insights from the Conversation Café on Doctoral Student Mentorship
Mentorship has been proposed as a key process for preparing doctoral students as effective educators. However, few models have been described in-depth. To address this challenge, four social work doctoral graduates and one senior faculty member shared their insights drawing on their study on collaborative teaching mentorship, reflecting on their mentorship experiences and inviting feedback from the conference audience in the Conversation Café forum. The resultant discussion supported findings from our research and reinforced that more systematic and reflective efforts are needed to adequately prepare doctoral students for future teaching responsibilities. Specific strategies are summarized.
Melanocytic Galectin-3 Is Associated with Tyrosinase-Related Protein-1 and Pigment Biosynthesis
Galectin-3 is a family member of the carbohydrate-binding proteins widely expressed by many cell types and exhibits multiple cellular functions. We demonstrate that melanocytes express galectin-3, which is predominantly localized to the cell body peripherally along the Golgi zone. Downregulation of galectin-3 in human melanocytes using short hairpin RNA technology resulted in the reduction of both melanin synthesis and expression/activity of tyrosinase-related protein-1 (Tyrp-1). In the cell body, galectin-3 colocalizes with melanosome-destined cargo, specifically tyrosinase and Tyrp-1. We studied melanocytes cultured from patients with forms of Hermansky–Pudlak syndrome (HPS) containing defects in trafficking steps governed by biogenesis of lysosome-related organelle complex-2 (BLOC-2) (HPS-5), BLOC-3 (HPS-1), and adaptin-3 (HPS-2). We found that galectin-3 expression mimicked the defective expression of the tyrosinase cargo in dendrites of HPS-5 melanocytes, but it was not altered in HPS-1 or HPS-2 melanocytes. In addition, galectin-3 colocalized predominantly with the HPS-5 component of BLOC-2 in normal human melanocytes. These data indicate that galectin-3 is a regulatory component in melanin synthesis affecting the expression of Tyrp-1
Towards Robust Offline Reinforcement Learning under Diverse Data Corruption
Offline reinforcement learning (RL) presents a promising approach for
learning reinforced policies from offline datasets without the need for costly
or unsafe interactions with the environment. However, datasets collected by
humans in real-world environments are often noisy and may even be maliciously
corrupted, which can significantly degrade the performance of offline RL. In
this work, we first investigate the performance of current offline RL
algorithms under comprehensive data corruption, including states, actions,
rewards, and dynamics. Our extensive experiments reveal that implicit
Q-learning (IQL) demonstrates remarkable resilience to data corruption among
various offline RL algorithms. Furthermore, we conduct both empirical and
theoretical analyses to understand IQL's robust performance, identifying its
supervised policy learning scheme as the key factor. Despite its relative
robustness, IQL still suffers from heavy-tail targets of Q functions under
dynamics corruption. To tackle this challenge, we draw inspiration from robust
statistics to employ the Huber loss to handle the heavy-tailedness and utilize
quantile estimators to balance penalization for corrupted data and learning
stability. By incorporating these simple yet effective modifications into IQL,
we propose a more robust offline RL approach named Robust IQL (RIQL). Extensive
experiments demonstrate that RIQL exhibits highly robust performance when
subjected to diverse data corruption scenarios.Comment: 31 pages, 17 figure
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