Malory’s Maladies: Determining Intention and Influence through Editorial Theory in Sir Thomas Malory’s Le Morte Darthur

By examining both William Caxton’s edition and the Winchester manuscript of Malory’s King Arthur tales, readers can begin to understand the editorial theory issues associated with these dissimilar texts. Questions concerning authorial intention, final intention, versions, and scholarly editing arise as scholars and readers try to negotiate which is the better version. However, each version offers advantages and disadvantages of Malory’s work, culminating in the need for both versions to exist and to be studied

Physician Couples: A Qualitative Inquiry Focused on Gendered Power and Marital Equality

How couples “do” gender and power in their marriages is a relevant topic for today’s couples. Despite social changes toward equality in many realms, gender continues to organize relationships in ways that give husbands more power than wives. However, some contemporary couples make conscious decisions to resist forces toward organizing according to stereotypical gender ideals and to “do” gender differently in their relationships. For couples in which one or both is a physician, power is also deeply embedded in the physician status, with families tending to organize around the physician’s demands. While these effects reinforce male dominance when the husband is the physician, they pull opposingly when the wife is the physician, which is increasingly common as greater numbers of women enter the medical profession. We do not know how forces of gender and physician status interplay and play out in physician marriages. This qualitative study uses a social constructionist feminist theoretical lens to examine data from 36 physician interviews to explore how gender and power organize physician family life. Using a grounded theory approach, we found that couples’ “undoing” gender was a core category around which three couple types emerged: traditional, gender-conflicted, and de-gendering. How couples manage gender and power depends on whether they continually counteract stereotypic gender roles, particularly by un-gendering their interactions. Among the couples in this study, even the most egalitarian ones, gender never gets completely undone; there are no cases in which women gain the kind of organizing power that men have. This study demonstrates how couples respond to societal pressures to conform with gendered expectations, from traditional couples, who continue to do gender in conventional patters, to gender-conflicted couples, who struggle with traditional ideals in the face of unconventional circumstances, to de-gendering couples, who adopt purposeful strategies to resist the societal pressures to conform to traditional gender ideals

Doctor of Philosophy

dissertationHIV-1 is an enveloped RNA virus that recruits cellular machinery to facilitate virus budding. HIV-1 Gag, the structural protein that drives the assembly and budding processes, binds directly to two cellular factors, TSG101 and ALIX. Both TSG101 and ALIX are proteins in the endosomal sorting complexes required for transport (ESCRT) pathway and are required for inward vesicle formation at late endosomes or multivesicular bodies (MVBs). Most ESCRT proteins are subunits one of five heterooligomeric complexes named ESCRT-0, ESCRT-I, ESCRT-II, ESCRT-III, and the VPS4 AAA ATPases (vacuolar protein sorting), which are sequentially recruited to sites of vesicle formation and virus budding. TSG101 is a member of the ESCRT-I complex and is involved in recognition of cargos and recruitment of ESCRT-II. ESCRT-II recruits ESCRT-III, which is composed of charged multivesicular body proteins (CHMPs) that coassemble to form a lattice on the surface of endosomal membranes. ALIX interacts with proteins in both ESCRT-I and ESCRT-III, but is not a constitutive member of either complex. ESCRT-III proteins bind directly to the VPS4 AAA ATPases, which are the only known enzymes in the pathway. ATP hydrolysis by the VPS4 ATPases releases all assembled ESCRT machinery, allowing multiple rounds of vesicle formation or viral egress. This thesis focuses on the identification and characterization of components of the human ESCRT protein network involved in HIV-1 budding

CHMP2B mutants linked to frontotemporal dementia impair maturation of dendritic spines.: CHMP2B and dendritic spines

International audienceThe highly conserved ESCRT-III complex is responsible for deformation and cleavage of membranes during endosomal trafficking and other cellular activities. In humans, dominant mutations in the ESCRT-III subunit CHMP2B cause frontotemporal dementia (FTD). The decade-long process leading to this cortical degeneration is not well understood. One possibility is that, akin to other neurodegenerative diseases, the pathogenic protein affects the integrity of dendritic spines and synapses before any neuronal death. Using confocal microscopy and 3D reconstruction, we examined whether expressing the FTD-linked mutants CHMP2B(intron5) and CHMP2B(Delta10) in cultured hippocampal neurons modified the number or structure of spines. Both mutants induced a significant decrease in the proportion of large spines with mushroom morphology, without overt degeneration. Furthermore, CHMP2B(Delta10) induced a drop in frequency and amplitude of spontaneous excitatory postsynaptic currents, suggesting that the more potent synapses were lost. These effects seemed unrelated to changes in autophagy. Depletion of endogenous CHMP2B by RNAi resulted in morphological changes similar to those induced by mutant CHMP2B, consistent with dominant-negative activity of pathogenic mutants. Thus, CHMP2B is required for spine growth. Taken together, these results demonstrate that a mutant ESCRT-III subunit linked to a human neurodegenerative disease can disrupt the normal pattern of spine development

Long-term Preservation of Deprecated Media: How Can Libraries Provide Information From Today’s CD-ROMs in the Future?

New data storage media advances in the 1990s brought changes to publishing practices. Storage media had gone through a series of progressions, and with falling costs of digital media, publishers now had new and affordable options for supplementing or publishing new works. Some print books included supplementary information on computer disks, and in other cases publishers made complete works available on computer disk instead of in print format. These changes in publishing are apparent in this library’s engineering collection, which now includes a large collection of resources acquired in CD-ROM format. Today, the library faces concerns about the long-term viability of these resources. Computer storage media have already evolved from 5.25” floppy disks to 3.5” floppy disks to CD-ROMs to DVD-ROMs to USB drives. Since computer manufacturers are phasing out optical drives, users now have few options for using library materials that are formatted on disks of any kind. This “technological obsolescence” has prompted the engineering librarians at this institution to investigate how to continue providing access to materials that are published on computer disk in a future age where computer users will have no resources available for reading the disks. Working with the library’s Digital Preservation Librarian, the engineering librarians will determine which of the engineering resources that are published in disk format must be preserved, and they will plan for best practices for preservation of, and access to, the selected resources. Only the complete works published on CD-ROM are reviewed in this project. This paper will report on methods used to evaluate and decisions about long-term retention and preservation of these resources, as well as strategies for avoiding this problem in the future.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146140/1/long-term-preservation-of-deprecated-media.pdfDescription of long-term-preservation-of-deprecated-media.pdf : Main Articl

Management of oral secretions in neurological disease.

Sialorrhoea is a common and problematic symptom that arises from a range of neurological conditions associated with bulbar or facial muscle dysfunction. Drooling can significantly affect quality of life due to both physical complications such as oral chapping, and psychological complications such as embarrassment and social isolation. Thicker, tenacious oral and pharyngeal secretions may result from the drying management approach to sialorrhoea. The management of sialorrhoea in neurological diseases depends on the underlying pathology and severity of symptoms. Interventions include anticholinergic drugs, salivary gland-targeted radiotherapy, salivary gland botulinum toxin and surgical approaches. The management of thick secretions involves mainly conservative measures such as pineapple juice as a lytic agent, cough assist, saline nebulisers and suctioning or mucolytic drugs like carbocisteine. Despite a current lack of evidence and variable practice, management of sialorrhoea should form a part of the multidisciplinary approach needed for long-term neurological conditions

A new affordable housing model in China : a case-based examination of a private developer's role

Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 2008.Includes bibliographical references (p. 107-111).This thesis examines the motivations behind Wanhuilou, the first affordable housing development to be initiated, constructed, and subsidized by a private developer--China Vanke. This case presents a pioneering firm and a radical project, as China Vanke is the first private real estate developer to build affordable housing without a land subsidy from a government-sponsored program. An innovative design, high standards for quality, and a range of amenities further distinguish Wanhuilou from China's other low-income housing. Moreover, China Vanke initiated this project in the city of Guangzhou, one of China's most expensive land and housing markets. Given Wanhuilou's extremely anomalous nature, this thesis aims to understand why a private developer would embark on such a project. This research is important because it examines a potential solution to a critical problem, China's affordable housing shortage. By exploring different behavioral models as possible explanations for China Vanke's motivations, my analysis reveals the particular elements that helped China Vanke take on this project. This thesis analyses the research question through four different hypotheses, testing if and how the market, national policy, local political economy, and corporate social responsibility can explain China Vanke's decision to build Wanhuilou. While this examination suggests that corporate social responsibility builds the strongest case for China Vanke's motivations, it also shows the interrelationships of these behavioral models. In fact, strategies from other models could complement China Vanke's current approach-although the firm's innovation is not enough to make Wanhuilou a replicable business model, a structural reform of housing, with help from the financial market and government policy, could potentially make Wanhuilou a sustainable enterprise.by Claudine C. Stuchell.M.C.P

The disordered N-terminal tail of SARS-CoV-2 Nucleocapsid protein forms a dynamic complex with RNA

The SARS-CoV-2 Nucleocapsid (N) protein is responsible for condensation of the viral genome. Characterizing the mechanisms controlling nucleic acid binding is a key step in understanding how condensation is realized. Here, we focus on the role of the RNA binding domain (RBD) and its flanking disordered N-terminal domain (NTD) tail, using single-molecule Förster Resonance Energy Transfer and coarse-grained simulations. We quantified contact site size and binding affinity for nucleic acids and concomitant conformational changes occurring in the disordered region. We found that the disordered NTD increases the affinity of the RBD for RNA by about 50-fold. Binding of both nonspecific and specific RNA results in a modulation of the tail configurations, which respond in an RNA length-dependent manner. Not only does the disordered NTD increase affinity for RNA, but mutations that occur in the Omicron variant modulate the interactions, indicating a functional role of the disordered tail. Finally, we found that the NTD-RBD preferentially interacts with single-stranded RNA and that the resulting protein:RNA complexes are flexible and dynamic. We speculate that this mechanism of interaction enables the Nucleocapsid protein to search the viral genome for and bind to high-affinity motifs

Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5

The HSPs (hereditary spastic paraplegias) are genetic conditions in which there is distal degeneration of the longest axons of the corticospinal tract, resulting in spastic paralysis of the legs. The gene encoding spartin is mutated in Troyer syndrome, an HSP in which paralysis is accompanied by additional clinical features. There has been controversy over the subcellular distribution of spartin. We show here that, at steady state, endogenous spartin exists in a cytosolic pool that can be recruited to endosomes and to lipid droplets. Cytosolic endogenous spartin is mono-ubiquitinated and we demonstrate that it interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin-interacting protein 4; WWP2 (WW domain-containing E3 ubiquitin protein ligase 2] and AIP5 (WWP1). Surprisingly, the PPXY motif, AIP4 and AIP5 are not required for spartin's ubiquitination, and so we propose that spartin acts as an adaptor for these proteins. Our results suggest that spartin is involved in diverse cellular functions, which may be of relevance to the complex phenotype seen in Troyer syndrome