Over the past decade there has been an explosion of social science research on smart cities, with focuses ranging from governance and activism to surveillance and place-based discrimination. As a ...result theories of digital appropriation, empowerment, and politics overrepresent urban experiences, producing a gap in our understanding of rural digital politics. Not only is rural information and communication technology (ICT) literature sparse, but it is also overly focused on technical issues of digital divides. This restrictive framing of rural ICT use reinforces the normalization of highly technocratic approaches to development in rural areas, thereby reinforcing neoliberal market forces and obscuring the innovative ways in which rural communities are appropriating digital technologies to build alternate social and economic practices. In response to this gap, this paper offers a case study of how the rural, indigenous community of Igloolik, Canada is using digital platforms to shape their resilience.
•Theories of the impact of digital technologies underexamine rural technology use.•Rural case studies offer understandings of technology use to produce alternate economies.•Indigenous communities use technology to support economic livelihoods grounded in local values.•Rural studies provide unique frameworks for analyzing technology and community empowerment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
While the impacts of information and communication technologies (ICTs) on society have been extensively studied, the most nuanced research approaches continue to focus on urban geographies in the ...Global North. There remains a paucity of critical work that focuses on ICT use in Indigenous, rural, and Global South communities. This paper responds to that gap by critically examining how the introduction of ICTs within Indigenous communities can exert epistemic violence against local knowledge systems. It does so through a case study of ICT usage within an Inuit community in the Canadian Arctic. I use a combination of participant observation, archival research, and semi-structured interviews to ask how the introduction of ICTs is transforming knowledge politics that impact Inuit Qaujimaningit (IQ; Inuit knowledge). I find that digital engagement erodes key components of the IQ system, including social practices within Inuit communities, travel outside of the community, and experiential learning while outside of the community. These findings have implications for the study of global digital geographies, applied research within the area of ICT for development, and Indigenous engagements with emerging technologies.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
New Zealand recognised the People's Republic of China in December 1972. In the ensuing half-century, the China-New Zealand diplomatic partnership has become one of New Zealand's most important and ...complex, making it one worth investing real expertise to sustain. Three themes have underlined New Zealand's recognition of the anniversary: tangata/people, aorangi/planet and tonuitanga/prosperity. Over the next 50 years, New Zealand will need to build New Zealand-inflected expertise on China, addressing a great failing of the last 50 years, if it is to recognise the challenges of responding to the People's Republic and its changing place in the world.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In humans, Hsp70 chaperones are ubiquitously expressed in the cytosol, endoplasmic reticulum and mitochondria. They fulfill important roles in protein folding and the protection of cells from stress. ...Different forms of Hsp70 have also been found to regulate specific signaling pathways, many related to cell death. Cancer cells are notably abnormally dependent on Hsp70 chaperones for their survival. The importance of Hsp70s as drug targets is increasingly being recognized, particularly as potential cancer therapeutics. This review surveys recent advances in understanding Hsp70 mechanisms and then moves to provide an overview of current efforts directed at inhibiting Hsp70s as a target in diseases such as cancer and neurodegenerative disease.
Therapeutic efforts to restore biosynthetic processing of the cystic fibrosis transmembrane conductance regulator lacking the F508 residue (ΔF508CFTR) are hampered by ubiquitin-dependent lysosomal ...degradation of nonnative, rescued ΔF508CFTR from the plasma membrane. Here, functional small interfering RNA screens revealed the contribution of chaperones, cochaperones, and ubiquitin-conjugating and -ligating enzymes to the elimination of unfolded CFTR from the cell surface, as part of a peripheral protein quality-control system. Ubiquitination of nonnative CFTR was required for efficient internalization and lysosomal degradation. This peripheral protein quality-control mechanism probably participates in the preservation of cellular homeostasis by degrading damaged plasma membrane proteins that have escaped from the endoplasmic reticulum quality control or are generated by environmental stresses in situ.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Molecular chaperones of the Hsp70 family have diverse functions in cells. They assist the folding of newly synthesized and stress-denatured proteins, as well as the import of proteins into ...organelles, and the dissociation of aggregated proteins. The well-conserved Hsp70 chaperones are ATP dependent: binding and hydrolysis of ATP regulates their interactions with unfolded polypeptide substrates, and ATPase cycling is necessary for their function. All cellular functions of Hsp70 chaperones use the same mechanism of ATP-driven polypeptide binding and release. The Hsp40 co-chaperones stimulate ATP hydrolysis by Hsp70 and the type 1 Hsp40 proteins are conserved from Escherichia coli to humans. Various nucleotide exchange factors also promote the Hsp70 ATPase cycle. Recent advances have added to our understanding of the Hsp70 mechanism at a molecular level.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Maintaining global peace as China rises is a key strategic goal of Western liberal democracies. Compared to other western liberal democracies, New Zealand's response to the 'rise of China' is notable ...for its absence of security and political frictions and for the achievement of a series of diplomatic 'firsts'. Can this be explained only by material concern over the national economic interest as China's role in the global economy increases or do ideational factors also underlay how New Zealand engages China? This paper employs the ontological security framework to demonstrate how New Zealand identity as a 'small trading nation' and 'good international citizen' has shaped its turn to Asia and response to the 'rise of China'. It first analyses the origins of New Zealand's outward facing identity and resultant foreign policy positions long before China became an important aspect of New Zealand trade policy. It then shows how New Zealand seeks ontological security as a 'small trading nation' and 'good international citizen' in its relations with China and how China has responded to this type of engagement. The paper illustrates the importance of ideational factors in Western liberal democracies' responses to the 'rise of China'.
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BFBNIB, DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission.
HIV-1 pol sequence data were analyzed to infer the ...local transmission network.
We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions.
HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p<0.0001). Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p<0.05).
Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network. The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Langerhans cell histiocytosis (LCH) can affect children and adults with a wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary ...(smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last decade, the discovery of clonality and MAPK-ERK pathway mutations in most cases led to the recognition of LCH as a hematopoietic neoplasm, opening the doors for treatment with targeted therapies. These advances have necessitated an update of the existing recommendations for the diagnosis and treatment of LCH in adults. This document presents consensus recommendations that resulted from the discussions at the annual Histiocyte Society meeting in 2019, encompassing clinical features, classification, diagnostic criteria, treatment algorithm, and response assessment for adults with LCH. The recommendations favor the use of 18F-Fluorodeoxyglucose positron emission tomography-based imaging for staging and response assessment in the majority of cases. Most adults with unifocal disease may be cured by local therapies, while the first-line treatment for single-system pulmonary LCH remains smoking cessation. Among patients not amenable or unresponsive to these treatments and/or have multifocal and multisystem disease, systemic treatments are recommended. Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with the emerging role of targeted (BRAF and MEK inhibitor) therapies. Despite documented responses to treatments, many patients struggle with a high symptom burden from pain, fatigue, and mood disorders that should be acknowledged and managed appropriately.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP