231 research outputs found
Low cost TV based messaging for remote desert communities
In recent years telecommunications services in remote Australia have received considerable attention, with services for indigenous desert communities a key focus. This project, known as Desert Interactive Remote Television (DIRT), uses existing community rebroadcast TV infrastructure to provide low cost multimedia messaging services for remote desert communities. The system architecture, key applications, and field trial outcomes are described
Targeted messages on TV screens in remote Indigenous communities
This paper describes a research project to enhance the viability of remote Indigenous communities through culturally-appropriate use of information and communications technologies (ICT). The project investigated the use of community rebroadcast TV infrastructure for new low cost communications services. A key part of the project was establishment of trusting relationships with the Ngaanyatjaara Lands communities of Irrunytju and Kanpa. Community members,administrative staff, and external service providers were involved in investigations into current communication problems and potential solutions. A working prototype of a messaging system using satellite broadcasting infrastructure to send multimedia messages to TV sets within remote communities was developed and evaluated. Such a system could be used by government agencies or remote communities themselves to deliver messages about visitors to the community (e.g.health workers), emergencies (e.g. bushfire); cultural business, sporting events, etc. The expected outcomes of such a system are increased social capital within the region, developed through more efficient and effective communication, leading to enhanced viability and sustainability of remote communities
ORC: Increasing cloud memory density via object reuse with capabilities
Cloud environments host many tenants, and typically there is substantial overlap between the application binaries and libraries executed by tenants. Thus, memory de-duplication can increase memory density by allocating memory for shared binaries only once. Existing de-duplication approaches, however, either rely on a shared OS to de-deduplicate binary objects, which provides unacceptably weak isolation; or exploit hypervisor-based de-duplication at the level of memory pages, which is blind to the semantics of the objects to be shared. We describe Object Reuse with Capabilities (ORC), which supports the fine-grained sharing of binary objects between tenants, while isolating tenants strongly through a small trusted computing base (TCB). ORC uses hardware sup- port for memory capabilities to isolate tenants, which permits shared objects to be accessible to multiple tenants safely. Since ORC shares binary objects within a single address space through capabilities, it uses a new relocation type to create per-tenant state when loading shared objects. ORC supports the loading of objects by an untrusted guest, outside of its TCB, only verifying the safety of the loaded data. Our experiments show that ORC achieves a higher memory density with a lower overhead than hypervisor-based de-deduplication
Informing additive manufacturing technology adoption: total cost and the impact of capacity utilisation
Informing Additive Manufacturing (AM) technology adoption decisions, this paper investigates the relationship between build volume capacity utilisation and efficient technology operation in an inter-process comparison of the costs of manufacturing a complex component used in the packaging industry. Confronting the reported costs of a conventional machining and welding pathway with an estimator of the costs incurred through an AM route utilising Direct Metal Laser Sintering (DMLS), we weave together four aspects: optimised capacity utilisation, ancillary process steps, the effect of build failure and design adaptation. Recognising that AM users can fill unused machine capacity with other, potentially unrelated, geometries, we posit a characteristic of ‘fungible’ build capacity. This aspect is integrated in the cost estimation framework through computational build volume packing, drawing on a basket of sample geometries. We show that the unit cost in mixed builds at full capacity is lower than in builds limited to a single type of geometry; in our study, this results in a mean unit cost overstatement of 157%. The estimated manufacturing cost savings from AM adoption range from 36 to 46%. Additionally, we indicate that operating cost savings resulting from design adaptation are likely to far outweigh the manufacturing cost advantage
Local protein kinase A action proceeds through intact holoenzymes
Hormones can transmit signals through adenosine 3’,5’-monophosphate (cAMP) to precise intracellular locations. The fidelity of these responses relies on the activation of localized protein kinase A (PKA) holoenzymes. Association of PKA regulatory (RII) subunits with A-kinase anchoring proteins (AKAPs) confers location, and catalytic (C) subunits phosphorylate substrates. Single-particle electron microscopy demonstrated that AKAP79 constrains RII-C sub-assemblies within 150 to 250Å of its targets. Native mass spectrometry established that these macromolecular assemblies incorporated stoichiometric amounts of cAMP. Chemical-biology and live-cell imaging techniques revealed that catalytically active PKA holoenzymes remained intact within the cytoplasm. In contrast, little, if any PKA activity was detected in the nucleus. Hence the parameters of anchored PKA holoenzyme action are much more restricted than originally anticipated
Automating Data Rights
This report documents the program and the outcomes of Dagstuhl Seminar 18181 “Towards
Accountable Systems”, which took place from April 29th to May 4th, 2018, at Schloss Dagstuhl –
Leibniz Center for Informatics. Researchers and practitioners from academia and industry were
brought together covering broad fields from computer and information science, public policy and
law.
Many risks and opportunities were discussed that relate to the alignment of systems technologies with developing legal and regulatory requirements and evolving user expectations.
This report summarises outcomes of the seminar by highlighting key future research directions
and challenges that lie on the path to developing systems that better align with accountability
concerns
Regulation of Human PINK1 ubiquitin kinase by Serine167, Serine228 and Cysteine412 phosphorylation.
Loss-of-function mutations in the human PINK1 kinase (hPINK1) are causative of early-onset Parkinson’s disease (PD). Activation of hPINK1 induces phosphorylated ubiquitin to initiate removal of damaged mitochondria by autophagy. Previously we solved the structure of the insect PINK1 orthologue, Tribolium castaneum PINK1, and showed that autophosphorylation of Ser205 was critical for ubiquitin interaction and phosphorylation (Kumar, Tamjar, Waddell et al., 2017). Here we report new findings on the regulation of hPINK1 by phosphorylation. We reconstitute E. coli expressed hPINK1 activity in vitro by direct incorporation of phosphoserine at the equivalent site Serine 228 (pSer228), providing direct evidence for a role for Ser228 phosphorylation in hPINK1 activation. Furthermore, using mass spectrometry, we identify six novel Ser/Thr autophosphorylation sites including regulatory Serine167 phosphorylation (pSer167), which in addition to pSer228 is required for ubiquitin recognition and phosphorylation. Strikingly, we also detect phosphorylation of a conserved Cysteine412 (pCys412) residue in the hPINK1 activation segment. Structural modelling suggests that pCys412 inhibits ubiquitin recognition and we demonstrate that mutation of Cys412 to Ala renders hPINK1 more active towards ubiquitin when expressed in human cells. These results outline new insights into hPINK1 activation by pSer167 and pSer228 and a novel inhibitory mechanism mediated by pCys412. These findings will aid in the development of small molecule activators of hPINK1
Regulation of Human PINK1 ubiquitin kinase by Serine167, Serine228 and Cysteine412 phosphorylation.
Loss-of-function mutations in the human PINK1 kinase (hPINK1) are causative of early-onset Parkinson’s disease (PD). Activation of hPINK1 induces phosphorylated ubiquitin to initiate removal of damaged mitochondria by autophagy. Previously we solved the structure of the insect PINK1 orthologue, Tribolium castaneum PINK1, and showed that autophosphorylation of Ser205 was critical for ubiquitin interaction and phosphorylation (Kumar, Tamjar, Waddell et al., 2017). Here we report new findings on the regulation of hPINK1 by phosphorylation. We reconstitute E. coli expressed hPINK1 activity in vitro by direct incorporation of phosphoserine at the equivalent site Serine 228 (pSer228), providing direct evidence for a role for Ser228 phosphorylation in hPINK1 activation. Furthermore, using mass spectrometry, we identify six novel Ser/Thr autophosphorylation sites including regulatory Serine167 phosphorylation (pSer167), which in addition to pSer228 is required for ubiquitin recognition and phosphorylation. Strikingly, we also detect phosphorylation of a conserved Cysteine412 (pCys412) residue in the hPINK1 activation segment. Structural modelling suggests that pCys412 inhibits ubiquitin recognition and we demonstrate that mutation of Cys412 to Ala renders hPINK1 more active towards ubiquitin when expressed in human cells. These results outline new insights into hPINK1 activation by pSer167 and pSer228 and a novel inhibitory mechanism mediated by pCys412. These findings will aid in the development of small molecule activators of hPINK1
Liver Graft Revascularization by Donor Portal Vein Arterialization Following “No Touch” Donor Hepatectomy
Unsatisfactory immediate function of the transplanted liver together with technical complications
contribute to a persisting early mortality for hepatic transplantation in the 20% range. We report our
initial clinical experience with methods, one not previously used clinically, that resulted in uniformly well-functioning
liver grafts in 11 patients and contributed to a satisfactory success rate for the procedure.
Donors were heart-beating. During the donor operation all manipulations of the liver were avoided until
after cold preservation, achieved by external cooling at the same time as circulatory interruption, donor
exsanguination and perfusion of the liver with cold oxygenated fluid of “extracellular̵ type. The organs
were then gently dissected. At transplantation the livers were revascularized with arterial blood shunted
from the recipient iliac artery to the graft portal vein after completion of the suprahepatic IVC
anastomosis. The infrahepatic IVCs and hepatic arteries were then joined, the iliac artery shunts
discontinued and the portal veins joined. Total ischaemic intervals for the allografts were 3½–8 (average
5). Anhepatic intervals were 1–2¼ (average 2). The arterio-portal shunts were operating for 18–85 (mean
46) min. Blood loss and haemodynamic, acid-base and electrolyte abnormalities at revascularization were
minimal. All grafts secreted bile immediately and all parameters reflected continuing improvement of
liver function thereafter. Nine patients (82%) are alive between 4 and 18 (mean 11) months after
transplantation. We conclude that these methods offer effective avoidance of serious organ damage
during donor hepatectomy and preservation, reduced allograft ischaemic interval and reduced recipient
anhepatic time. They result in avoidance of blood loss at the time of revascularization, together with
minimal haemodynamic, acid-base or biochemical changes. In addition, they allow the surgeon to
perform and test all anastomoses without time constraints, provide the capability to deal with unexpected
complications, and assure good early graft function
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