TMT common software update

TMT Common Software (CSW). CSW consists of software services and library code that is used by developers to create the subsystems and components that participate in the software system. CSW also defines the types of components that can be constructed and their functional roles in the software system. TMT CSW has recently passed its preliminary design review. The unique features of CSW include its use of multiple, open-source products as the basis for services, and an approach that works to reduce the amount of CSW-provided infrastructure code. Considerable prototyping was completed during this phase to mitigate risk with results that demonstrate the validity of this design approach and the selected service implementation products. This paper describes the latest design of TMT CSW, key features, and results from the prototyping effort

TMT Approach to Observatory Software Development Process

The purpose of the Observatory Software System (OSW) is to integrate all software and hardware components of the Thirty Meter Telescope (TMT) to enable observations and data capture; thus it is a complex software system that is defined by four principal software subsystems: Common Software (CSW), Executive Software (ESW), Data Management System (DMS) and Science Operations Support System (SOSS), all of which have interdependencies with the observatory control systems and data acquisition systems. Therefore, the software development process and plan must consider dependencies to other subsystems, manage architecture, interfaces and design, manage software scope and complexity, and standardize and optimize use of resources and tools. Additionally, the TMT Observatory Software will largely be developed in India through TMT’s workshare relationship with the India TMT Coordination Centre (ITCC) and use of Indian software industry vendors, which adds complexity and challenges to the software development process, communication and coordination of activities and priorities as well as measuring performance and managing quality and risk. The software project management challenge for the TMT OSW is thus a multi-faceted technical, managerial, communications and interpersonal relations challenge. The approach TMT is using to manage this multifaceted challenge is a combination of establishing an effective geographically distributed software team (Integrated Product Team) with strong project management and technical leadership provided by the TMT Project Office (PO) and the ITCC partner to manage plans, process, performance, risk and quality, and to facilitate effective communications; establishing an effective cross-functional software management team composed of stakeholders, OSW leadership and ITCC leadership to manage dependencies and software release plans, technical complexities and change to approved interfaces, architecture, design and tool set, and to facilitate effective communications; adopting an agile-based software development process across the observatory to enable frequent software releases to help mitigate subsystem interdependencies; defining concise scope and work packages for each of the OSW subsystems to facilitate effective outsourcing of software deliverables to the ITCC partner, and to enable performance monitoring and risk management. At this stage, the architecture and high-level design of the software system has been established and reviewed. During construction each subsystem will have a final design phase with reviews, followed by implementation and testing. The results of the TMT approach to the Observatory Software development process will only be preliminary at the time of the submittal of this paper, but it is anticipated that the early results will be a favorable indication of progress

Protein kinase A stimulates Kv7.1 surface expression by regulating Nedd4-2-dependent endocytic trafficking

The potassium channel Kv7.1 plays critical physiological roles in both heart and epithelial tissues. In heart, Kv7.1 and the accessory subunit KCNE1 forms the slowly activating delayed-rectifier potassium current current, which is enhanced by protein kinase A (PKA)-mediated phosphorylation. The observed current increase requires both phosphorylation of Kv7.1 and the presence of KCNE1. However, PKA also stimulates Kv7.1 currents in epithelial tissues, such as colon, where the channel does not coassemble with KCNE1. Here, we demonstrate that PKA activity significantly impacts the subcellular localization of Kv7.1 in Madin-Darby canine kidney cells. While PKA inhibition reduced the fraction of channels at the cell surface, PKA activation increased it. We show that PKA inhibition led to intracellular accumulation of Kv7.1 in late endosomes/lysosomes. By mass spectroscopy we identified eight phosphorylated residues on Kv7.1, however, none appeared to play a role in the observed response. Instead, we found that PKA acted by regulating endocytic trafficking involving the ubiquitin ligase Nedd4-2. We show that a Nedd4-2-resistant Kv7.1-mutant displayed significantly reduced intracellular accumulation upon PKA inhibition. Similar effects were observed upon siRNA knockdown of Nedd4-2. However, although Nedd4-2 is known to regulate Kv7.1 by ubiquitylation, biochemical analyses demonstrated that PKA did not influence the amount of Nedd4-2 bound to Kv7.1 or the ubiquitylation level of the channel. This suggests that PKA influences Nedd4-2-dependent Kv7.1 transport though a different molecular mechanism. In summary, we identify a novel mechanism whereby PKA can increase Kv7.1 current levels, namely by regulating Nedd4-2-dependent Kv7.1 transport

Cerebrospinal fluid osmolality cannot predict development or surgical outcome of idiopathic normal pressure hydrocephalus

BACKGROUND: The etiology of idiopathic normal pressure hydrocephalus (iNPH) is currently unknown. With no visible obstructions, altered cerebrospinal fluid (CSF) dynamics may explain the accumulation of ventricular fluid. We hypothesized that elevated osmolality in the CSF of iNPH patients could potentiate formation of ventricular fluid and thereby cause the disease progression and/or predict the surgical outcome. To address this hypothesis, we determined the lumbar and ventricular CSF osmolality of iNPH patients at different disease stages and compared with lumbar CSF samples obtained from control subjects. METHODS: The osmolality of CSF was determined on a total of 35 iNPH patients at diagnosis and at the subsequent treatment with shunt surgery (n = 20) and compared with the CSF osmolality from 20 control subjects. Simultaneously collected lumbar and ventricular CSF samples from experimental pigs were used to evaluate the compatibility between CSF from different compartments. RESULTS: We found no evidence of increased osmolality in the CSF of iNPH patients upon diagnosis or at the time of shunt treatment months after the diagnosis, compared with control individuals. CSF tapped from the lumbar space could be used as a read-out for ventricular CSF osmolality, as these were similar in both the patient group and in experimental pigs. We further observed no correlation between the CSF osmolality in iNPH patients and their responsiveness to shunt surgeries. CONCLUSIONS: The osmolality of lumbar CSF is a reliable reflection of the ventricular CSF osmolality, and is not elevated in iNPH patients. iNPH therefore does not appear to arise as a function of osmotic imbalances in the CSF system and CSF osmolality cannot serve as a biomarker for iNPH or as a predictive tool for shunt responsiveness