Microtubules gate tau condensation to spatially regulate microtubule functions.

Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule

Development of Aluminum LEKIDs for Balloon-Borne Far-IR Spectroscopy

We are developing lumped-element kinetic inductance detectors (LEKIDs) designed to achieve background-limited sensitivity for far-infrared (FIR) spectroscopy on a stratospheric balloon. The Spectroscopic Terahertz Airborne Receiver for Far-InfraRed Exploration (STARFIRE) will study the evolution of dusty galaxies with observations of the [CII] 158 $\mu$m and other atomic fine-structure transitions at $z=0.5-1.5$, both through direct observations of individual luminous infrared galaxies, and in blind surveys using the technique of line intensity mapping. The spectrometer will require large format ($\sim$1800 detectors) arrays of dual-polarization sensitive detectors with NEPs of $1 \times 10^{-17}$ W Hz$^{-1/2}$. The low-volume LEKIDs are fabricated with a single layer of aluminum (20 nm thick) deposited on a crystalline silicon wafer, with resonance frequencies of $100-250$ MHz. The inductor is a single meander with a linewidth of 0.4 $\mu$m, patterned in a grid to absorb optical power in both polarizations. The meander is coupled to a circular waveguide, fed by a conical feedhorn. Initial testing of a small array prototype has demonstrated good yield, and a median NEP of $4 \times 10^{-18}$ W Hz$^{-1/2}$.Comment: accepted for publication in Journal of Low Temperature Physic

Congestion Avoidance Testbed Experiments

DARTnet provides an excellent environment for executing networking experiments. Since the network is private and spans the continental United States, it gives researchers a great opportunity to test network behavior under controlled conditions. However, this opportunity is not available very often, and therefore a support environment for such testing is lacking. To help remedy this situation, part of SRI's effort in this project was devoted to advancing the state of the art in the techniques used for benchmarking network performance. The second objective of SRI's effort in this project was to advance networking technology in the area of traffic control, and to test our ideas on DARTnet, using the tools we developed to improve benchmarking networks. Networks are becoming more common and are being used by more and more people. The applications, such as multimedia conferencing and distributed simulations, are also placing greater demand on the resources the networks provide. Hence, new mechanisms for traffic control must be created to enable their networks to serve the needs of their users. SRI's objective, therefore, was to investigate a new queueing and scheduling approach that will help to meet the needs of a large, diverse user population in a "fair" way

Status of SuperSpec: A Broadband, On-Chip Millimeter-Wave Spectrometer

SuperSpec is a novel on-chip spectrometer we are developing for multi-object, moderate resolution (R = 100 - 500), large bandwidth (~1.65:1) submillimeter and millimeter survey spectroscopy of high-redshift galaxies. The spectrometer employs a filter bank architecture, and consists of a series of half-wave resonators formed by lithographically-patterned superconducting transmission lines. The signal power admitted by each resonator is detected by a lumped element titanium nitride (TiN) kinetic inductance detector (KID) operating at 100-200 MHz. We have tested a new prototype device that is more sensitive than previous devices, and easier to fabricate. We present a characterization of a representative R=282 channel at f = 236 GHz, including measurements of the spectrometer detection efficiency, the detector responsivity over a large range of optical loading, and the full system optical efficiency. We outline future improvements to the current system that we expect will enable construction of a photon-noise-limited R=100 filter bank, appropriate for a line intensity mapping experiment targeting the [CII] 158 micron transition during the Epoch of ReionizationComment: 16 pages, 10 figures, Proceedings of the SPIE Astronomical Telescopes + Instrumentation 2014 Conference, Vol 9153, Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy VI

Student participation in the design of learning and teaching: Disentangling the terminology and approaches

Background: Students are ever more involved in the design of educational practices, which is reflected in the growing body of literature about approaches to student participation. Similarities and differences between these approaches often remain vague since the terms are used interchangeably. This confusing and fragmented body of literature hampers our understanding the process and outcomes of student participation and choosing the most suitable approach for it. Method: We identified the three most frequently used terms related to the design of learning and teaching–design-based research (DBR), participatory design (PD), and co-creation–and disentangled the terminology by focusing on relevant definitions, aims, involvement of students, outcomes, and related terminology. Results: Differences between the approaches to student participation can be found in the degree to which students are the central actors and the degree to which the design is informed by educational theory. Conclusion: It is important to align the level of student participation with the purpose of the approach

The Scalable Commutativity Rule: Designing Scalable Software for Multicore Processors

What fundamental opportunities for scalability are latent in interfaces, such as system call APIs? Can scalability opportunities be identified even before any implementation exists, simply by considering interface specifications? To answer these questions this paper introduces the following rule: Whenever interface operations commute, they can be implemented in a way that scales. This rule aids developers in building more scalable software starting from interface design and carrying on through implementation, testing, and evaluation. To help developers apply the rule, a new tool named Commuter accepts high-level interface models and generates tests of operations that commute and hence could scale. Using these tests, Commuter can evaluate the scalability of an implementation. We apply Commuter to 18 POSIX calls and use the results to guide the implementation of a new research operating system kernel called sv6. Linux scales for 68% of the 13,664 tests generated by Commuter for these calls, and Commuter finds many problems that have been observed to limit application scalability. sv6 scales for 99% of the tests.Engineering and Applied Science

An integrated concurrency and core-ISA architectural envelope definition, and test oracle, for IBM POWER multiprocessors

Funding: Scottish Funding Council (SICSA Early Career Industry Fellowship)Weakly consistent multiprocessors such as ARM and IBM POWER have been with us for decades, but their subtle programmer-visible concurrency behaviour remains challenging, both to implement and to use; the traditional architecture documentation, with its mix of prose and pseudocode, leaves much unclear. In this paper we show how a precise architectural envelope model for such architectures can be defined, taking IBM POWER as our example. Our model specifies, for an arbitrary test program, the set of all its allowable executions, not just those of some particular implementation. The model integrates an operational concurrency model with an ISA model for the fixedpoint non-vector user-mode instruction set (largely automatically derived from the vendor pseudocode, and expressed in a new ISA description language). The key question is the interface between these two: allowing all the required concurrency behaviour, without overcommitting to some particular microarchitectural implementation, requires a novel abstract structure. Our model is expressed in a mathematically rigorous language that can be automatically translated to an executable test-oracle tool; this lets one either interactively explore or exhaustively compute the set of all allowed behaviours of intricate test cases, to provide a reference for hardware and software development.Postprin

Regular Topologies for Gigabit Wide-Area Networks

In general terms, this project aimed at the analysis and design of techniques for very high-speed networking. The formal objectives of the project were to: (1) Identify switch and network technologies for wide-area networks that interconnect a large number of users and can provide individual data paths at gigabit/s rates; (2) Quantitatively evaluate and compare existing and proposed architectures and protocols, identify their strength and growth potentials, and ascertain the compatibility of competing technologies; and (3) Propose new approaches to existing architectures and protocols, and identify opportunities for research to overcome deficiencies and enhance performance. The project was organized into two parts: 1. The design, analysis, and specification of techniques and protocols for very-high-speed network environments. In this part, SRI has focused on several key high-speed networking areas, including Forward Error Control (FEC) for high-speed networks in which data distortion is the result of packet loss, and the distribution of broadband, real-time traffic in multiple user sessions. 2. Congestion Avoidance Testbed Experiment (CATE). This part of the project was done within the framework of the DARTnet experimental T1 national network. The aim of the work was to advance the state of the art in benchmarking DARTnet's performance and traffic control by developing support tools for network experimentation, by designing benchmarks that allow various algorithms to be meaningfully compared, and by investigating new queueing techniques that better satisfy the needs of best-effort and reserved-resource traffic. This document is the final technical report describing the results obtained by SRI under this project. The report consists of three volumes: Volume 1 contains a technical description of the network techniques developed by SRI in the areas of FEC and multicast of real-time traffic. Volume 2 describes the work performed under CATE. Volume 3 contains the source code of all software developed under CATE

From the cell membrane to the nucleus: unearthing transport mechanisms for Dynein

Mutations in the motor protein cytoplasmic dynein have been found to cause Charcot-Marie-Tooth disease, spinal muscular atrophy, and severe intellectual disabilities in humans. In mouse models, neurodegeneration is observed. We sought to develop a novel model which could incorporate the effects of mutations on distance travelled and velocity. A mechanical model for the dynein mediated transport of endosomes is derived from first principles and solved numerically. The effects of variations in model parameter values are analysed to find those that have a significant impact on velocity and distance travelled. The model successfully describes the processivity of dynein and matches qualitatively the velocity profiles observed in experiments