Disruption of large-scale neuronal activity patterns in Alzheimer’s disease models

The overexpression and aggregation of tau is observed in a class of neurodegenerative diseases termed tauopathies. Individuals with tauopathy, and animal models of tauopathy, show a loss of behavioural and cognitive function, but the neural underpinnings of these symptoms are poorly understood. We investigated changes in neural function in in the Tg4510 model of tauopathy in primary visual cortex (V1) - an area where the relationship between stimulus features, single unit responses, and the circuits and mechanisms underlying them, is relatively well characterised - and in CA1. We conducted chronic awake head-fixed recordings in V1 of 5-6.5 month old mice, presenting a variety of visual stimuli, including drifting grating stimuli that varied across feature dimensions such as orientation, contrast, or size. Mice were also trained to run in a virtual reality environment, either closed loop, open loop (playback) or in the dark. Tau+ and Tau- mice displayed clear differences in the oscillatory local field potentials in V1 and CA1, notably Tau+ mice showed a large decrease in high frequency power as well as minor changes in stimulus-evoked power and power in relation to running speed. Single unit responses in V1 of Tau+ mice were also altered. Tau+ mice showed greater orientation selectivity and suppression following orientation adaptation, and improved contrast tuning, but worse selectivity in response to sparse noise stimuli. Responses to other stimulus features, such as spatial frequency and size, were unchanged between the two groups. In conclusion, tauopathy in the Tg4510 mouse shows clear effects on information processing in the visual cortex and in CA1. This was not through a non-selective decrease in responsiveness, but instead enhanced some types of processing, such as orientation selectivity, while disrupting others such as responses to sparse noise. These selective effects on neural function may reflect selective patterns of tauopathy on different cell classes or brain areas

Identification of geometrical and elastostatic parameters of heavy industrial robots

The paper focuses on the stiffness modeling of heavy industrial robots with gravity compensators. The main attention is paid to the identification of geometrical and elastostatic parameters and calibration accuracy. To reduce impact of the measurement errors, the set of manipulator configurations for calibration experiments is optimized with respect to the proposed performance measure related to the end-effector position accuracy. Experimental results are presented that illustrate the advantages of the developed technique.Comment: arXiv admin note: substantial text overlap with arXiv:1311.667

Modelling of the gravity compensators in robotic manufacturing cells

The paper deals with the modeling and identification of the gravity compensators used in heavy industrial robots. The main attention is paid to the geometrical parameters identification and calibration accuracy. To reduce impact of the measurement errors, the design of calibration experiments is used. The advantages of the developed technique are illustrated by experimental result

VR Force Feedback Gloves

The goal of this project is to produce a manufacturing plan for a consumer VR glove. The total addressable market of VR is over 170 million global users as of 2022 (Kolmar , 2022) with a serviceable available market of 300,000 users on Meta’s own social platform (Heath, 2022). The targeted Quest 2 platform utilizes handheld controllers, which causes a lack of immersivity in social settings and gaming scenarios. One common use of the platform involves social platforms such as “Horizons” where users meet in a virtual world to interact; handheld controllers don’t allow users to shake hands, make finger gestures, or touch each other’s avatars. Furthermore, users enjoy a breadth of different immersive games from first person shooters to rhythm block slicing games; in this setting, users often interact with physical objects and cannot sense their shape or their mass, nor can they finely interact with simple virtual mechanisms like weapon triggers. At the current time of writing, VR gloves that are readily available for purchase start at $5,000 and can go up to$10,000. However, the previously mentioned 300,000 users of Horizons fall into the consumer market, where accessibility/cost is more constraining; the hardware they use, the Meta Quest 2, costs $400 (Meta, 2022). Thus, these consumer users are unserved by the current market options. This project aims to provide increased immersivity in social and gaming scenarios at a price point that Quest 2 users can afford. Without a thorough customer analysis other than overall sentiment for mass adoption of VR glove technology, this project aims to produce the necessary manufacturing plan and demonstration to appropriately crowd-fund further efforts in offering a product. Deliverables of this project include two prototype demonstrations of the electrical system, mechanical system, and firmware as well as a manufacturing and production plan

Thermoelectric effect in high mobility single layer epitaxial graphene

The thermoelectric response of high mobility single layer epitaxial graphene on silicon carbide substrates as a function of temperature and magnetic field have been investigated. For the temperature dependence of the thermopower, a strong deviation from the Mott relation has been observed even when the carrier density is high, which reflects the importance of the screening effect. In the quantum Hall regime, the amplitude of the thermopower peaks is lower than a quantum value predicted by theories, despite the high mobility of the sample. A systematic reduction of the amplitude with decreasing temperature suggests that the suppression of the thermopower is intrinsic to Dirac electrons in graphene.Comment: 5 pages, 4 figure

Weak antilocalization in epitaxial graphene: evidence for chiral electrons

Transport in ultrathin graphite grown on silicon carbide is dominated by the electron-doped epitaxial layer at the interface. Weak anti-localization in 2D samples manifests itself as a broad cusp-like depression in the longitudinal resistance for magnetic fields 10 mT$< B <$ 5 T. An extremely sharp weak-localization resistance peak at B=0 is also observed. These features quantitatively agree with graphene weak-(anti)localization theory implying the chiral electronic character of the samples. Scattering contributions from the trapped charges in the substrate and from trigonal warping due to the graphite layer on top are tentatively identified. The Shubnikov-de Haas oscillations are remarkably small and show an anomalous Berry's phase.Comment: 5 pages, 4 figures. Minor change

Into the Woods: A Biologic Patent Thicket Analysis

Some drug companies, brand biologic companies, in particular, have been accused of covering only a single drug with more than eighty patents. These drug patents accumulate to what critics claim as one of the major culprits of high drug prices— “patent thickets.” However, current literature mostly focuses on the substantial patent counts and less on the characteristics and the causes of these patent thickets; but to effectively understand and tackle this issue, more thorough discussions are necessary. This article aims to provide further insight into this issue by analyzing and comparing the U.S. patents that cover top-selling biologics and small-molecule drugs. Results not only confirm the existence of biologic patent thickets—in which two of the three selected top-selling biologics have accumulated more than forty patents— but also show that more patents cover biologics than small-molecule drugs. Based on more in-depth analysis, this article further argues that the so-called “patent thicket” is, in fact, a cooperative effort of two types of patent thickets—Type I and Type II—that should be distinguished due to their differences in nature and the causes that give rise to them. Defined as large numbers of non-overlapping or inventive patents that cover different aspects of the drug, Type I Patent Thickets are formed due to the complex nature of biologics and biosimilars. Type II Patent Thickets, on the other hand, are arguably overlapping or non-inventive patents that are prone to double patenting. They cover the same aspect of the drug and owe their existence to the utilization of terminal disclaimers. The two types of patent thickets jointly contribute to the large number of patents that fend off patent challenges; the stretched year spans of collective patent terms that delay biosimilar entry; and the exorbitant drug prices that harm patients. In order to prevent the negative impacts of patent thickets without completely sacrificing the merits patents themselves provide, this article presents two proposals: one being the election of patents to assert to mitigate the adverse effects of Type II Patent Thickets, and the other being a more transformative reform that would target against both types of patent thickets

Understanding Contextual Differences in Residential LTC Provision for Cross-National Research : Identifying Internationally Relevant CDEs

Long-term care (LTC) reflects a growing emphasis on person-centered care (PCC), with services oriented around individuals' needs and preferences. Addressing contextual and cultural differences across countries offers important insight into factors that facilitate or hinder application of PCC practices within and across countries. This article takes an international lens to consider country-specific contexts of LTC, describing preliminary steps to develop common data elements that capture contextual differences across LTC settings globally. Through an iterative series of online, telephone, and in-person sessions, we engaged in in-depth discussions with 11 colleague experts in residential LTC and coauthors from six countries (China and Hong Kong, England, Sweden, Thailand, Trinidad and Tobago, and the United States). Our discussions yielded rich narrative describing a vast range in types of LTC settings, leading to our development of a working definition of residential LTC. Scope of services, funding, ownership, and regulations varied greatly across countries and across different residential LTC settings within countries. Moving forward, we recommend expanding our activities to countries that reflect different stages of residential LTC development. Our goal is to contribute to a larger initiative underway by the WE-THRIVE consortium to establish a global research measurement infrastructure that advances PCC internationally.Peer reviewe