Regulation of distance selling methods

This paper examines New Zealand’s distance selling regulation, in particular the changes made in the course of the recent consumer law reform. First, the paper assesses the reforms with regard to telemarketing. While some criticism is expressed as to the content of the prescribed disclosure by the supplier, the approach followed is approved of in general. The paper then examines the merits of a general right of withdrawal in distance selling contracts as it exists in the European Union. Analysing withdrawal rights from an economical, psychological and ethical perspective, the paper argues that both from a supplier’s and from a consumer’s point of view, the advantages are outweighed by the disadvantages that come with withdrawal rights

Appointment, discipline and removal of judges: A comparison of the Swiss and New Zealand judiciaries

This paper gives an overview of the legal system of Switzerland and then compares the judiciaries of Switzerland and New Zealand. As far as Switzerland is concerned, it covers both the system of the Swiss Federation and the systems in the Cantons. After analysing the powers enjoyed by the judiciary via the legislature, the paper examines the appointment of judges in detail. The author explains how in Switzerland openly political and other considerations are weighed in the course of electing judges and how the appointment of lay judges is balanced with an active role of law clerks. In contrast, New Zealand has a proud tradition of apolitical judicial appointments that are made solely based on merit. The author criticises that Swiss judges are elected for a term of office, whereas New Zealand judges enjoy the security of tenure and thus, a greater judicial independence. Lastly, the paper covers the removal and discipline of judges, where the author, while he commends the recent reform in New Zealand, speaks out for a system where the ultimate decision is given to an independent judicial body rather than a parliament

Multilingual Workflows in Bullinger Digital: Data Curation for Latin and Early New High German

This paper presents how we enhanced the accessibility and utility of historical linguistic data in the project Bullinger Digital. The project involved the transformation of 3,100 letters, primarily available as scanned PDFs, into a dynamic, fully digital format. The expanded digital collection now includes 12,000 letters, 3,100 edited, 5,400 transcribed, and 3,500 represented through detailed metadata and results from handwritten text recognition. Central to our discussion is the innovative workflow developed for this multilingual corpus. This includes strategies for text normalisation, machine translation, and handwritten text recognition, particularly focusing on the challenges of code-switching within historical documents. The resulting digital platform features an advanced search system, offering users various filtering options such as correspondent names, time periods, languages, and locations. It also incorporates fuzzy and exact search capabilities, with the ability to focus searches within specific text parts, like summaries or footnotes. Beyond detailing the technical process, this paper underscores the project’s contribution to historical research and digital humanities. While the Bullinger Digital platform serves as a model for similar projects, the corpus behind it demonstrates the vast potential for data reuse in historical linguistics. The project exemplifies how digital humanities methodologies can revitalise historical text collections, offering researchers access to and interaction with historical data. This paper aims to provide readers with a comprehensive understanding of our project’s scope and broader implications for the field of digital humanities, highlighting the transformative potential of such digital endeavours in historical linguistic research

Multi-level regulation of myotubularin-related protein-2 phosphatase activity by myotubularin-related protein-13/set-binding factor-2

Mutations in myotubularin-related protein-2 (MTMR2) or MTMR13/set-binding factor-2 (SBF2) genes are responsible for the severe autosomal recessive hereditary neuropathies, Charcot-Marie-Tooth disease (CMT) types 4B1 and 4B2, both characterized by reduced nerve conduction velocities, focally folded myelin sheaths and demyelination. MTMRs form a large family of conserved dual-specific phosphatases with enzymatically active and inactive members. We show that homodimeric active Mtmr2 interacts with homodimeric inactive Sbf2 in a tetrameric complex. This association dramatically increases the enzymatic activity of the complexed Mtmr2 towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate. Mtmr2 and Sbf2 are considerably, but not completely, co-localized in the cellular cytoplasm. On membranes of large vesicles formed under hypo-osmotic conditions, Sbf2 favorably competes with Mtmr2 for binding sites. Our data are consistent with a model suggesting that, at a given cellular location, Mtmr2 phosphatase activity is highly regulated, being high in the Mtmr2/Sbf2 complex, moderate if Mtmr2 is not associated with Sbf2 or functionally blocked by competition through Sbf2 for membrane-binding site

How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network

Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks

Cell-specific activity-dependent fractionation of layer 2/3→5B excitatory signaling in mouse auditory cortex

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Neuroscience 35 (2015): 3112-3123, doi:10.1523/JNEUROSCI.0836-14.2015.Auditory cortex (AC) layer 5B (L5B) contains both corticocollicular neurons, a type of pyramidal-tract neuron projecting to the inferior colliculus, and corticocallosal neurons, a type of intratelencephalic neuron projecting to contralateral AC. Although it is known that these neuronal types have distinct roles in auditory processing and different response properties to sound, the synaptic and intrinsic mechanisms shaping their input–output functions remain less understood. Here, we recorded in brain slices of mouse AC from retrogradely labeled corticocollicular and neighboring corticocallosal neurons in L5B. Corticocollicular neurons had, on average, lower input resistance, greater hyperpolarization-activated current (Ih), depolarized resting membrane potential, faster action potentials, initial spike doublets, and less spike-frequency adaptation. In paired recordings between single L2/3 and labeled L5B neurons, the probabilities of connection, amplitude, latency, rise time, and decay time constant of the unitary EPSC were not different for L2/3→corticocollicular and L2/3→corticocallosal connections. However, short trains of unitary EPSCs showed no synaptic depression in L2/3→corticocollicular connections, but substantial depression in L2/3→corticocallosal connections. Synaptic potentials in L2/3→corticocollicular connections decayed faster and showed less temporal summation, consistent with increased Ih in corticocollicular neurons, whereas synaptic potentials in L2/3→corticocallosal connections showed more temporal summation. Extracellular L2/3 stimulation at two different rates resulted in spiking in L5B neurons; for corticocallosal neurons the spike rate was frequency dependent, but for corticocollicular neurons it was not. Together, these findings identify cell-specific intrinsic and synaptic mechanisms that divide intracortical synaptic excitation from L2/3 to L5B into two functionally distinct pathways with different input–output functions.This work was supported by National Institutes of Health grants DC013272 (T.T. and G.M.G.S.), DC007905 (T.T.), NS061963 (G.M.G.S), R03DC012585 (J.W.M.), T32DC011499 (C.T.A.), and F32DC013734 (C.T.A), and by the Albert and Ellen Grass Faculty Award (T.T. and G.M.G.S.) and Charles Evans Foundation Award (T.T. and G.M.G.S.).2015-08-1

Ephus: Multipurpose Data Acquisition Software for Neuroscience Experiments

Physiological measurements in neuroscience experiments often involve complex stimulus paradigms and multiple data channels. Ephus (http://www.ephus.org) is an open-source software package designed for general-purpose data acquisition and instrument control. Ephus operates as a collection of modular programs, including an ephys program for standard whole-cell recording with single or multiple electrodes in typical electrophysiological experiments, and a mapper program for synaptic circuit mapping experiments involving laser scanning photostimulation based on glutamate uncaging or channelrhodopsin-2 excitation. Custom user functions allow user-extensibility at multiple levels, including on-line analysis and closed-loop experiments, where experimental parameters can be changed based on recently acquired data, such as during in vivo behavioral experiments. Ephus is compatible with a variety of data acquisition and imaging hardware. This paper describes the main features and modules of Ephus and their use in representative experimental applications

E-Biothon: an experimental platform for BioInformatics

International audienceThe E-Biothon platform is an experimental Cloud platform to help speed up and advance research in biology, health and environment. It is based on a Blue Gene/P system and a web portal that allow members of the bioinformatics community to easily launch their scientific applications. We describe in this paper the technical capacities of the platform, the different applications supported and finally a set of user experiences on the platform

Placing a Price on Medical Device Innovation: The Example of Total Knee Arthroplasty

Background: Total knee arthroplasty (TKA) is common, effective, and cost-effective. Innovative implants promising reduced long-term failure at increased cost are under continual development. We sought to define the implant cost and performance thresholds under which innovative TKA implants are cost-effective. Methods: We performed a cost-effectiveness analysis using a validated, published computer simulation model of knee osteoarthritis. Model inputs were derived using published literature, Medicare claims, and National Health and Nutrition Examination Survey data. We compared projected TKA implant survival, quality-adjusted life expectancy (QALE), lifetime costs, and cost-effectiveness (incremental cost-effectiveness ratios or ICERs) of standard versus innovative TKA implants. We assumed innovative implants offered 5–70% decreased long-term TKA failure rates at costs 20–400% increased above standard implants. We examined the impact of patient age, comorbidity, and potential increases in short-term failure on innovative implant cost-effectiveness. Results: Implants offering ≥50% decrease in long-term TKA failure at ≤50% increased cost offered ICERs <$100,000 regardless of age or baseline comorbidity. An implant offering a 20$150,000 per QALY gained only among healthy 50–59-year-olds. Increasing short-term failure, consistent with recent device failures, reduced cost-effectiveness across all groups. Increasing the baseline likelihood of long-term TKA failure among younger, healthier and more active individuals further enhanced innovative implant cost-effectiveness among younger patients. Conclusions: Innovative implants must decrease actual TKA failure, not just radiographic wear, by 50–55% or more over standard implants to be broadly cost-effective. Comorbidity and remaining life span significantly affect innovative implant cost-effectiveness and should be considered in the development, approval and implementation of novel technologies, particularly in orthopedics. Model-based evaluations such as this offer valuable, unique insights for evaluating technological innovation in medical devices