Dendritic spike induction of postsynaptic cerebellar LTP

The architecture of parallel fiber (PF) axons contacting cerebellar Purkinje neurons (PNs) retains spatial information over long distances. PF synapses can trigger local dendritic calcium spikes, but whether and how this calcium signal leads to plastic changes that decode the PF input organization is unknown. By combining voltage and calcium imaging, we show that PF-elicited calcium signals, mediated by voltage-gated calcium channels, increase non-linearly during high-frequency bursts of electrically constant calcium spikes because they locally and transiently saturate the endogenous buffer. We demonstrate that these non-linear calcium signals, independently of NMDA or metabotropic glutamate receptor activation, can induce PF long-term potentiation (LTP). Two-photon imaging in coronal slices revealed that calcium signals inducing LTP can be observed by stimulating either the PF or the ascending fiber pathway. We propose that local dendritic calcium spikes, evoked by synaptic potentials, provide a unique mechanism to spatially decode PF signals into cerebellar circuitry changes

Adaptive Management of Multimodel Data and Heterogeneous Workloads

Data management systems are facing a growing demand for a tighter integration of heterogeneous data from different applications and sources for both operational and analytical purposes in real-time. However, the vast diversification of the data management landscape has led to a situation where there is a trade-off between high operational performance and a tight integration of data. The difference between the growth of data volume and the growth of computational power demands a new approach for managing multimodel data and handling heterogeneous workloads. With PolyDBMS we present a novel class of database management systems, bridging the gap between multimodel database and polystore systems. This new kind of database system combines the operational capabilities of traditional database systems with the flexibility of polystore systems. This includes support for data modifications, transactions, and schema changes at runtime. With native support for multiple data models and query languages, a PolyDBMS presents a holistic solution for the management of heterogeneous data. This does not only enable a tight integration of data across different applications, it also allows a more efficient usage of resources. By leveraging and combining highly optimized database systems as storage and execution engines, this novel class of database system takes advantage of decades of database systems research and development. In this thesis, we present the conceptual foundations and models for building a PolyDBMS. This includes a holistic model for maintaining and querying multiple data models in one logical schema that enables cross-model queries. With the PolyAlgebra, we present a solution for representing queries based on one or multiple data models while preserving their semantics. Furthermore, we introduce a concept for the adaptive planning and decomposition of queries across heterogeneous database systems with different capabilities and features. The conceptual contributions presented in this thesis materialize in Polypheny-DB, the first implementation of a PolyDBMS. Supporting the relational, document, and labeled property graph data model, Polypheny-DB is a suitable solution for structured, semi-structured, and unstructured data. This is complemented by an extensive type system that includes support for binary large objects. With support for multiple query languages, industry standard query interfaces, and a rich set of domain-specific data stores and data sources, Polypheny-DB offers a flexibility unmatched by existing data management solutions

On the Induction of Postsynaptic Granule Cell-Purkinje Neuron LTP and LTD

In the last decade, several experimental studies have demonstrated that particular patterns of synaptic activity can induce postsynaptic parallel fiber (PF) long-term potentiation (LTP). This form of plasticity can reverse postsynaptic PF long-term depression (LTD), which has been traditionally considered as the principal form of plasticity underlying cerebellar learning. Postsynaptic PF-LTP requires a transient increase in intracellular Ca2+ concentration and, in contrast to PF-LTD, is induced without concomitant climbing fiber (CF) activation. Thus, it has been postulated that the polarity of long-term synaptic plasticity is determined by the amplitude of the Ca2+ transient during the induction protocol, with PF-LTP induced by smaller Ca2+ signals without concomitant CF activation. However, this hypothesis is contradicted by recent studies. A quantitative analysis of Ca2+ signals associated with induction of PF-LTP indicates that the bidirectional induction of long-term plasticity is regulated by more complex mechanisms. Here we review the state-of-the-art of research on postsynaptic PF-LTP and PF-LTD and discuss the principal open questions on this topi

Characterization and Verification Environment for the RD53A Pixel Readout Chip in 65 nm CMOS

The RD53 collaboration is currently designing a large scale prototype pixel readout chip in 65 nm CMOS technology for the phase 2 upgrades at the HL-LHC. The RD53A chip will be available by the end of the year 2017 and will be extensively tested to confirm if the circuit and the architecture make a solid foundation for the final pixel readout chips for the experiments at the HL-LHC. A test and data acquisition system for the RD53A chip is currently under development to perform single-chip and multi-chip module measurements. In addition, the verification of the RD53A design is performed in a dedicated simulation environment. The concept and the implementation of the test and data acquisition system and the simulation environment, which are based on a modular data acquisition and system testing framework, are presented in this work

Combining Voltage and Calcium Imaging from Neuronal Dendrites

The ability to monitor membrane potential (V m) and calcium (Ca2+) transients at multiple locations on the same neuron can facilitate further progress in our understanding of neuronal function. Here we describe a method to combine V m and Ca2+ imaging using styryl voltage sensitive dyes and Fura type UV-excitable Ca2+ indicators. In all cases V m optical signals are linear with membrane potential changes, but the calibration of optical signals on an absolute scale is presently possible only in some neurons. The interpretation of Ca2+ optical signals depends on the indicator Ca2+ buffering capacity relative to the cell endogenous buffering capacity. In hippocampal CA1 pyramidal neurons, loaded with JPW-3028 and 300μM Bis-Fura-2, V m optical signals cannot be calibrated and the physiological Ca2+ dynamics are compromised by the presence of the indicator. Nevertheless, at each individual site, relative changes in V m and Ca2+ fluorescence signals under different conditions can provide meaningful new information on local dendritic integration. In cerebellar Purkinje neurons, loaded with JPW-1114 and 1mM Fura-FF, V m optical signals can be calibrated in terms of mV and Ca2+ optical signals quantitatively reveal the physiological changes in free Ca2+. Using these two examples, the method is explained in detai

Icarus: Towards a Multistore Database System

The last years have seen a vast diversification on the database market. In contrast to the "one-size-fits-all" paradigm according to which systems have been designed in the past, today's database management systems (DBMSs) are tuned for particular workloads. This has led to DBMSs optimized for high performance, high throughput read/write workload in online transaction processing (OLTP) and systems optimized for complex analytical queries (OLAP). However, this approach reaches a limit when systems have to deal with mixed workloads that are neither pure OLAP nor pure OLTP workloads. In such cases, polystores are increasingly gaining popularity. Rather than supporting one single database paradigm and addressing one particular workload, polystores encompass several DBMSs that store data in different schemas and allow to route requests at a per-query-level to the most appropriate system. In this paper, we introduce the polystore Icarus. In our evaluation based on a workload that combines OLTP and OLAP elements, We show that Icarus is able to speed-up queries up to a factor of 3 by properly routing queries to the best underlying DBMS

Using the eSana Framework in Dermatology to improve the Information Flow between Patients and Doctors

Mobile devices are becoming ubiquitous in every day\u27s life; their time and place independence are reasons for using them in different areas. One such area is electronic health, where patients can install small applications on their mobile devices that help or guide them in the management of their disease. The eSana framework offers a set of tools and approaches that allow the transmission of discrete physiological values electronically in order to evaluate them by medical experts. This paper presents an application scenario in the field of dermatology. It illustrates the information flow between patient and dermatologist including all transformation services. One speciality is the combination of binary image data and structured information about a given condition sent over a mobile network. The main goal is to show a set of necessary components in order to support the relationship between patients and their dermatologists by using medical standards

Evaluation of Drug Delivery and Efficacy of Ciprofloxacin-Loaded Povidone Foils and Nanofiber Mats in a Wound-Infection Model Based on Ex Vivo Human Skin

Topical treatment of wound infections is often a challenge due to limited drug availability at the site of infection. Topical drug delivery is an attractive option for reducing systemic side effects, provided that a more selective and sustained local drug delivery is achieved. In this study, a poorly water-soluble antibiotic, ciprofloxacin, was loaded on polyvinylpyrrolidone (PVP)-based foils and nanofiber mats using acetic acid as a solubilizer. Drug delivery kinetics, local toxicity, and antimicrobial activity were tested on an ex vivo wound model based on full-thickness human skin. Wounds of 5 mm in diameter were created on 1.5 × 1.5 cm skin blocks and treated with the investigated materials. While nanofiber mats reached the highest amount of delivered drug after 6 h, foils rapidly achieved a maximum drug concentration and maintained it over 24 h. The treatment had no effect on the overall skin metabolic activity but influenced the wound healing process, as observed using histological analysis. Both delivery systems were efficient in preventing the growth of Pseudomonas aeruginosa biofilms in ex vivo human skin. Interestingly, foils loaded with 500 µg of ciprofloxacin accomplished the complete eradication of biofilm infections with 1 × 109 bacteria/wound. We conclude that antimicrobial-loaded resorbable PVP foils and nanofiber mats are promising delivery systems for the prevention or topical treatment of infected wounds