Scalable positioning of commodity mobile devices using audio signals

This thesis explores the problem of computing a position map for co-located mobile devices. The positioning should happen in a scalable manner without requiring specialized hardware and without requiring specialized infrastructure (except basic Wi-Fi or cellular access). At events like meetings, talks, or conferences, a position map can aid spontaneous communication among users based on their relative position in two ways. First, it enables users to choose message recipients based on their relative position, which also enables the position-based distribution of documents. Second, it enables senders to attach their position to messages, which can facilitate interaction between speaker and audience in a lecture hall and enables the collection of feedback based on users’ location. In this thesis, we present Sonoloc, a mobile app and system that, by relying on acoustic signals, allows a set of commodity smart devices to determine their relative positions. Sonoloc can position any number of devices within acoustic range with a constant number of acoustic signals emitted by a subset of devices. Our experimental evaluation with up to 115 devices in real rooms shows that – despite substantial background noise – the system can locate devices with an accuracy of tens of centimeters using no more than 15 acoustic signals.Diese Dissertation befasst sich mit dem Problem, eine Positionskarte von sich am gleichen Ort befindenden mobilen Geräten zu berechnen. Dies soll skalierbar, ohne Verwendung von spezialisierter Hardware oder Infrastruktur (ausgenommen einfache WLAN- oder Mobilfunkzugang) erfolgen. Bei Veranstaltungen wie Meetings, Diskussionen oder Konferenzen kann eine Positionskarte die Benutzer bei spontaner Kommunikation mithilfe der relativen Positionen in zweierlei Hinsicht unterstützen. Erstens ermöglicht sie den Benutzern, die Empfänger von Nachrichten aufgrund deren Position zu wählen, was auch eine positionsabhängige Verteilung von Unterlagen erlaubt. Zweitens ermöglicht sie den Sendern, ihre Position in die Nachrichten zu integrieren, was eine Interaktion zwischen Referent und Zuhörer in einem Hörsaal und die Sammlung von positionsabhängigen Rückmeldungen erlaubt. In dieser Dissertation stellen wir die Mobile-App und das System Sonoloc vor, das mithilfe von Tonsignalen erlaubt, die relative Position handelsüblicher, intelligenter Geräte zu bestimmen. Sonoloc kann eine beliebige Zahl von Geräten innerhalb des Hörbereichs durch eine gleichbleibende Zahl von Tonsignalen, die von einer Teilmenge der Geräte gesendet werden, lokalisieren. Unsere experimentelle Analyse mit bis zu 115 Geräten in echten Räumen zeigt, dass das System trotz signifikanter Hintergrundgeräusche unter Verwendung von bis zu 15 Tonsignalen mit einer Genauigkeit von wenigen Dezimetern Geräte lokalisieren kann.This work was supported in part by the European Research Council (ERC Synergy imPACT 610150), the German Science Foundation (DFG CRC 1223), the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research (A), KAKENHI Grant Number 16H01735), and the National Science Foundation (NSF Awards CNS 1526635 and CNS 1314857)

Developmentally regulated autophagy is required for eye formation in Drosophila

The compound eye of the fruit fly Drosophila melanogaster is one of the most intensively studied and best understood model organs in the field of developmental genetics. Herein we demonstrate that autophagy, an evolutionarily conserved selfdegradation process of eukaryotic cells, is essential for eye development in this organism. Autophagic structures accumulate in a specific pattern in the developing eye disc, predominantly in the morphogenetic furrow (MF) and differentiation zone. Silencing of several autophagy genes (Atg) in the eye primordium severely affects the morphology of the adult eye through triggering ectopic cell death. In Atg mutant genetic backgrounds however genetic compensatory mechanisms largely rescue autophagic activity in, and thereby normal morphogenesis of, this organ. We also show that in the eye disc the expression of a key autophagy gene, Atg8a, is controlled in a complex manner by the anterior Hox paralog lab (labial), a master regulator of early development. Atg8a transcription is repressed in front of, while activated along, the MF by lab. The amount of autophagic structures then remains elevated behind the moving MF. These results indicate that eye development in Drosophila depends on the cell death-suppressing and differentiating effects of the autophagic process. This novel, developmentally regulated function of autophagy in the morphogenesis of the compound eye may shed light on a more fundamental role for cellular self-digestion in differentiation and organ formation than previously thought

Condition-Dependent Functional Shift of Two Drosophila Mtmr Lipid Phosphatases in Autophagy Control

Myotubularin (MTM) and myotubularin-related (MTMR) lipid phosphatases catalyze the removal of a phosphate group from certain phosphatidylinositol derivatives. Because some of these substrates are required for macroautophagy/autophagy, during which unwanted cytoplasmic constituents are delivered into lysosomes for degradation, MTM and MTMRs function as important regulators of the autophagic process. Despite its physiological and medical significance, the specific role of individual MTMR paralogs in autophagy control remains largely unexplored. Here we examined two Drosophila MTMRs, EDTP and Mtmr6, the fly orthologs of mammalian MTMR14 and MTMR6 to MTMR8, respectively, and found that these enzymes affect the autophagic process in a complex, condition-dependent way. EDTP inhibited basal autophagy, but did not influence stress-induced autophagy. In contrast, Mtmr6 promoted the process under nutrient-rich settings, but effectively blocked its hyperactivation in response to stress. Thus, Mtmr6 is the first identified MTMR phosphatase with dual, antagonistic roles in the regulation of autophagy, and shows conditional antagonism/synergism with EDTP in modulating autophagic breakdown. These results provide a deeper insight into the adjustment of autophagy. Abbreviations: Atg, autophagy-related; BDSC, Bloomington Drosophila Stock Center; DGRC, Drosophila Genetic Resource Center; EDTP, Egg-derived tyrosine phosphatase; FYVE, zinc finger domain from Fab1 (yeast ortholog of PIKfyve), YOTB, Vac1 (vesicle transport protein) and EEA1 cysteine-rich proteins; LTR, LysoTracker Red; MTM, myotubularin; MTMR, myotubularin-related; PI, phosphatidylinositol; Pi3K59F, Phosphotidylinositol 3 kinase 59F; PtdIns3P, phosphatidylinositol-3-phosphate; PtdIns(3,5)P(2), phosphatidylinositol-3,5-bisphosphate; PtdIns5P, phosphatidylinositol-5-phosphate; ref(2)P, refractory to sigma P; Syx17, Syntaxin 17; TEM, transmission electron microscopy; UAS, upstream activating sequence; Uvrag, UV-resistance associated gene; VDRC, Vienna Drosophila RNAi Center; Vps34, Vacuolar protein sorting 34

HCN channels at the cell soma ensure the rapid electrical reactivity of fast-spiking interneurons in human neocortex

Accumulating evidence indicates that there are substantial species differences in the properties of mammalian neurons, yet theories on circuit activity and information processing in the human brain are based heavily on results obtained from rodents and other experimental animals. This knowledge gap may be particularly important for understanding the neocortex, the brain area responsible for the most complex neuronal operations and showing the greatest evolutionary divergence. Here, we examined differences in the electrophysiological properties of human and mouse fast-spiking GABAergic basket cells, among the most abundant inhibitory interneurons in cortex. Analyses of membrane potential responses to current input, pharmacologically isolated somatic leak currents, isolated soma outside-out patch recordings, and immunohistochemical staining revealed that human neocortical basket cells abundantly express hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel isoforms HCN1 and HCN2 at the cell soma membrane, whereas these channels are sparse at the rodent basket cell soma membrane. Antagonist experiments showed that HCN channels in human neurons contribute to the resting membrane potential and cell excitability at the cell soma, accelerate somatic membrane potential kinetics, and shorten the lag between excitatory postsynaptic potentials and action potential generation. These effects are important because the soma of human fast-spiking neurons without HCN channels exhibit low persistent ion leak and slow membrane potential kinetics, compared with mouse fast-spiking neurons. HCN channels speed up human cell membrane potential kinetics and help attain an input–output rate close to that of rodent cells. Computational modeling demonstrated that HCN channel activity at the human fast-spiking cell soma membrane is sufficient to accelerate the input–output function as observed in cell recordings. Thus, human and mouse fast-spiking neurons exhibit functionally significant differences in ion channel composition at the cell soma membrane to set the speed and fidelity of their input–output function. These HCN channels ensure fast electrical reactivity of fast-spiking cells in human neocortex

HCN channels at the cell soma ensure the rapid electrical reactivity of fast-spiking interneurons in human neocortex.

Accumulating evidence indicates that there are substantial species differences in the properties of mammalian neurons, yet theories on circuit activity and information processing in the human brain are based heavily on results obtained from rodents and other experimental animals. This knowledge gap may be particularly important for understanding the neocortex, the brain area responsible for the most complex neuronal operations and showing the greatest evolutionary divergence. Here, we examined differences in the electrophysiological properties of human and mouse fast-spiking GABAergic basket cells, among the most abundant inhibitory interneurons in cortex. Analyses of membrane potential responses to current input, pharmacologically isolated somatic leak currents, isolated soma outside-out patch recordings, and immunohistochemical staining revealed that human neocortical basket cells abundantly express hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel isoforms HCN1 and HCN2 at the cell soma membrane, whereas these channels are sparse at the rodent basket cell soma membrane. Antagonist experiments showed that HCN channels in human neurons contribute to the resting membrane potential and cell excitability at the cell soma, accelerate somatic membrane potential kinetics, and shorten the lag between excitatory postsynaptic potentials and action potential generation. These effects are important because the soma of human fast-spiking neurons without HCN channels exhibit low persistent ion leak and slow membrane potential kinetics, compared with mouse fast-spiking neurons. HCN channels speed up human cell membrane potential kinetics and help attain an input-output rate close to that of rodent cells. Computational modeling demonstrated that HCN channel activity at the human fast-spiking cell soma membrane is sufficient to accelerate the input-output function as observed in cell recordings. Thus, human and mouse fast-spiking neurons exhibit functionally significant differences in ion channel composition at the cell soma membrane to set the speed and fidelity of their input-output function. These HCN channels ensure fast electrical reactivity of fast-spiking cells in human neocortex

Prevalence of Coxiella burnetii in Hungary: screening of dairy cows, sheep, commercial milk samples, and ticks

Q fever is an important zoonotic disease caused by Coxiella burnetii. There are few reliable data about C. burnetii infection available. The aim of this study was to assess the importance and potential infectious sources of Q fever in Hungary. A total of 215 milk samples (10 individual samples from each herd and 1 bulk tank milk sample from each cattle herd), and 400 serum samples (20 from each herd) were tested from 15 dairy cattle herds and 5 sheep flocks located in different parts of Hungary. The study found 19.3% (58/300) and 38.0% (57/150) seropositivity in cattle, and 0% (0/100) and 6.0% (3/50) seropositivity in sheep, by complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA), respectively. C. burnetii DNA was detected by IS1111 element-based TaqMan real-time polymerase chain reaction (PCR) in 8.7% (13/150) of individual dairy cow milk samples, 4.0% (2/50) of individual sheep milk samples, and 66.7% (10/15) of dairy bulk tank milk samples. Samples taken from nine different commercially-available pasteurized cow milk products from different Hungarian producers were also tested for the presence of C. burnetii DNA, and eight of these samples were found to be positive (88.9%). The real-time PCR examination of 5402 ixodid ticks collected from different parts of the country yielded negative results. Knowledge of the true prevalence of Q fever is crucial for policymakers involved in evidence-based decision making

Developmentally regulated autophagy is required for eye formation in <i>Drosophila</i>

<p>The compound eye of the fruit fly <i>Drosophila melanogaster</i> is one of the most intensively studied and best understood model organs in the field of developmental genetics. Herein we demonstrate that autophagy, an evolutionarily conserved selfdegradation process of eukaryotic cells, is essential for eye development in this organism. Autophagic structures accumulate in a specific pattern in the developing eye disc, predominantly in the morphogenetic furrow (MF) and differentiation zone. Silencing of several autophagy genes (<i>Atg</i>) in the eye primordium severely affects the morphology of the adult eye through triggering ectopic cell death. In <i>Atg</i> mutant genetic backgrounds however genetic compensatory mechanisms largely rescue autophagic activity in, and thereby normal morphogenesis of, this organ. We also show that in the eye disc the expression of a key autophagy gene, <i>Atg8a</i>, is controlled in a complex manner by the anterior Hox paralog Lab (Labial), a master regulator of early development. <i>Atg8a</i> transcription is repressed in front of, while activated along, the MF by Lab. The amount of autophagic structures then remains elevated behind the moving MF. These results indicate that eye development in <i>Drosophila</i> depends on the cell death-suppressing and differentiating effects of the autophagic process. This novel, developmentally regulated function of autophagy in the morphogenesis of the compound eye may shed light on a more fundamental role for cellular self-digestion in differentiation and organ formation than previously thought.</p> <p><b>Abbreviations</b>: αTub84B, α-Tubulin at 84B; <i>Act5C, Actin5C</i>; AO, acridine orange; Atg, autophagy-related; Ato, Atonal; CASP3, caspase 3; Dcr-2; Dicer-2; Dfd, Deformed; DZ, differentiation zone; eGFP, enhanced green fluorescent protein; EM, electron microscopy; <i>exd, extradenticle; ey, eyeless</i>; FLP, flippase recombinase; FRT, FLP recognition target; <i>Gal4</i>, gene encoding the yeast transcription activator protein GAL4; GFP, green fluorescent protein; GMR, Glass multimer reporter; Hox, homeobox; <i>hth, homothorax; lab, labial</i>; L3F, L3 feeding larval stage; L3W, L3 wandering larval stage; lf, loss-of-function; MAP1LC3, microtubule-associated protein 1 light chain 3; MF, morphogenetic furrow; PE, phosphatidylethanolamine; PBS, phosphate-buffered saline; PI3K/PtdIns3K, class III phosphatidylinositol 3-kinase; PZ, proliferation zone; Ref(2)P, refractory to sigma P, RFP, red fluorescent protein; RNAi, RNA interference; RpL32, Ribosomal protein L32; RT-PCR, reverse transcription-coupled polymerase chain reaction; S.D., standard deviation; SQSTM1, Sequestosome-1, Tor, Target of rapamycin; TUNEL, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay; UAS, upstream activation sequence; qPCR, quantitative real-time polymerase chain reaction; <i>w, white</i></p