This thesis describes a series of experiments to investigate the effect of thermal stimulation on corticospinal excitability using transcranial magnetic stimulation (TMS). Experiment I showed that innocuous cooling or warming of a single digit, produced short-lasting and mixed patterns of modulation only during actual thermal stimulation, with the inhibition being the most common pattern observed. In line with this finding, cooling stimulation applied to a larger area (i.e. multi-digits) produced variable but more sustained modulation in motor evoked potential (MEP) amplitude in the post-cooling phase (Exp II). Notably, the responses to cooling in terms of either suppressed or enhanced corticospinal excitability tended to be fairly consistent in a given individual with repeated applications. When examining possible sources of the observed variable MEP modulation, we found that individual characteristics such as age, sex and changes in skin temperature had no major influences. We hypothesized that the variability of responses might be related to individual differences in the excitability of intra-cortical circuits involved in sensorimotor integration. To test this hypothesis, we performed Experiment III using conditioning TMS paradigms. This experiment revealed that TMS markers of sensorimotor integration (SAI and SAF levels) were good predictors of individual variations in cooling-induced modulation in corticospinal excitability. This provided evidence supporting the role of SAI and SAF as markers to predict individual’s response to focal thermal stimulation. The identification of such predictors could enhance the therapeutic applicability of this form of stimulation in neurorehabilitation. Collectively, these findings advance our understanding of the neurophysiological basis of thermal stimulation and shed light on the development of a more rational application of neurofacilitation techniques based on afferent stimulation in clinical populations, such as stroke survivors.

Mobile terminals allow users to access service while on the move. This unique feature has driven the rapid growth in the mobile network industry, changing it from a new technology into a massive industry in less than two decades. In this thesis, an in-depth study of the handover effects of mobile WiMAX networks is carried out. The mobile WiMAX technology is first presented as literature study and then the technologies of handovers for previous generations are introduced in detail. Further, the hard handover of the mobile WiMAX is simulated by Network Simulator-2 (NS-2). In addition, the "ping-pang" effect of handover was investigated and the call blocking and dropping probabilities are implemented using MATLAB. The goal is to find out which parameters have the significant impact on the handover performance. The results showed that the threshold and hysteresis margin of the handover should be selected by considering the tradeoff between the "ping-pang" effect and the extra interference causing to neighboring cells due to the poor quality link. The handover latency of mobile WiMAX is below 50 ms with the traveling speed of mobile station up to 20 m/s.

This project evaluates the applicability of network edge computing to reduce global latencies of client applications. It determines the dimension of latency reduction network edge computing can provide compared to common cloud computing architectures. Furthermore, this project examines whether Compute@Edge, an exemplary and modern edge computing service, enables the replacement of many latency-sensitive cloud systems by an adequate versatility and a reasonable costbenefit ratio. Compute@Edge is a new, serverless edge computing platform by Fastly built on WebAssembly. A prototype that replicates a globally utilized server of Spotify was implemented on Compute@Edge. To compare the latencies of cloud and edge computing, an experiment captured the latencies of the prototype and the original system using a Spotify client that generated almost 26 million data points from all over the world. Next to the experiment, the implementation of the prototype allows accurate insights into the possibilities of Compute@Edge and whether WebAssembly is a promising approach for edge computing. Successes of this work include data showing that network edge computing can reduce latencies significantly. It offers arguments to ramp up the usage of edge computing, WebAssembly and Compute@Edge for applications that require low latencies. The results of the experiment show that network edge computing is capable of reducing network latency compared to cloud computing by at least 38%. The lower latencies combined with the versatility and feasibility of Compute@Edge show that modern edge platforms enable a much higher utilization for applications like Spotify. / Projektet utvärderar hur applicerbart nätverks edge computing är för att minska global latens av kundapplikationer. Den avgör att dimensionen av fördröjnings minskningen i nätverks edge computing kan ge i jämförelse till vanliga cloud computing arkitekturer. Projektet undersöker också om Compute@Edge, en exemplarisk och modernt edge computing service, möjliggör ett byte av många latens-känsliga cloud system och då med en lämplig användbarhet och ett rimlig kostnads-nyttoförhållande. Compute@Edge är en ny serverlös edge computing platform av Fastly, byggt på WebAssembly. En prototype som replikerar en globalt använd server av Spotify var implementerad på Compute@Edge. För att jämföra latenserna av cloud och edge computing, genomfördes ett experiment som fångade upp latenserna av prototypen och det ursprungliga systemet med hjälp från en Spotify kund som genererade runt 26 millioner globala datapunkter. Med experimentet, ger prototypimplementeringen exakta insikter till möjligheterna med Compute@Edge och om WebAssembly är en lovande lösning till edge computing. Arbetes framgång inkluderar data som visar att nätverks edge computing kan minska latensen betydligt. Det visar också argument för att öka på användingen av edge computing, WebAssembly och Compute@Edge till applikationer som behöver låga latens. Experimentets resultat visar att nätverks edge computing kan minska nätverkslatens i jämförelse till cloud computing med åtminstone 38%. De lägre latenserna kombinerade med användbarheten och möjligheten av Compute@Edge visar att moderna edge plattformar ger möjligheter till mycket mer bättre översättning för applikationer som Spotify.

It is widely accepted that low energy consumption is the most important requirement when designing components and systems for a wireless sensor network (WSN). The greatest energy consumer of each node within a WSN is the radio transceiver and as such, it is important that this component be used in an extremely energy e±cient manner. One method of reducing the amount of energy consumed by the radio transceiver is to turn it off and allow nodes to enter a sleep mode. The algorithms that directly control the radio transceiver are traditionally grouped into the Medium Access Control (MAC) layer of a communication protocol stack. This thesis introduces the emerging field of wireless sensor networks and outlines the requirements of a MAC protocol for such a network. Current MAC protocols are reviewed in detail with a focus on how they utilize this energy saving sleep mode as well as performance problems that they suffer from. A proposed new method of coordinating the use of this sleep mode between nodes in the network is specifed and described. The proposed new protocol is analytically compared with existing protocols as well as with some fundamental performance limits. The thesis concludes with an analysis of the results as well as some recommendations for future work.

Increased attention towards threatening stimuli in both the external and internal environments is thought to be a factor in the causation and maintenance of pathological anxiety. Attentional biases for threatening information have been demonstrated in anxiety disorders, however the cortical mechanisms involved remain unclear. In this investigation, an Emotional Stroop task consisting of neutral, positive, depression-related and anxietyrelated words, was used to investigate attentional biases in 14 Panic Disorder patients and 32 psychiatrically healthy controls. The standard colour-word Stroop was also performed to determine whether any general cognitive deficits exist in Panic Disorder. Steady-state probe topography (SSPT), a brain electrical activity imaging methodology, was used to investigate participants' brain activity during performance of the tasks. It was hypothesised that Panic Disorder is associated with specific biases for disorder-specific information and thus patients would exhibit increased interference for anxiety-related words only, compared to neutral words. Mean reaction times for the Standard Stroop was similar for the two groups. For the Emotional Stroop task, neither group showed an interference effect for any emotional category. However, Panic Disorder patients performed the Emotional Stroop significantly more slowly than the Controls. The SSPT data suggest that the Standard and Emotional Stroop tasks are associated with different patterns of brain activity in the Control and Panic Disorder groups despite the similarities in the reaction time data. Specifically, the Standard Stroop was marked by strong temporo-parietal excitation in the Panic Disorder group only. In addition, anterior SSVEP patterns further differentiated between the Control and Panic Disorder groups. The most striking finding for the Emotional Stroop was strong sustained bilateral temporo-parieto-occipital excitation in the Panic Disorder group. In addition, a subgroup of the Controls exhibited increased interference for anxiety-related words and therefore the brain activity for this group and the remainder of Controls who did not show interference was analysed separately. It was found that the presence of interference for anxiety-related words was associated with right prefrontal inhibition prior to response. Other time-varying changes in the SSVEP further distinguished between the subgroup of Controls who showed an interference effect and those who did not.

<p>This thesis work investigates the effects of crosstalk on on-chip interconnects. We use optimal repeater insertion as a reference and derive analytical expressions for signal latency, maximum data-rate and power consumption. Through calculations and simulations we show that despite large uncertainties in arrival time of a signal that is subject to crosstalk, we are able to make predictions about the maximum data-rate on a bus. We also show that data-rates can exceed the classical limit of the latency inverted by using wave pipelining. To increase the data-rate, we can increase the number of repeaters to a limit, at the cost of additional latency and power. Savings in power consumption can be achieved by using fewer repeaters, paying in latency and data-rate. Through fewer repeaters, the top metal layer shows better performance in all investigated aspects.</p>

<p>The continuous miniaturization of integrated circuits has opened the path towards System-on-Chip realizations. Process shrinking into the nanometer regime improves transistor performancewhile the delay of global interconnects, connecting circuit blocks separated by a long distance, significantly increases. In fact, global interconnects extending across a full chip can have a delay corresponding to multiple clock cycles. At the same time, global clock skew constraints, not only between blocks but also along the pipelined interconnects, become even tighter. On-chip interconnects have always been considered <em>RC</em>-like, that is exhibiting long <em>RC</em>-delays. This has motivated large efforts on alternatives such as on-chip optical interconnects, which have not yet been demonstrated, or complex schemes utilizing on-chip F-transmission or pulsed current-mode signaling.</p><p>In this thesis, we show that well-designed electrical global interconnects, behaving as transmission lines, have the capacity of very high data rates (higher than can be delivered by the actual process) and support near velocity-of-light delay for single-ended voltage-mode signaling, thus mitigating the <em>RC</em>-problem. We critically explore key interconnect performance measures such as data delay, maximum data rate, crosstalk, edge rates and power dissipation. To experimentally demonstrate the feasibility and superior properties of on-chip transmission line interconnects, we have designed and fabricated a test chip carrying a 5 mm long global communication link. Measurements show that we can achieve 3 Gb/s/wire over the 5 mm long, repeaterless on-chip bus implemented in a standard 0.18 μm CMOS process, achieving a signal velocity of 1/3 of the velocity of light in vacuum.</p><p>To manage the problems due to global wire delays, we describe and implement a Synchronous Latency Insensitive Design (SLID) scheme, based on source-synchronous data transfer between blocks and data re-timing at the receiving block. The SLIDtechnique not onlymitigates unknown globalwire delays, but also removes the need for controlling global clock skew. The high-performance and high robustness capability of the SLID-method is practically demonstrated through a successful implementation of a SLID-based, 5.4 mm long, on-chip global bus, supporting 3 Gb/s/wire and dynamically accepting ± 2 clock cycles of data-clock skew, in a standard 0.18 μm CMOS porcess.</p><p>In the context of technology scaling, there is a tendency for interconnects to dominate chip power dissipation due to their large total capacitance. In this thesis we address the problem of interconnect power dissipation by proposing and analyzing a transition-energy cost model aimed for efficient power estimation of performancecritical buses. The model, which includes properties that closely capture effects present in high-performance VLSI buses, can be used to more accurately determine the energy benefits of e.g. transition coding of bus topologies. We further show a power optimization scheme based on appropriate choice of reduced voltage swing of the interconnect and scaling of receiver amplifier. Finally, the power saving impact of swing reduction in combination with a sense-amplifying flip-flop receiver is shown on a microprocessor cache bus architecture used in industry.</p>

The continuous miniaturization of integrated circuits has opened the path towards System-on-Chip realizations. Process shrinking into the nanometer regime improves transistor performancewhile the delay of global interconnects, connecting circuit blocks separated by a long distance, significantly increases. In fact, global interconnects extending across a full chip can have a delay corresponding to multiple clock cycles. At the same time, global clock skew constraints, not only between blocks but also along the pipelined interconnects, become even tighter. On-chip interconnects have always been considered RC-like, that is exhibiting long RC-delays. This has motivated large efforts on alternatives such as on-chip optical interconnects, which have not yet been demonstrated, or complex schemes utilizing on-chip F-transmission or pulsed current-mode signaling. In this thesis, we show that well-designed electrical global interconnects, behaving as transmission lines, have the capacity of very high data rates (higher than can be delivered by the actual process) and support near velocity-of-light delay for single-ended voltage-mode signaling, thus mitigating the RC-problem. We critically explore key interconnect performance measures such as data delay, maximum data rate, crosstalk, edge rates and power dissipation. To experimentally demonstrate the feasibility and superior properties of on-chip transmission line interconnects, we have designed and fabricated a test chip carrying a 5 mm long global communication link. Measurements show that we can achieve 3 Gb/s/wire over the 5 mm long, repeaterless on-chip bus implemented in a standard 0.18 μm CMOS process, achieving a signal velocity of 1/3 of the velocity of light in vacuum. To manage the problems due to global wire delays, we describe and implement a Synchronous Latency Insensitive Design (SLID) scheme, based on source-synchronous data transfer between blocks and data re-timing at the receiving block. The SLIDtechnique not onlymitigates unknown globalwire delays, but also removes the need for controlling global clock skew. The high-performance and high robustness capability of the SLID-method is practically demonstrated through a successful implementation of a SLID-based, 5.4 mm long, on-chip global bus, supporting 3 Gb/s/wire and dynamically accepting ± 2 clock cycles of data-clock skew, in a standard 0.18 μm CMOS porcess. In the context of technology scaling, there is a tendency for interconnects to dominate chip power dissipation due to their large total capacitance. In this thesis we address the problem of interconnect power dissipation by proposing and analyzing a transition-energy cost model aimed for efficient power estimation of performancecritical buses. The model, which includes properties that closely capture effects present in high-performance VLSI buses, can be used to more accurately determine the energy benefits of e.g. transition coding of bus topologies. We further show a power optimization scheme based on appropriate choice of reduced voltage swing of the interconnect and scaling of receiver amplifier. Finally, the power saving impact of swing reduction in combination with a sense-amplifying flip-flop receiver is shown on a microprocessor cache bus architecture used in industry.

Relapsing fever (RF) is a disease caused by tick- or louse-transmitted bacteria of the genus Borrelia. It occurs worldwide but is most common in Africa where it is one of the most prevalent bacterial diseases. The main manifestation is a recurring fever which coincides with massive numbers of bacteria in the blood. Severity ranges from asymptomatic to fatal. RF is usually considered a transient disease. In contrast, B. duttonii causes a persistent, residual brain infection in C57BL/6 mice which remains long time after the bacteria are cleared from the blood. The host gene expression pattern is indistinguishable from that of uninfected animals, indicating that persistent bacteria are not recognized by the immune system nor do they cause noticeable tissue damage. This is probably due to the quite low number of bacteria residing in the brain. The silent infection can be reactivated by immunosuppression allowing bacteria to re-enter the blood. To investigate if the residual infection is in a quiescent state or if the bacteria are actively dividing, mice with residual brain infection were treated with the cell-wall disrupting antibiotic ceftriaxone, which is only active against dividing bacteria. Since all mice were cured by ceftriaxone we conclude that the bacteria are actively growing in the brain rather than being in a latent, dormant state. The brain is used as an immunoprivileged site to escape host immune defence and probably as a reservoir for bacteria. RF is a common cause of pregnancy complications, miscarriage and neonatal death in sub-Saharan Africa. We established a murine model of gestational relapsing fever to study the pathological development of these complications. B. duttonii infection during pregnancy results in intrauterine growth retardation as well as placental damage and inflammation. Spirochetes cross the maternal-foetal barrier, resulting in congenital infection. Further, pregnancy has a protective effect, resulting in milder disease during pregnancy. A clinic-based study to investigate the presence of RF in Togo was performed. Blood from patients with fever were examined for RF by microscopy, GlpQ ELISA and PCR. About 10% of the patients were positive by PCR and 13% had antibodies to GlpQ. Many RF patients originally had a misdiagnosis of malaria, which resulted in ineffective treatment. The inability of microscopic analysis to detect spirochetes demonstrates the need for tests with greater sensitivity. To provide simple, fast, cheap and sensitive diagnostics using equipment available in small health centres, a method based on enrichment of bacteria by centrifugation and detection by Giemsa staining was developed which detects <10 spirochetes/ml. To study the phylogeny of RF, IGS and glpQ were sequenced and neighbor joining trees were constructed. B. persica and B. hispanica were distant from the other species iswhereas B. crocidurae appeared to be a heterogeneous species. B. duttonii is polyphyletic in relation to B. recurrentis suggesting that the two species may in fact be the same or have a polyphyletic origin.

As disturbed binocular functions in small children may lead to severe amblyopia it is of interest to detect it as early as possible. Most tests for binocular functions, however, demand active cooperation and may be unreliable in children up to 4-5 years of age. This study therefore aims to employ visual evoked potentials (VEP) to enable the examiner to evaluate the binocular function in a subject without need of active cooperation from the subject. Initially we studied the relation of suprathreshold contrast to the latency of the transient pattern VEP (tpVEP). Although suprathreshold contrast independently influenced the tpVEP latency, interindividual variation was too large to suggest tpVEP as a possible method for objectively measuring contrast sensitivity in a subject. The tpVEP latency in normal and microstrabismic adult subjects was examined. It was significantly shorter with binocular viewing in normals, but not in the microstrabismic group. Contrast sensitivity and tpVEP latency was examined in adults, both with normal binocularity and with microstrabismus, using both luminance (black-and-white) contrast and colour contrast patterns. The tpVEP latency to colour contrast, like that to luminance contrast, is shorter in normal subjects who view the stimulus binocularly. Interindividual variation or overlap between the normal and microstrabismic groups did not improve with colour contrast. The most significant features of the tpVEP are amplitude and latency. Depending on stimulus conditions, the response may show variations in configuration, amplitude and, to a lesser degree, latency. To decrease the influence of such variations steady-state VEP (ssVEP) can be used. The stimulus is presented in a fast repetitive manner, yielding a VEP response shaped as a continuous curve. The frequency components of this curve can be analysed using Fast Fourier Analysis. Fast Fourier analysis of ssVEP in children aged 8-15 years with normal binocularity and with microstrabismus showed that the power of the second harmonic (the double frequency of stimulus frequency) of the response with binocular viewing was larger than with monocular viewing, both in normals and microstrabismic subjects. For higher stimulus frequencies, microstrabismic subjects showed a significantly lower power of the second harmonic compared with subjects with normal binocularity, when the stimulus was presented binocularly. Finally, Fast Fourier analysed ssVEP in pre-school children aged 4-5 years was studied. A normal group was compared with a group with microstrabismus and a group with significant amblyopia. Amblyopic subjects had significant interocular differences in the first harmonic. We confirmed the significant difference found between microstrabismic subjects and subjects with normal binocularity regarding the second harmonic’s power with higher temporal frequency binocular stimulation, although at a slightly lower frequency than for older children. A low power of the second harmonic in the ssVEP to a binocular stimulus with high temporal frequency is a strong indicator of disturbed binocular function. / För att förhindra amblyopi (ensidig synsvaghet) hos barn är det viktigt att upptäcka störningar i samsynsfunktionerna så tidigt som möjligt. Samsynstester kräver dock aktiv medverkan och kan ge osäkra resultat hos barn upp till 4-5 års ålder. Den här avhandlingen studerar möjligheterna att utifrån tidsmässiga (temporala) egenskaper hos visual evoked potentials (VEP) undersöka samsynsfunktioner objektivt, utan att den undersökte behöver medverka aktivt. Första delstudien visar att ett synstimulus kontrastnivå i relation till kontrastkänslighetströskeln oberoende påverkar latensen i VEP, men variationer mellan individer gör metoden olämplig som objektiv kontrastkänslighetstest. Andra delstudien jämför latensen i VEP hos individer med normal samsyn med den hos personer med mikroskelning. Stimulering av båda ögonen gav signifikant kortare latens än stimulering av ett öga hos normala, men inte hos mikroskelare. I den tredje delstudien jämfördes känslighet för luminanskontrast och färgkontrast hos individer med normal samsyn och personer med mikroskelning. Både luminansmönster (svart-vita) och färgkontrastmönster upptäcktes vid lägre kontrast om båda ögonen stimulerades istället för ett i taget hos normalseende. Mikroskelare uppfattade mönstren sämre med båda ögonen än med ett öga (det dominanta). Latensen i VEP mättes i båda grupperna för både luminans- och färgkontrastmönster. Båda typerna av kontrast gav förkortning av latensen när båda ögonen stimulerades vid normal samsyn, men denna förkortning uteblev hos mikroskelare. Både luminans- och färgkontrast gav för varierande resultat för att utnyttja metoden för objektiv undersökning av samsynen. Fourier-analys innebär att en kurvform delas upp i sinuskurvor med olika frekvens, amplitud och fas. Om ett stimulus växlar hastigt får man ett steady-state VEP (ssVEP), dvs en kontinuerligt vågformad VEP-kurva, som kan delas upp i delsinuskurvor med Fourieranalys. Detta gör att man särskilt kan studera frekvenser som är relaterade till stimuleringsfrekvensen, till exempel grundton och övertoner (multipler av grundtonsfrekvensen). Barn 8-15 år gamla, med normal samsyn och med mikroskelning undersöktes med ssVEP i det fjärde delarbetet. Den första övertonen (= ”second harmonic”) var statistiskt signifikant svagare hos mikroskelare jämfört med normala individer, när stimuleringsfrekvensen var hög. Det femte och sista delarbetet undersökte ssVEP hos 4-5 år gamla förskolebarn på motsvarande sätt. I denna studie deltog också en grupp barn med amblyopi (synsvaghet) på ena ögat. På en något lägre stimuleringsfrekvens bekräftades den svagare första övertonen hos barnen med mikroskelning jämfört med barnen med normal samsyn. De amblyopa barnen visade tydligast förändringar vid lägre stimuleringsfrekvenser och i ssVEP:s grundtonsfrekvens (= ”first harmonic” eller ”fundamental harmonic”). Resultaten i de olika grupperna är så pass åtskilda att metoden verkar lämpa sig för objektiv undersökning av samsynsfunktioner, i det att en svag första överton i binokulärt ssVEP utlöst av hög stimuleringsfrekvens inger en stark misstanke om störd samsyn, medan en stor skillnad i grundtonens styrka i höger respektive vänster ögas ssVEP tyder på amblyopi.