Multimodal (EEG-fMRI) functional connectivity study of levodopa effect in Parkinson’s disease

Aim: To assess if the intake of levodopa in patients with Parkinson’s Disease (PD) changes cerebral connectivity, as revealed by simultaneous recording of hemodynamic (functional MRI, or fMRI) and electric (electroencephalogram, EEG) signals. Particularly, we hypothesize that the strongest changes in FC will involve the motor network, which is the most impaired in PD. Methods: Eight patients with diagnosis of PD “probable”, therapy with levodopa exclusively, normal cognitive and affective status, were included. Exclusion criteria were: moderate-severe rest tremor, levodopa induced dyskinesia, evidence of gray or white matter abnormalities on structural MRI. Scalp EEG (64 channels) were acquired inside the scanner (1.5 Tesla) before and after the intake of levodopa. fMRI functional connectivity was computed from four regions of interest: right and left supplementary motor area (SMA) and right and left precentral gyrus (primary motor cortex). Weighted partial directed coherence (w-PDC) was computed in the inverse space after the removal of EEG gradient and cardioballistic artifacts. Results and discussion: fMRI group analysis shows that the intake of levodopa increases hemodynamic functional connectivity among the SMAs / primary motor cortex and: sensory-motor network itself, attention network and default mode network. w-PDC analysis shows that EEG connectivity among regions of the motor network has the tendency to decrease after the intake the levodopa; furthermore, regions belonging to the DMN have the tendency to increase their outflow toward the rest of the brain. These findings, even if in a small sample of patients, suggest that other resting state physiological functional networks, beyond the motor one, are affected in patients with PD. The behavioral and cognitive tasks corresponding to the affected networks could benefit from the intake of levodopa.

Konzeption, Entwicklung und Test einer Apparatur zur Messung der elektrischen Ladung des Neutrons

Die elektrische Ladung des Neutrons ist eng mit der Frage nach der Existenz der Ladungsquantisierung verknüpft: Sollte das Neutron eine Ladung tragen, kann die Ladung nicht in Einheiten der Elementarladung e quantisiert sein.rnrnIm Rahmen der Elektrodynamik und des minimalen Standardmodells ist die Quantisierung der Ladung nicht enthalten. Eine mögliche Neutronenladung würde ihnen also nicht widersprechen. Allerdings geht sie aus den Weiterentwicklungen dieser Modelle hervor. Die sogenannten Grand Unified Theories sagen die Möglichkeit des Protonenzerfalls vorher. Dieser ist nur möglich, wenn die Ladung quantisiert ist.rnrnDurch die Messung einer elektrischen Ladung des Neutrons können die verschiedenen Theorien überprüft werden.rnrnIm Rahmen dieser Arbeit wurde eine Apparatur entwickelt, mit der die elektrische Ladung des Neutrons gemessen werden kann. Als Grundlage diente das Prinzip einer Messung von 1988. Mit einem flüssigen Neutronenspiegel aus Fomblin ist es zum ersten mal überhaupt gelungen, einen flüssigen Spiegel für Neutronen einzusetzen. Durch diese und andere Verbesserungen konnte die Sensitivität der Apparatur um einen Faktor 5 im Vergleich zum Experimentrnvon 1988 verbessert werden. Eine mögliche Ladung des Neutrons kann mit δq_n = 2,15·10^(−20)·e/√day gemessen werden. rnrnDie Messung der elektrischen Ladung soll im Winter 2014 durchgeführt werden. Bis dahin soll die Präzision aufrnδq_n = 1,4·10^(−21)·e/√day erhöht werden.

Untersuchung der Ladung des Neutrons

Die Quantisierung der elektrischen Ladung ist eine der größten Fragestellungen der Physik, die bis heute nicht verstanden ist. Im Standardmodell der Teilchenphysik ist sie beispielsweise nicht mathematisch inhärent erklärbar. Dadurch wäre es möglich, dass das Neutron eine winzige Ladung tragen kann. In dieser Arbeit wurde eine Apparatur auf Grundlage eines Vorgängerexperiments entwickelt, mit der eine Untersuchung der Ladung des Neutrons mit höchster Präzision durchgeführt werden kann. Dabei werden ultrakalte Neutronen in einem optischen System einem elektrischen Feld zwischen zwei Elektrodenplatten ausgesetzt. In der ersten Ladungsmessung mit dieser Apparatur konnte eine statistische Sensitivität von δq≈2,4∙10⁻²⁰ e/√d erreicht werden. Diese Sensitivität ist die höchste, die bisher mit ultrakalten Neutronen für eine Ladungsmessung erreicht werden konnte. In dieser Arbeit wurde das Konzept des Vorgängerexperiments grundlegend überarbeitet, um die Sensitivität der Apparatur zu erhöhen. Es wurden detaillierte Untersuchungen der Systematik der Apparatur durchgeführt und das theoretische Potential der Sensitivität von derzeit δq≈10⁻²¹ e/√d ermittelt. Mit dieser Apparatur wurde der Grundstein für die Messung einer neuen niedrigeren oberen Grenze der elektrischen Ladung des Neutrons gelegt. In nächster Zeit kann dadurch eine niedrigere obere Grenze für die Ladung des Neutrons von q≈10⁻²² e erzielt werden.

The Scrum approach to software development

Agile methodologies have become the standard approach to software development. The most popular and used one is Scrum. Scrum is a very simple and flexible framework that respond to unpredictability in a really effective way. However, his implementation must be correct, and since Scrum tells you what to do but not how to do it, this is not trivial. In this thesis I will describe the Scrum Framework, how to implement it and a tool that can help to do this. The thesis is divided into three parts. The first part is called Scrum. Here I will introduce the framework itself, its key concepts and its components. In Scrum there are three components: roles, meetings and artifacts. Each of these is meant to accomplish a series of specific tasks. After describing the “what to do”, in the second part, Best Practices, I will focus on the “how to do it”. For example, how to decide which items should be included in the next sprint, how to estimate tasks, and how should the team workspace be. Finally, in the third part called Tools, I will introduce Visual Studio Online, a cloud service from Microsoft that offers Git and TFVC repositories and the opportunity to manage projects with Scrum. == Versione italiana: I metodi Agile sono diventati l’approccio standard per lo sviluppo di software. Il più famoso ed utilizzato è Scrum. Scrum è un framework molto semplice e flessibile che risponde ai cambiamenti in una maniera molto efficace. La sua implementazione deve però essere corretta, e visto che Scrum ci dice cosa fare ma non come farlo, questo non risulta essere immediato. In questa tesi descriverò Scrum, come implementarlo ed uno strumento che ci può aiutare a farlo. La tesi è divisa in tre parti. La prima parte è chiamata Scrum. Qui introdurrò il framework, i suoi concetti base e le sue componenti. In Scrum ci sono tre componenti: i ruoli, i meeting e gli artifact. Ognuno di questi è studiato per svolgere una serie di compiti specifici. Dopo aver descritto il “cosa fare”, nella seconda parte, Best Practices, mi concentrerò sul “come farlo”. Ad esempio, come decidere quali oggetti includere nella prossima sprint, come stimare ogni task e come dovrebbe essere il luogo di lavoro del team. Infine, nella terza parte chiamata Tools, introdurrò Visual Studio Online, un servizio cloud della Microsoft che offre repository Git e TFVC e l’opportunità di gestire un progetto con Scrum.

Das Paläolithikum der Magdalenahöhle bei Gerolstein

Die vorliegende Arbeit hat das von 1969 – 1972 ergrabene Inventar der Magdalenahöhle bei Gerolstein unter kritischer Berücksichtigung der Originaldokumentation sowie der stratigraphischen und sedimentologischen Beschreibungen erneut untersucht und v.a. hinsichtlich zweier Arbeitshypothesen überprüft. Daneben fanden jedoch auch die Schmuckobjekte und in kursorischer Weise die Tierknochen Betrachtung. Die Elfenbeinobjekte setzen sich aus elf Fragmenten zusammen, die bereits in zerbrochenem Zustand in die Höhle gelangt sein müssen. Sie sind mit mehreren Linienbündeln verziert, die teilweise aus v- oder zickzack-förmigen Motiven bestehen. Auch gestanzte Punktreihen treten auf. In ihrer Größe und Form sind die Elfenbeinobjekte einzigartig. Lediglich aus der Csákvár-Höhle in Ungarn gibt es vergleichbare Stücke, deren genaue Altersstellung jedoch unklar ist. Daneben kommen in der Magdalenahöhle zwei vollständige durchlochte Hirschgrandeln sowie die Fragmente einer durchlochten Grandel sowie eines durchlochten Wolfzahns vor. Diese tragen teilweise Spuren einer Aufhängung bzw. Befestigung. Der Grund für ihre Niederlegung vor Ort ist indes nicht endgültig zu klären. Die überlieferten Tierknochen besitzen verschiedene Grade von Verfärbung und Erhaltung, lassen sich dadurch jedoch nicht verschiedenen Schichten zuordnen. Neben Modifikationen von Carnivoren, darunter v.a. durch Verdauungsprozesse, sind auch an einigen Exemplaren Schnittspuren festgestellt worden. Eine Bärenphalange aus der Fundschicht b1 eröffnet so die Perspektive, die menschliche Belegung erneut mit der Radiokohlenstoffmethode direkt zu datieren. Der Untere paläolithische Fundhorizont besteht aus relativ unspezifischen Quarzartefakten, die von einer opportunistischen Abschlags- und Werkzeugsgewinnung aus lokalen Schottern zeugen. Für den Oberen paläolithischen Fundhorizont zeigt die Steinartefaktanalyse, dass die Abschläge als Herstellungsreste dünner bifazieller Geräte angesprochen werden können. Während dieser Befund alleine auch im Zusammenhang mit den spätmittelpaläolithischen Blattspitzengruppen gesehen werden kann, sprechen die bereits erwähnten vergesellschafteten Schmuckobjekte, der Nachweis eines Klingenabbaus sowie die fast ausschließliche Verwendung exogenen Rohmaterials für einen jungpaläolithischen Kontext, d.h. für eine Affinität zum Solutréen. Die Steinartefakte der Magdalenahöhle zeugen gleichzeitig von einer sehr mobilen Lebensweise, da lediglich eine Phase des Herstellungsprozesses des bifaziellen Geräts vor Ort stattgefunden hat. Gleichzeitig wurden früher an anderem Ort gewonnene Abschläge mitgebracht und als Werkzeug verwendet. Ebenso wie der Kern selbst wurden Abschläge auch wieder abtransportiert. Insgesamt kann daher eine Rohmaterial konservierende Strategie rekonstruiert werden, in der neben dem Kern als Gerät selbst auch die Abschläge Verwendung finden. Da die Magdalenahöhle als östlicher Niederschlag des Solutréen und als Beleg für das maximale Verbreitungsgebiet dieses Technokomplexes gewertet werden muss, reiht sie sich in eine Reihe von Fundstellen und Argumenten ein, wonach das zentrale Mitteleuropa während des LGM s.l. nicht menschenleer war, sondern in sporadischen Exkursionen begangen wurde. Obwohl sich daran noch keine dauerhafte Wiederbesiedlung anschloss, muss vom Bild einer absoluten Siedlungsleere Abstand genommen werden. Weitere Fundstellen und absolutchronologische Datierungen, u.a. der Magdalenahöhle, könnten in Zukunft zu einem noch besseren Verständnis der menschlichen Anpassungsstragien an kaltzeitliche Umwelten beitragen.

Analysis of retrieved shoulder prostheses

In the last years the number of shoulder arthroplasties has been increasing. Simultaneously the study of their shape, size and strength and the reasons that bring to a possible early explantation have not yet been examined in detail. The research carried out directly on explants is practically nonexistent, this means a poor understanding of the mechanisms leading the patient and so the surgeon, to their removal. The analysis of the mechanisms which are the cause of instability, dislocation, broken, fracture, etc, may lead to a change in the structure or design of the shoulder prostheses and lengthen the life of the implant in situ. The idea was to analyze 22 explants through three methods in order to find roughness, corrosion and surface wear. In the first method, the humeral heads and/or the glenospheres were examined with the interferometer, a machine that through electromagnetic waves gives information about the roughness of the surfaces under examination. The output of the device was a total profile containing both roughness and information on the waves (representing the spatial waves most characteristic on the surface). The most important value is called "roughness average" and brings the average value of the peaks found in the local defects of the surfaces. It was found that 42% of the prostheses had considerable peak values in the area where the damage was caused by the implant and not only by external events, such as possibly the surgeon's hand. One of the problems of interest in the use of metallic biomaterials is their resistance to corrosion. The clinical significance of the degradation of metal implants has been the purpose of the second method; the interaction between human body and metal components is critical to understand how and why they arrive to corrosion. The percentage of damage in the joints of the prosthetic components has been calculated via high resolution photos and the software ImageJ. The 40% and 50% of the area appeared to have scratches or multiple lines due to mechanical artifacts. The third method of analysis has been made through the use of electron microscopy to quantify the wear surface in polyethylene components. Different joint movements correspond to different mechanisms of damage, which were imprinted in the parts of polyethylene examined. The most affected area was located mainly in the side edges. The results could help the manufacturers to modify the design of the prostheses and thus reduce the number of explants. It could also help surgeons in choosing the model of the prosthesis to be implanted in the patient.

Rapidly excised and cryofixed rat tissue

All preparation efforts of biological samples in electron microscopy are focused to preserve structures as close as possible to the native state. To achieve this goal with tissues, it is of advantage to have a very short time between excision and fixation. The most common approach is chemical fixation: cross-linking of the tissue samples with aldehydes followed by postfixation with osmium tetroxide. Here, the fastest approach for tissue samples is perfusion. However, the diffusion of the fixation solution from blood vessels into the depth of the tissue is still slow and does not allow an overall instant fixation of a single cell. As a result, osmotic effects become evident (swelling or shrinkage of cell organelles). Another possibility is to take a tissue sample from the experimental animal. Excision of tissue can last quite some time, which results in even more pronounced autolytic induced osmotic effects. Furthermore, the animal does not survive the procedure in most cases. Alternatively, microbiopsies are an elegant technique to rapidly excise small quantities of tissue. Some tissues, such as liver and muscle, may be obtained using a non-lethal approach. To avoid the artifacts introduced by chemical fixation, high-pressure freezing of microbiopsies (brain, liver, kidney, and muscle) is a powerful alternative to chemical fixation. Here, we describe the microbiopsy method, and high-pressure freezing/freeze-substitution (HPF/FS) as a follow-up procedure. Cryosectioning of high-pressure frozen samples is optimally preserving the ultrastructure; however, it is not considered to be a routine approach yet.

Lamellar body ultrastructure revisited: high-pressure freezing and cryo-electron microscopy of vitreous sections

Lamellar bodies are the storage sites for lung surfactant within type II alveolar epithelial cells. The structure-function models of lamellar bodies are based on microscopic analyses of chemically fixed tissue. Despite available alternative fixation methods that are less prone to artifacts, such as cryofixation by high-pressure freezing, the nature of the lung, being mostly air filled, makes it difficult to take advantage of these improved methods. In this paper, we propose a new approach and show for the first time the ultrastructure of intracellular lamellar bodies based on cryo-electron microscopy of vitreous sections in the range of nanometer resolution. Thus, unspoiled by chemical fixation, dehydration and contrasting agents, a close to native structure is revealed. Our approach uses perfluorocarbon to substitute the air in the alveoli. Lung tissue was subsequently high-pressure frozen, cryosectioned and observed in a cryo-electron microscope. The lamellar bodies clearly show a tight lamellar morphology. The periodicity of these lamellae was 7.3 nm. Lamellar bifurcations were observed in our cryosections. The technical approach described in this paper allows the examination of the native cellular ultrastructure of the surfactant system under near in vivo conditions, and therefore opens up prospectives for scrutinizing various theories of lamellar body biogenesis, exocytosis and recycling.

The effect of arts speech therapy on cerebral oxygenation and low frequency hemodynamic oscillations measured using functional near-infrared spectroscopy

Introduction: As a previous study revealed, arts speech therapy (AST) affects cardiorespiratory interaction [1]. The aim of the present study was to investigate whether AST also has effects on brain oxygenation and hemodynamics measured non-invasively using near-infrared spectroscopy (NIRS). Material and methods: NIRS measurements were performed on 17 subjects (8 men and 9 women, mean age: 35.6 ± 12.7 y) during AST. Each measurement lasted 35 min, comprising 8 min pre-baseline, 10 min recitation and 20 min post-baseline. For each subject, measurements were performed for three different AST recitation tasks (recitation of alliterative, hexameter and prose verse). Relative concentration changes of oxyhemoglobin (Δ[O2Hb]) and deoxyhemoglobin (Δ[HHb]) as well as the tissue oxygenation index (TOI) were measured using a Hamamatsu NIRO300 NIRS device and a sensor placed on the subjects forehead. Movement artifacts were removed using a novel method [2]. Statistical analysis (Wilcoxon test) was applied to the data to investigate (i) if the recitation causes changes in the median values and/or in the Mayer wave power spectral density (MW-PSD, range: 0.07–0.13 Hz) of Δ[O2Hb], Δ[HHb] or TOI, and (ii) if these changes vary between the 3 recitation forms. Results: For all three recitation styles a significant (p < 0.05) decrease in Δ[O2Hb] and TOI was found, indicating a decrease in blood flow. These decreases did not vary significantly between the three styles. MW-PSD increased significantly for Δ[O2Hb] when reciting the hexameter and prose verse, and for Δ[HHb] and TOI when reciting alliterations and hexameter, representing an increase in Mayer waves. The MW-PSD increase for Δ[O2Hb] was significantly larger for the hexameter verse compared to alliterative and prose verse Conclusion: The study showed that AST affects brain hemodynamics (oxygenation, blood flow and Mayer waves). Recitation caused a significant decrease in cerebral blood flow for all recitation styles as well as an increase in Mayer waves, particularly for the hexameter, which may indicate a sympathetic activation. References 1. D. Cysarz, D. von Bonin, H. Lackner, P. Heusser, M. Moser, H. Bettermann. Am J Physiol Heart Circ Physiol, 287 (2) (2004), pp. H579–H587 2. F. Scholkmann, S. Spichtig, T. Muehlemann, M. Wolf. Physiol Meas, 31 (5) (2010), pp. 649–662

Software Cartography: Thematic Software Visualization with Consistent Layout

Software visualizations can provide a concise overview of a complex software system. Unfortunately, as software has no physical shape, there is no `natural' mapping of software to a two-dimensional space. As a consequence most visualizations tend to use a layout in which position and distance have no meaning, and consequently layout typically diverges from one visualization to another. We propose an approach to consistent layout for software visualization, called Software Cartography, in which the position of a software artifact reflects its vocabulary, and distance corresponds to similarity of vocabulary. We use Latent Semantic Indexing (LSI) to map software artifacts to a vector space, and then use Multidimensional Scaling (MDS) to map this vector space down to two dimensions. The resulting consistent layout allows us to develop a variety of thematic software maps that express very different aspects of software while making it easy to compare them. The approach is especially suitable for comparing views of evolving software, as the vocabulary of software artifacts tends to be stable over time. We present a prototype implementation of Software Cartography, and illustrate its use with practical examples from numerous open-source case studies.

A differential concentration-dependent effect of IVIg on neutrophil functions: relevance for anti-microbial and anti-inflammatory mechanisms

Background Polymorphonuclear neutrophils (PMN) play a key role in host defences against invading microorganisms but can also potentiate detrimental inflammatory reactions in case of excessive or misdirected responses. Intravenous immunoglobulins (IVIg) are used to treat patients with immune deficiencies and, at higher doses, in autoimmune, allergic and systemic inflammatory disorders. Methodology/Principal Findings We used flow cytometry to examine the effects of IVIg on PMN functions and survival, using whole-blood conditions in order to avoid artifacts due to isolation procedures. IVIg at low concentrations induced PMN activation, as reflected by decreased L-selectin and increased CD11b expression at the PMN surface, oxidative burst enhancement, and prolonged cell survival. In contrast, IVIg at higher concentrations inhibited LPS-induced CD11b degranulation and oxidative burst priming, and counteracted LPS-induced PMN lifespan prolongation. Conclusions/Significance IVIg appears to have differential, concentration-dependent effects on PMN, possibly supporting the use of IVIg as either an anti-microbial or an anti-inflammatory agent.

Scott Joplin: Treemonisha

Scott Joplin’s (1867–1917) opera Treemonisha is the only opera in existence about the Reconstruction era African-American experience written by a black man who actually lived through it. This fact alone makes the opera a work of tremendous significance. Further, Joplin’s music is profoundly expressive and as stylistically unique as anything ever created in America. Through his score and libretto, Joplin vividly documented a culture that has left us few other artifacts: The echoes of the “field hollers,” spirituals, fiddle tunes, revival hymns, and ancient African dances of his rural childhood are all heard, along with the dialects of his people rising up from slavery. Yet for all of its obvious significance, Treemonisha has been a deeply misunderstood work. The opera was complex and virtually unprecedented, two reasons why 1910s America could not embrace it. And tragically, Joplin's original 1911 materials for the opera were almost entirely destroyed in the early 1960s. In the early 1970s several attempts were made to reconstruct it, but for the most part these were not concerned with the opera’s cultural origins or historic authenticity. But now, on the centennial of this extraordinary creation, comes this new recording of a completely authentic reconstruction of Treemonisha by Rick Benjamin, based on eighteen years of research.

Restricted or severely hindered diffusion of intramyocellular lipids in human skeletal muscle shown by in vivo proton MR spectroscopy

Although magnetic resonance spectroscopy can be used as a unique tool to study molecular diffusion, it is rarely used to measure the diffusion properties of intramyocellular and extramyocellular lipids. Lipids have very low apparent diffusion coefficients (ADCs), which make these measurements difficult and necessitate strong diffusion gradients and long diffusion times. Consequence is that these measurements have inherently low signal-to-noise ratio and are prone to artifacts. The addition of physiological triggering and individual storage and processing of the spectra is seen to be a possible approach to maximize signal intensity and achieve high reproducibility of the experiments. Thus, the optimized measurement protocol was used to investigate the diffusion properties of lipids in human skeletal muscle in vivo. At a diffusion time of about 110 ms, intramyocellular lipids show a significantly lower ADC (2.0 × 10(-6) mm(2)/s, 95% confidence interval 1.10 × 10(-6) to 2.94 × 10(-6) mm(2)/s) than extramyocellular lipids (1.58 × 10(-5) mm(2)/s, 95% confidence interval 1.41 × 10(-5) to 1.75 × 10(-5) mm(2)/s). Because the chemical properties of both lipid pools can be assumed to be similar, the difference can only be attributed to restricted or severely hindered diffusion in the intramyocellular droplets.

Assessment of coronary artery disease by post-mortem cardiac MR

Minimally invasive or virtual autopsies are being advocated as alternative to traditional autopsy, but have limited abilities to detect coronary artery disease. It was the objective of this study to assess if the occurrence of chemical shift artifacts (CSA) along the coronary arteries on non-contrast, post-mortem cardiac MR may be used to investigate coronary artery disease.

The Politics of Purchasing Power: Feminist Tourism and Women's Development in Nepal

My purpose in this essay is to explore how ideas about women and development are created and circulated at the moment of consumption of wares produced at a women's development project in Nepal. I analyze the project as an example of the ways that women's development is an object of material and discursive consumption. Artifacts produced and sold by Nepali women, and purchased by tourists from the "first world," become part of an international exchange of power, money, and meaning. Based on a survey of consumers and ethnographic observations, I conclude that feminist tourists forge relations with disempowered "Others" through the pleasurable activity of an alienated market transaction. Consumers of crafts produced at a women's development project assume a position of empowerment and enlightenment, ready to help out their "women" counterparts through their support of an enterprise with circular logic: within the industry of development (although not necessarily for feminist tourists themselves), at least one of the central projects of development is the development project itself. At the same time, feminist tourists locate themselves outside the oppressive structures and ideologies affecting their "third-world sisters." This is a relation of sympathy and imagined empathy, with no sense of differential location within systems of oppression. They fail to examine or articulate the global link between their own purchasing power and local living conditions of Maithil women; the connection is effectively built out of the discourse.