Quantum Phase Transitions and Vortex Dynamics in Superconducting Networks

Josephson junction arrays are ideal model systems where a variety of phenomena, phase transitions, frustration effects, vortex dynamics, chaos, to mention a few of them, can be studied in a controlled way. In this review we focus on the quantum dynamical properties of low capacitance Josephson junction arrays. The two characteristic energy scales in these systems are the Josephson energy, associated to the tunneling of Cooper pairs between neighboring islands, and the charging energy, which is the energy cost to add an extra electron charge to a neutral island. The phenomena described in this review stem from the competition between single electron effects with the Josephson effect. One example is the (quantum) Superconductor-Insulator phase transition which occurs by varying the ratio between the coupling constants and/or by means of external magnetic/electric fields. We will describe how the phase diagram depends on the various control paramters and the transport properties close to the quantum critical point. The relevant topological excitations on the superconducting side of the phase diagram are vortices. In low capacitance junction arrays vortices behave as massive underdamped particles that can exhibit quantum behaviour. We will report on the various experiments and theoretical treatments on quantum vortex dynamics.Comment: To be published in Physics Reports. Better quality figures can be obtained upon reques

A unified framework for building ontological theories with application and testing in the field of clinical trials

The objective of this research programme is to contribute to the establishment of the emerging science of Formal Ontology in Information Systems via a collaborative project involving researchers from a range of disciplines including philosophy, logic, computer science, linguistics, and the medical sciences. The re­searchers will work together on the construction of a unified formal ontology, which means: a general framework for the construction of ontological theories in specific domains. The framework will be constructed using the axiomatic-deductive method of modern formal ontology. It will be tested via a series of applications relating to on-going work in Leipzig on medical taxonomies and data dictionaries in the context of clinical trials. This will lead to the production of a domain-specific ontology which is designed to serve as a basis for applications in the medical field

A pattern-based approach to a cell tracking ontology

Time-lapse microscopy has thoroughly transformed our understanding of biological motion and developmental dynamics from single cells to entire organisms. The increasing amount of cell tracking data demands the creation of tools to make extracted data searchable and interoperable between experiment and data types. In order to address that problem, the current paper reports on the progress in building the Cell Tracking Ontology (CTO): An ontology framework for describing, querying and integrating data from complementary experimental techniques in the domain of cell tracking experiments. CTO is based on a basic knowledge structure: the cellular genealogy serving as a backbone model to integrate specific biological ontologies into tracking data. As a first step we integrate the Phenotype and Trait Ontology (PATO) as one of the most relevant ontologies to annotate cell tracking experiments. The CTO requires both the integration of data on various levels of generality as well as the proper structuring of collected information. Therefore, in order to provide a sound foundation of the ontology, we have built on the rich body of work on top-level ontologies and established three generic ontology design patterns addressing three modeling challenges for properly representing cellular genealogies, i.e. representing entities existing in time, undergoing changes over time and their organization into more complex structures such as situations

Non-Canonical Odor Coding Ensures Robust Mosquito Attraction to Humans

Aedes aegypti mosquitoes spread deadly diseases, including dengue, Zika, yellow fever, and chikungunya. Only female mosquitoes bite, and they do so because they require a blood-meal for reproduction. Aedes aegypti prefer to bite human hosts, which contributes to their effectiveness as a deadly disease vector. Mosquitoes rely heavily on chemosensory cues, including carbon dioxide (CO2) emitted from breath and human body odor, which is a mixture of more than 200 different individual odorants. Although the exact odor profile of people varies considerably, Aedes aegypti are incredibly reliable in finding humans to bite, despite widespread efforts to by humans to mask our odor. Even mosquitoes with genetic mutations that eliminate entire families of chemosensory receptors are still able to find and bite humans. It remains unknown how the mosquito olfactory system is seemingly infallible in its ability to detect humans for taking a blood meal. In the well-studied olfactory systems of Drosophila melanogaster and Mus musculus, individual olfactory sensory neurons express a single type of olfactory receptor and project their axons to discrete regions, called glomeruli, in the antennal lobe or olfactory bulb, respectively. This organization is believed to be a widespread motif in olfactory systems and has been established dogma since the mid-2000s and is hypothesized to permit the brain to parse which subpopulation of olfactory neurons is activated by a given odor. To understand how human odor is encoded in the mosquito olfactory system, we developed a CRISPR-Cas9-based genetic knock-in strategy in Aedes aegypti and generated a suite of transgenic mosquito strains that label populations of olfactory sensory neurons. Surprisingly, we find that the olfactory system of Aedes aegypti does not have the expected “one-receptor-to-one-neuron-to-oneglomerulus” organization seen in other insects. Rather, there are many more receptors than glomeruli. We frequently observe co-expression of multiple chemosensory receptors within individual olfactory sensory neurons and individual glomeruli are commonly innervated by olfactory sensory neurons expressing different receptors. What is the functional consequence of this unconventional organization? To understand how co-expression of multiple chemosensory families affects human odor detection by mosquitoes, we examined a minimal mixture that drives host seeking behavior. Mosquitoes are attracted to the combination of the two human-derived, cues CO2 and lactic acid. We found that the same neurons that sense CO2 also sense volatile amines, including triethyl amine. These amines are detected by separate chemosensory receptor genes and we discovered that these cues can be interchanged to drive attraction in the presence of lactic acid. This sensory organization, in which multiple receptors that respond to very different types of chemicals are co-expressed, suggests a redundancy in the odor code at the level of the olfactory sensory neurons for cues that signal the presence of a human to bite. We speculate that this design supports the robust human host-seeking seen in this olfactory specialist

Three essays on firm strategies influenced by antitrust authorities

This thesis contains three essays which are all from the broader field of the theories on competition, collusion, and antitrust enforcement. The essays in chapter 2 and 3 provide models where firms try to sustain horizontal collusive agreements under the review of an antitrust authority. The essay in chapter 2 deals with information spillovers between the antitrust authority and collusive firms in an environment of imperfect information. The model investigates how the sustainability of collusive agreements in uncertain environments is affected by an antitrust authority that shares information with firms and by an authority that keeps the information secret. The analysis involves leniency programs as well. The subsequent essay in chapter 3 focuses on the deterrence effect of excluding ringleaders from leniency programs. In particular, the model investigates if ringleaders of cartels should be eligible for a fine reduction when cooperating with the antitrust authority or whether they should be excluded from such programs. Chapter 4 extends the topic to vertical integration, where firms interact in a vertical-merger game under the review of an antitrust authority. The model investigates how side payments can be crucial to explain the development of a market structure where a vertically integrated firm co-exists with separated competitors in a successive duopoly

Dual-color chromogen In Situ hybridization (CISH) for the determination of Her2 status in breast cancer tissue sections

Background: A factor associated with breast cancer development is the mutation of the Her2/neu gene located on chromosome 17. Chromogen in situ hybridization (CISH) in which the color is generated with an enzymatic reaction is a promising alternative detection method to fluorescence in situ hybridization (FISH) which is nowadays used in clinical practice. The resulting color is stable and therefore usable for permanent storage, the use of a normal brightfield microscope is possible and the morphology of the sample can be evaluated more easily than with a fluorescence microscope. For the visualization of Her2/neu it is however important to also detect chromosome 17 and use it as a reference chromosome. The aim of the study is: to select the best substrates considering color production, background staining, reactivity and localization. Secondly to develop a dualcolor procedure visualizing Her2/neu and chromosome 17 to examine the possibility of using CISH as a standardized method for the detection of Her2 positive tumors and finally to compare these results with FISH. Methods: Single target CISH with eight substrates for the enzyme horseradish peroxidase (PO) and six substrates for alkaline phosphatase (AP) was performed on cervical cancer cell lines with centromere 1 (C1) and 1p36 as targets. The best substrates were subjectively selected with the use of a brightfield microscope. The procedure was expanded to a dual-color detection on cells and formalin-fixed, paraffin embedded (FFPE) breast cancer tissue sections with Her2/neu and centromere 17 (C17) as targets. In this procedure the best conjugate detection systems were worked out. Results: In the single target detection procedure the substrates DAB, Vina Green and Seramun Grün for PO and Ferangi Blue and Vulcan Fast Red for AP were found to give the best color reactions. The dual-color detection on tissue sections showed strong and good distinguishable color reactions when combining the substrates Vina Green for C17 and Vulcan Fast Red for Her2. Results of CISH and FISH were comparable when using immersion oil for the detection of the fluorescent signals. Discussion and Conclusion: Vina Green for C17 and Vulcan Fast Red for Her2/neu are the best substrates considering background staining, color distinguishability and localization and give comparable results to FISH. The study gives a further step in the direction of introducing CISH as a standardized method for the detection of Her2/neu amplification

Radiosynthesis and biological evaluation of [68Ga]Ga-NOTA-Folate in experimental atherosclerosis and myocardial infarction models.

While many folate-receptor (FR) targeting radiotracers have been studied for imaging cancers, there is a need for tracers that target inflammation for diagnostic and monitoring purposes. Two diseases in which inflammation plays a key role are atherosclerosis and myocardial infarction (MI). Inflammation is critical to the development and progression of atherosclerosis, which can lead to MI. Higher macrophage levels have been associated with adverse remodeling effects in post-MI healing. Given the commonality of these potentially fatal conditions, it is of great interest to have a reliable radiotracer available for non-invasive detection and monitoring. As FR-β expression is upregulated in active macrophages, it serves as a great target for imaging of inflammation. [68Ga]Ga-NOTA-Folate, a new FR-targeting radiotracer, was synthesized and biologically evaluated to assess its ability to target inflammation in mouse and human atherosclerotic lesions. Mice were studied using in vivo positron emission tomography and ex vivo digital autoradiography of aorta sections. Human carotid artery tissues were studied in vitro for tracer binding. In addition, rat heart tissue sections were incubated in vitro with [68Ga]Ga-NOTA-Folate to evaluate post-MI healing. Upon analyzing the in vitro binding, [68Ga]Ga-NOTA-Folate showed significantly higher binding in atherosclerotic lesions when compared to tissues treated with folate glucosamine, a FR blocker, indicating specificity of [68Ga]Ga-NOTA-Folate via FRs. As the atherosclerotic lesions observed in the experimental mice were not so extensive, more in vivo studies should be done to verify the results

Intervention In The Foreign Exchange Markets: How Effective Is It?

Intervention in the foreign-exchange markets by the central banks of the major industrial nations has been the norm for a little over 40 years. The level of intervention exercised by these central banks during these 40 years has ranged from very heavy to very light. At one extreme was the Bretton Woods period which was characterized by extensive, cooperative intervention among central banks to maintain fixed exchange rates between currencies. At the other extreme were periods like the early to mid-1970\u27s and the early to mid-1980\u27s which were characterized by the use of only occasional intervention. The most recent round of extensive interventions took place from 1985 through early 1988. These recent interventions represented a concerted effort by the United States, Great Britain, West Germany, France, and Japan (the G-5) to force the U.S. dollar down more rapidly than the foreign-exchange market was driving it down. Subsequently, the dollar\u27s fall required further interventions by the G-5 to maintain the dollar in a certain target zone. The entire effort by the G-5 was initiated to aid the United States in correcting its massive trade deficit. This effort was unsuccessful in reaching its goal. While the United States\u27 trade deficit with the other countries of the G-5 and the countries of the European Economic Community did improve, the U.S. trade deficit with many of the countries whose currencies were tied to the U.S. dollar did not improve. The United States continued to run a massive trade deficit. Despite this huge trade deficit, the dollar began to rise again on the foreign-exchange markets in the spring of 1989. A currency, such as the U.S. dollar, which rises in value when the country is experiencing a huge trade deficit is not following the 11 rules 11 of the basic monetary systems. Possible reasons for the dollar\u27s ability to break the 11 rules 11 include that the U.S. dollar is a reserve currency for the rest of the world and that the United States is a profitable and safe place to invest. The existence of these reasons and the unlikelihood that they will be removed indicate that intervention on behalf of the U.S. dollar will not be very effective. vi