385 research outputs found
Regional to Interhemispheric Connectivity of the Atlantic Ocean Circulation
This thesis investigates the connectivity and interaction of remote regions in the Atlantic Ocean based on high-resolution model experiments. Connectivity between remote regions has important implications on a range of spatial and temporal scales. It can affect global climate variability, the coherence of circulation changes on regional scales and the spreading of marine organisms. Based on several advancements in modelling, it is demonstrated how interhemispheric connectivity contributes to changes of the Atlantic Meridional Overturning Circulation (AMOC) on climate timescales. At the same time, the effect of wind-forcing and the interaction of individual AMOC pathways with eddies on regional scales are shown to be highly important to understand AMOC variability on sub-decadal timescales, with further implications on interdisciplinary research questions
Logical Positivism or Critical Theory as the Methodological Foundation of The Authoritarian Personality?
In this paper, the central research question discusses to what extent logical positivism or critical theory forms the methodological core of the seminal work on the authoritarian personality. A central thesis is that due to her background in psychology, logical positivism and psychoanalysis and her neglected but central role in the authoritarian personality study, Else Frenkel-Brunswik has had a much more lasting and productive influence on authoritarianism research than Adorno as the repÂresentative of critical theory. This was certainly not reflected in the public discourse or in intellectual discussions, at least in Europe. This article shows how the original F-Scale was changed in subseÂquent research and how the application of psychometric techniques improved. However, by employÂing Lakatos’ concept of the research programme, I analyse how authoritarianism research developed in a degenerative way by reducing the number of factors from nine to three and giving up the psyÂchoanalytic explanation of the underlying mechanisms, a systematic test of sociological and contexÂtual factors, and the original mixed method approach of combining surveys and qualitative interÂviews. Finally, the issue of the effects of idealisation of parents on the measurement of the items and the use of typologies were not tackled in later research. Employing data from the German General Social Survey (ALLBUS), I describe how some of Frenkel-Brunswik’s central methodological and theoretical ideas have been tested using confirmatory factor analyses and structural equation modÂels. Finally I summarise the way in which the research programme can be developed more fruitfully by integrating developmental psychology, sociology, political science, psychoanalysis and statistical generalised latent variable models
Connect 02/1999: Zeitschrift des Rechenzentrums der Universität Augsburg
Mitteilungsblatt des Rechenzentrums der Universität AugsburgJournal of the Computer Centre at the University of Augsbur
A critical role of the transcription factor Miz-1 in T cell activation and maturation
A functional immune system is important to protect the organism against various pathogens and to induce an adequate response to vaccinations. B and T lymphocytes are the main drivers of adaptive immunity. An important regulator of their development is the MYC-interacting zinc finger protein 1 (Miz-1). The transcription factor Miz-1 is highly necessary for adequate T cell development by restricting apoptosis during V(D)J recombination. However, the importance of Miz-1 in mature T cells is yet not fully understood. To provide new insights into the role of Miz-1 for T lymphocytes, mice possessing a conditional knockout of Miz-1 either in all hematopoietic cells (Vav-Cre x Miz-1fl/fl) or specifically in T cells (CD4 Cre x Miz-1fl/fl) were used. As the POZ domain of Miz-1 is necessary for its transcriptional activity, this domain was targeted by Cre-mediated deletion in both mouse models. Phenotypical analysis of these mice showed severe perturbations of the peripheral T cells, resulting in a reduction of mature T cells in several secondary lymphoid organs. Likewise, this decrease was observed in CD4+ as well as in CD8+ T cells. T cell activation experiments showed that Miz-1 controls proliferation as well as apoptosis of peripheral T cells. Miz-1 deficiency resulted in a faster proliferation but also an excessive induction of apoptosis. Furthermore, the process of apoptosis seems to be p53-independent and induced via the extrinsic apoptosis pathway. Flow cytometry experiments revealed that Miz-1 is a novel regulator of T cell aging, since young mice possessing a functional Miz-1 deletion exhibited similar distributions of T cell populations as old control mice. Due to Miz-1 deficiency, the numbers of naĂŻve T cells dropped while frequencies of memory T cells were increased. Thus, Miz-1 is necessary to maintain the homeostasis of naĂŻve and memory T cells in the course of aging
Spatial-Temporal Data Mining for Ocean Science: Data, Methodologies, and Opportunities
With the increasing amount of spatial-temporal~(ST) ocean data, numerous
spatial-temporal data mining (STDM) studies have been conducted to address
various oceanic issues, e.g., climate forecasting and disaster warning.
Compared with typical ST data (e.g., traffic data), ST ocean data is more
complicated with some unique characteristics, e.g., diverse regionality and
high sparsity. These characteristics make it difficult to design and train STDM
models. Unfortunately, an overview of these studies is still missing, hindering
computer scientists to identify the research issues in ocean while discouraging
researchers in ocean science from applying advanced STDM techniques. To remedy
this situation, we provide a comprehensive survey to summarize existing STDM
studies in ocean. Concretely, we first summarize the widely-used ST ocean
datasets and identify their unique characteristics. Then, typical ST ocean data
quality enhancement techniques are discussed. Next, we classify existing STDM
studies for ocean into four types of tasks, i.e., prediction, event detection,
pattern mining, and anomaly detection, and elaborate the techniques for these
tasks. Finally, promising research opportunities are highlighted. This survey
will help scientists from the fields of both computer science and ocean science
have a better understanding of the fundamental concepts, key techniques, and
open challenges of STDM in ocean
Optimal Generators for Quantum Sensing
We propose a computationally efficient method to derive the unitary evolution
that a quantum state is most sensitive to. This allows one to determine the
optimal use of an entangled state for quantum sensing, even in complex systems
where intuition from canonical squeezing examples breaks down. In this paper we
show that the maximal obtainable sensitivity using a given quantum state is
determined by the largest eigenvalue of the quantum Fisher information matrix
(QFIM) and, importantly, the corresponding evolution is uniquely determined by
the coinciding eigenvector. Since we optimize the process of parameter encoding
rather than focusing on state preparation protocols, our scheme is relevant for
any quantum sensor. This procedure naturally optimizes multiparameter
estimation by determining, through the eigenvectors of the QFIM, the maximal
set of commuting observables with optimal sensitivity.Comment: 7 pages, 2 figure
The impacts of climate variability and change on the physical and social-ecological dynamics of the Kuroshio and North Pacific Transition Zone
There is growing recognition that climate change is impacting the ocean's western boundary current system. In the Pacific, the Kuroshio and its offshore Kuroshio-Oyashio Extension (KOE) play a central role in the North Pacific climate and impact the social-ecological dynamics of countries that rely on marine ecosystem services (e.g. fisheries). In the thesis, we have used a combination of observations and modeling approaches to understand how past and projected changes in the physical environment of KOE impact social-ecological dynamics linked to the fish industry of Japan and the North Pacific more widely. The thesis is articulated in 3 Chapters.
In Chapter 1 we have introduced the problem and the main motivation that lead us to perform this study.
In Chapter 2, we analyze the climate variability and change of the KOE over the historical and future projection period 1920-2100. We perform this task using Coupled Model Intercomparison Project 5 (CMIP5) models and a large ensemble from the Community Earth System Model (CESM-LE) output runs. The reason for considering also the CESM-LE runs is that they give the possibility to explore how the variance of the KOE in one model (e.g. a fixed set of dynamics) responds to anthropogenic forcing when compared to the range of natural variability of the CESM-LE model. In this way, we can perform a scenario which goes beyond the time of the observational data.
In Chapter 3, we have used an Empirical Dynamical Model approach to characterize the joint statistics of the physical and social-ecological environmental system (SEES) that is relevant to climate and fisheries. To define the states of the SEES we use three international fish databases, (1) the Large Marine Ecosystem (LME, 9,000 fish stocks), (2) the NOAA fishery database referred to as Restricted Access Management (RAM, 300 fish stock) and the (3) the Food and Agriculture Organization (FAO, 1400 fish stocks). Among the approaches used to explore the relationship between KOE’s climate and the SEES response, we have developed a Linear Inverse Model (LIM) approach that has been very successful to simulate and predict the KOE physical climate and its relation to large-scale Pacific dynamics such as El Niño Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO), and others.Ph.D
Technical Dimensions of Programming Systems
Programming requires much more than just writing code in a programming language. It is usually done in the context of a stateful environment, by interacting with a system through a graphical user interface. Yet, this wide space of possibilities lacks a common structure for navigation. Work on programming systems fails to form a coherent body of research, making it hard to improve on past work and advance the state of the art.
In computer science, much has been said and done to allow comparison of programming languages, yet no similar theory exists for programming systems; we believe that programming systems deserve a theory too.
We present a framework of technical dimensions which capture the underlying characteristics of programming systems and provide a means for conceptualizing and comparing them.
We identify technical dimensions by examining past influential programming systems and reviewing their design principles, technical capabilities, and styles of user interaction. Technical dimensions capture characteristics that may be studied, compared and advanced independently. This makes it possible to talk about programming systems in a way that can be shared and constructively debated rather than relying solely on personal impressions.
Our framework is derived using a qualitative analysis of past programming systems. We outline two concrete ways of using our framework. First, we show how it can analyze a recently developed novel programming system. Then, we use it to identify an interesting unexplored point in the design space of programming systems.
Much research effort focuses on building programming systems that are easier to use, accessible to non-experts, moldable and/or powerful, but such efforts are disconnected. They are informal, guided by the personal vision of their authors and thus are only evaluable and comparable on the basis of individual experience using them. By providing foundations for more systematic research, we can help programming systems researchers to stand, at last, on the shoulders of giants
ELD607 is a Novel, Specific Inhibitor of the Orai1 Calcium Channel
Orai1 is a ubiquitous plasma membrane Ca2+ channel that is an essential regulator of innate immunity. Short palate lung and nasal epithelial clone 1 (SPLUNC1) is a secreted protein and its α6 region is the endogenous modulator of Orai1. In chronic inflammatory diseases, such as cystic fibrosis (CF), SPLUNC1/α6 is degraded by the acidic and protease-rich lung environment and is therefore unable to negatively regulate Orai1. The lack of Orai1 modulation could cause increased neutrophil recruitment and T-cell activation, chronic inflammation, and progressive lung damage. ELD607 was developed as an optimized peptidomimetic of SPLUNC1’s α6 region that is protease resistant and able to rescue Orai1 modulation. Therefore, ELD607 is a promising anti-inflammatory therapeutic. To support the utility of Orai1 inhibition as a potential therapeutic, we first wanted to evaluate the expression/activation of Orai1 in CF and asthmatic lungs. Using super resolution microscopy, RNAscope, and immunostaining, we showed that Orai1 activation is upregulated in CF and asthma lungs and CF patients peripheral blood neutrophils making Orai1 a valid target for anti-inflammatory drugs in these patients. Then, we elucidated the mechanism of ELD607’s inhibition of Orai1. We first studied Orai1 trafficking after ELD607 treatment. We tracked Orai1 from the plasma membrane through the endosomes to the lysosomes where Orai1 was degraded. During the trafficking studies, we discovered that ELD607 induces Orai1 puncta formation. Since Orai1 puncta formation is characteristic of Orai1 activation, we further explored this phenomenon. First, we demonstrated that ELD607-induced puncta formation was physiologically relevant, as both ELD607 and SPLUNC1 induced Orai1 puncta formation in primary pulmonary cells. Second, we found that ELD607-induced Orai1 puncta formation was independent of ubiquitination and STIM1. Proteomics identified actin associated proteins as Orai1 binding partners after ELD607 treatment, leading us to posit that ELD607 binding caused a conformational change in Orai1 that led to puncta formation aided by cytoskeleton rearrangement, ubiquitination, internalization, and finally degradation. In conclusion, my work presents evidence that Orai1 is a valid target for anti-inflammatory therapeutics in patients with inflammatory diseases and increases the understanding of endogenous ion channel modulation with the discovery of a unique method of Orai1 inhibition.Doctor of Philosoph
An HPA-1a-positive platelet-depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia: a randomized, single-blind, placebo-controlled, single-center, phase 1/2 proof-of-concept study
Background: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a rare and
potentially life-threatening bleeding disorder of the fetus/newborn. Antibodies against
human platelet antigen 1a (HPA-1a) are associated with the most frequent FNAIT
cases. There are no approved therapies for FNAIT prevention or treatment. RLYB211 is
a polyclonal HPA-1a hyperimmune IgG being developed to prevent FNAIT.
Objectives: To investigate whether a single dose of anti–HPA-1a (1000 IU) could
markedly accelerate the elimination of HPA-1ab platelets transfused into healthy, HPA1a–negative participants as compared with placebo.
Methods: This randomized, single-blind, placebo–controlled, single-center, phase 1/2
proof-of-concept study (EudraCT: 2019-003459-12) included HPA-1a– and HLA-A2–
negative healthy men. Cohort 1 received intravenous RLYB211 or placebo 1 hour after
transfusion of HPA-1ab platelets. Cohort 1B received RLYB211 or placebo, followed by
platelet transfusion 1 week later. Primary endpoint was the half-life of transfused
platelets in circulation after administration of RLYB211 or placebo, determined by flow
cytometry. Proof of concept was ≥90% reduction of half-life relative to placebo.
Results: Twelve participants were allocated to cohort 1 or 1B and randomized to
receive RLYB211 (n = 9) or placebo (n = 3). RLYB211 markedly accelerated the elimination of HPA-1ab platelets in all participants vs placebo. In cohort 1B, this effect was observed 7 days after RLYB211 administration. Two treatment–emergent adverse
events were possibly related to treatment, both in RLYB211–treated participants. No
participants developed HPA-1a antibodies at 12 or 24 weeks.
Conclusion: These data support the hypothesis that anti–HPA-1a could be used as
prophylaxis in women at risk of having an FNAIT–affected pregnancy
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