Deployed at the end of 2010 at the Pierre Auger Observatory, the first stage of the Auger Engineering Radio Array, AERA24, consists of 24 radio stations covering an area of 0.5km2. AERA measures the ...radio emission from cosmic-ray induced air showers. The amplitude of this radio emission is used to constrain the characteristics of the primary particle: arrival direction, energy and nature. These studies are possible thanks to an instrumentation development allowing self-triggered and externally triggered measurements in the MHz domain and an improved understanding of radio emission processes. In May 2013, 100 new stations were installed to cover an area of ≃6km2, for a total of 124 stations. This stage 2 will provide higher statistics and will enhance both the estimate of the nature of the primary cosmic ray and the energy resolution above 1017 eV as an addition to detectors such as the Auger fluorescence telescopes and particle detectors. We will present the main results obtained with the stage 1 of AERA and the current status of the experiment. We will end with a brief overview of the GHz-experiments installed at the Pierre Auger Observatory.
Après plus d'un siècle d'études, l'origine des rayons cosmiques d’ultra-haute énergie reste mal comprise. En améliorant la connaissance de la composition des rayons cosmiques détectés sur Terre, il ...est possible de contraindre les modèles concernant leur origine, ainsi que leur mécanisme de production dans les sources astrophysiques. Les simulations montrent que le champ électrique émis par les gerbes est sensible à leur développement dans l'atmosphère. Ce champ électrique peut être mesuré avec un cycle utile élevé, faisant du signal radio une observable prometteuse pour identifier le rayon cosmique primaire. Le signal radio permet également de mesurer sa direction d'arrivée et son énergie. Depuis 2006, l'observatoire Pierre Auger accueille plusieurs réseaux de radio détection des rayons cosmiques. Des démonstrateurs équipés de quelques stations (RAuger,MAXIMA) ont permis une caractérisation efficace de l'environnement radio du site, ils ont également apporté des contraintes sur les mécanismes responsables de l'émission du champ électrique par les gerbes dans le domaine du MHz. Les prototypes ont mené à la construction d’AERA (Auger Engineering Radio Array) qui, avec 124 stations couvrant 6 km², est le premier réseau grande échelle de radio détection des gerbes dans le domaine du MHz. AERA est déployé dans l'extension basse énergie de l'observatoire afin de bénéficier d'une statistique plus importante. Le réseau permet d'intéressantes mesures hybrides ; son emplacement permet en effet de croiser les données obtenues par la radio avec celles provenant du réseau de surface (SD) et des télescopes à fluorescence (FD) proches du réseau. Cette thèse est dédiée à la caractérisation de signaux transitoires radio détectés par RAuger et AERA. Comme un des défis de la radio détection des gerbes atmosphériques est de supprimer les bruits de fond anthropiques causant des déclenchements accidentels, des méthodes de réjection du bruit de fond et de sélection des coïncidences SD-AERA ont été développées. Une étude de la corrélation entre le développement de la gerbe dans l'atmosphère (profil longitudinal) et le champ électrique mesuré par les stations radio est également présentée. Cette étude valide le lien direct entre le champ électrique et le développement de la gerbe dans l'atmosphère et confirme l’intérêt du signal radio pour l’estimation de la nature des rayons cosmiques d'ultra-haute énergie.
After more than a century of studies, one of the challenging questions related to ultra-high energy cosmic rays concerns their nature, which remains unclear. Improving the knowledge about the composition of cosmic rays will permit to constrain the models concerning their origins and the production mechanisms in the astrophysical sources. Simulations show that, the electric field emitted by the shower is sensitive to its development. This electric-field can be measured with a high duty cycle, and thus is apromising technique to identify an observable sensitive to the nature of the primary cosmic ray. The radio signal is also used to measure its arrival direction and its energy. Since 2006, the Pierre Auger Observatory hosts several radio detection arrays of cosmic rays, starting from small size prototypes (RAuger, MAXIMA) to achieve a large scale array of 124 radio stations: AERA, the Auger Engineering Radio Array covering 6 km². These different arrays allow the study of the radio emission during the development of the shower in the MHz domain. AERA is deployed in the low energy extension of the Pierre Auger Observatory in order to have a larger statistics. It enables interesting hybrid measurements, with the comparison of radio observable with those obtained with the surface detector (SD) and the fluorescence telescopes close to the array. This thesis is dedicated to the characterization of the radio transient signals detected by RAuger and AERA. As one of the challenges of the radio detection of air-shower is to remove the anthropic background causing accidental triggering, methods for background rejection and SD-AERA coincidences selection have been developed. A study of the correlation between the shower development in the atmosphere (longitudinal profile) and the electric-field measured by the radio stations is also presented. This study shows the relationship between the electric-field and the shower development in the atmosphere and confirms that the radio signal is a powerful tool to study the nature of the ultra-high energy cosmic rays.
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Political Science, 2011.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 471-501).
Advocates of ...diplomatic engagement with states of concern argue that talking to both allies and adversaries is essential for advancing U.S. foreign policy interests. Critics of this approach argue that engagement with these regimes is tantamount to appeasement and signals acceptance of behavior that ought to be condemned. In their view, little can be gained by talking to these states. Thus, diplomatic sanctions are seen as a low-cost means of isolating and delegitimizing regimes. This perspective, however, fails to recognize that maintaining diplomatic sanctions may actually entail a number of substantial costs to the United States and may even undermine economic sanctions' effectiveness. Although the U.S. has employed policies of diplomatic disengagement in approximately 30% of its economic sanctions episodes, studies have focused solely on economic sanctions. Seeking to weigh in on this debate, my doctoral dissertation focuses on two central questions: (1) What are the effects of diplomatic sanctions as a foreign policy tool? and (2) Do diplomatic sanctions increase or decrease the likelihood of target state compliance with U.S. demands? I develop and test a new theory of sanctions effectiveness focusing on the role of information, communication, and diplomatic ties. I argue that diplomatic sanctions and disengagement result in unintended consequences, including a loss of valuable intelligence, increased difficulty of communication, and reduced capabilities for public diplomacy in the target state. I also argue that when United States is more diplomatically engaged with the target state, economic sanctions are more likely to be effective in getting the target state to comply with U.S. demands. To reach these conclusions, I use both quantitative and qualitative analysis. I use economic sanctions data from 1945-2000 from the Hufbauer, Schott and Elliott database, along with original data on diplomatic sanctions. I conduct ordered logit multivariate regressions to test the diplomatic sanctions hypotheses and assess whether or not diplomatic sanctions impact the effectiveness of economic sanctions. I also conduct comprehensive longitudinal case studies of Sudan and Libya, along with a series of shorter mini-case studies focusing on Afghanistan, South Africa and Burma.
by Tara Maller.
Ph.D.
In earlier work we defined a computational saddle transition problem which arises in the dynamics of certain hyperbolic toral automorphisms, and proved, using the shadowing lemma, that in an ...appropriate model of computation this problem is in Oracle NP, up to a highly restricted oracle. In this note we show similar methods can be extended to a far larger class of dynamical systems, a class which is dense in the C0-topology on Diff1(T2). We adapt the fitted diffeomorphisms of Shub and Sullivan on the 2-Torus to a computational framework. Just as in their case, the resulting “well-fitted” toral automorphisms are structurally stable, and C0-dense, and we show the associated saddle transition problems are, in our model, in Oracle NP.
p11 (S100A10), a member of a large family of S100 proteins, interacts with serotonin receptor 1B (5-HTR1B), modulates 5-HT1B receptor signal transduction, and is required for antidepressant responses ...to activation of this receptor. In the current study, we investigated the specificity of the interaction between 5-HTR1B and p11 by screening brain-expressed S100 proteins against serotonin and noradrenergic receptors. The data indicate that p11 is unique among its family members for its interactions with defined serotonin receptors. We identify a novel p11-interacting receptor (5-HTR4) and characterize the interaction between p11 and 5-HTR4, demonstrating that (1) p11 and 5-HTR4 mRNA and protein are coexpressed in brain regions that are relevant for major depression, (2) p11 increases 5-HTR4 surface expression and facilitates 5-HTR4 signaling, and (3) p11 is required for the behavioral antidepressant responses to 5-HTR4 stimulation in vivo. The essential role played by p11 in modulating signaling through 5-HT4 as well as 5-HT1B receptors supports the concept that this protein may be a key determinant of vulnerability to depression.
Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of this risk are unclear in people not ascertained for neuropsychiatric ...symptoms. Using several large ASD consortium and population-based resources (total n > 38,000), we find genome-wide genetic links between ASDs and typical variation in social behavior and adaptive functioning. This finding is evidenced through both LD score correlation and de novo variant analysis, indicating that multiple types of genetic risk for ASDs influence a continuum of behavioral and developmental traits, the severe tail of which can result in diagnosis with an ASD or other neuropsychiatric disorder. A continuum model should inform the design and interpretation of studies of neuropsychiatric disease biology.
It has been argued that the limited genetic diversity and reduced allelic heterogeneity observed in isolated founder populations facilitates discovery of loci contributing to both Mendelian and ...complex disease. A strong founder effect, severe isolation, and substantial inbreeding have dramatically reduced genetic diversity in natives from the island of Kosrae, Federated States of Micronesia, who exhibit a high prevalence of obesity and other metabolic disorders. We hypothesized that genetic drift and possibly natural selection on Kosrae might have increased the frequency of previously rare genetic variants with relatively large effects, making these alleles readily detectable in genome-wide association analysis. However, mapping in large, inbred cohorts introduces analytic challenges, as extensive relatedness between subjects violates the assumptions of independence upon which traditional association test statistics are based. We performed genome-wide association analysis for 15 quantitative traits in 2,906 members of the Kosrae population, using novel approaches to manage the extreme relatedness in the sample. As positive controls, we observe association to known loci for plasma cholesterol, triglycerides, and C-reactive protein and to a compelling candidate loci for thyroid stimulating hormone and fasting plasma glucose. We show that our study is well powered to detect common alleles explaining >/=5% phenotypic variance. However, no such large effects were observed with genome-wide significance, arguing that even in such a severely inbred population, common alleles typically have modest effects. Finally, we show that a majority of common variants discovered in Caucasians have indistinguishable effect sizes on Kosrae, despite the major differences in population genetics and environment.
•What is currently known about this topic?•Subcutaneous ports may be stuck at the time of removal.•The treatment characteristics associated with this problem are not entirely known.•What new ...information is contained in this article?•Subcutaneous ports placed at diagnosis for the two-year treatment of acute lymphoblastic leukemia are associated with difficult removal.
We sought to identify clinical features associated with difficult subcutaneous port removals in children.
Ports placed between April 2014 and September 2017 at our institution were prospectively tracked for difficult removals. A case-control analysis was performed. Patients with ports that were difficult to remove (stuck; cases) were compared to biological sex and age-matched controls in a ratio of 1:3. Logistic regression determined the association between case/control status and clinical features adjusting for biological sex and age as covariates. A multivariable analysis was performed to identify independent associations.
57 stuck ports (28 extreme 10 endovascular intervention and 29 moderate) and 171 controls were analyzed. Stuck ports were associated with a diagnosis of acute lymphoblastic leukemia (86% cases versus 22.2% controls; p < 0.001) and a longer placement duration (median 2.6 years interquartile range (IQR) 2.5–2.6 versus 0.8 years IQR 0.5–1.4; p < 0.001). On univariate analysis, procedural and device features associated with stuck ports included subclavian access (71.9% cases versus 48.5% controls; p = 0.0126), a polyurethane versus silicone catheter (96.5% cases versus 79.9% controls; p = 0.001), and a rough catheter appearance at removal (92.6% cases versus 9.4% controls; p < 0.0001). A diagnosis of ALL and duration of line placement were associated with having a stuck port on multivariate analysis.
Polyurethane central venous catheters placed for the two-year treatment of acute lymphoblastic leukemia may become difficult to remove. This constellation of factors warrants more extensive preoperative discussion of risk, endovascular backup availability, and scheduling for longer operating room time.
Triple-negative breast cancers (TNBCs) are associated with poor survival mediated by treatment resistance. TNBCs are fibrotic, yet little is known regarding how the extracellular matrix (ECM) evolves ...following therapy and whether it impacts treatment response. Analysis revealed that while primary untreated TNBCs are surrounded by a rigid stromal microenvironment, chemotherapy-resistant residual tumors inhabit a softer niche. TNBC organoid cultures and xenograft studies showed that organoids interacting with soft ECM exhibit striking resistance to chemotherapy, ionizing radiation, and death receptor ligand TRAIL. A stiff ECM enhanced proapoptotic JNK activity to sensitize cells to treatment, whereas a soft ECM promoted treatment resistance by elevating NF-κB activity and compromising JNK activity. Treatment-resistant residual TNBCs residing within soft stroma had elevated activated NF-κB levels, and disengaging NF-κB activity sensitized tumors in a soft matrix to therapy. Thus, the biophysical properties of the ECM modify treatment response, and agents that modulate stiffness-dependent NF-κB or JNK activity could enhance therapeutic efficacy in patients with TNBC.
Cardiac conduction, as assessed by electrocardiographic PR interval and QRS duration, is an important electrophysiological trait and a determinant of arrhythmia risk.
We sought to identify common ...genetic determinants of these measures.
We examined 1604 individuals from the island of Kosrae, Federated States of Micronesia, an isolated founder population. We adjusted for covariates and estimated the heritability of quantitative electrocardiographic QRS duration and PR interval and, secondarily, its subcomponents, P-wave duration and PR segment. Finally, we performed a genome-wide association study (GWAS) in a subset of 1262 individuals genotyped using the Affymetrix GeneChip Human Mapping 500K microarray.
The heritability of PR interval was 34% (standard error SE 5%, P = 4 x 10(-18)); of PR segment, 31% (SE 6%, P = 3.2 x 10(-13)); and of P-wave duration, 17% (SE 5%, P = 5.8 x 10(-6)), but the heritablility of QRS duration was only 3% (SE 4%, P = .20). Hence, GWAS was performed only for the PR interval and its subcomponents. A total of 338,049 single nucleotide polymorphisms (SNPs) passed quality filters. For the PR interval, the most significantly associated SNPs were located in and downstream of the alpha-subunit of the cardiac voltage-gated sodium channel gene SCN5A, with a 4.8 ms (SE 1.0) or 0.23 standard deviation increase in adjusted PR interval for each minor allele copy of rs7638909 (P = 1.6 x 10(-6), minor allele frequency 0.40). These SNPs were also associated with P-wave duration (P = 1.5 x 10(-4)) and PR segment (P = .01) but not with QRS duration (P > or =.22).
The PR interval and its subcomponents showed substantial heritability in a South Pacific islander population and were associated with common genetic variation in SCN5A.
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