An Algorithmic Framework for Labeling Network Maps

Drawing network maps automatically comprises two challenging steps, namely laying out the map and placing non-overlapping labels. In this paper we tackle the problem of labeling an already existing network map considering the application of metro maps. We present a flexible and versatile labeling model. Despite its simplicity, we prove that it is NP-complete to label a single line of the network. For a restricted variant of that model, we then introduce an efficient algorithm that optimally labels a single line with respect to a given weighting function. Based on that algorithm, we present a general and sophisticated workflow for multiple metro lines, which is experimentally evaluated on real-world metro maps.Comment: Full version of COCOON 2015 pape

Climbing the Jaynes-Cummings Ladder and Observing its Sqrt(n) Nonlinearity in a Cavity QED System

The already very active field of cavity quantum electrodynamics (QED), traditionally studied in atomic systems, has recently gained additional momentum by the advent of experiments with semiconducting and superconducting systems. In these solid state implementations, novel quantum optics experiments are enabled by the possibility to engineer many of the characteristic parameters at will. In cavity QED, the observation of the vacuum Rabi mode splitting is a hallmark experiment aimed at probing the nature of matter-light interaction on the level of a single quantum. However, this effect can, at least in principle, be explained classically as the normal mode splitting of two coupled linear oscillators. It has been suggested that an observation of the scaling of the resonant atom-photon coupling strength in the Jaynes-Cummings energy ladder with the square root of photon number n is sufficient to prove that the system is quantum mechanical in nature. Here we report a direct spectroscopic observation of this characteristic quantum nonlinearity. Measuring the photonic degree of freedom of the coupled system, our measurements provide unambiguous, long sought for spectroscopic evidence for the quantum nature of the resonant atom-field interaction in cavity QED. We explore atom-photon superposition states involving up to two photons, using a spectroscopic pump and probe technique. The experiments have been performed in a circuit QED setup, in which ultra strong coupling is realized by the large dipole coupling strength and the long coherence time of a superconducting qubit embedded in a high quality on-chip microwave cavity.Comment: ArXiv version of manuscript published in Nature in July 2008, 5 pages, 5 figures, hi-res version at http://www.finkjohannes.com/SqrtNArxivPreprint.pd

A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity

Nonlinear response of the vacuum Rabi resonance

On the level of single atoms and photons, the coupling between atoms and the electromagnetic field is typically very weak. By employing a cavity to confine the field, the strength of this interaction can be increased many orders of magnitude to a point where it dominates over any dissipative process. This strong-coupling regime of cavity quantum electrodynamics has been reached for real atoms in optical cavities, and for artificial atoms in circuit QED and quantum-dot systems. A signature of strong coupling is the splitting of the cavity transmission peak into a pair of resolvable peaks when a single resonant atom is placed inside the cavity - an effect known as vacuum Rabi splitting. The circuit QED architecture is ideally suited for going beyond this linear response effect. Here, we show that increasing the drive power results in two unique nonlinear features in the transmitted heterodyne signal: the supersplitting of each vacuum Rabi peak into a doublet, and the appearance of additional peaks with the characteristic sqrt(n) spacing of the Jaynes-Cummings ladder. These constitute direct evidence for the coupling between the quantized microwave field and the anharmonic spectrum of a superconducting qubit acting as an artificial atom.Comment: 6 pages, 4 figures. Supplementary Material and Supplementary Movies are available at http://www.eng.yale.edu/rslab/publications.htm

Beyond the Jaynes-Cummings model: circuit QED in the ultrastrong coupling regime

In cavity quantum electrodynamics (QED), light-matter interaction is probed at its most fundamental level, where individual atoms are coupled to single photons stored in three-dimensional cavities. This unique possibility to experimentally explore the foundations of quantum physics has greatly evolved with the advent of circuit QED, where on-chip superconducting qubits and oscillators play the roles of two-level atoms and cavities, respectively. In the strong coupling limit, atom and cavity can exchange a photon frequently before coherence is lost. This important regime has been reached both in cavity and circuit QED, but the design flexibility and engineering potential of the latter allowed for increasing the ratio between the atom-cavity coupling rate and the cavity transition frequency above the percent level. While these experiments are well described by the renowned Jaynes-Cummings model, novel physics is expected in the ultrastrong coupling limit. Here, we report on the first experimental realization of a superconducting circuit QED system in the ultrastrong coupling limit and present direct evidence for the breakdown of the Jaynes-Cummings model.Comment: 5 pages, 3 figure

Synoptic timescale linkage between midlatitude winter troughs Sahara temperature patterns and northern Congo rainfall: A building block of regional climate variability

A coherent synoptic sequence, mostly over North Africa, is identified whereby an upper-level midlatitude trough (in November–March) excites several days of quasi-stationary near-surface warming across the Sahara, leading to rainfall events over northern Congo (NC), and perturbed weather more widely. Ahead of NC rainfall events, composite sequences first identify troughs for several days near Iberia, followed by relatively quick transfer to the Central Mediterranean (CMed). Iberia and CMed daily trough-strength indices reveal that both lead to warming and NC rainfall. Iberia trough linkages develop through West Africa and take longer to reach NC, while CMed linkages reach NC faster (2–3 days), with impact extent focused mostly south and east of CMed. Building up to the rainfall events, initial warming over the central Sahara migrates southeastward close to NC, ultimately with typical magnitude of about 1–2°C at 10–15°N. Such anomalies are statistically predictive for NC daily rainfall and associated nearby atmospheric features: anomalous low-level southerly wind and increased moisture; anomalous low-level westerly wind and vertical easterly shear to 600 hPa; increased mid-level moisture (600 hPa), which along with low-level moisture, connects northward into midlatitudes. A secondary route identified by which Iberia troughs can impact NC rainfall is through direct atmospheric teleconnection with precipitation to the west of NC, and subsequent migration of that convection eastward into NC. The eastern side of NC generally shows a small lag on western parts, and links more strongly to CMed troughs. Taken together, the lagged synoptic expression of Iberia and CMed troughs is widespread over several days, including much of North Africa (to equatorial latitudes), southwestern Asia, eastern Africa and the western Indian Ocean. Overall, these results can contribute to situational awareness for weather forecasters across the zones influenced by the troughs, while also providing a framework for climate timescale analyses

An adult cystic fibrosis patient presenting with persistent dyspnea: case report

BACKGROUND: Persistent dyspnea is a common finding in the cystic fibrosis patient that typically leads to further work up of an alternative pulmonary etiology. Adult cystic fibrosis patients; however, are growing in numbers and they are living into the ages in which coronary artery disease becomes prevalent. Coronary disease should be included in the consideration of diagnostic possibilities. CASE PRESENTATION: A 52-year-old white male with cystic fibrosis was evaluated for exertional dyspnea associated with vague chest discomfort. Diagnostic testing revealed normal white blood cell, hemoglobin and platelet count, basic metabolic panel, fasting lipid profile, HbA1c, with chest radiograph confirming chronic cystic findings unchanged from prior radiographs and an electrocardiogram that revealed sinus rhythm with left anterior fascicular block. Stress thallium testing demonstrated a reversible anteroseptal perfusion defect with a 55% left ventricular ejection fraction. Heart catheterization found a 99% occlusion of the left anterior descending artery extending into the two diagonal branches, with 100% obstruction of the left anterior descending artery at the trifurcation and 70% lesion affecting the first posterior lateral branch of the circumflex artery. CONCLUSION: This case report represents the first description in the medical literature of a cystic fibrosis patient diagnosed with symptomatic coronary artery disease. Applying a standard clinical practice guide proved useful toward evaluating a differential diagnosis for a cystic fibrosis patient presenting with dyspnea and chest discomfort

Serial Examination of an Inducible and Reversible Dilated Cardiomyopathy in Individual Adult Drosophila

Recent work has demonstrated that Drosophila can be used as a model of dilated cardiomyopathy, defined as an enlarged cardiac chamber at end-diastole when the heart is fully relaxed and having an impaired systolic function when the heart is fully contracted. Gene mutations that cause cardiac dysfunction in adult Drosophila can result from abnormalities in cardiac development or alterations in post-developmental heart function. To clarify the contribution of transgene expression to post-developmental cardiac abnormalities, we applied strategies to examine the temporal and spacial effects of transgene expression on cardiac function. We engineered transgenic Drosophila based on the well-characterized temperature-sensitive Gal80 protein in the context of the bipartite Gal4/UAS transgenic expression system in Drosophila employing the cardiac specific driver, tinCΔ4-Gal4. Then, we developed a strategy using optical coherence tomography to serially measure cardiac function in the individual flies over time course of several days. As a proof of concept we examined the effects of the expression of a human mutant delta-sarcoglycan associated with familial heart failure and observed a reversible, post-developmental dilated cardiomyopathy in Drosophila. Our results show that the unique imaging strategy based on the non-destructive, non-invasive properties of optical coherence tomography can be applied to serially examine cardiac function in individual adult flies. Furthermore, the induction and reversal of cardiac transgene expression can be investigated in adult flies thereby providing insight into the post-developmental effects of transgene expression

Wnt/β-catenin Signalling Is Active in a Highly Dynamic Pattern during Development of the Mouse Cerebellum

The adult cerebellum is composed of several distinct cell types with well defined developmental origins. However, the molecular mechanisms that govern the generation of these cell types are only partially resolved. Wnt/β-catenin signalling has a wide variety of roles in generation of the central nervous system, though the specific activity of this pathway during cerebellum development is not well understood. Here, we present data that delineate the spatio-temporal specific pattern of Wnt/β-catenin signaling during mouse cerebellum development between E12.5 and P21. Using the BAT-gal Wnt/β-catenin reporter mouse, we found that Wnt/β-catenin activity is present transiently at the embryonic rhombic lip but not at later stages during the expansion of cell populations that arise from there. At late embryonic and early postnatal stages, Wnt/β-catenin activity shifts to the cerebellar ventricular zone and to cells arising from this germinal centre. Subsequently, the expression pattern becomes progressively restricted to Bergmann glial cells, which show expression of the reporter at P21. These results indicate a variety of potential functions for Wnt/β-catenin activity during cerebellum development

Bifidobacterium bifidum Actively Changes the Gene Expression Profile Induced by Lactobacillus acidophilus in Murine Dendritic Cells

Dendritic cells (DC) play a pivotal regulatory role in activation of both the innate as well as the adaptive immune system by responding to environmental microorganisms. We have previously shown that Lactobacillus acidophilus induces a strong production of the pro-inflammatory and Th1 polarizing cytokine IL-12 in DC, whereas bifidobacteria do not induce IL-12 but inhibit the IL-12 production induced by lactobacilli. In the present study, genome-wide microarrays were used to investigate the gene expression pattern of murine DC stimulated with Lactobacillus acidophilus NCFM and Bifidobacterium bifidum Z9. L. acidophilus NCFM strongly induced expression of interferon (IFN)-β, other virus defence genes, and cytokine and chemokine genes related to the innate and the adaptive immune response. By contrast, B. bifidum Z9 up-regulated genes encoding cytokines and chemokines related to the innate immune response. Moreover, B. bifidum Z9 inhibited the expression of the Th1-promoting genes induced by L. acidophilus NCFM and had an additive effect on genes of the innate immune response and Th2 skewing genes. The gene encoding Jun dimerization protein 2 (JDP2), a transcription factor regulating the activation of JNK, was one of the few genes only induced by B. bifidum Z9. Neutralization of IFN-β abrogated L. acidophilus NCFM-induced expression of Th1-skewing genes, and blocking of the JNK pathway completely inhibited the expression of IFN-β. Our results indicate that B. bifidum Z9 actively inhibits the expression of genes related to the adaptive immune system in murine dendritic cells and that JPD2 via blocking of IFN-β plays a central role in this regulatory mechanism