Characterizing and Improving the Reliability of Broadband Internet Access

In this paper, we empirically demonstrate the growing importance of reliability by measuring its effect on user behavior. We present an approach for broadband reliability characterization using data collected by many emerging national initiatives to study broadband and apply it to the data gathered by the Federal Communications Commission's Measuring Broadband America project. Motivated by our findings, we present the design, implementation, and evaluation of a practical approach for improving the reliability of broadband Internet access with multihoming.Comment: 15 pages, 14 figures, 6 table

Data-driven modelling of biological multi-scale processes

Biological processes involve a variety of spatial and temporal scales. A holistic understanding of many biological processes therefore requires multi-scale models which capture the relevant properties on all these scales. In this manuscript we review mathematical modelling approaches used to describe the individual spatial scales and how they are integrated into holistic models. We discuss the relation between spatial and temporal scales and the implication of that on multi-scale modelling. Based upon this overview over state-of-the-art modelling approaches, we formulate key challenges in mathematical and computational modelling of biological multi-scale and multi-physics processes. In particular, we considered the availability of analysis tools for multi-scale models and model-based multi-scale data integration. We provide a compact review of methods for model-based data integration and model-based hypothesis testing. Furthermore, novel approaches and recent trends are discussed, including computation time reduction using reduced order and surrogate models, which contribute to the solution of inference problems. We conclude the manuscript by providing a few ideas for the development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and Multiscale Dynamics (American Scientific Publishers

Algebraic Multigrid for Meshfree Methods

This thesis deals with the development of a new Algebraic Multigrid method (AMG) for the solution of linear systems arising from Generalized Finite Difference Methods (GFDM). In particular, we consider the Finite Pointset Method, which is based on GFDM. Being a meshfree method, FPM does not rely on a mesh and can therefore deal with moving geometries and free surfaces is a natural way and it does not require the generation of a mesh before the actual simulation. In industrial use cases the size of the linear systems often becomes large, which means that classical linear solvers often become the bottleneck in terms of simulation run time, because their convergence rate depends on the discretization size. Multigrid methods have proven to be very efficient linear solvers in the domain of mesh-based methods. Their convergence is independent of the discretization size, yielding a run time that only scales linearly with the problem size. AMG methods are a natural candidate for the solution of the linear systems arising in the FPM, as this thesis will show. They need to be tuned to the specific characteristics of GFDM, though. The AMG methods that are developed in this thesis achieve a speed-up of up to 33x compared to the classical linear solvers and therefore allow much more accurate simulations in the future.Diese Dissertation beschäftigt sich mit der Entwicklung einer neuen Algebraischen Mehrgittermethode für die Lösung linearer Gleichungssysteme aus Generalisierten Finite Differenzen Methoden. Im Speziellen betrachten wir die sogenannte Finite Pointset Method, eine gitterfreie Lagrange Methode, welche auf Generalisierten Finite Differenzen Methoden basiert. Die Finite Pointset Method wurde insbesondere für Simulationen von Vorgängen mit freien Oberflächen und bewegten Geometrien entwickelt, bei denen der gitterfreie Charakter der Methode besonders große Vorteile liefert: An den freien Oberflächen und nahe der Geometrie muss zu keinem Zeitpunkt – auch nicht zu Beginn der Simulation – ein Gitter erstellt oder angepasst werden. Dies ist ein großer Vorteil gegenüber klassischen gitterbasierten Methoden. Wie in gitterbasierten Methoden entstehen auch in der Finite Pointset Method und anderen Generalisierten Finite Differenzen Methoden große, dünn besetze lineare Gleichungssysteme. Das Lösen dieser Gleichungssysteme wird bei fein aufgelösten Simulationen, wie sie in der Industrie oft nötig sind, schnell zum zeitlichen Flaschenhals der Gesamtsimulation. Ohne eine geeignete Methode zur Lösung dieser Gleichungssysteme dauern Simulationen oft sehr lange oder sind praktisch nicht durchführbar. Auch kann es vorkommen, dass klassische Lösungsverfahren divergieren und die Simulation damit unmöglich wird. Im Kontext von gitterbasierten Methoden sind Mehrgittermethoden ein etabliertes Werkzeug, um die entstehenden linearen Gleichungssysteme effizient und robust zu lösen. Besonders hervorzuheben ist dabei die lineare Skalierbarkeit dieser Methoden in der Größe der Matrix. Damit eignen sie sich besonders für fein aufgelöste Simulationen. Algebraische Mehrgittermethoden sind natürliche Kandidaten für die Lösung der Gleichungssysteme aus Generalisierten Finite Differenzen Methoden, wie diese Dissertation zeigen wird. Außerdem entwickeln wir eine neue Algebraische Mehrgittermethode, die auf den Einsatz in der Finite Pointset Method zugeschnitten ist und die Besonderheiten dieser Methode beachtet. Dazu zählen die Eigenschaften der einzelnen Matrizen, die wir ebenfalls analysieren werden, und auch die Veränderung der Matrizen über mehrere Zeitschritte hinweg, die im Vergleich mit gitterbasierten Verfahren eine größere Schwierigkeit darstellt. Wir evaluieren unsere neue Methode anhand von akademischen und realen Beispielen, sowohl mit nur einem Prozess als auch mit mehreren (MPI-)Prozessen. Die hier neu entwickelte Algebraische Mehrgittermethode ist um ein Vielfaches schneller als klassische Verfahren zur Lösung linearer Gleichungssysteme und erlaubt damit neue, genauere Simulationen mit gitterfreien Methoden

Servicios y otros pagados por anticipado en la municipalidad Distrital de Coasa, Puno, Período 2017-2019

Para la presente tesis, el objetivo de estudio fue analizar la situación de los servicios y otros pagados por anticipado en la Municipalidad Distrital de Coasa (período 2017-2019). La metodología utilizada correspondió a la de un trabajo de investigación aplicada, con diseño no experimental, descriptivo. La población fue el estado de situación financiera; la muestra fue los reportes correspondientes a 03 periodos (2017-2019); el método de análisis fue el analítico. Los resultados indicaron que la situación de los servicios y otros pagados por anticipado en la Municipalidad Distrital de Coasa, período 2017-2019, se caracterizó por que tuve una evolución favorable. Las conclusiones señalaron que los saldos de la cuenta de servicios y otros pagados por anticipado pasaron de S/. 5,689,854.47 (2017) a S/. 1,341,222.79 (2019) sin embargo aún se ha observado que las rendiciones siguen realizándose fuera del plazo establecido según la directiva N° 001- 2007- EF/77.15 del Sistema Nacional de Tesorería, quedando aún pendientes cuentas por rendir

liCTLA-4 is not linked to diabetes protection

CTLA-4 is a critical "checkpoint" regulator in autoimmunity. Variation in CTLA-4 isoform expression has been linked to type 1 diabetes development in human and NOD mouse studies. In the NOD mouse, a causative link between increased expression of the minor isoform ligand-independent CTLA-4 and a reduction in diabetes has become widely accepted. Altered splicing of CTLA-4 has been attributed to a single nucleotide polymorphism (SNP) in Ctla4 exon2 (e2_77A/G). To investigate this link, we have used NOD embryonic stem (ES) cells to generate a novel NOD transgenic line with the 77A/G SNP. This strain phenocopies the increase in splicing toward the liCTLA4 isoform seen in B10 Idd5.1 mice. Crucially, the SNP does not alter the spontaneous incidence of diabetes, the incidence of cyclophosphamide-induced diabetes, or the activation of diabetogenic T-cell receptor transgenic CD4(+) T cells after adoptive transfer. Our results show that one or more of the many other linked genetic variants between the B10 and NOD genome are required for the diabetes protection conferred by Idd5.1. With the NOD mouse model closely mimicking the human disease, our data demonstrate that knock-in transgenic mice on the NOD background can test causative mutations relevant in human diabetes.FJ was supported by an MRC Studentship and we acknowledge the support of the Wellcome Trust and the Department of Pathology.This is the author accepted manuscript. The final version is available from American Diabetes Association via http://dx.doi.org/10.2337/db15-117

The Molecular Gas Reservoirs of z∼2z\sim 2 Galaxies: A comparison of CO(1-0) and dust-based molecular gas masses

We test the use of long-wavelength dust continuum emission as a molecular gas tracer at high redshift, via a unique sample of 12, z~2 galaxies with observations of both the dust continuum and CO(1-0) line emission (obtained with the Atacama Large Millimeter Array and Karl G. Jansky Very Large Array, respectively). Our work is motivated by recent, high redshift studies that measure molecular gas masses (\ensuremath{\rm{M}_{\rm{mol}}}) via a calibration of the rest-frame $850\mu$m luminosity ($L_\mathrm{850\mu m,rest}$) against the CO(1-0)-derived \ensuremath{\rm{M}_{\rm{mol}}}\ of star-forming galaxies. We hereby test whether this method is valid for the types of high-redshift, star-forming galaxies to which it has been applied. We recover a clear correlation between the rest-frame $850\mu$m luminosity, inferred from the single-band, long-wavelength flux, and the CO(1-0) line luminosity, consistent with the samples used to perform the $850\mu$m calibration. The molecular gas masses, derived from $L_\mathrm{850\mu m,rest}$, agree to within a factor of two with those derived from CO(1-0). We show that this factor of two uncertainty can arise from the values of the dust emissivity index and temperature that need to be assumed in order to extrapolate from the observed frequency to the rest-frame at 850$\mathrm{\mu m}$. The extrapolation to 850$\mathrm{\mu m}$ therefore has a smaller effect on the accuracy of \Mmol\ derived via single-band dust-continuum observations than the assumed CO(1-0)-to-\ensuremath{\rm{M}_{\rm{mol}}}\ conversion factor. We therefore conclude that single-band observations of long-wavelength dust emission can be used to reliably constrain the molecular gas masses of massive, star-forming galaxies at $z\gtrsim2$

Neural Video Compression using GANs for Detail Synthesis and Propagation

We present the first neural video compression method based on generative adversarial networks (GANs). Our approach significantly outperforms previous neural and non-neural video compression methods in a user study, setting a new state-of-the-art in visual quality for neural methods. We show that the GAN loss is crucial to obtain this high visual quality. Two components make the GAN loss effective: we i) synthesize detail by conditioning the generator on a latent extracted from the warped previous reconstruction to then ii) propagate this detail with high-quality flow. We find that user studies are required to compare methods, i.e., none of our quantitative metrics were able to predict all studies. We present the network design choices in detail, and ablate them with user studies.Comment: First two authors contributed equally. ECCV Camera ready versio

High-resolution Observations of Molecular Lines in Arp 220: Kinematics, Morphology, and Limits on the Applicability of the Ammonia Thermometer

We observe Arp 220, the nearest ultra-luminous infrared galaxy, over 4 GHz in the K and Ka bands, providing constraints for the kinematics and morphology, and identifying molecular species on scales resolving both nuclei (0".6 or 230 pc). We detect multiple molecular species, including hydroxyl (OH ^2Π_(3/2)J = 9/2 F= 4-4; 5-5) in both cores, and tentatively detect H_2O(6_(15)-5_(23)) at ~21.84 GHz in both nuclei, indicating the likely presence of maser emission. The observed frequency range also contains metastable ammonia transitions from (J, K) = (1, 1)–(5, 5), as well as the (9, 9) inversion line; together, they are a well-known thermometer of dense molecular gas. Furthermore, the non-metastable (4, 2) and (10, 9), and possibly the (3, 1), lines are also detected. We apply a standard temperature analysis to Arp 220; however, the analysis is complicated in that standard local thermal equilibrium (LTE) assumptions do not hold. There are indications that a substantial fraction of ammonia could be in the non-metastable transitions, as opposed to only the metastable ones. Thus, the non-metastable transitions could be essential to constraining the temperature. We compare all of these data to ALMA observations of this source, confirming the outflow previously observed by other tracers in both nuclei

First report on brorphine : the next opioid on the deadly new psychoactive substance horizon?

New psychoactive substances (NPS) continue to appear on the drug market. Until recently, new synthetic opioids, which are amongst the most dangerous NPS, primarily encompassed analogues of the potent analgesic fentanyl. Lately, also other new synthetic opioids have increasingly started to surface. This is the first report on the identification and full chemical characterization of brorphine, a novel potent synthetic opioid with a piperidine benzimidazolone structure. Brorphine was identified in a powder and in the serum of a patient seeking medical help for detoxification. Liquid chromatography–high resolution mass spectrometry (LC–HRMS) identified an exact mass of m/z 400.1020 and 402.1005 for the compound, corresponding to both bromine isotopes. Further chemical characterization was performed by gas chromatography–mass spectrometry (GC–MS), LC–diode array detection (DAD) and Fourier-transform infrared (FT-IR) spectroscopy analyses. Finally, the structure was confirmed by performing 1H- and 13C-NMR spectroscopy. In vitro biological activity of brorphine was determined by a cell-based µ-opioid receptor (MOR) activation assay, resulting in an EC50 of 30.9 nM (13.5 ng/mL) and an Emax of 209% relative to hydromorphone, confirming the high potency and efficacy of this compound. In a serum sample of the patient, brorphine and a hydroxy-metabolite were found using the LC–HRMS screening method. The presence of opioid activity in the serum was also confirmed via the activity-based opioid screening assay. The occurrence of brorphine is yet another example of how the illicit drug market is continuously evolving in an attempt to escape international legislation. Its high potency poses a serious and imminent health threat for any user

CO(1-0) in z ≳ 4 Quasar Host Galaxies: No Evidence for Extended Molecular Gas Reservoirs

We present ^(12)CO(J = 1 → 0) observations of the high-redshift quasi-stellar objects (QSOs) BR 1202-0725 (z = 4.69), PSS J2322+1944 (z = 4.12), and APM 08279+5255 (z = 3.91) using the NRAO Green Bank Telescope (GBT) and the MPIfR Effelsberg 100 m telescope. We detect, for the first time, the CO ground-level transition in BR 1202-0725. For PSS J2322+1944 and APM 08279+5255, our observations result in line fluxes that are consistent with previous NRAO Very Large Array (VLA) observations, but they reveal the full line profiles. We report a typical lensing-corrected velocity-integrated intrinsic ^(12)CO(J = 1 → 0) line luminosity of L'_(CO) = 5 × 10^(10) K km s^(-1) pc^2 and a typical total H_2 mass of M(H_2) = 4 × 10^(10) M_☉ for the sources in our sample. The CO/FIR luminosity ratios of these high-z sources follow the same trend as seen for low-z galaxies, leading to a combined solution of log L_(FIR) = (1.39 ± 0.05) log L_(CO) - 1.76. It has previously been suggested that the molecular gas reservoirs in some quasar host galaxies may exhibit luminous, extended ^(12)CO(J = 1 → 0) components that are not observed in the higher J CO transitions. Using the line profiles and the total intensities of our observations and large velocity gradient (LVG) models based on previous results for higher J CO transitions, we derive that emission from all CO transitions is described well by a single gas component in which all molecular gas is concentrated in a compact nuclear region. Thus, our observations and models show no indication of a luminous extended, low surface brightness molecular gas component in any of the high-redshift QSOs in our sample. If such extended components exist, their contribution to the overall luminosity is limited to at most 30%