Luminosities of High-Redshift Objects in an Accelerating Universe

The results from the Supernova Cosmology Project indicate a relation between cosmic distance and redshift that corresponds to an accelerating Universe, and, as a consequence, the presence of an energy component with negative pressure. This necessitates a re-evaluation of such astrophysical luminosities that have been derived through conventional redshift analyses of, e.g., gamma-ray bursts and quasars. We have calculated corrected luminosity distances within two scenarios; the standard one with a non-zero cosmological constant, and the more recently proposed ``quintessence'', with a slowly evolving energy-density component. We find luminosity corrections from +30 to -40 per cent for redshifts with $z=0 - 10$. This finding implicates that the SCP data do not, by themselves, require a revision of the current, rather qualitative modeling of gamma-ray bursts and quasar properties.Comment: RevTeX, 4 pages, 2 postscript figures, submitted to PR

Moving targets: Target groups of active labour market policies and transitions to employment in Europe

This study drew on recurrent debates related to labour market mobility among the unemployed and those outside the labour force and asked to what extent active labour market policies (ALMP) increase employment in these two groups. By utilising new programme-level data on ALMP, the study analysed the impact of core programmes directed towards registered unemployed; peripheral programmes that target the inactive part of the working age population; and mixed programmes targeting both groups. The programme data were combined with individual-level panel data from the European Survey on Income and Living Conditions and analysed using multilevel analysis. The main results show that both resources devoted to programmes and their size were related to employment transitions. Transitions among the unemployed were mainly associated with spending on core programmes, whereas the inactive seemed to benefit from increased spending on all types of programmes, as well as increased scope of mixed programmes

Chasing the Smokestack: Strategic Policymaking With Multiple Instruments

Empirical evidence suggesting that a considerable amount of horizontal strategic interaction exists amongst governments is important in light of recent devolutionary trends of many important public programs. The empirical approach in these studies typically relies on estimating reaction functions in a uni-dimensional policy framework, where a nonzero slope estimate is interpreted as evidence in support of strategic interactions. While this framework is a useful representation within certain contexts, it is potentially too restrictive; for example, in models of resource competition, localities may use multiple instruments in their recruiting pursuits, leading to potential strategic interactions across policy instruments. In this study, we first develop a simple theoretic construct that includes resource competition in a world of three-dimensional policy choice. The model suggests that while a zero-sloped reaction function may exist for any particular policy, this does not necessarily imply the absence of strategic interactions. We examine the implications of the model empirically using US state-level panel data over the period 1977-1994. The results suggest that important cross-policy strategic interactions exist, lending support in favor of the multi-dimensional framework, and indicate that uni-dimensional frameworks may present lower bound estimates of the degree of strategic interaction.

Diseño de un juego infantil

[ES] El presente proyecto tiene como objeto el diseño de un juego para niños de 4 a 10 años, que promueva el aprendizaje de la lógica de programación , sin necesidad de ahondar en un lenguaje concreto, permitiendo el una mejora en las competencias de pensamiento crítico y resolución de problemas. El producto se encontrará dentro del marco de promoción del desarrollo de habilidades útiles en la ciencia, tecnología, ingeniería y matemáticas (CTIM, o STEM en siglas inglesas), y favorecerá también el cultivo de habilidades personales (creatividad, lógica, solución de problemas, colaboración, experimentación…). Ha de cumplir los siguientes requisitos: -Asequible : precios competitivos como estrategia de mercado. -Sin límites fijos: Que ofrezca diversas maneras de jugar, sin una solución fija o que requiera colaboración de otros jugadores. Esto incentiva la creatividad, exploración y demuestra mejor entendimiento de las reglas, patrones y lógica. -Estéticamente cuidado: un diseño atractivo para fomentar el juego. -Inclusivo.Ojeda Domínguez, L. (2018). Diseño de un juego infantil. Universitat Politècnica de València. http://hdl.handle.net/10251/110075TFG

Comparative Politics and Environmental Taxation: Theory and Quasi-Experimental Evidence

Abstract In this paper, we take a step towards understanding the role of democratic institutions on the level of pollution taxation. The theory predicts that presidential-congressional regimes set lower pollution taxes than parliamentary regimes. This results from the checks and balances built into the former, and the higher degree of legislative cohesion in the latter. We test the prediction using the method of propensity score matching along with data on gasoline prices from 86 democratic countries. The empirical evidence is consonant with the theory: we find that ceteris paribus the average price of super gasoline is $0.14 -$0.20 less per liter in presidentialcongressional systems; the average price of diesel gasoline is $0.11 -$0.14 less per liter

Sequencing of breast cancer stem cell populations indicates a dynamic conversion between differentiation states in vivo

Peer reviewe

Identification of a neurovascular signaling pathway regulating seizures in mice

ObjectiveA growing body of evidence suggests that increased blood–brain barrier (BBB) permeability can contribute to the development of seizures. The protease tissue plasminogen activator (tPA) has been shown to promote BBB permeability and susceptibility to seizures. In this study, we examined the pathway regulated by tPA in seizures.MethodsAn experimental model of kainate‐induced seizures was used in genetically modified mice, including mice deficient in tPA (tPA−/−), its inhibitor neuroserpin (Nsp−/−), or both (Nsp:tPA−/−), and in mice conditionally deficient in the platelet‐derived growth factor receptor alpha (PDGFRα).ResultsCompared to wild‐type (WT) mice, Nsp−/− mice have significantly reduced latency to seizure onset and generalization; whereas tPA−/− mice have the opposite phenotype, as do Nsp:tPA−/− mice. Furthermore, interventions that maintain BBB integrity delay seizure propagation, whereas osmotic disruption of the BBB in seizure‐resistant tPA−/− mice dramatically reduces the time to seizure onset and accelerates seizure progression. The phenotypic differences in seizure progression between WT, tPA−/−, and Nsp−/− mice are also observed in electroencephalogram recordings in vivo, but absent in ex vivo electrophysiological recordings where regulation of the BBB is no longer necessary to maintain the extracellular environment. Finally, we demonstrate that these effects on seizure progression are mediated through signaling by PDGFRα on perivascular astrocytes.InterpretationTogether, these data identify a specific molecular pathway involving tPA‐mediated PDGFRα signaling in perivascular astrocytes that regulates seizure progression through control of the BBB. Inhibition of PDGFRα signaling and maintenance of BBB integrity might therefore offer a novel clinical approach for managing seizures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112290/1/acn3209.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112290/2/acn3209-sup-0001-TableS1.pd

Sequencing-based breast cancer diagnostics as an alternative to routine biomarkers

Sequencing-based breast cancer diagnostics have the potential to replace routine biomarkers and provide molecular characterization that enable personalized precision medicine. Here we investigate the concordance between sequencing-based and routine diagnostic biomarkers and to what extent tumor sequencing contributes clinically actionable information. We applied DNA- and RNA-sequencing to characterize tumors from 307 breast cancer patients with replication in up to 739 patients. We developed models to predict status of routine biomarkers (ER, HER2,Ki-67, histological grade) from sequencing data. Non-routine biomarkers, including mutations in BRCA1, BRCA2 and ERBB2(HER2), and additional clinically actionable somatic alterations were also investigated. Concordance with routine diagnostic biomarkers was high for ER status (AUC = 0.95;AUC(replication) = 0.97) and HER2 status (AUC = 0.97;AUC(replication) = 0.92). The transcriptomic grade model enabled classification of histological grade 1 and histological grade 3 tumors with high accuracy (AUC = 0.98;AUC(replication) = 0.94). Clinically actionable mutations in BRCA1, BRCA2 and ERBB2(HER2) were detected in 5.5% of patients, while 53% had genomic alterations matching ongoing or concluded breast cancer studies. Sequencing-based molecular profiling can be applied as an alternative to histopathology to determine ER and HER2 status, in addition to providing improved tumor grading and clinically actionable mutations and molecular subtypes. Our results suggest that sequencing-based breast cancer diagnostics in a near future can replace routine biomarkersNonePublishe

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Differences in Cell Division Rates Drive the Evolution of Terminal Differentiation in Microbes

Multicellular differentiated organisms are composed of cells that begin by developing from a single pluripotent germ cell. In many organisms, a proportion of cells differentiate into specialized somatic cells. Whether these cells lose their pluripotency or are able to reverse their differentiated state has important consequences. Reversibly differentiated cells can potentially regenerate parts of an organism and allow reproduction through fragmentation. In many organisms, however, somatic differentiation is terminal, thereby restricting the developmental paths to reproduction. The reason why terminal differentiation is a common developmental strategy remains unexplored. To understand the conditions that affect the evolution of terminal versus reversible differentiation, we developed a computational model inspired by differentiating cyanobacteria. We simulated the evolution of a population of two cell types –nitrogen fixing or photosynthetic– that exchange resources. The traits that control differentiation rates between cell types are allowed to evolve in the model. Although the topology of cell interactions and differentiation costs play a role in the evolution of terminal and reversible differentiation, the most important factor is the difference in division rates between cell types. Faster dividing cells always evolve to become the germ line. Our results explain why most multicellular differentiated cyanobacteria have terminally differentiated cells, while some have reversibly differentiated cells. We further observed that symbioses involving two cooperating lineages can evolve under conditions where aggregate size, connectivity, and differentiation costs are high. This may explain why plants engage in symbiotic interactions with diazotrophic bacteria