Coexistence of amplitude and frequency modulations in intracellular calcium dynamics

The complex dynamics of intracellular calcium regulates cellular responses to information encoded in extracellular signals. Here, we study the encoding of these external signals in the context of the Li-Rinzel model. We show that by control of biophysical parameters the information can be encoded in amplitude modulation, frequency modulation or mixed (AM and FM) modulation. We briefly discuss the possible implications of this new role of information encoding for astrocytes.Comment: 4 pages, 4 figure

The Krakow Receptor Modelling Inter-Comparison Exercise

Second to oil, coal is globally the biggest energy source. Coal combustion is utilized mainly for power generation in industry, but in many metropolitan areas in East Europe and Asia also for residential heating in small stoves and boilers. The present investigation, carried out as a case study in a typical major city situated in a European coal combustion region (Krakow, Poland), aims at quantifying the impact on the urban air quality of residential heating by coal combustion in comparison with other potential pollution sources such as power plants, industry and traffic. For that purpose, gaseous emissions (NOx, SO2) were measured for 20 major sources, including small stoves and boilers, and the emissions of particulate matter (PM) was chemically analyzed for 52 individual compounds together with outdoor and indoor PM10 collected during typical winter pollution episodes. The data was analyzed using multivariate receptor modeling yielding source apportionments for PM10, B(a)P and other regulated air pollutants associated with PM10, namely Cd, Ni, As, and Pb. The source apportionment was accomplished using the chemical mass balance modeling (CMB) and constrained positive matrix factorization (CMF) and compared to five other multivariate receptor models (PMF, PCA-MLRA, UNMIX, SOM, CA). The results are potentially very useful for planning abatement strategies in all areas of the world, where coal combustion in small appliances is significant. During the pollution episodes under investigation the PM10 and B(a)P concentrations were up to 8-200times higher than the European limit values. The major culprit for these extreme pollution levels was shown to be residential heating by coal combustion in small stoves and boilers (>50% for PM10 and >90% B(a)P), whereas road transport (<10% for PM10 and <3% for B(a)P), and industry (4-15% for PM10 and <6% for B(a)P) played a lesser role. The indoor PM10 and B(a)P concentrations were not much lower than the outdoor concentrations and were found to have the same sources as outdoor PM10 and B(a)P The inorganic secondary aerosol component of PM10 amounted to around 30%, which may be attributed for a large part to the industrial emission of the precursors SO2 and NOX.JRC.H.4-Transport and air qualit

The Association of a classical left bundle Branch Block Contraction Pattern by vendor-independent strain echocardiography and outcome after cardiac resynchronization therapy

Background: The association of a Classical left bundle branch block (LBBB) contraction pattern and better outcome after cardiac resynchronization therapy (CRT) has only been studied using vendor-specific software for echocardiographic speckle-tracked longitudinal strain analysis. The purpose of this study was to assess whether a Classical LBBB contraction pattern on longitudinal strain analysis using vendor-independent software is associated with clinical outcome in CRT recipients with LBBB. Methods: This was a retrospective cohort study including CRT recipients with LBBB, heart failure, and left ventricular (LV) ejection fraction ≤35%. Speckle-tracked echocardiographic longitudinal strain analysis was performed retrospectively on echocardiograms using vendor-independent software. The presence of a Classical LBBB contraction pattern was determined by consensus of two readers. The primary end point was a composite of time to death, heart transplantation or LV assist device implantation. Secondary outcome was ≥15% reduction in LV end-systolic volume. Intra- and inter-reader agreement of the longitudinal strain contraction pattern was assessed by calculating Cohen's κ. Results: Of 283 included patients, 113 (40%) were women, mean age was 66 ± 11 years, and 136 (48%) had ischemic heart disease. A Classical LBBB contraction pattern was present in 196 (69%). The unadjusted hazard ratio for reaching the primary end point was 1.93 (95% confidence interval, 1.36-2.76, p &lt; 0.001) when comparing patients without to patients with a Classical LBBB contraction pattern. Adjusted for ischemic heart disease and QRS duration &lt; 150 milliseconds the hazard ratio was 1.65 (95% confidence interval, 1.12-2.43, p = 0.01). Of the 123 (43%) patients with a follow-up echocardiogram, 64 of 85 (75%) of patients with a Classical LBBB contraction pattern compared to 13 of 38 (34%) without, had ≥15% reduction in LV end-systolic volume (p &lt; 0.001). Cohen's κ were 0.86 (95% confidence interval, 0.71-1.00) and 0.42 (95% confidence interval, 0.30-0.54) for intra- and inter-reader agreement, respectively. Conclusion: Using vendor-independent strain software, a Classical LBBB contraction pattern is associated with better outcome in CRT recipients with LBBB, but inter-reader agreement for the classification of contraction pattern is only moderate.</p

Using Model Test Data to Assess VIV Factor of Safety for SCR and TTR in GOM

This paper presents results obtained as part of the DeepStar Phase 10 program on VIV Factors of Safety. The objective was to develop a general methodology to calibrate Factors of Safety for VIV-induced fatigue and to apply it to partially straked risers. This was achieved using reliability methods, accepted industry VIV prediction software and state-of-the-art model test experiments. Most oil companies use a Factor of Safety of 20 when predicting VIV damage using VIV software tools. There are numerous software tools currently in use in industry to predict VIV damage to straked risers and each of them will have different accuracy, and therefore an intrinsic level of conservatism. Understanding the level of conservatism in different VIV prediction software is therefore critical to determining what Factor of Safety to use. This study benchmarks the latest generation of industry accepted VIV design tools at the time of the study (2011): SHEAR7v4.6, VIVAv6.5 and VIVANAv3.7.24 against high quality VIV data from three separate straked riser experiments. A bias distribution (predicted to measured VIV damage results) is obtained for each software tool as a function of the strake coverage. A novel reliability framework approach is then developed to incorporate all uncertainties associated with VIV fatigue prediction into a limit state function, including variability in met-ocean conditions and variability in the fatigue resistance of the material characterized by a design S-N curve. The limit state function is analyzed using First Order Reliability Methods to develop Factors of Safety for target probabilities of failure. The general method is then applied on two case studies involving an SCR and TTR in Gulf of Mexico loop currents, but it can be easily extended to different locations and riser configurations. The resulting FoS range from about 1 to 15 for most software, and are lower than industry standards for VIV prediction. The FoS do not vary markedly for different riser configurations, indicating the possibility of reducing excess conservatism when predicting VIV damage on straked risers.DeepStar (Consortium)SHEAR7 JI

Assessment of algorithms for mitosis detection in breast cancer histopathology images

The proliferative activity of breast tumors, which is routinely estimated by counting of mitotic figures in hematoxylin and eosin stained histology sections, is considered to be one of the most important prognostic markers. However, mitosis counting is laborious, subjective and may suffer from low inter-observer agreement. With the wider acceptance of whole slide images in pathology labs, automatic image analysis has been proposed as a potential solution for these issues. In this paper, the results from the Assessment of Mitosis Detection Algorithms 2013 (AMIDA13) challenge are described. The challenge was based on a data set consisting of 12 training and 11 testing subjects, with more than one thousand annotated mitotic figures by multiple observers. Short descriptions and results from the evaluation of eleven methods are presented. The top performing method has an error rate that is comparable to the inter-observer agreement among pathologists

Measurement of unique magnetic and superconducting phases in oxygen-doped high-temperature superconductors La_2-xSr_xCuO_4+y

We present a combined magnetic neutron scattering and muon spin rotation study of the nature of the magnetic and superconducting phases in electronically phase separated La(2-x)Sr(x)CuO(4+y), x = 0.04, 065, 0.09. For all samples, we find long-range modulated magnetic order below T_N ~ T_c = 39 K. In sharp contrast wit oxygen-stoichiometric La(2-x)Sr(x)CuO(4), we find that the magnetic propagation vector as well as the ordered magnetic moment is independent of Sr content and consistent with that of the 'striped' cuprates. Our study provides direct proof that superoxygenation in La(2-x)Sr(x)CuO(4+y) allows the spin stripe ordered phase to emerge and phase separate from superconducting regions with the hallmarks of optimally doped oxygen-stoichiometric La(2-x)Sr(x)CuO(4)

The politicisation of evaluation: constructing and contesting EU policy performance

Although systematic policy evaluation has been conducted for decades and has been growing strongly within the European Union (EU) institutions and in the member states, it remains largely underexplored in political science literatures. Extant work in political science and public policy typically focuses on elements such as agenda setting, policy shaping, decision making, or implementation rather than evaluation. Although individual pieces of research on evaluation in the EU have started to emerge, most often regarding policy “effectiveness” (one criterion among many in evaluation), a more structured approach is currently missing. This special issue aims to address this gap in political science by focusing on four key focal points: evaluation institutions (including rules and cultures), evaluation actors and interests (including competencies, power, roles and tasks), evaluation design (including research methods and theories, and their impact on policy design and legislation), and finally, evaluation purpose and use (including the relationships between discourse and scientific evidence, political attitudes and strategic use). The special issue considers how each of these elements contributes to an evolving governance system in the EU, where evaluation is playing an increasingly important role in decision making

A mouse model of the schizophrenia-associated 1q21.1 microdeletion syndrome exhibits altered mesolimbic dopamine transmission

Abstract 1q21.1 hemizygous microdeletion is a copy number variant leading to eightfold increased risk of schizophrenia. In order to investigate biological alterations induced by this microdeletion, we generated a novel mouse model (Df(h1q21)/+) and characterized it in a broad test battery focusing on schizophrenia-related assays. Df(h1q21)/+ mice displayed increased hyperactivity in response to amphetamine challenge and increased sensitivity to the disruptive effects of amphetamine and phencyclidine hydrochloride (PCP) on prepulse inhibition. Probing of the direct dopamine (DA) pathway using the DA D1 receptor agonist SKF-81297 revealed no differences in induced locomotor activity compared to wild-type mice, but Df(h1q21)/+ mice showed increased sensitivity to the DA D2 receptor agonist quinpirole and the D1/D2 agonist apomorphine. Electrophysiological characterization of DA neuron firing in the ventral tegmental area revealed more spontaneously active DA neurons and increased firing variability in Df(h1q21)/+ mice, and decreased feedback reduction of DA neuron firing in response to amphetamine. In a range of other assays, Df(h1q21)/+ mice showed no difference from wild-type mice: gross brain morphology and basic functions such as reflexes, ASR, thermal pain sensitivity, and motor performance were unaltered. Similarly, anxiety related measures, baseline prepulse inhibition, and seizure threshold were unaltered. In addition to the central nervous system-related phenotypes, Df(h1q21)/+ mice exhibited reduced head-to tail length, which is reminiscent of the short stature reported in humans with 1q21.1 deletion. With aspects of both construct and face validity, the Df(h1q21)/+ model may be used to gain insight into schizophrenia-relevant alterations in dopaminergic transmission

Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases

Although these conditions are rare, a proportion of patients with interstitial lung diseases (ILDs) may develop a progressive-fibrosing phenotype. Progressive fibrosis is associated with worsening respiratory symptoms, lung function decline, limited response to immunomodulatory therapies, decreased quality of life and, potentially, early death. Idiopathic pulmonary fibrosis may be regarded as a model for other progressive-fibrosing ILDs. Here we focus on other ILDs that may present a progressive-fibrosing phenotype, namely idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, connective tissue disease-associated ILDs (e.g. rheumatoid arthritis-related ILD), fibrotic chronic hypersensitivity pneumonitis, fibrotic chronic sarcoidosis and ILDs related to other occupational exposures. Differential diagnosis of these ILDs can be challenging, and requires detailed consideration of clinical, radiological and histopathological features. Accurate and early diagnosis is crucial to ensure that patients are treated optimally