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Plateau bursting is typical of many electrically excitable cells, such as endocrine cells that secrete hormones and some types of neurons that secrete neurotransmitters. Although in many of these cell types the bursting patterns are regulated by the interplay between voltage-gated calcium channels and calcium-sensitive potassium channels, they can be very different. For example, in insulin-secreting pancreatic β-cells, plateau bursting is characterized by well-defined spikes during the depolarized phase whereas in pituitary cells, bursting features fast, irregular, small amplitude spikes. The latter has been termed “pseudo-plateau bursting” because the spikes are transients around a depolarized steady state rather than stable oscillations in the fast subsystem. In this study we systematically investigate the bursting patterns found in endocrine cell models. We show that this class of voltage and calcium gated conductance based models can be reduced to the polynomial model of Hindmarsh and Rose (25). This reduction preserves the main properties of the biophysical class of models that we consider and allows for detailed bifurcation analysis of the full fast-slow system. Our analysis does not require decomposition of the full system into fast and slow subsystems and reveals properties of endocrine bursting that are not captured by the standard fast-slow analysis.

Subject of this work is a dynamic simulation strategy for PCCI combustion that can be used in closed-loop control development. A detailed multi-zone chemistry model for the high-pressure part of the engine cycle is extended by a mean value model accounting for the gas exchange losses. The resulting stationary model is capable of describing PCCI combustion sufficiently well. It is at the same time very economic with respect to computational costs. The model is further extended by identified system dynamics influencing the stationary inputs. For this, a Wiener model is set up that uses the stationary model as a nonlinear system representation. In this way, a dynamic nonlinear model for the representation of the controlled plant Diesel engine is created. This paper summarizes an important outcome of the the Collaborative Research Centre "SFB 686 - Modellbasierte Regelung der homogenisierten Niedertemperatur-Verbrennung" at RWTH Aachen University and Bielefeld University, Germany.

International audience; The influence of surface-bound Fe(II) on uranium oxidation state and speciation was studied as a function of time (6 min−72 h) and pH (6.1−8.5) in a U(VI)−Fe(II)-montmorillonite (Ca-montmorillonite, MONT) system under CO2-free, anoxic (O2 <1 ppmv) conditions. The results show a rapid removal of U(VI) from the aqueous solution within 1 h under all pH conditions. U LIII-edge X-ray absorption near-edge structure spectroscopy shows that 96% of the total sorbed U(VI) is reduced at pH 8.5. However, the extent of reduction significantly decreases at lower pH values as specifically sorbed Fe(II) concentration decreases. The reduction kinetics followed by X-ray photoelectron spectroscopy during 24 h at pH 7.5 demonstrates the presence of partially reduced surface species containing U(VI) and U(IV). Thermodynamically predicted mixed valence solids like U3O8/β-U3O7/U4O9 do not precipitate as verified by transmission electron microscopy and extended X-ray absorption fine-structure spectroscopy. This is also supported by the bicarbonate extraction results. The measured redox potentials of Fe(II)/Fe(III)−MONT suspensions are controlled by the Fe(II)/hydrous ferric oxide [HFO(s)] couple at pH 6.2 and by the Fe(II)/lepidocrocite [γ-FeOOH(s)] couple at pH 7.5. The key finding of our study is the formation of a sorbed molecular form of U(IV) in abiotic reduction of U(VI) by sorbed Fe(II) at the surface of montmorillonite.

Abstract Organisms evolve in response to their natural environment. Consideration of natural ecological parameters are thus of key importance for our understanding of an organism’s biology. Curiously, the natural ecology of the model species Caenorhabditis elegans has long been neglected, even though this nematode has become one of the most intensively studied models in biological research. This lack of interest changed ∼10 yr ago. Since then, an increasing number of studies have focused on the nematode’s natural ecology. Yet many unknowns still remain. Here, we provide an overview of the currently available information on the natural environment of C. elegans. We focus on the biotic environment, which is usually less predictable and thus can create high selective constraints that are likely to have had a strong impact on C. elegans evolution. This nematode is particularly abundant in microbe-rich environments, especially rotting plant matter such as decomposing fruits and stems. In this environment, it is part of a complex interaction network, which is particularly shaped by a species-rich microbial community. These microbes can be food, part of a beneficial gut microbiome, parasites and pathogens, and possibly competitors. C. elegans is additionally confronted with predators; it interacts with vector organisms that facilitate dispersal to new habitats, and also with competitors for similar food environments, including competitors from congeneric and also the same species. Full appreciation of this nematode’s biology warrants further exploration of its natural environment and subsequent integration of this information into the well-established laboratory-based research approaches.

We previously demonstrated that the transcription factor Pax4 is important for beta-cell replication and survival in rat islets. Herein, we investigate Pax4 expression in islets of non-diabetic and diabetic donors, its regulation by mitogens, glucose and the incretin GLP-1 and evaluate its effect on human islet proliferation. Pax4 expression was increased in islets derived from Type 2 diabetic donors correlating with hyperglycaemia. In vitro studies on non diabetic islets demonstrated that glucose, betacellulin, activin A, GLP-1 and insulin increased Pax4 mRNA levels. Glucose-induced Pax4 expression was abolished by the inhibitors LY294002, PD98050 or H89. Surprisingly, increases in Pax4 expression did not prompt a surge in human islet cell replication. Furthermore, expression of the proliferation marker gene Id2 remained unaltered. Adenoviral-mediated expression of human Pax4 resulted in a small increase in Bcl-xL expression while Id2 transcript levels and cell replication were unchanged in human islets. In contrast, overexpression of mouse Pax4 induced human islet cell proliferation. Treatment of islets with 5-Aza-2'-deoxycytidine induced Pax4 without stimulating Bcl-xL and Id2 expression. Human Pax4 DNA binding activity was found to be lower than that of the mouse homologue. Thus, human pax4 gene expression is epigenetically regulated and induced by physiological stimuli through the concerted action of multiple signalling pathways. However, it is unable to initiate the transcriptional replication program likely due to post-translational modifications of the protein. The latter highlights fundamental differences between human and rodent islet physiology and emphasizes the importance of validating results obtained with animal models in human tissues.

The dayside high-latitude trough is a persistent feature of the post-noon wintertime auroral ionosphere. Radio tomography observations have been used to map its location and latitudinal structure under quiet geomagnetic conditions (<i>K_p</i>&le;2) near winter solstice. The trough is also a clear feature in the ion density distribution of the Coupled Thermosphere-Ionosphere-Plasmasphere model (CTIP) under similar geophysical conditions. Comparisons of the measured and modelled distributions show that the plasma production equatorward of the trough is mainly controlled by solar radiation, but there are also other processes maintaining the equatorward trough-wall that are open to debate. The poleward trough-wall is produced by particle precipitation, but the densities are significantly overestimated by the model. At the trough minimum the observed densities are consistent with low nighttime densities convecting sunward to displace the higher daytime densities, but this is not borne out by the CTIP model. The study shows the potential of combining radio tomography and modelling to interpret the balance of the physical processes responsible for large-scale structuring of the high-latitude ionosphere, and highlights the role of tomographic imaging in validating and developing physical models.

BACKGROUND: Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes and recombinants during 1990-2015. METHODS: We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published between Jan 1, 1990, and Dec 31, 2015. We collected additional unpublished HIV-1 subtyping data through a global survey. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. We grouped countries into 14 regions and analysed data for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV (PLHIV) in each country to generate regional and global estimates of HIV-1 diversity in each time period. The primary outcome was the number of samples designated as HIV-1 subtypes A, B, C, D, F, G, H, J, K, CRFs, and URFs. The systematic review is registered with PROSPERO, number CRD42017067164. FINDINGS: This systematic review and global survey yielded 2203 datasets with 383 519 samples from 116 countries in 1990-2015. Globally, subtype C accounted for 46·6% (16 280 897/34 921 639 of PLHIV) of all HIV-1 infections in 2010-15. Subtype B was responsible for 12·1% (4 235 299/34 921 639) of infections, followed by subtype A (10·3%; 3 587 003/34 921 639), CRF02_AG (7·7%; 2 705 110/34 921 639), CRF01_AE (5·3%; 1 840 982/34 921 639), subtype G (4·6%; 1 591 276/34 921 639), and subtype D (2·7%; 926 255/34 921 639). Subtypes F, H, J, and K combined accounted for 0·9% (311 332/34 921 639) of infections. Other CRFs accounted for 3·7% (1 309 082/34 921 639), bringing the proportion of all CRFs to 16·7% (5 844 113/34 921 639). URFs constituted 6·1% (2 134 405/34 921 639), resulting in recombinants accounting for 22·8% (7 978 517/34 921 639) of all global HIV-1 infections. The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally. At a global level during 2005-15, subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased. CRF01_AE, other CRFs, and URFs increased, leading to a consistent increase in the global proportion of recombinants over time. INTERPRETATION: Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines. FUNDING: None. ispartof: LANCET INFECTIOUS DISEASES vol:19 issue:2 pages:143-155 ispartof: location:United States status: published

International audience; Depleted CMOS active sensors (DMAPS) are being developed for high-energy particle physics experiments in high radiation environments, such as in the ATLAS High Luminosity Large Hadron Collider (HL-LHC). Since charge collection by drift is mandatory for harsh radiation environment, the application of high bias voltage to high resistive sensor material is needed. In this work, a prototype of a DMAPS was fabricated in a 150nm CMOS process on a substrate with a resistivity of >2 k{\Omega}cm that was thinned to 100 {\mu}m. Full depletion occurs around 20V, which is far below the breakdown voltage of 110 V. A readout chip has been attached for fast triggered readout. Presented prototype also uses a concept of sub-pixel en/decoding three pixels of the prototype chip are readout by one pixel of the readout chip. Since radiation tolerance is one of the largest concerns in DMAPS, the CCPD_LF chip has been irradiated with X-rays and neutrons up to a total ionization dose of 50 Mrad and a fluence of 10E15neq/cm2, respectively.

We report on an all-sky search for continuous gravitational waves in the frequency band 20-2000 Hz and with a frequency time derivative in the range of [-1.0,+0.1]×10-8 Hz/s. Such a signal could be produced by a nearby, spinning and slightly nonaxisymmetric isolated neutron star in our Galaxy. This search uses the LIGO data from the first six months of Advanced LIGO's and Advanced Virgo's third observational run, O3. No periodic gravitational wave signals are observed, and 95% confidence-level (C.L.) frequentist upper limits are placed on their strengths. The lowest upper limits on worst-case (linearly polarized) strain amplitude h0 are ∼1.7×10-25 near 200 Hz. For a circularly polarized source (most favorable orientation), the lowest upper limits are ∼6.3×10-26. These strict frequentist upper limits refer to all sky locations and the entire range of frequency derivative values. For a population-averaged ensemble of sky locations and stellar orientations, the lowest 95% C.L. upper limits on the strain amplitude are ∼1.4×10-25. These upper limits improve upon our previously published all-sky results, with the greatest improvement (factor of ∼2) seen at higher frequencies, in part because quantum squeezing has dramatically improved the detector noise level relative to the second observational run, O2. These limits are the most constraining to date over most of the parameter space searched. This work was supported by MEXT, JSPS Leading-edge Research Infrastructure Program, JSPS Grant-in-Aid for Specially Promoted Research 26000005, JSPS Grant-in-Aid for Scientific Research on Innovative Areas 2905: JP17H06358, JP17H06361 and JP17H06364, JSPS Core-to-Core Program A. Advanced Research Networks, JSPS Grant-in-Aid for Scientific Research (S) 17H06133, the joint research program of the Institute for Cosmic Ray Research, University of Tokyo, National Research Foundation (NRF) and Computing Infrastructure Project of KISTI-GSDC in Korea, Academia Sinica (AS), AS Grid Center (ASGC) and the Ministry of Science and Technology (MoST) in Taiwan under grants including ASCDA-105-M06, Advanced Technology Center (ATC) of NAOJ, and Mechanical Engineering Center of KEK Abbott, R. (LIGO Scientific Collaboration, Virgo Collaboration, KAGRA Collaboration)

Bats and birds are key providers of ecosystem services in forests. How climate and habitat jointly shape their communities is well studied, but whether biotic predictors from other trophic levels may improve bird and bat diversity models is less known, especially across large bioclimatic gradients. Here, we achieved multi-taxa surveys in 209 mature forests replicated in six European countries from Spain to Finland, to investigate the importance of biotic predictors (i.e. the abundance or activity of defoliating insects, spiders, earthworms and wild ungulates) for bat and bird taxonomic and functional diversity. We found that nine out of 12 bird and bat diversity metrics were best explained when biotic factors were added to models including climate and habitat variables, with a mean gain in explained variance of 38 for birds and 15 for bats. Tree functional diversity was the most important habitat predictor for birds, while bats responded more to understorey structure. The best biotic predictors for birds were spider abundance and defoliating insect activity, while only bat functional evenness responded positively to insect herbivory. Accounting for potential biotic interactions between bats, birds and other taxa of lower trophic levels will help to understand how environmental changes along large biogeographical gradients affect higher-level predator diversity in forest ecosystems. FunDiv EUROPE