1,537 research outputs found
The c- Jun N-terminal kinase JNK participates in cytokine- and isolation stress-induced rat pancreatic islet apoptosis
Aims/hypothesis: The protocols used for the preparation of human pancreatic islets immediately induce a sustained and massive activation of the c-Jun-N-terminal kinase (JNK). JNK, which participates in apoptosis of insulin-secreting cells, is activated by mechanical stresses, as well as by exposure to pro-inflammatory cytokines. Here, we investigated whether the delivery of a protease-resistant JNK inhibitory peptide (D-JNKI) through a protein transduction system during pancreatic digestion might impair JNK signalling throughout the transplantation procedure. Methods: Rat pancreases were treated with D-JNKI through the pancreatic duct and cells then isolated by enzymatic digestion. Protein extracts were prepared to determine JNK activity by kinase assays and total RNA was extracted to measure gene expressions by a Light-Cycler technique. Cell apoptosis rate was determined by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and by scoring cells displaying pycnotic nuclei. Results: Our data establish that the peptide transduction system used here efficiently transfects islets, allowing for stable in vivo (up to 2days) transfection of human islets transplanted under the kidney capsule. Further, D-JNKI decreases intracellular JNK signalling during isolation and following cytokine exposure in both human and rat islets, as measured by kinase assays and reduced c-fos expression; D-JNKI also confers protection against apoptosis induced during the rat islet preparation and subsequent to IL-1β exposure. Conclusions/interpretation: JNK signalling participates in islet isolation- and IL-1β-induced apoptosis in rat islets. Furthermore, the system we used might be more generally applicable for the persistent blockage (several days) of pro-apoptotic pathways in the transplanted islets; this days-long protection might potentially be an absolute prerequisite to help transplanted islets better survive the first wave of the non-specific inflammatory attac
Block-Transitive Designs in Affine Spaces
This paper deals with block-transitive - designs in affine
spaces for large , with a focus on the important index case. We
prove that there are no non-trivial 5- designs admitting a
block-transitive group of automorphisms that is of affine type. Moreover, we
show that the corresponding non-existence result holds for 4- designs,
except possibly when the group is one-dimensional affine. Our approach involves
a consideration of the finite 2-homogeneous affine permutation groups.Comment: 10 pages; to appear in: "Designs, Codes and Cryptography
Analytical pre-test support of boil-down test QUENCH-11
Analytische Unterstützung zur Vorbereitung des Ausdampf-Versuchs QUENCH-11
Im QUENCH-Vorhaben des Forschungszentrums Karlsruhe soll das Fluten eines teilweise zerstörten Kerns untersucht werden. Der zweite LACOMERA Versuch Q-L2 (QUENCH-11) beginnt mit einer Ausdampfphase des Bündels, bis der Wasserspiegel das untere Bündel¬ende erreicht hat. Ein derartiger Versuch wurde bislang noch nicht in der QUENCH-Anlage durchgeführt, so dass mit SCDAP/RELAP5 mod3.2.irs eine Machbarkeitsstudie erforderlich war. Die Ergebnisse zeigen, dass eine Zusatzheizung im unteren Plenum notwendig ist, um den Wasserstand und die Verdampfungsrate (Dampfmassenstrom in der Ausdampfphase) unabhängig von der angestrebten Maximaltemperatur im Bündel zu regeln. Für eine verläss¬liche Versuchsplanung sowie zur Erstellung der Energiebilanz muss die Zusatzheizung in¬nerhalb des unteren Plenums unterhalb der Wasseroberfläche installiert werden, damit die Heizleistung vollständig in das Wasser eingekoppelt wird. Um die Verdampfungsrate über längere Zeit aufrecht zu erhalten, muss zusätzlich Wasser in das untere Plenum eingespeist werden.
Anhand dieser Rechnungen wird der Testablauf im Detail diskutiert. Eine entsprechende Studie zeigte die Durchführbarkeit eines solchen Ausdampftests und war die Grundlage für die oben erwähnten Änderungen in der Anlage und der Versuchs-Durchführung gegenüber früheren Tests. Eine Reihe von Vorversuche wurde durchgeführt, um die Brauchbarkeit der Änderungen an der Anlage und der geplanten Versuchsführung zu prüfen und um Daten für das thermohydraulische Verhalten der Anlage zu bekommen, an denen die Code-Modelle für die Voraus- und Nachrechnungen von QUENCH-11 getestet werden können. Im Anschluss an die Vorversuche wurden wie bei früheren QUENCH-Tests detaillierte Vorausrechnungen mit verschiedenen Codes zu Versuchsablauf und -steuerung durchgeführt. Drei Forschungs¬einrichtungen in der EU waren beteiligt. Die berechneten Ergebnisse reagieren empfindlich auf Änderungen der Versuchsparameter wie das anfängliche axiale Temperaturprofil und die eingespeiste elektrische Leistung, wie es auch für die untersuchten physikalischen Bedin¬gungen im Versuch erwartet werden kann
Origins and composition of fine atmospheric carbonaceous aerosol in the Sierra Nevada Mountains, California
In this paper we report chemically resolved measurements
of organic aerosol (OA) and related tracers during the Biosphere Effects on Aerosols and Photochemistry Experiment (BEARPEX) at the Blodgett Forest Research Station, California from 15 August–10 October 2007. OA contributed the majority of the mass to the fine atmospheric particles and was predominately oxygenated (OOA). The highest concentrations of OA were during sporadic wildfire influence when aged plumes were impacting the site. In
situ measurements of particle phase molecular markers were dominated by secondary compounds and along with gas phase compounds could be categorized into six factors or sources: (1) aged biomass burning emissions and oxidized urban emissions, (2) oxidized urban emissions (3) oxidation products of monoterpene emissions, (4) monoterpene emissions, (5) anthropogenic emissions and (6) local
methyl chavicol emissions and oxidation products. There were multiple biogenic components that contributed to OA at this site whose contributions varied diurnally, seasonally and in response to changing meteorological conditions, e.g. temperature and precipitation events. Concentrations of isoprene oxidation products were larger when temperatures were higher during the first half of the campaign (15 August–12 September) due to more substantial emissions of isoprene and enhanced photochemistry. The oxidation of methyl chavicol, an oxygenated terpene emitted by
ponderosa pine trees, contributed similarly to OA throughout the campaign. In contrast, the abundances of monoterpene oxidation products in the particle phase were greater during the cooler conditions in the latter half of the campaign (13 September–10 October), even though emissions of the precursors were lower, although the mechanism is not known. OA was correlated with the anthropogenic tracers 2-propyl nitrate and carbon monoxide (CO), consistent with previous observations, while being comprised of mostly non-fossil carbon (>75%). The correlation between OA and an anthropogenic tracer does not necessarily identify the source of the carbon as being anthropogenic but instead suggests a coupling between the anthropogenic and biogenic components in the air mass that might be related to the source of the oxidant and/or the aerosol sulfate. Observations of organosulfates of isoprene and α-pinene provided evidence for the likely importance of aerosol sulfate in spite of neutralized aerosol although acidic plumes might have played a role upwind of the site. This is in contrast to laboratory studies where strongly acidic seed aerosols were needed in order to form these compounds. These compounds together represented only a minor fraction (<1%) of the total OA mass, which may be the result of the neutralized aerosol at the site or because only a small number of organosulfates were quantified. The low contribution of organosulfates to total OA suggests that other mechanisms, e.g. NO_x enhancement of oxidant levels, are likely responsible for the majority of the anthropogenic enhancement of biogenic secondary organic aerosol observed at this site
The influence of chemical composition and mixing state of Los Angeles urban aerosol on CCN number and cloud properties
International audienceThe relationship between cloud condensation nuclei (CCN) number and the physical and chemical properties of the atmospheric aerosol distribution is explored for a polluted urban data set from the Study of Organic Aerosols at Riverside I (SOAR-1) campaign conducted at Riverside, California, USA during summer 2005. The mixing state and, to a lesser degree, the average chemical composition are shown to be important parameters in determining the activation properties of those particles around the critical activation diameters for atmospherically-realistic supersaturation values. Closure between predictions and measurements of CCN number at several supersaturations is attempted by modeling a number of aerosol chemical composition and mixing state schemes of increasing complexity. It is shown that a realistic treatment of the state of mixing of the urban aerosol distribution is critical in order to eliminate model bias. Fresh emissions such as elemental carbon and small organic particles must be treated as non-activating and explicitly accounted for in the model scheme. The relative number concentration of these particles compared to inorganics and oxygenated organic compounds of limited hygroscopicity plays an important role in determining the CCN number. Furthermore, expanding the different composition/mixing state schemes to predictions of cloud droplet number concentration in a cloud parcel model highlights the dependence of cloud optical properties on the state of mixing and hygroscopic properties of the different aerosol modes, but shows that the relative differences between the different schemes are reduced compared to those from the CCN model
Major components of atmospheric organic aerosol in southern California as determined by hourly measurements of source marker compounds
We report the first hourly in-situ measurements of speciated organic aerosol
(OA) composition in an urban environment. Field measurements were made in
southern California at the University of California–Riverside during the
2005 Study of Organic Aerosol at Riverside (SOAR), which included two
separate measurement periods: a summer study (15 July–15 August) and a
fall study (31 October–28 November). Hourly measurements of over 300
semivolatile and nonvolatile organic compounds were made using the thermal
desorption aerosol gas chromatograph (TAG). Positive matrix factorization
(PMF) was performed on a subset of these compounds to identify major
components contributing to submicron (i.e., PM<sub>1</sub>) OA at the site, as
measured by an aerosol mass spectrometer (AMS). PMF analysis was performed
on an 11-day focus period in each season, representing average seasonal
conditions during the summer and a period of urban influence during the
fall. As a result of this analysis, we identify multiple types of primary
and secondary OA (POA and SOA). Secondary sources contribute substantially
to fine OA mass at Riverside, which commonly receives regional air masses
that pass through metropolitan Los Angeles during the summer. Four
individual summertime SOA components are defined, and when combined, they
are estimated to contribute an average 88% of the total fine OA mass
during summer afternoons according to PMF results. These sources appear to
be mostly from the oxidation of anthropogenic precursor gases, with one SOA
component having contributions from oxygenated biogenics. During the fall,
three out of four aerosol components that contain SOA are inseparable from
covarying primary emissions, and therefore we cannot estimate the fraction
of total OA that is secondary in nature during the fall study. Identified
primary OA components are attributed to vehicle emissions, food cooking,
primary biogenics, and biomass burning aerosol. While a distinction between
local and regional vehicle emissions is made, a combination of these two
factors accounted for approximately 11% of observed submicron OA during
both sampling periods. Food cooking operations contributed ~10% of
submicron OA mass during the summer, but was not separable from SOA during
the fall due to high covariance of sources. Biomass burning aerosol
contributed a larger fraction of fine OA mass during the fall (~11%) than compared to summer (~7%). Primary biogenic aerosol
was also identified during the summer, contributing ~1% of the OA,
but not during the fall. While the contribution of both local and regional
primary vehicle OA accounts for only ~11% of total OA during both
seasons, gas-phase vehicle emissions likely create a substantial fraction of
the observed SOA as a result of atmospheric processing
The c-Jun N-terminal kinase JNK participates in cytokine- and isolation stress-induced rat pancreatic islet apoptosis
AIMS/HYPOTHESIS: The protocols used for the preparation of human pancreatic islets immediately induce a sustained and massive activation of the c-Jun-N-terminal kinase (JNK). JNK, which participates in apoptosis of insulin-secreting cells, is activated by mechanical stresses, as well as by exposure to pro-inflammatory cytokines. Here, we investigated whether the delivery of a protease-resistant JNK inhibitory peptide (D-JNKI) through a protein transduction system during pancreatic digestion might impair JNK signalling throughout the transplantation procedure. METHODS: Rat pancreases were treated with D-JNKI through the pancreatic duct and cells then isolated by enzymatic digestion. Protein extracts were prepared to determine JNK activity by kinase assays and total RNA was extracted to measure gene expressions by a Light-Cycler technique. Cell apoptosis rate was determined by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and by scoring cells displaying pycnotic nuclei. RESULTS: Our data establish that the peptide transduction system used here efficiently transfects islets, allowing for stable in vivo (up to 2 days) transfection of human islets transplanted under the kidney capsule. Further, D-JNKI decreases intracellular JNK signalling during isolation and following cytokine exposure in both human and rat islets, as measured by kinase assays and reduced c-fos expression; D-JNKI also confers protection against apoptosis induced during the rat islet preparation and subsequent to IL-1beta exposure. CONCLUSIONS/INTERPRETATION: JNK signalling participates in islet isolation- and IL-1beta-induced apoptosis in rat islets. Furthermore, the system we used might be more generally applicable for the persistent blockage (several days) of pro-apoptotic pathways in the transplanted islets; this days-long protection might potentially be an absolute prerequisite to help transplanted islets better survive the first wave of the non-specific inflammatory attack
- …