2,217 research outputs found
The Weak-Coupling Limit of 3D Simplicial Quantum Gravity
We investigate the weak-coupling limit, kappa going to infinity, of 3D
simplicial gravity using Monte Carlo simulations and a Strong Coupling
Expansion. With a suitable modification of the measure we observe a transition
from a branched polymer to a crinkled phase. However, the intrinsic geometry of
the latter appears similar to that of non-generic branched polymer, probable
excluding the existence of a sensible continuum limit in this phase.Comment: 3 pages 4 figs. LATTICE99(Gravity
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
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
Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy.
The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not. We used this model to study the role of Ang II in trophoblast invasion, which is shallow in human PE but deeper in this model. We investigated the following groups: PE rats, opposite-cross rats, Ang II–infused rats (1000 ng/kg per day), and control rats. Ang II infusion increased only circulating Ang II levels (267.82 pg/mL), opposite cross influenced only uteroplacental Ang II (13.52 fmol/mg of protein), and PE increased both circulating (251.09 pg/mL) and uteroplacental (19.24 fmol/mg of protein) Ang II. Blood pressure and albuminuria occurred in the models with high circulating Ang II but not in the other models. Trophoblast invasion increased in PE and opposite-cross rats but not in Ang II–infused rats. Correspondingly, uterine artery resistance index increased in Ang II–infused rats but decreased in PE rats. We then studied human trophoblasts and villous explants from first-trimester pregnancies with time-lapse microscopy. Local Ang II dose-dependently increased migration by 75%, invasion by 58%, and motility by 282%. The data suggest that local tissue Ang II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function. Conceivably, upregulation of tissue Ang II in the maternal part of the placenta represents an important growth factor for trophoblast invasion and migration
The Weak-Coupling Limit of Simplicial Quantum Gravity
In the weak-coupling limit, kappa_0 going to infinity, the partition function
of simplicial quantum gravity is dominated by an ensemble of triangulations
with the ratio N_0/N_D close to the upper kinematic limit. For a combinatorial
triangulation of the D--sphere this limit is 1/D. Defining an ensemble of
maximal triangulations, i.e. triangulations that have the maximal possible
number of vertices for a given volume, we investigate the properties of this
ensemble in three dimensions using both Monte Carlo simulations and a
strong-coupling expansion of the partition function, both for pure simplicial
gravity and a with a suitable modified measure. For the latter we observe a
continuous phase transition to a crinkled phase and we investigate the fractal
properties of this phase.Comment: 32 pages, latex2e + 17 eps file
Signature of Electronic Correlations in the Optical Conductivity of the Doped Semiconductor Si:P
Electronic transport in highly doped but still insulating silicon at low
temperatures is dominated by hopping between localized states; it serves as a
model system of a disordered solid for which the electronic interaction can be
investigated. We have studied the frequency-dependent conductivity of
phosphorus-doped silicon in the THz frequency range (30 GHz to 3 THz) at low
temperatures K. The crossover in the optical conductivity from a
linear to a quadratic frequency dependence as predicted by Efros and Shklovskii
is observed qualitatively; however, the simple model does not lead to a
quantitative agreement. Covering a large range of donor concentration, our
temperature- and frequency-dependent investigations reveal that electronic
correlation effects between the localized states play an important and complex
role at low temperatures. In particular we find a super-linear frequency
dependence of the conductivity that highlights the influence of the density of
states, i.e. the Coulomb gap, on the optical conductivity. When approaching the
metal-to-insulator transition by increasing doping concentration, the
dielectric constant and the localization length exhibit critical behavior.Comment: 9 pages, 8 figures, 1 tabl
The Huntington's disease mutation impairs Huntingtin's role in the transport of NF-κB from the synapse to the nucleus
Expansion of a polyglutamine (polyQ) tract in the Huntingtin (Htt) protein causes Huntington's disease (HD), a fatal inherited neurodegenerative disorder. Loss of the normal function of Htt is thought to be an important pathogenetic component of HD. However, the function of wild-type Htt is not well defined. Htt is thought to be a multifunctional protein that plays distinct roles in several biological processes, including synaptic transmission, intracellular transport and neuronal transcription. Here, we show with biochemical and live cell imaging studies that wild-type Htt stimulates the transport of nuclear factor κ light-chain-enhancer of activated B cells (NF-κB) out of dendritic spines (where NF-κB is activated by excitatory synaptic input) and supports a high level of active NF-κB in neuronal nuclei (where NF-κB stimulates the transcription of target genes). We show that this novel function of Htt is impaired by the polyQ expansion and thus may contribute to the etiology of HD
Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.
There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease
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