Swirling granular solidlike clusters

Experiments and three-dimensional numerical simulations are presented to elucidate the dynamics of granular material in a cylindrical dish driven by a horizontal, periodic motion. The following phenomena are obtained both in the experiments and in the simulations: First, for large particle numbers N the particles describe hypocycloidal trajectories. In this state the particles are embedded in a solidlike cluster ("pancake") which counter-rotates with respect to the external driving (reptation). Self-organization within the cluster occurs such that the probability distribution of the particles consists of concentric rings. Second, the system undergoes phase transitions. These can be identified by changes of the quantity dE(kin)/dN (E(kin) is the mean kinetic energy) between zero (rotation), positive (reptation), and negative values (appearance of the totality of concentric rings).

Activation of astroglial phospholipase D activity by phorbol ester involves ARF and Rho proteins.

Primary cultures of rat cortical astrocytes express phospholipase D (PLD) isoforms 1 and 2 as determined by RT-PCR and Western blot. Basal PLD activity was strongly (10-fold) increased by 4beta-phorbol-12beta,13alpha-dibutyrate (PDB) (EC(50): 56 nM), an effect which was inhibited by Ro 31-8220 (0.1-1 microM), an inhibitor of protein kinase C (PKC), and by brefeldin A (10-100 microg/ml), an inhibitor of ADP-ribosylating factor (ARF) activation. Pretreatment of the cultures with Clostridium difficile toxin B-10463 (0.1-1 ng/ml), which inactivates small G proteins of the Rho family, led to a breakdown of the astroglial cytoskeleton; concomitantly, PLD activation by PDB was reduced by up to 50%. In contrast, inactivation of proteins of the Ras family by Clostridium sordellii lethal toxin 1522 did not affect PLD activation. In parallel experiments, serum-induced PLD activation was sensitive to brefeldin A, but not to Ro 31-8220 and not to clostridial toxins. We conclude that, in astrocytes, the PLD isoform which is activated by phorbol ester requires PKC, ARF and Rho proteins for full activity and probably represents PLD1.

Inhibition of astroglial cell proliferation by alcohols: interference with the protein kinase C-phospholipase D signaling pathway.

Ethanol inhibits astroglial cell proliferation, an effect that may contribute to the development of alcoholic embryopathy in humans. In the present study, we investigated inhibitory effects of ethanol and butanol isomers (1-, 2- and t-butanol) on astroglial cell proliferation induced by the strongly mitogenic phorbol ester, 4beta-phorbol-12alpha,13beta-dibutyrate (PDB). 4beta-Phorbol-12alpha,13beta-dibutyrate (PDB) induced a 10-fold increase of [3H] thymidine incorporation in cortical astrocytes prepared from newborn rats (EC50: 70 nM) which was blocked by Ro 31-8220, a cell-permeable protein kinase C (PKC) inhibitor. Ethanol blocked PDB-induced astroglial proliferation in a concentration-dependent manner; significant effects were already seen at 0.1% (v/v). Concomitantly, ethanol caused the formation of phosphatidylethanol (PEth) by phospholipase D (PLD) and reduced PLD-mediated formation of phosphatidic acid (PA). The butanols also inhibited the mitogenic action of phorbol ester; the inhibitory potency of the butanols was 1-butanol > 2-butanol > t-butanol. The same range of potencies was observed for the inhibitory activity of the butanols towards protein kinase C activity measured in vitro. At 0.3% concentration, 1-butanol potently suppressed the PDB-induced formation of phosphatidic acid while 2- and t-butanol were less active. Taken together, our results suggest that ethanol and 1-butanol exert a specific inhibitory effect on PKC-dependent astroglial cell proliferation by synergistically inhibiting PKC activity and the PLD signaling pathway.

Ethanol inhibits astroglial cell proliferation by disruption of phospholipase D-mediated signaling.

The activation of phospholipase D (PLD) is a common response to mitogenic stimuli in various cell types. As PLD-mediated signaling is known to be disrupted in the presence of ethanol, we tested whether PLD is involved in the ethanol-induced inhibition of cell proliferation in rat cortical primary astrocytes. Readdition of fetal calf serum (FCS) to serum-deprived astroglial cultures caused a rapid, threefold increase of PLD activity and a strong mitogenic response; both effects were dependent on tyrosine kinases but not on protein kinase C. Ethanol (0.1-2%) suppressed the FCS-induced, PLD-mediated formation of phosphatidic acid (PA) as well as astroglial cell proliferation in a concentration-dependent manner. Moreover, exogenous bacterial PLD increased astroglial proliferation in an ethanol-sensitive manner, whereas exogenous PA or lysophosphatidic acid was less effective. Formation of PA and astroglial proliferation were strongly inhibited by 1-butanol (0.1-1%), a substrate of PLD, but were unaffected by t-butanol, a non-substrate; 2-butanol had intermediate effects. Platelet-derived growth factor and endothelin-1 mimicked the mitogenic effect of FCS; their effects were also inhibited by the butanols in the potency order 1-butanol > 2-butanol > tert-butanol. Our results, in particular, the differential effects of 1-, 2-, and tert-butanol with respect to PA formation and astroglial proliferation, strongly suggest that the antiproliferative effects of ethanol in glial cells are due to the disruption of the PLD signaling pathway. This mechanism may also contribute to the inhibition of astroglial growth and brain development observed in alcoholic embryopathy.

Adrenergic modulation of astroglial phospholipase D activity and cell proliferation.

As phospholipase D (PLD) activation has been associated with mitogenic signalling in several cell types, we tested an association between adrenergic activation of PLD and cellular proliferation in primary cultures of rat cortical astrocytes. In 2-week old cultures, PLD activation by noradrenaline (EC50: 0.49 microM) was inhibited by prazosin, a specific antagonist at alpha1-adrenergic receptors (IC50: 0.23 microM). Adrenergic PLD activation was not affected by genistein, an inhibitor of tyrosine kinases, or by Ro 31-8220, an inhibitor of protein kinase C (PKC), but was dose-dependently depressed in the presence of brefeldin A (1-100 microg/ml), an inhibitor of ARF activation. In experiments measuring cell proliferation, noradrenaline potently (EC50: 20 nM) reduced [3H]thymidine incorporation to 20-30% of basal values. This action was mimicked by the beta-specific agonist isoprenaline and was inhibited by the beta-antagonist propranolol in a concentration-dependent manner. The alpha1-adrenergic agonists, phenylephrine and methoxamine, also reduced DNA synthesis. The adrenergic inhibition of astroglial DNA synthesis was not reduced, but further potentiated in the presence of brefeldin A, ethanol, and 1- and 2-butanol; 1-butanol, a substrate of PLD, was equally effective as 2-butanol, a non-substrate. We conclude that adrenergic PLD activation in astrocytes is not involved in mitogenic signalling. The involvement of ARF in the activation of PLD via alpha1-adrenoceptors indicates a role in protein trafficking.

Shell structures with "magic numbers" of spheres in a swirled dish.

Molecular dynamic simulations of a low number N< or = 54 of spheres in a swirled dish yield solid-like shell structures with stable rings. In contrast to known granular media, solidification occurs only at singular values of N: 7, 8, 12, 14, 19, 21, 30, 37, 40. Otherwise, we obtain intermittent switching of particles between rings -- the average switching time scaling exponentially with a control parameter -- or fluid-like disorder. Stable shell structures can be classified by particular geometrical arrangements (one-centered hexagonal, one-centered "quasicircular," three centered, and four centered).

[Bellows or bag? Testing 10 ventilators and some medical history comments]. / Balg oder Beutel? Zehn Handbeatmungsgeräte im Test und einige medizinhistorische Bemerkungen.

We compared a new bellows ventilator (Kendall Cardiovent) with two other bellows (Dräger Resutator 63, Tagg Breathsaver) and seven bag or ball ventilators (Aerodyne Hope, Ambu Mark 3, Ambu Silicon, Dräger Resutator 2000, Laerdal Resu, Mercury CPR, Weinmann Combibag). Tidal volumes were measured with two Laerdal Recording Resusci Annies, one lying on the floor, one in a bed. Twelve participants performed mask ventilation with all ten devices on both manikins for two minutes, trying to achieve tidal volumes of between 0.8 and 1.21 as recommended by the AHA. The last ten ventilations each on the graphic strips were analysed for volume. The participants scored handling of the devices on a 6-point scale (1 = very good, 6 = insufficient). The results of the Cardiovent were compared to those of the other devices by rank sum test (percentage of correct ventilations) and sign test (subjective handling). The Cardiovent provided exact ventilation with 95% of ventilations) on the floor and 78% of ventilations in bed in the recommended range. However, the percentage of correct ventilations with the Cardiovent was not significantly different to the other devices except for a lower percentage of correct ventilations with the Combibag in the in bed setting. Concerning subjective handling, the Cardiovent was significantly superior to several ball ventilators.

[Neurologic symptoms in acute thoracic aortic dissection--a case report]. / Neurologische Symptome bei akuter thorakaler Aortendissektion--ein Fallbericht.

Acute thoracic aortic dissection is a life-threatening illness. It is often difficult to diagnose preclinically due to its many possible symptoms. One out of three patients has neurological deficits. The prognosis depends on rapid diagnosis and immediate adequate therapy. Therefore, every emergency physician should know the signs and risk factors of this disease. The most important goals of prehospital therapy are management of pain and anxiety and pharmacological control of the systolic blood pressure and heart rate. We report on a 46-year-old female patient who developed neurological deficits caused by an acute thoracic aortic dissection.

[The mutagenicity of surface water, waste water and drinking water in the Rhine-Neckar region in the Salmonella microsome test (Ames Test)]. / Zur Mutagenität von Oberflächenwasser, Abwasser und Trinkwasser des Rhein-Neckar-Raums im Salmonella-Mikrosomen-Test (Ames-Test).

We have shown recently that the quality of surface water in urban and industrialized regions is of dubious hygienic. Therefore, in further studies we examined 46 water samples between October and November 1986 from the Rhine-river and its tributaries between km 400 and 440 using the Salmonella mutagenicity test (Ames-test). Additionally, we examined 8 samples from the waterworks of Mannheim and 4 samples from a lake in the Mannheim area. Each of our 464 samples was examined using Salmonella strains TA 97, TA 98, TA 100 and TA 102 with and without Aroclor-1254-induced S9-fraction from rat liver. 9.7% of the water samples showed mutagenic effects in the Ames test, the majority (70%) with low activity. High mutagenic effects were found in the waste water of the purification plants of Mannheim and Ludwigshafen and of some small but very highly contaminated brooks (Kraichbach, Leimbach). Two out of 8 untreated water samples of the waterworks of Mannheim showed mutagenic effects in the undiluted water following metabolic activation. We never found mutagenic effects in all samples taken from the same site. The Ames-test is a useful screening procedure for the determination of mutagenic or cancerogenic effects of environmental contaminants. It allows an evaluation of mixtures of anthropogenically polluted environmental samples for potentially genotoxic effects. Our results show that our water resources pose ecological hazards. This should be prevented by a better control of the industrial and communal waste water before it is allowed to flow into the river.

Alternative processing during development of a macronuclear chromosome family in Oxytricha fallax.

Macronuclear chromosomes in Oxytricha fallax, a hypotrichous ciliate, are very short. They often belong to small families of cross-hybridizing chromosomes of two or three different sizes. For example, the 81-MAC family consists of three sizes of macronuclear chromosomes (4.9, 2.9, and 1.6 kbp) (Cartinhour and Herrick 1984). We show that the family actually consists of two closely related sets of three each and that the two sets are independently created by alternative processing of two separate precursor (micronuclear) versions. Chromosomes of a set share a common 1.6-kbp region, which contains a transcribed gene coding for a 25-kD protein. Different-sized macronuclear chromosomes of a set result from alternative choices of positions for telomere formation. All six members of the family are reproducibly generated in each developing macronucleus, and their copy numbers are stably maintained during vegetative replication of the macronucleus (Herrick et al. 1987). Here we argue for the existence of three distinct copy control elements in the 81-MAC family chromosomes. A model is discussed in which, following polytenization of the micronuclear chromosomes, different chromatids are processed differently, and, subsequently, replication-competent macronuclear chromosome products are amplified under the influence of the vegetative copy control elements.

Multiple sequence versions of the Oxytricha fallax 81-MAC alternate processing family.

The 81-MAC family consists of three sizes of macronuclear chromosomes in Oxytricha fallax. Clones of these and of micronuclear homologs have been classified according to DNA sequence into three highly homologous (95.9-97.9%), but distinct versions. Version A is represented by a micronuclear clone and by clones of two different-sized macronuclear chromosomes, showing that alternate processing of micronuclear DNA is responsible for the variety of sizes of macronuclear chromosomes. Three Internal Eliminated Sequences (IES's) are demonstrated in Version A micronuclear DNA. Two have been sequenced and show short, flanking direct repeats but no inverted terminal repeats. Version C micronuclear DNA has interruptions in the macronuclear homology which correspond closely to the Version A IES's. Whether they are true IES's is unknown because no Version C macronuclear DNA has been demonstrated. Version C micronuclear DNA may be "macronuclear-homologous" but "micronucleus-limited" and not "macronucleus-destined." Version B is represented by macronuclear DNA clones, but no micronuclear clones. Vegetative micronuclear aneuploidy is suggested. The possible role of micronuclear defects in somatic karyonidal senescence is discussed in light of the precise macronuclear chromosome copy controls demonstrated within the 81-MAC family. These controls apparently operate throughout karyonidal life to maintain 1) a constant absolute amount of 81-MAC sequences in the macronucleus and 2) a constant stoichiometry within the family, both according to version and chromosome size.