Two-dimensional magnetized plasmas and geostrophic fluids exhibit a common nonlinearity due to the advection of vorticity. It is shown here that due to this nonlinearity, the propagation of small scale wave packets is accompanied by instability of a low frequency, long wavelength component. This instability is the coherent hydrodynamic generalization of the resonant type mean flow instability identified recently [P. H. Diamond, M. N. Rosenbluth, F. L. Hinton, M. Malkov, J. Fleischer, and A. Smolyakov, 17th IAEA Fusion Energy Conference, IAEA-CN-69/TH3/1, Yokohama, 1998 (to be published, International Atomic Energy Agency, Vienna)]. The mechanism discussed here, along with the resonant type, constitutes the “hydrodynamic” and “kinetic” regimes of the same process, similar to the case of plasma-beam instabilities. It is suggested that this generic mechanism is responsible for the generation of mean flow in atmospheres of rotating planets and magnetized plasmas.

A 71-year-old man presented with numerous pruritic seborrheic keratoses, with an eruptive onset over the course of 3 months. At presentation, he was also found to have hypopigmented tumors diffusely scattered throughout his body that were found to be mycosis fungoides on histologic examination. A theory regarding the pathophysiology of the development of eruptive seborrheic keratoses in the presence of mycosis fungoides is briefly discussed and 10 previous case reports of the Leser-Trélat sign in the setting of mycosis fungoides are reviewed.

Background

Understanding the design logic of living systems requires the understanding and comparison of proteomes. Proteomes define the commonalities between organisms more precisely than genomic sequences. Because uncertainties remain regarding the accuracy of proteomic data, several issues need to be resolved before comparative proteomics can be fruitful.

Results

The Saccharomyces cerevisiae proteome presents the highest quality proteomic data available. To evaluate the accuracy of these data, we intensively mapped a proteomic environment, termed 'Chromatin Central', which encompasses eight protein complexes, including the major histone acetyltransferases and deacetylases, interconnected by twelve proteomic hyperlinks. Using sequential tagging and a new method to eliminate background, we confirmed existing data but also uncovered new subunits and three new complexes, including ASTRA, which we suggest is a widely conserved aspect of telomeric maintenance, and two new variations of Rpd3 histone deacetylase complexes. We also examined the same environment in fission yeast and found a very similar architecture based on a scaffold of orthologues comprising about two-thirds of all proteins involved, whereas the remaining one-third is less constrained. Notably, most of the divergent hyperlinks were found to be due to gene duplications, hence providing a mechanism for the fixation of gene duplications in evolution.

Conclusions

We define several prerequisites for comparative proteomics and apply them to examine a proteomic environment in unprecedented detail. We suggest that high resolution mapping of proteomic environments will deliver the highest quality data for comparative proteomics.

SCFCdc4 (Skp1, Cdc53/cullin, F-box protein) defines a family of modular ubiquitin ligases (E3s) that regulate diverse processes including cell cycle, immune response, and development. Mass spectrometric analysis of proteins copurifying with Cdc53 identified the RING-H2 finger protein Hrt1 as a subunit of SCF. Hrt1 shows striking similarity to the Apc11 subunit of anaphase-promoting complex. Conditional inactivation of hrt1(ts) results in stabilization of the SCFCdc4 substrates Sic1 and Cln2 and cell cycle arrest at G1/S. Hrt1 assembles into recombinant SCF complexes and individually binds Cdc4, Cdc53 and Cdc34, but not Skp1. Hrt1 stimulates the E3 activity of recombinant SCF potently and enables the reconstitution of Cln2 ubiquitination by recombinant SCFGrr1. Surprisingly, SCF and the Cdc53/Hrt1 subcomplex activate autoubiquitination of Cdc34 E2 enzyme by a mechanism that does not appear to require a reactive thiol. The highly conserved human HRT1 complements the lethality of hrt1Delta, and human HRT2 binds CUL-1. We conclude that Cdc53/Hrt1 comprise a highly conserved module that serves as the functional core of a broad variety of heteromeric ubiquitin ligases.

The introduction of functional groups with varying electron-donating/-withdrawing properties at the β-position of diketopyrrolopyrrole (DPP) has been shown to affect the optoelectronic properties of the polymers. We report the synthesis of a new diketopyrrolopyrrole monomer wherein a strong electron-donating substituent, a methoxy group, was incorporated at the β-position in an effort to modulate polymer properties. Homopolymers and co-polymers of the new β-methoxy DPP and nonderivatized DPP were synthesized, and their properties were measured by cyclic voltammetry and UV-vis-near-infrared. Density functional theory computations also were employed to predict the degree of planarity of β-methoxy oligomers to probe the significance of the newly introduced S-O conformational lock. The combined experimental and computational results showed a reduction in the gap between highest occupied molecular orbital/lowest unoccupied molecular orbital levels, a redshift toward the near-infrared region, and an increased planarity in the β-methoxy polymers.

Spherical tokamak plasmas are typically overdense and thus inaccessible to externally-injected microwaves in the electron cyclotron range. The electrostatic electron Bernstein wave (EBW), however, provides a method to access the plasma core for heating and diagnostic purposes. Understanding the details of the coupling process to electromagnetic waves is thus important both for the interpretation of microwave diagnostic data and for assessing the feasibility of EBW heating and current drive. While the coupling is reasonably well-understood in the linear regime, nonlinear physics arising from high input power has not been previously quantified. To tackle this problem, we have performed one- and two-dimensional fully kinetic particle-in-cell simulations of the two possible coupling mechanisms, namely X-B and O-X-B mode conversion. We find that the ion dynamics has a profound effect on the field structure in the nonlinear regime, as high amplitude short-scale oscillations of the longitudinal electric field are excited in the region below the high-density cut-off prior to the arrival of the EBW. We identify this effect as the instability of the X wave with respect to resonant scattering into an EBW and a lower-hybrid wave. We calculate the instability rate analytically and find this basic theory to be in reasonable agreement with our simulation results.

High electron affinity (EA) molecules p-type dope low ionization energy (IE) polymers, resulting in an equilibrium doping level based on the energetic driving force (IE-EA), reorganization energy, and dopant concentration. Anion exchange doping (AED) is a process whereby the dopant anion is exchanged with a stable ion from an electrolyte. We show that the AED level can be predicted using an isotherm equilibrium model. The exchange of the dopant anion (FeCl₃^-) for a bis(trifluoromethanesulfonamide) (TFSI^-) anion in the polymers poly(3-hexylthiophene-2,5-diyl) (P3HT) and poly[3-(2,2-bithien-5-yl)-2,5-bis(2-hexyldecyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione-6,5-diyl] (PDPP-2T) highlights two cases in which the process is nonspontaneous and spontaneous, respectively. For P3HT, FeCl₃ provides a high doping level but an unstable counterion, so exchange results in an air stable counterion with a marginal increase in doping. For PDPP-2T, FeCl₃ is a weak dopant, but the exchange of FeCl₃^- for TFSI^- is spontaneous, so the doping level increases by >10× with AED.

Despite the essential roles of sphingolipids both as structural components of membranes and critical signalling molecules, we have a limited understanding of how cells sense and regulate their levels. Here we reveal the function in sphingolipid metabolism of the ORM genes (known as ORMDL genes in humans)-a conserved gene family that includes ORMDL3, which has recently been identified as a potential risk factor for childhood asthma. Starting from an unbiased functional genomic approach in Saccharomyces cerevisiae, we identify Orm proteins as negative regulators of sphingolipid synthesis that form a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma.

The retinoblastoma protein (pRb/p105) tumor suppressor plays a pivotal role in cell cycle regulation by blockage of the G1-to-S-phase transition. pRb tumor suppressor activity is governed by a variety of posttranslational modifications, most notably phosphorylation by cyclin-dependent kinase (Cdk) complexes. Here we report a novel regulation of pRb through protein arginine methyltransferase 4 (PRMT4)-mediated arginine methylation, which parallels phosphorylation. PRMT4 specifically methylates pRb at the pRb C-terminal domain (pRb C(term)) on arginine (R) residues R775, R787, and R798 in vitro and R787 in vivo. Arginine methylation is important for efficient pRb C(term) phosphorylation, as manifested by the reduced phosphorylation of a methylation-impaired mutant, pRb (R3K). A methylmimetic form of pRb, pRb (R3F), disrupts the formation of the E2F-1/DP1-pRb complex in cells as well as in an isolated system. Finally, studies using a Gal4-E2F-1 reporter system show that pRb (R3F) expression reduces the ability of pRb to repress E2F-1 transcriptional activation, while pRb (R3K) expression further represses E2F-1 transcriptional activation relative to that for cells expressing wild-type pRb. Together, our results suggest that arginine methylation negatively regulates the tumor suppressor function of pRb during cell cycle control, in part by creating a better substrate for Cdk complex phosphorylation and disrupting the interaction of pRb with E2F-1.