פרסומים

The small nematode Caenorhabditis elegans displays a spectrum of DNA damage responses similar to humans. In order to identify new DNA damage response genes, we isolated in a forward genetic screen 14 new mutations conferring hypersensitivity to ionizing radiation. We present here our characterization of lem-3, one of the genes identified in this screen. LEM-3 contains a LEM domain and a GIY nuclease domain. We confirm that LEM-3 has DNase activity in vitro. lem-3(lf) mutants are hypersensitive to various types of DNA damage, including ionizing radiation, UV-C light and crosslinking agents. Embryos from irradiated lem-3 hermaphrodites displayed severe defects during cell division, including chromosome mis-segregation and anaphase bridges. The mitotic defects observed in irradiated lem-3 mutant embryos are similar to those found in baf-1 (barrier-to-autointegration factor) mutants. The baf-1 gene codes for an essential and highly conserved protein known to interact with the other two C. elegans LEM domain proteins, LEM-2 and EMR-1. We show that baf-1, lem-2, and emr-1 mutants are also hypersensitive to DNA damage and that loss of lem-3 sensitizes baf-1 mutants even in the absence of DNA damage. Our data suggest that BAF-1, together with the LEM domain proteins, plays an important role following DNA damage - possibly by promoting the reorganization of damaged chromatin.

In this review the authors present recent progress on lyotropic liq. crystals (LLC) as delivery vehicles for cosmetoceuticals, nutraceuticals, and drugs. LLC were known for decades and their potential as delivery vehicles is well recognized. Yet, the 2 major mesophases, reverse hexagonal (HII) and bicontinuous cubic (primitive, gyroid, and diamond), are relatively hard gels with very slow release kinetics of the bioactives. In recent years a discontinuous cubic micellar mesophase (QL) was characterized and studied, showing significant potential as a delivery vehicle. In addn., the HII mesophase formed could be much more fluid and produced at room temp. Recent studies concd. on establishing methods to evaluate solubilization capacity and relationship between the diam. and length of the cylinders and the nature of the solubilizates. Special attention was given to finding methods to target the vehicles to the lumen and to trigger the release of the bioactives. This review summarizes the efforts of the authors' group along with work by numerous other scientists in this area. All these efforts suggest that the lyotropic mesophases and the corresponding dispersed soft particles (cubosomes, hexosomes, micellosomes) are now more than ever ready to become drug delivery vehicles for transport across the skin and the gut. [on SciFinder(R)]

The present work investigates a system composed of a ternary reversed hexagonal mesophase (HII) loaded with a lipase for modulating drug delivery capabilities of the system. Thermomyces lanuginosa lipase was solubilized into HII mesophase for the benefits of continuing lipolysis of the lipids, consequently disordering and decompg. the hexagonal mesophase and thereby enhancing the diffusion of the encapsulated drug. A single transition from the HII structure to a random micellar phase was detected during the lipolysis. In the first lipolysis stage the hexagonal system (glycerol monooleate, tricaprylin, and water) preserved its symmetry within ca. 200 min. During this step about 40-60% molar of the lipids were hydrolyzed, and a gradual shrinking of the HII cylinders (decrease of 8 \AA in lattice parameter) was detected. In the second lipolysis stage, the HII mesophase gradually disintegrated (faster rate) and the release of a model drug (sodium diclofenac) was significantly enhanced, which was assumed to be lipolysis rate-controlled. After about 15 h the HII mesophase was disintegrated into two dispersed immiscible phases. The release obeyed two-step Higuchi kinetics with two consecutive linear correlations of the drug release. [on SciFinder(R)]

Ultrafast UV excitation can prepare a nonstationary coherent superposition of molecular electronic states. The purely electronic dynamics before the onset of nuclear motion can be probed by a sudden XUV ionization of the electronic wave packet. Dynamical computations at the many-electron level on the LiH and 1-azabicyclo[3.3.3]undecane (C10H19N) molecules show that molecular frame photoelectron angular distributions reflect the spatial localization and undulations of the electronic coherent superposition accessed by the initial ultrafast UV excitation. The sudden ionization is sensitive to interference effects.

The Toffoli and Fredkin gates were suggested as a means to exhibit logic reversibility and thereby reduce energy dissipation associated with logic operations in dense computing circuits. We present a construction of the logically reversible Toffoli and Fredkin gates by implementing a library of predesigned Mg2+-dependent DNAzymes and their respective substrates. Although the logical reversibility, for which each set of inputs uniquely correlates to a set of outputs, is demonstrated, the systems manifest thermodynamic irreversibility originating from two quite distinct and nonrelated phenomena. (i) The physical readout of the gates is by fluorescence that depletes the population of the final state of the machine. This irreversible, heat-releasing process is needed for the generation of the output. (ii) The DNAzyme-powered logic gates are made to operate at a finite rate by invoking downhill energy-releasing processes. Even though the three bits of Toffoli’s and Fredkin’s logically reversible gates manifest thermodynamic irreversibility, we suggest that these gates could have important practical implication in future nanomedicine.

We investigate the performance of inhomogeneously broadened spin ensembles as quantum memories under continuous dynamical decoupling. The role of the continuous driving field is twofold: firstly, it decouples individual spins from magnetic noise; secondly, and more importantly, it suppresses and reshapes the spectral inhomogeneity of spin ensembles. We show that a continuous driving field, which itself may also be inhomogeneous over the ensemble, can considerably enhance the decay of the tails of the inhomogeneous broadening distribution. This fact enables a spin-ensemble-based quantum memory to exploit the effect of cavity protection and achieve a much longer storage time. In particular, for a spin ensemble with a Lorentzian spectral distribution, our calculations demonstrate that continuous dynamical decoupling has the potential to improve its storage time by orders of magnitude for the state-of-the-art experimental parameters.

The article examines centrality of voice to acting, the relation of voice to existential amplification and the role of actor’s voice in seven dimensions of the relationship between character and thought. It is stated that striking, memorable acting is bound with effects created by modifications in the actor’s voice. Royal Shakespeare Company voice trainer Cicely Berry stated that young actors shun intense work on their voices since it threatens the performer with artificiality and loss of self.

Ly6C(hi) monocytes seed the healthy intestinal lamina propria to give rise to resident CX(3)CR1(+) macrophages that contribute to the maintenance of gut homeostasis. Here we report on two alternative monocyte fates in the inflamed colon. We showed that CCR2 expression is essential to the recruitment of Ly6C(hi) monocytes to the inflamed gut to become the dominant mononuclear cell type in the lamina propria during settings of acute colitis. In the inflammatory microenvironment, monocytes upregulated TLR2 and NOD2, rendering them responsive to bacterial products to become proinflammatory effector cells. Ablation of Ly6C(hi) monocytes ameliorated acute gut inflammation. With time, monocytes differentiated into migratory antigen-presenting cells capable of priming naive T cells, thus acquiring hallmarks reminiscent of dendritic cells. Collectively, our results highlight cellular dynamics in the inflamed colon and the plasticity of Ly6C(hi) monocytes, marking them as potential targets for inflammatory bowel disease (IBD) therapy.

"Pray what authors should she read, who in Classics would succeed?" the director of a new women's university is asked in W. S. Gilbert's comic opera libretto, Princess Ida. In the new schools and colleges that were extending formal education to women and to the poor, the core curriculum was still selected "classic" Latin and Greek writers as it had been in the traditional boys schools of the rich. The director's three selected "classic" authors, Ovid, Aristophanes, and Juvenal (in that order) would have surprised Gilbert's audience, since they mark a progression from risqué sexual allusiveness to crude and overt sexual satire. Then she adds: "if you're well advised, you will get them Bowdlerised." Dr. Bowdler's removal of elements he considered tasteless made his name synonymous with sexual censorship. But sexual reference, overt or oblique, is not the most important element altered in the public presentation of classical poetry in the nineteenth and much of the twentieth centuries. Educators were no less anxious about inflammatory or revolutionary political ideas and wanted "classic" texts that could be used to enhance a patriotic agenda. The only ancient epic that suited their needs was Virgil's Aeneid. This paper discusses why and how Gilbert's libretti were (and still are) misread as supportive of the very ideas he was criticizing; why Virgil's Aeneid was, by a process of judicious excerpting, represented throughout Europe as a paean of praise to Rome and Augustus, and why it has been as difficult for us to escape this nineteenth century view of the Aeneid as it has been to escape from Freud's understanding of Oedipus or Nietzsche's reading of Greek Tragedy. © 2012 Project MUSE.