Laser-Induced Periodic Surface Structures on Layered GaSe Crystals: Structural Coloring and Infrared Antireflection.

We study structural and morphological transformations caused by multipulse femtosecond-laser exposure of Bridgman-grown ϵ-phase GaSe crystals, a van der Waals semiconductor promising for nonlinear optics and optoelectronics. We unveil, for the first time, the laser-driven self-organization regimes in GaSe allowing the formation of regular laser-induced periodic surface structures (LIPSSs) that originate from interference of the incident radiation and interface surface plasmon waves. LIPSSs formation causes transformation of the near-surface layer to amorphous Ga2Se3 at negligible oxidation levels, evidenced from comprehensive structural characterization. LIPSSs imprinted on both output crystal facets provide a 1.2-fold increase of the near-IR transmittance, while the ability to control local periodicity by processing parameters enables multilevel structural color marking of the crystal surface. Our studies highlight direct fs-laser patterning as a multipurpose application-ready technology for precise nanostructuring of promising van der Waals semiconductors, whose layered structure restricts application of common nanofabrication approaches.

Silicon microprotrusions with tailored chirality enabled by direct femtosecond laser ablation.

Here, we report on formation of nanoprotrusions on the surface of a bulk crystalline silicon wafer under femtosecond-laser ablation with a donut-shaped laser beam. By breaking circular symmetry of the irradiating donut-shaped fs-pulse beam, a switch in geometry of the formed surface nanoprotrusions from regular to chiral was demonstrated. The chirality of the obtained Si nanostructures was promoted with an asymmetry degree of the laser beam. An uneven helical flow of laser-melted Si caused by asymmetry of the initial intensity and temperature pattern on the laser-irradiated Si surface explains this phenomenon. Chirality of the formed protrusions was confirmed by visualizing cross-sectional cuts produced by focused ion beam milling as well as Raman activity of these structures probed by circularly polarized light with opposite handedness. Our results open a pathway towards easy-to-implement inexpensive fabrication of chiral all-dielectric nanostructures for advanced nanophotonic applications and sensing of chiral molecules.

Characterization of azimuthal and radial velocity fields induced by rotors in flows with a low Reynolds number.

We theoretically and experimentally investigate the flow field that emerges from a rodlike microrotor rotating about its center in a nonaxisymmetric manner. A simple theoretical model is proposed that uses a superposition of two rotlets as a fundamental solution to the Stokes equation. The predictions of this model are compared to measurements of the azimuthal and radial microfluidic velocity field components that are induced by a rotor composed of fused microscopic spheres. The rotor is driven magnetically and the fluid flow is measured with the help of a probe particle fixed by an optical tweezer. We find considerable deviations of the mere azimuthal flow pattern induced by a single rotating sphere as it has been reported by Di Leonardo et al. [Phys. Rev. Lett. 96, 134502 (2006)]. Notably, the presence of a radial velocity component that manifests itself by an oscillation of the probe particle with twice the rotor frequency is observed. These findings open up a way to discuss possible radial transport in microfluidic devices.

Beyond traditional pharmacology: new tools and approaches.

Traditional pharmacology is defined as the science that deals with drugs and their actions. While small molecule drugs have clear advantages, there are many cases where they have proved to be ineffective, prone to unacceptable side effects, or where due to a particular disease aetiology they cannot possibly be effective. A dominant feature of the small molecule drugs is their single mindedness: they provide either continuous inhibition or continuous activation of the target. Because of that, these drugs tend to engage compensatory mechanisms leading to drug tolerance, drug resistance or, in some cases, sensitization and consequent loss of therapeutic efficacy over time and/or unwanted side effects. Here we discuss new and emerging therapeutic tools and approaches that have potential for treating the majority of disorders for which small molecules are either failing or cannot be developed. These new tools include biologics, such as recombinant hormones and antibodies, as well as approaches involving gene transfer (gene therapy and genome editing) and the introduction of specially designed self-replicating cells. It is clear that no single method is going to be a 'silver bullet', but collectively, these novel approaches hold promise for curing practically every disorder.

Fractal energy spectrum of a polariton gas in a Fibonacci quasiperiodic potential.

We report on the study of a polariton gas confined in a quasiperiodic one-dimensional cavity, described by a Fibonacci sequence. Imaging the polariton modes both in real and reciprocal space, we observe features characteristic of their fractal energy spectrum such as the opening of minigaps obeying the gap labeling theorem and log-periodic oscillations of the integrated density of states. These observations are accurately reproduced solving an effective 1D Schrödinger equation, illustrating the potential of cavity polaritons as a quantum simulator in complex topological geometries.

Caspase-cleaved arrestin-2 and BID cooperatively facilitate cytochrome C release and cell death.

Apoptosis is programmed cell death triggered by activation of death receptors or cellular stress. Activation of caspases is the hallmark of apoptosis. Arrestins are best known for their role in homologous desensitization of G protein-coupled receptors (GPCRs). Arrestins quench G protein activation by binding to activated phosphorylated GPCRs. Recently, arrestins have been shown to regulate multiple signalling pathways in G protein-independent manner via scaffolding signalling proteins. Here we demonstrate that arrestin-2 isoform is cleaved by caspases during apoptosis induced via death receptor activation or by DNA damage at evolutionarily conserved sites in the C-terminus. Caspase-generated arrestin-2-(1-380) fragment translocates to mitochondria increasing cytochrome C release, which is the key checkpoint in cell death. Cells lacking arrestin-2 are significantly more resistant to apoptosis. The expression of wild-type arrestin-2 or its cleavage product arrestin-2-(1-380), but not of its caspase-resistant mutant, restores cell sensitivity to apoptotic stimuli. Arrestin-2-(1-380) action depends on tBID: at physiological concentrations, arrestin-2-(1-380) directly binds tBID and doubles tBID-induced cytochrome C release from isolated mitochondria. Arrestin-2-(1-380) does not facilitate apoptosis in BID knockout cells, whereas its ability to increase caspase-3 activity and facilitate cytochrome C release is rescued when BID expression is restored. Thus, arrestin-2-(1-380) cooperates with another product of caspase activity, tBID, and their concerted action significantly contributes to cell death.

Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder.

Alterations of multiple G protein-mediated signaling pathways are detected in schizophrenia. G protein-coupled receptor kinases (GRKs) and arrestins terminate signaling by G protein-coupled receptors exerting a powerful influence on receptor functions. Modifications of arrestin and/or GRKs expression may contribute to schizophrenia pathology. Cortical expression of arrestins and GRKs was measured postmortem in control and subjects with schizophrenia or schizoaffective disorder. Additionally, arrestin/GRK expression was determined in elderly patients with schizophrenia and age-matched control. Patients with schizophrenia, but not schizoaffective disorder, displayed a reduced concentration of arrestin and GRK mRNAs and GRK3 protein. Arrestins and GRK significantly decreased with age. In elderly patients, GRK6 was reduced, with other GRKs and arrestins unchanged. A reduced cortical concentration of GRKs in schizophrenia (resembling that in aging) may result in altered G protein-dependent signaling, thus contributing to prefrontal deficits in schizophrenia. The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder.

Dielectric barrier discharges in analytical chemistry.

The present review reflects the importance of dielectric barrier discharges in analytical chemistry. Special about this discharge is-and in contrast to usual discharges with direct current-that the plasma is separated from one or two electrodes by a dielectric barrier. This gives rise to two main features of the dielectric barrier discharges; it can serve as dissociation and excitation device and as ionization mechanism, respectively. The article portrays the various application fields for dielectric barrier discharges in analytical chemistry, for example the use for elemental detection with optical spectrometry or as ionization source for mass spectrometry. Besides the introduction of different kinds of dielectric barrier discharges used for analytical chemistry from the literature, a clear and concise classification of dielectric barrier discharges into capacitively coupled discharges is provided followed by an overview about the characteristics of a dielectric barrier discharge concerning discharge properties and the ignition mechanism.

Self-organized nanopatterns in thin layers of superheated liquid metals.

In this paper experimental observations of self-organized patterns in resolidified thin films of liquid superheated metals are reported. The superheated melt layers represent an example of a system driven far from equilibrium, which undergoes explosive boiling and solidifies afterward. The melts appear in the course of single-shot femtosecond laser heating of metal samples. Self-organized cells, solitonlike structures, periodic stripes, and transient patterns are observed. Pattern properties and mechanisms leading to the pattern formation as well as possible applications for nanotechnology are discussed.

Generalized Lyapunov exponent and transmission statistics in one-dimensional Gaussian correlated potentials.

The distribution of the transmission coefficient T of a long system with a correlated Gaussian disorder is studied analytically and numerically in terms of the generalized Lyapunov exponent (LE) and the cumulants of ln T. The effect of the disorder correlations on these quantities is considered in weak, moderate, and strong disorder for different models of correlation. Scaling relations between the cumulants of ln T are obtained. The cumulants are treated analytically within the semiclassical approximation in strong disorder and numerically for an arbitrary strength of the disorder. A small correlation scale approximation is developed for calculation of the generalized LE in a general correlated disorder. An essential effect of the disorder correlations on the transmission statistics is found. In particular, obtained relations between the cumulants and between them and the generalized LE show that, beyond weak disorder, transmission fluctuations and deviation of their distribution from the log-normal form (in a long but finite system) are greatly enhanced due to the disorder correlations. Parametric dependence of these effects upon the correlation scale is presented.

Arrestin-1 expression level in rods: balancing functional performance and photoreceptor health.

In rod photoreceptors, signaling persists as long as rhodopsin remains catalytically active. Phosphorylation by rhodopsin kinase followed by arrestin-1 binding completely deactivates rhodopsin. Timely termination prevents excessive signaling and ensures rapid recovery. Mouse rods express arrestin-1 and rhodopsin at ∼0.8:1 ratio, making arrestin-1 the second most abundant protein in the rod. The biological significance of wild type arrestin-1 expression level remains unclear. Here we investigated the effects of varying arrestin-1 expression on its intracellular distribution in dark-adapted photoreceptors, rod functional performance, recovery kinetics, and morphology. We found that rod outer segments isolated from dark-adapted animals expressing arrestin-1 at wild type or higher level contain much greater fraction of arrestin-1 than previously estimated, 15-25% of the total. The fraction of arrestin-1 residing in the outer segments (OS) in animals with low expression (4-12% of wild type) is much lower, 5-7% of the total. Only 4% of wild type arrestin-1 level in the outer segments was sufficient to maintain near-normal retinal morphology, whereas rapid recovery required at least ∼12%. Supra-physiological arrestin-1 expression improved light sensitivity and facilitated photoresponse recovery, but was detrimental for photoreceptor health, particularly in the peripheral retina. Thus, physiological level of arrestin-1 expression in rods reflects the balance between short-term functional performance of photoreceptors and their long-term health.

Arrestins as multi-functional signaling adaptors.

Arrestins are versatile regulators of cellular signaling expressed in every cell in the body. Arrestins bind active phosphorylated forms of their cognate G-protein-coupled receptors, shutting down G-protein activation and linking receptors to alternative signaling pathways. Arrestins directly interact with more than 20 surprisingly diverse proteins, such as several Src family kinases, ubiquitin ligases, protein phosphatases, microtubules, etc., and serve as scaffolds facilitating signaling in two MAP kinase cascades, leading to the activation of ERK1/2 and JNK3. A number of arrestin-binding partners are key players in signaling pathways that regulate cell proliferation, survival, and apoptotic death, which make arrestin interactions with these proteins inviting targets for therapeutic intervention. For example, enhancement of pro-survival or pro-apoptotic arrestin-dependent signaling is a promising strategy in treating disorders such as neurodegenerative diseases or cancer, respectively. Recent studies show that in the cell arrestin exists in at least three distinct conformations, free, receptor-bound, and microtubule-bound, with very different signaling capabilities. Precise identification of arrestin elements mediating its interactions with each partner and elucidation of conformational dependence of these interactions will pave the way to the development of molecular tools for targeted enhancement or attenuation of arrestin interactions with individual partners. This structural information is necessary to devise conventional drug-based approaches and to engineer specialized "designer" arrestins that can compensate for defects in receptor regulation associated with congenital disorders and/or redirect arrestin-mediated signaling to desired pathways. Arrestins are at the crossroads of crucial pathways that determine cell fate and behavior. Therefore, targeted manipulation of arrestin-dependent signaling has an enormous therapeutic potential.

Arrestins and two receptor kinases are upregulated in Parkinson's disease with dementia.

Arrestins and G proteins-coupled receptor kinases (GRKs) regulate signaling and trafficking of G protein-coupled receptors. We investigated changes in the expression of arrestins and GRKs in the striatum of patients with Parkinson's disease without (PD) or with dementia (PDD) at postmortem using Western blotting and ribonuclease protection assay. Both PD and PDD groups had similar degree of dopamine depletion in all striatal regions. Arrestin proteins and mRNAs were increased in the PDD group throughout striatum. Protein and mRNA of GRK5, the major subtype in the human striatum, and GRK3 were also upregulated, whereas GRK2 and 6 were mostly unchanged. The PD group had lower concentration of arrestins and GRKs than the PDD group. There was no statistical link between the load of Alzheimer's pathology and the expression of these signaling proteins. Upregulation of arrestins and GRK in PDD may confer resistance to the therapeutic effects of levodopa often observed in these patients. In addition, increased arrestin and GRK concentrations may lead to dementia via perturbation of multiple signaling mechanisms.

Pathogenesis of levodopa-induced dyskinesia: focus on D1 and D3 dopamine receptors.

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease. Taking advantage of a monkey brain bank constituted to study the pathophysiology of levodopa-induced dyskinesia, we here report the changes affecting D1, D2 and D3 dopamine receptors within the striatum of four experimental groups of non-human primates: normal, parkinsonian, parkinsonian treated with levodopa without or with dyskinesia. We also report the possible role of arrestin and G protein-coupled receptor kinases.

L-DOPA reverses the MPTP-induced elevation of the arrestin2 and GRK6 expression and enhanced ERK activation in monkey brain.

Dysregulation of dopamine receptors (DARs) is believed to contribute to Parkinson disease (PD) pathology. G protein-coupled receptors (GPCR) undergo desensitization via activation-dependent phosphorylation by G protein-coupled receptor kinases (GRKs) followed by arrestin binding. Using quantitative Western blotting, we detected profound differences in the expression of arrestin2 and GRKs among four experimental groups of nonhuman primates: (1) normal, (2) parkinsonian, (3) parkinsonian treated with levodopa without or (4) with dyskinesia. Arrestin2 and GRK6 expression was significantly elevated in the MPTP-lesioned group in most brain regions; GRK2 was increased in caudal caudate and internal globus pallidus. Neither levodopa-treated group differed significantly from control. The only dyskinesia-specific change was an elevation of GRK3 in the ventral striatum of the dyskinetic group. Changes in arrestin and GRK expression in the MPTP group were accompanied by enhanced ERK activation and elevated total ERK expression, which were also reversed by L-DOPA. The data suggest the involvement of arrestins and GRKs in Parkinson disease pathology and the effects of levodopa treatment.

Rotating hexagonal pattern in a dielectric barrier discharge system.

Here, we report on the experimental observation of a rotating hexagonal pattern in a continuous dissipative medium. The system under investigation is a planar dielectric barrier gas-discharge cell. The pattern consists of a set of current filaments occupying the whole discharge area and rotating as a rigid body. The symmetry of the rotating hexagons is lower than the symmetry of the stationary hexagonal pattern. We study the dynamics of the pattern, especially peculiarities of its rotational velocity. The temperature of the gas is found to be an important quantity influencing the rotating hexagons.

[A missing link in classification of occupational pulmonary diseases--occupational chronic obstructive lung diseases]. / O nedostaiushchem zvene v klassifikatsii professional'nykh zabolevanii legkikh--professional'noi khronicheskoi obstruktivnoi bolezni legkikh.

The authors justified a suggestion on including chronic obstructive lung diseases (COLD) into Occupational Diseases Register.

Role of surface charges in dc gas-discharge systems with high-ohmic electrodes.

Surface charge of the electrodes is investigated for planar dc gas-discharge systems. Both analytical estimates and experimental data show that such a charge plays an important role for the dc systems with a high-ohmic electrode. This is demonstrated by several experiments concerning discharge establishment and pattern formation phenomena. The surface charge has an inhibitory role, as it diminishes the electric field in the gas. Due to the low mobility of the surface charges, their distribution can be nonuniform giving rise to the observable filamentary structure of the discharge. It is also shown that the surface charge effect can be naturally incorporated in existing phenomenological models of the planar discharge. Thereby one can explain several observable phenomena, such as stability, multiplicity, and motion of the localized structures.

[Some aspects of occupational spinal diseases]. / Nekotorye aspekty professional'noi vertebrogennoi patologii.

Prevalence of neurologic cervical and lumbar disorders among workers does not depend upon hardness of work conditions. First diagnosed occupational vertebral syndromes were clinically divided into reflectory and compression ones. Length of service, age and X-ray signs appeared not to differ significantly between the groups.