Guanidinoneomycin B recognition of an HIV-1 RNA helix

Aminoglycoside antibiotics are small-molecule drugs that bind RNA. The affinity and specificity of aminoglycoside binding to RNA can be increased through chemical modification, such as guanidinylation. Here, we report the binding of guanidinoneomycin B (GNB) to an RNA helix from the HIV-1 frameshift site. The binding of GNB increases the melting temperature (T(m)) of the frameshift-site RNA by at least 10 degrees C, to a point at which a melting transition is not even observed in 2 M urea. A structure of the complex was obtained by using multidimensional heteronuclear NMR spectroscopic methods. We also used a novel paramagnetic-probe assay to identify the site of GNB binding to the surface of the RNA. GNB makes major-groove contacts to two sets of Watson-Crick bases and is in van der Waals contact with a highly structured ACAA tetraloop. Rings I and II of GNB fit into the major groove and form the binding interface with the RNA, whereas rings III and IV are exposed to the solvent and disordered. The binding of GNB causes a broadening of the major groove across the binding site.     

Physiological parameter monitoring from optical recordings with a mobile phone

We show that a mobile phone can serve as an accurate monitor for several physiological variables, based on its ability to record and analyze the varying color signals of a fingertip placed in contact with its optical sensor. We confirm the accuracy of measurements of breathing rate, cardiac R-R intervals, and blood oxygen saturation, by comparisons to standard methods for making such measurements (respiration belts, ECGs, and pulse-oximeters, respectively). Measurement of respiratory rate uses a previously reported algorithm developed for use with a pulse-oximeter, based on amplitude and frequency modulation sequences within the light signal. We note that this technology can also be used with recently developed algorithms for detection of atrial fibrillation or blood loss.     

The dimensionality of job characteristics: Some neglected issues.

Examined variation in job characteristics across job categories by reanalyzing the original Job Diagnostic Survey database (G. R. Oldham et al, 1979), which includes information on job characteristics for 6,930 employees working on 876 jobs in 56 organizations. Previous research has focused investigation within jobs. A 3-factor solution was found to match best to an a priori structure using principal axis factor anaysis, oblique factor rotations, and a procrustes transformation. This solution retained task identity and job feedback as legitimate job dimensions but detected a 3rd dimension that collapsed skill variety, task significance, and autonomy into a single factor. Additionally, person (age, education) and situational/contextual (position level) variables were found to influence the ability to differentiate among job characteristics. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Scheduling directives: Accelerating shared-memory many-core processor execution

We consider many-core processors with a task-graph oriented programming model, whereby scheduling constraints among tasks are decided offline, and are then enforced by the runtime system using dedicated hardware. Here, exposing and beneficially exploiting fine grain data and control parallelism is increasingly important. Therefore, high expressive power for stating such constraints/directives, along with the ability to implement them in fast, simple hardware, is critical for success. In this paper, we focus on the relationship among different duplicable (multi-instance) tasks, which are used to express and exploit data parallelism. We extend the conventional Start-After-Complete (precedence) constraint to also be usable between replicas of different such tasks rather than only between entire tasks, thereby increasing the exposable parallelism. Additionally, we propose the parameterized Start-After-Start constraint, which can be used to control the degree of “lockstep” among multiple such tasks, e.g., in order to improve cache performance when the tasks work on the same data. Also, we briefly describe several additional interesting directives. Finally, we show that the directives can be supported efficiently in hardware. Hypercore, a very efficient CREW PRAM-like shared-cache architecture, which is very challenging because it has extremely fast dispatching for basic constraints, is used in the discussion. However, the new directives have broader applicability. Having shown the possibility of simple implementation and indications of benefit, this motivates further exploration of these directives and their implementation in hardware, as well as their support by programming tools.     

Cooperative, heparan sulfate-dependent cellular uptake of dimeric guanidinoglycosides

Oligoarginine and guanidinium-rich molecular transporters have been shown to facilitate the intracellular delivery of a diverse range of biologically relevant cargos. Several such transporters have been suggested to interact with cell-surface heparan sulfate proteoglycans as part of their cell-entry pathway. Unlike for other guanidinium-rich transporters, the cellular uptake of guanidinoglycosides at nanomolar concentrations is exclusively heparan sulfate dependent. As distinct cells differ in their expression levels and/or the composition of cell-surface heparan sulfate proteoglycans, one might be able to exploit such differences to selectively target certain cell types. To systematically investigate the nature of their cell-surface interactions, monomeric and dimeric guanidinoglycosides were synthesized by using neomycin, paromomycin, and tobramycin as scaffolds. These transporters differ in the number and 3D arrangement of their guanidinium groups. Their cellular uptake was measured by flow cytometry in wild-type and mutant Chinese hamster ovary cells after the corresponding fluorescent streptavidin-phycoerythrin-Cy5 conjugates had been generated. All derivatives showed negligible uptake in mutant cells lacking heparan sulfate. Decreasing the number of guanidinium groups diminished uptake, but the three dimensional arrangement of these groups was less important for cellular delivery. Whereas conjugates prepared with the monomeric carriers showed significantly reduced uptake in mutant cells expressing heparan sulfate chains with altered patterns of sulfation, conjugates prepared with the dimeric guanidinoglycosides could overcome this deficiency and maintain high levels of uptake in such deficient cells. This finding suggests that cellular uptake depends on the valency of the transporter and both the content and arrangement of the sulfate groups on the cell-surface receptors. Competition studies with chemically desulfated or carboxy-reduced heparin derivatives corroborated these observations. Taken together, these findings show that increasing the valency of the transporters retains heparan sulfate specificity and provides reagents that could distinguish different cell types based on the specific composition of their cell-surface heparan sulfate proteoglycans.     

Turbulence strength estimation from an arbitrary set of atmospherically degraded images

In remote sensing, atmospheric turbulence and aerosols usually limit the image quality. For many practical cases, turbulence is shown to be dominant, especially for horizontal close-to-earth imaging in hot environments. In a horizontal long-range imaging, it is usually impractical to calculate path-averaged refractive index structure constant C(2)(n) (which characterizes the turbulence strength) with conventional equipment. We propose a method for estimating C(2)(n) from the available atmospherically degraded video sequence by calculating temporal intensity fluctuations in spatially high variance areas. Experimental comparison with C(2)(n) measurements using a scintillometer shows reliable estimation results.     

DILUENT EFFECTS IN SOLVENT EXTRACTION

The empirical diluent parameters DP, introduced by Shmidt et al. several years ago, describe the extraction of mineral acids or metal complexes by the expression log K_ex = log K_ex ° + const. DP. They have now been related to independently obtainable properties of the diluents. The best correlation is with Dimroth and Reichardt's polarity index E_T, with Hildebrand's solubility parameter δ as an additional parameter causing some improvement. The new expression is: log K_ex = log K_ex ° + const₁. E_T + const₂. δ.