The Effect of N-Terminal Cyclization on the Function of the HIV Entry Inhibitor 5P12-RANTES.

Despite effective treatment for those living with Human Immunodeficiency Virus (HIV), there are still two million new infections each year. Protein-based HIV entry inhibitors, being highly effective and specific, could be used to protect people from initial infection. One of the most promising of these for clinical use is 5P12-RANTES, a variant of the chemokine RANTES/CCL5. The N-terminal amino acid of 5P12-RANTES is glutamine (Gln; called Q0), a residue that is prone to spontaneous cyclization when at the N-terminus of a protein. It is not known how this cyclization affects the potency of the inhibitor or whether cyclization is necessary for the function of the protein, although the N-terminal region of RANTES has been shown to be critical for receptor interactions, with even small changes having a large effect. We have studied the kinetics of cyclization of 5P12-RANTES as well as N-terminal variations of the protein that either produce an identical cyclized terminus (Glu0) or that cannot similarly cyclize (Asn0, Phe0, Ile0, and Leu0). We find that the half life for N-terminal cyclization of Gln is roughly 20 h at pH 7.3 at 37 °C. However, our results show that cyclization is not necessary for the potency of this protein and that several replacement terminal amino acids produce nearly-equally potent HIV inhibitors while remaining CC chemokine receptor 5 (CCR5) antagonists. This work has ramifications for the production of active 5P12-RANTES for use in the clinic, while also opening the possibility of developing other inhibitors by varying the N-terminus of the protein

Recommendations and illustrations for the evaluation of photonic random number generators

The never-ending quest to improve the security of digital information combined with recent improvements in hardware technology has caused the field of random number generation to undergo a fundamental shift from relying solely on pseudo-random algorithms to employing optical entropy sources. Despite these significant advances on the hardware side, commonly used statistical measures and evaluation practices remain ill-suited to understand or quantify the optical entropy that underlies physical random number generation. We review the state of the art in the evaluation of optical random number generation and recommend a new paradigm: quantifying entropy generation and understanding the physical limits of the optical sources of randomness. In order to do this, we advocate for the separation of the physical entropy source from deterministic post-processing in the evaluation of random number generators and for the explicit consideration of the impact of the measurement and digitization process on the rate of entropy production. We present the Cohen-Procaccia estimate of the entropy rate $h(\epsilon,\tau)$ as one way to do this. In order to provide an illustration of our recommendations, we apply the Cohen-Procaccia estimate as well as the entropy estimates from the new NIST draft standards for physical random number generators to evaluate and compare three common optical entropy sources: single photon time-of-arrival detection, chaotic lasers, and amplified spontaneous emission

The Composition of Comets

This paper is the result of the International Cometary Workshop, held in Toulouse, France in April 2014, where the participants came together to assess our knowledge of comets prior to the ESA Rosetta Mission. In this paper, we look at the composition of the gas and dust from the comae of comets. With the gas, we cover the various taxonomic studies that have broken comets into groups and compare what is seen at all wavelengths. We also discuss what has been learned from mass spectrometers during flybys. A few caveats for our interpretation are discussed. With dust, much of our information comes from flybys. They include {\it in situ} analyses as well as samples returned to Earth for laboratory measurements. Remote sensing IR observations and polarimetry are also discussed. For both gas and dust, we discuss what instruments the Rosetta spacecraft and Philae lander will bring to bear to improve our understanding of comet 67P/Churyumov-Gerasimenko as "ground-truth" for our previous comprehensive studies. Finally, we summarize some of the initial Rosetta Mission findings.Comment: To appear in Space Science Review

Thirty Years of Cometary Spectroscopy from McDonald Observatory

We report on the results of a spectroscopic survey of 130 comets that was conducted at McDonald observatory from 1980 through 2008. Some of the comets were observed on only one night, while others were observed repeatedly. For 20 of these comets, no molecules were detected. For the remaining 110 comets, some emission from CN, OH, NH, C$_{3}$, C$_{2}$, CH, and NH$_{2}$ molecules were observed on at least one occasion. We converted the observed molecular column densities to production rates using a Haser (1957) model. We defined a restricted data set of comets that had at least 3 nights of observations. The restricted data set consists of 59 comets. We used ratios of production rates to study the trends in the data. We find two classes of comets: typical and carbon-chain depleted comets. Using a very strict definition of depleted comets, requiring C$_{2}$ \underline{and} C$_{3}$ to both be depleted, we find 9% of our restricted data set comets to be depleted. Using a more relaxed definition that requires only C$_{2}$ to be below a threshold (similar to other researchers), we find 25% of the comets are depleted. Two-thirds of the depleted comets are Jupiter Family comets, while one-third are Long Period comets. 37% of the Jupiter Family comets are depleted, while 18.5% of the Long Period comets are depleted. We compare our results with other studies and find good agreement.Comment: Accepted for Icarus; 15 figures, 9 tables (some multi-page and in landscape mode

Multidimensional Coherent Spectroscopy of a Semiconductor Microcavity

Rephasing and non-rephasing two-dimensional coherent spectra map the anti-crossing associated with normal-mode splitting in a semiconductor microcavity. For a 12-meV detuning range near zero detuning, it is observed that there are two diagonal features related to the intra-action of exciton-polariton branches and two off-diagonal features related to coherent interaction between the polaritons. At negative detuning, the lineshape properties of the diagonal intra-action features are distinguishable and can be associated with cavity-like and exciton-like modes. A biexcitonic companion feature is observed, shifted from the exciton feature by the biexciton binding energy. Closer to zero detuning, all features are enhanced and the diagonal intra-action features become nearly equal in amplitude and linewidth. At positive detuning the exciton- and cavity-like characteristics return to the diagonal intra-action features. Off-diagonal interaction features exhibit asymmetry in their amplitudes throughout the detuning range. The amplitudes are strongly modulated (and invert) at small positive detuning, as the lower polariton branch crosses the bound biexciton energy determined from negative detuning spectra.Comment: 13 pages, 4 figure

Optical techniques for 3D surface reconstruction in computer-assisted laparoscopic surgery

One of the main challenges for computer-assisted surgery (CAS) is to determine the intra-opera- tive morphology and motion of soft-tissues. This information is prerequisite to the registration of multi-modal patient-specific data for enhancing the surgeon’s navigation capabilites by observ- ing beyond exposed tissue surfaces and for providing intelligent control of robotic-assisted in- struments. In minimally invasive surgery (MIS), optical techniques are an increasingly attractive approach for in vivo 3D reconstruction of the soft-tissue surface geometry. This paper reviews the state-of-the-art methods for optical intra-operative 3D reconstruction in laparoscopic surgery and discusses the technical challenges and future perspectives towards clinical translation. With the recent paradigm shift of surgical practice towards MIS and new developments in 3D opti- cal imaging, this is a timely discussion about technologies that could facilitate complex CAS procedures in dynamic and deformable anatomical regions

One pot solvothermal synthesis of organic acid coated magnetic iron oxide nanoparticles

Indexación: ScieloABSTRACT In this work we present the synthesis and characterization of iron oxide nanoparticles (IONPs), which were structurally and magnetically characterized. The use of iron salts and an organic acid (l-serine or ascorbic acid) as precursors under solvothermal conditions yielded these coated IONPs. The powder X-ray diffraction pattern of FeO-1 and FeO-2 is consistent with hematite (α-Fe2O3) and hematite-maghemite ((α-Fe2O3/γ-Fe2O3) respectively. The TEM analysis permits to estimate an average size of 10 nm for the FeO-1 sample. The magnetic characterization of the samples through the M(H) plots showed a very low coercivity value for both samples, being 53 Oe for FeO-1 and 10 Oe for FeO-2, indicating the very weak ferromagnetic character of the synthesized iron oxide species. Even though both organic acids under solvothermal conditions permit to obtain coated IONPs in one pot reaction, l-serine produces a more narrow-size distribution

Consistent alleviation of abiotic stress with silicon addition: a meta-analysis

1. Hundreds of single species studies have demonstrated the facility of silicon (Si) to alleviate diverse abiotic stresses in plants. Understanding of the mechanisms of Si-mediated stress alleviation is progressing, and several reviews have brought information together. A quantitative assessment of the alleviative capacity of Si, however, which could elucidate plant Si function more broadly, was lacking. 2. We combined the results of 145 experiments, predominantly on agricultural species, in a meta-analysis to statistically assess the responses of stressed plants to Si supply across multiple plant families and abiotic stresses. We interrogated our database to determine whether stressed plants increased in dry mass and net assimilation rate, oxidative stress markers were reduced, antioxidant responses were increased and whether element uptake showed consistent changes when supplied with Si. 3. We demonstrated that across plant families and stress types, Si increases dry weight, assimilation rate and chlorophyll biosynthesis and alleviates oxidative damage in stressed plants. In general, results indicated that plant family (as a proxy for accumulator type) and stress type had significant explanatory power for variation in responses. The consistent reduction in oxidative damage was not mirrored by consistent increases in antioxidant production, indicative of the several different stress alleviation mechanisms in which Si is involved. Silicon addition increased K in shoots, decreased As and Cd in roots and Na and Cd in shoots. Silicon addition did not affect Al, Ca or Mn concentration in shoots and roots of stressed plants. Plants had significantly lower concentrations of Si accumulated in shoots but not in roots when stressed. 4. Meta-analyses showed consistent alleviation by Si of oxidative damage caused by a range of abiotic stresses across diverse species. Our findings indicate that Si is likely to be a useful fertilizer for many crops facing a spectrum of abiotic stresses. Similarities in responses across families provide strong support for a role of Si in the alleviation of abiotic stress in natural systems, where it has barely been explored. We suggest this role may become more important under a changing climate and more experiments using non-agricultural species are now needed