Odorranalectin Is a Small Peptide Lectin with Potential for Drug Delivery and Targeting

BACKGROUND: Lectins are sugar-binding proteins that specifically recognize sugar complexes. Based on the specificity of protein-sugar interactions, different lectins could be used as carrier molecules to target drugs specifically to different cells which express different glycan arrays. In spite of lectin's interesting biological potential for drug targeting and delivery, a potential disadvantage of natural lectins may be large size molecules that results in immunogenicity and toxicity. Smaller peptides which can mimic the function of lectins are promising candidates for drug targeting. PRINCIPAL FINDINGS: Small peptide with lectin-like behavior was screened from amphibian skin secretions and its structure and function were studied by NMR, NMR-titration, SPR and mutant analysis. A lectin-like peptide named odorranalectin was identified from skin secretions of Odorrana grahami. It was composed of 17 aa with a sequence of YASPKCFRYPNGVLACT. L-fucose could specifically inhibit the haemagglutination induced by odorranalectin. (125)I-odorranalectin was stable in mice plasma. In experimental mouse models, odorranalectin was proved to mainly conjugate to liver, spleen and lung after i.v. administration. Odorranalectin showed extremely low toxicity and immunogenicity in mice. The small size and single disulfide bridge of odorranalectin make it easy to manipulate for developing as a drug targeting system. The cyclic peptide of odorranalectin disclosed by solution NMR study adopts a beta-turn conformation stabilized by one intramolecular disulfide bond between Cys6-Cys16 and three hydrogen bonds between Phe7-Ala15, Tyr9-Val13, Tyr9-Gly12. Residues K5, C6, F7, C16 and T17 consist of the binding site of L-fucose on odorranalectin determined by NMR titration and mutant analysis. The structure of odorranalectin in bound form is more stable than in free form. CONCLUSION: These findings identify the smallest lectin so far, and show the application potential of odorranalectin for drug delivery and targeting. It also disclosed a new strategy of amphibian anti-infection

Charged hadron multiplicity fluctuations in Au+Au and Cu+Cu collisions from sqrt(s_NN) = 22.5 to 200 GeV

A comprehensive survey of event-by-event fluctuations of charged hadron multiplicity in relativistic heavy ions is presented. The survey covers Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV, and Cu+Cu collisions sqrt(s_NN) = 22.5, 62.4, and 200 GeV. Fluctuations are measured as a function of collision centrality, transverse momentum range, and charge sign. After correcting for non-dynamical fluctuations due to fluctuations in the collision geometry within a centrality bin, the remaining dynamical fluctuations expressed as the variance normalized by the mean tend to decrease with increasing centrality. The dynamical fluctuations are consistent with or below the expectation from a superposition of participant nucleon-nucleon collisions based upon p+p data, indicating that this dataset does not exhibit evidence of critical behavior in terms of the compressibility of the system. An analysis of Negative Binomial Distribution fits to the multiplicity distributions demonstrates that the heavy ion data exhibit weak clustering properties.Comment: 464 authors from 60 institutions, 17 pages, 12 figures, 1 table. Submitted to Physical Review C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Transverse-energy distributions at midrapidity in pp++pp, dd++Au, and Au++Au collisions at sNN=62.4\sqrt{s_{_{NN}}}=62.4--200~GeV and implications for particle-production models

Measurements of the midrapidity transverse energy distribution, d\Et/d\eta, are presented for $p$$+$$p$, $d$$+$Au, and Au$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV and additionally for Au$+$Au collisions at $\sqrt{s_{_{NN}}}=62.4$ and 130 GeV. The d\Et/d\eta distributions are first compared with the number of nucleon participants $N_{\rm part}$, number of binary collisions $N_{\rm coll}$, and number of constituent-quark participants $N_{qp}$ calculated from a Glauber model based on the nuclear geometry. For Au$+$Au, \mean{d\Et/d\eta}/N_{\rm part} increases with $N_{\rm part}$, while \mean{d\Et/d\eta}/N_{qp} is approximately constant for all three energies. This indicates that the two component ansatz, $dE_{T}/d\eta \propto (1-x) N_{\rm part}/2 + x N_{\rm coll}$, which has been used to represent $E_T$ distributions, is simply a proxy for $N_{qp}$, and that the $N_{\rm coll}$ term does not represent a hard-scattering component in $E_T$ distributions. The $dE_{T}/d\eta$ distributions of Au$+$Au and $d$$+$Au are then calculated from the measured $p$$+$$p$ $E_T$ distribution using two models that both reproduce the Au$+$Au data. However, while the number-of-constituent-quark-participant model agrees well with the $d$$+$Au data, the additive-quark model does not.Comment: 391 authors, 24 pages, 19 figures, and 15 Tables. Submitted to Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are publicly available at http://www.phenix.bnl.gov/papers.htm

System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV

We present azimuthal angle correlations of intermediate transverse momentum (1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and semi-central collisions in all the systems. The broadening and peak location are found to depend upon the number of participants in the collision, but not on the collision energy or beam nuclei. These results are consistent with sound or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Improved Measurement of Double Helicity Asymmetry in Inclusive Midrapidity pi^0 Production for Polarized p+p Collisions at sqrt(s)=200 GeV

We present an improved measurement of the double helicity asymmetry for pi^0 production in polarized proton-proton scattering at sqrt(s) = 200 GeV employing the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The improvements to our previous measurement come from two main factors: Inclusion of a new data set from the 2004 RHIC run with higher beam polarizations than the earlier run and a recalibration of the beam polarization measurements, which resulted in reduced uncertainties and increased beam polarizations. The results are compared to a Next to Leading Order (NLO) perturbative Quantum Chromodynamics (pQCD) calculation with a range of polarized gluon distributions.Comment: 389 authors, 4 pages, 2 tables, 1 figure. Submitted to Phys. Rev. D, Rapid Communications. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration

Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (p_T), elliptic flow, two-particle correlations, non-statistical fluctuations, and suppression of particle production at high p_T. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted to Nuclear Physics A as a regular article; v3 has minor changes in response to referee comments. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study

Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation. Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3 days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure. Results: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3 days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60\u20131.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14\u20131.64). Conclusion: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely

Saturation of azimuthal anisotropy in Au + Au collisions at sqrt(s_NN) = 62 - 200 GeV

New measurements are presented for charged hadron azimuthal correlations at mid-rapidity in Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV. They are compared to earlier measurements obtained at sqrt(s_NN) = 130 GeV and in Pb+Pb collisions at sqrt(s_NN) = 17.2 GeV. Sizeable anisotropies are observed with centrality and transverse momentum (p_T) dependence characteristic of elliptic flow (v_2). For a broad range of centralities, the observed magnitudes and trends of the differential anisotropy, v_2(p_T), change very little over the collision energy range sqrt(s_NN) = 62-200 GeV, indicating saturation of the excitation function for v_2 at these energies. Such a saturation may be indicative of the dominance of a very soft equation of state for sqrt(s_NN) = 62-200 GeV.Comment: 432 authors, 7 pages text, 4 figures, REVTeX4. To be submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm