Systematic evaluation of fluorination as modification for peptide-based fusion inhibitors against HIV-1 infection

With the emergence of novel viruses, the development of new antivirals is more urgent than ever. A key step in human immunodeficiency virus type 1 (HIV-1) infection is six-helix bundle formation within the envelope protein subunit gp41. Selective disruption of bundle formation by peptides has been shown to be effective; however, these drugs, exemplified by T20, are prone to rapid clearance from the patient. The incorporation of non-natural amino acids is known to improve these pharmacokinetic properties. Here, we evaluate a peptide inhibitor in which a critical Ile residue is replaced by fluorinated analogues. We characterized the influence of the fluorinated analogues on the biophysical properties of the peptide. Furthermore, we show that the fluorinated peptides can block HIV-1 infection of target cells at nanomolar levels. These findings demonstrate that fluorinated amino acids are appropriate tools for the development of novel peptide therapeutics

Temporal dynamics of selective attention and conflict resolution during cross-dimensional go-nogo decisions

<p>Abstract</p> <p>Background</p> <p>Decision-making is a fundamental capacity which is crucial to many higher-order psychological functions. We recorded event-related potentials (ERPs) during a visual target-identification task that required go-nogo choices. Targets were identified on the basis of cross-dimensional conjunctions of particular colors and forms. Color discriminability was manipulated in three conditions to determine the effects of color distinctiveness on component processes of decision-making.</p> <p>Results</p> <p>Target identification was accompanied by the emergence of prefrontal P2a and P3b. Selection negativity (SN) revealed that target-compatible features captured attention more than target-incompatible features, suggesting that intra-dimensional attentional capture was goal-contingent. No changes of cross-dimensional selection priorities were measurable when color discriminability was altered. Peak latencies of the color-related SN provided a chronometric measure of the duration of attention-related neural processing. ERPs recorded over the frontocentral scalp (N2c, P3a) revealed that color-overlap distractors, more than form-overlap distractors, required additional late selection. The need for additional response selection induced by color-overlap distractors was severely reduced when color discriminability decreased.</p> <p>Conclusion</p> <p>We propose a simple model of cross-dimensional perceptual decision-making. The temporal synchrony of separate color-related and form-related choices determines whether or not distractor processing includes post-perceptual stages. ERP measures contribute to a comprehensive explanation of the temporal dynamics of component processes of perceptual decision-making.</p

Determination of the B(E3, 0(+) -> 3(-))-excitation strength in octupole-correlated nuclei near A approximate to 224 by the means of Coulomb excitation at REX-ISOLDE

Volume: 533Peer reviewe

Do nuclei go pear-shaped? Coulomb excitation of Rn-220 and Ra-224 at REX-ISOLDE (CERN)

Volume: 93The IS475 collaboration conducted Coulomb-excitation experiments with post-accelerated radioactive Rn-220 and Ra-224 beams at the REX-ISOLDE facility. The beam particles (E-beam: 2.83 MeV/u) were Coulomb excited using Ni-60, Cd-14, and Sn-120 scattering targets. De-excitation gamma-rays were detected employing the Miniball array and scattered particles were detected in a silicon detector. Exploiting the Coulomb-excitation code GOSIA for each nucleus several matrix elements could be obtained from the measured gamma-ray yields. The extracted matrix element allows for the conclusion that, while Rn-220 represents an octupole vibrational system, Ra-224 has already substantial octupole correlations in its ground state. This finding has i(m)plications for the search of CP-violating Schiff moments in the atomic systems of the adjacent odd-mass nuclei.Peer reviewe

Isomers in Pd128 and Pd126: Evidence for a Robust Shell Closure at the Neutron Magic Number 82 in Exotic Palladium Isotopes

The level structures of the very neutron-rich nuclei Pd128 and Pd126 have been investigated for the first time. In the r-process waiting-point nucleus Pd128, a new isomer with a half-life of 5.8(8) μs is proposed to have a spin and parity of 8+ and is a

Study of Isomeric States in ^{198,200,202,206}Pb and ²⁰⁶Hg Populated in Fragmentation Reactions

Isomeric states in isotopes in the vicinity of doubly-magic 208Pb were populated following reactions of a relativistic 208Pb primary beam impinging on a 9Be fragmentation target. Secondary beams of 198;200;202;206Pb and 206Hg were isotopically separated and implanted in a passive stopper positioned in the focal plane of the GSI Fragment Separator. Delayed γ rays were detected with the Advanced GAmma Tracking Array (AGATA). Decay schemes were re-evaluated and interpreted with shell-model calculations. The momentum-dependent population of isomeric states in the two-nucleon hole nuclei 206Pb/206Hg was found to differ from the population of multi neutron-hole isomeric states in 198;200;202Pb

EMDR Effects on Pursuit Eye Movements

This study aimed to objectivize the quality of smooth pursuit eye movements in a standard laboratory task before and after an Eye Movement Desensitization and Reprocessing (EMDR) session run on seven healthy volunteers. EMDR was applied on autobiographic worries causing moderate distress. The EMDR session was complete in 5 out of the 7 cases; distress measured by SUDS (Subjective Units of Discomfort Scale) decreased to a near zero value. Smooth pursuit eye movements were recorded by an Eyelink II video system before and after EMDR. For the five complete sessions, pursuit eye movement improved after their EMDR session. Notably, the number of saccade intrusions—catch-up saccades (CUS)—decreased and, reciprocally, there was an increase in the smooth components of the pursuit. Such an increase in the smoothness of the pursuit presumably reflects an improvement in the use of visual attention needed to follow the target accurately. Perhaps EMDR reduces distress thereby activating a cholinergic effect known to improve ocular pursuit

New and comprehensive β - and βp-decay spectroscopy results in the vicinity of Sn 100

26 pags., 30 figs., 11 tabs.A decay spectroscopy experiment on proton-rich nuclei in the vicinity of the doubly magic Sn100 was carried out at RIKEN Nishina Center. More than 20 nuclei with 43≤Z≤50 and N≤51, produced by fragmentation reactions were investigated via analyses of β-decay, βp-decay, and subsequent γ-ray data. Owing to higher statistics, the precision on the half-lives of many of the ground states and isomers was improved. β-decay endpoint energies of 11 states in 8 nuclei were measured for the first time, and the corresponding QEC and excitation energies were generally consistent with various mass models. Many β-delayed proton emission branching ratios were measured either for the first time or with higher precision compared to literature values, and some of them differed by more than 2σ. Many of the large discrepancies were associated with nuclei with long-lived isomeric states, highlighting large systematic uncertainties involved in these measurements. Twenty-five new γ rays were observed, and ten new states are proposed with unambiguous excitation energies, spins, and parities. Most of the energies of the excited states were consistent within 300 keV or 20%, whichever was greater, compared to shell model predictions in the proton/neutron (p1/2,g9/2) model space assuming a Sr76 core. A signature of a new (1/2-) isomer in Cd97 with T1/2=0.73(7) s was found, in good agreement with shell model predictions.The authors would like to thank the personnel at the RIKEN Nishina Center for providing the exotic radioactive isotope beam with record intensities. This experiment was performed at RI Beam Factory operated by RIKEN Nishina Center and CNS, University of Tokyo. We acknowledge the EUROBALL Owners Committee for loaning the germanium detectors and the PreSpec Collaboration for the readout electronics of the cluster detectors of EURICA. Support for the WAS3ABi setup was provided by the Rare Isotope Science Project, funded by the Ministry of Education, Science and Technology (MEST) and National Research Foundation (NRF) of Korea, as well as KAKENHI (Grant No. 25247045) of Japan Society for the Promotion of Science (JSPS). The authors acknowledge the support of the DFG cluster of excellence “Origin and Structure of the Universe,” German BMBF under Contract No. 05P15PKFNA and the Spanish Ministerio de Economía y Competitividad via Project No. FPA2017- 84756-C4-2-P. Part of the research was funded by the Natural Sciences and Engineering Research Council (NSERC) of Canada and also supported by FJ-NSP (French-Japanese International Associated Laboratory for Nuclear Structure Problems)

Shell evolution of N = 40 isotones towards 60Ca: First spectroscopy of 62Ti

Excited states in the N=40 isotone 62Ti were populated via the 63V(p,2p)62Ti reaction at ∼200 MeV/nucleon at the Radioactive Isotope Beam Factory and studied using γ-ray spectroscopy. The energies of the 21+→0gs+ and 41+→21+ transitions, observed here for the first time, indicate a deformed 62Ti ground state. These energies are increased compared to the neighboring 64Cr and 66Fe isotones, suggesting a small decrease of quadrupole collectivity. The present measurement is well reproduced by large-scale shell-model calculations based on effective interactions, while ab initio and beyond mean-field calculations do not yet reproduce our findings. The shell-model calculations for 62Ti show a dominant configuration with four neutrons excited across the N=40 gap. Likewise, they indicate that the N=40 island of inversion extends down to Z=20, disfavoring a possible doubly magic character of the elusive 60Ca