The use of peptides in therapy presents several limitations, from physicochemical characteristics to inadequate pharmacokinetic profiles for oral absorption. As peptides are gaining importance in the ...therapeutic arsenal, there is an increasing need to rationalize the main characteristics of this compound class in the market. Therefore, we performed an extensive analysis of all known peptide drugs and clinical candidates based on their peptide features, physicochemical and structural properties, and correlated these with their administration route and therapeutic classes. Peptide drugs are widely distributed across drug and pharmacological space, covering several therapeutic areas with structural diversity and complexity, distributed between groups of cyclic and linear compounds. Although structural and physicochemical properties are clear within these groups, we counter the consensus that cyclic peptides have better oral availability than linear peptides, as most of the orally administrated peptides have linear structures. This study and review furnishes information that could support peptide drug design, with a new cutoff of known descriptors that go beyond the Rule of Five.
Context. Gamma-ray bursts (GRBs) occurring in the local Universe constitute an interesting sub-class of the GRB family, since their luminosity is on average lower than that of their cosmological ...analogs. Attempts to understand in a global way this peculiar behaviour is still not possible, since the sample of low redshift GRBs is small, and the properties of individual objects are too different from each other. In addition, their closeness (and consequently high fluxes) make these sources ideal targets for extensive follow-up even with small telescopes, considering also that these GRBs are conclusively associated with supernova (SN) explosions. Aims. We aim to contribute to the study of local bursts by reporting the case of GRB 171205A. This source was discovered by Swift Burst Alert Telescope (BAT) on 2017, December 5 and soon associated with a low redshift host galaxy (z = 0.037), and an emerging SN (SN 2017iuk). Methods. We analyzed the full Swift dataset, comprising the UV-Optical Telescope (UVOT), X-ray Telescope (XRT) and BAT data. In addition, we employed the Konus-Wind high energy data as a valuable extension at γ-ray energies. Results. The photometric SN signature is clearly visible in the UVOT u, b and ν filters. The maximum emission is reached at ∼13 (rest frame) days, and the whole bump resembles that of SN 2006aj, but lower in magnitude and with a shift in time of +2 d. A prebump in the ν-band is also clearly visible, and this is the first time that such a feature is not observed achromatically in GRB–SNe. Its physical origin cannot be easily explained. The X-ray spectrum shows an intrinsic Hydrogen column density NH,int = 7.4+4.1−3.6 × 1020 N H , int = 7 . 4 − 3.6 + 4.1 × 10 20 $ N_{\mathrm{H,int}} = 7.4^{+4.1}_{-3.6}\times 10^{20} $ cm−2, which is at the low end of the N H, int, even considering just low redshift GRBs. The spectrum also features a thermal component, which is quite common in GRBs associated with SNe, but whose origin is still a matter of debate. Finally, the isotropic energy in the γ-ray band, Eiso = 2.18+0.63−5.0 × 1049 E iso = 2 . 18 − 0.50 + 0.63 × 10 49 $ E_{\mathrm{iso}} = 2.18^{+0.63}_{-0.50} \times 10^{49} $ erg, is lower than those of cosmological GRBs. Combining this value with the peak energy in the same band, Ep = 125+141−37 E p = 125 − 37 + 141 $ E_{\mathrm{p}}=125^{+141}_{-37} $ keV, implies that GRB 171205A is an outlier of the Amati relation, as are some other low redshift GRBs, and its emission mechanism should be different from that of canonical, farther away GRBs.
Abstract
Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural, or electrical cardiac disorders are associated with SCD in ...young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly over the last decade; pushed by a growing body of scientific data that both tests proposed criteria sets and establishes new evidence to guide refinements. On 26–27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington, to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD.
ABSTRACT
We report observations and analysis of the nearby gamma-ray burst GRB 161219B (redshift z = 0.1475) and the associated Type Ic supernova (SN) 2016jca. GRB 161219B had an isotropic gamma-ray ...energy of ∼1.6 × 1050 erg. Its afterglow is likely refreshed at an epoch preceding the first photometric points (0.6 d), which slows down the decay rates. Combined analysis of the SN light curve and multiwavelength observations of the afterglow suggest that the GRB jet was broad during the afterglow phase (full opening angle ∼42° ± 3°). Our spectral series shows broad absorption lines typical of GRB supernovae (SNe), which testify to the presence of material with velocities up to ∼0.25c. The spectrum at 3.73 d allows for the very early identification of an SN associated with a GRB. Reproducing it requires a large photospheric velocity ($35\, 000 \pm 7000$ km s−1). The kinetic energy of the SN is estimated through models to be Ekin≈4 × 1052 erg in spherical symmetry. The ejected mass in the explosion was Mej≈6.5 ± 1.5 M⊙, much less than that of other GRB-SNe, demonstrating diversity among these events. The total amount of 56Ni in the explosion was 0.27 ± 0.05 M⊙. The observed spectra require the presence of freshly synthesized 56Ni at the highest velocities, at least three times more than a standard GRB-SN. We also find evidence for a decreasing 56Ni abundance as a function of decreasing velocity. This suggests that SN 2016jca was a highly aspherical explosion viewed close to on-axis, powered by a compact remnant. Applying a typical correction for asymmetry, the energy of SN 2016jca was ∼(1–3) × 1052 erg, confirming that most of the energy produced by GRB-SNe goes into the kinetic energy of the SN ejecta.
Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural or electrical cardiac disorders are associated with SCD in young ...athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly, advanced by a growing body of scientific data and investigations that both examine proposed criteria sets and establish new evidence to guide refinements. On 26-27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington (USA), to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD.
Abstract Cardiovascular evaluation and care of college student-athletes is gaining increasing attention from both the public and medical communities. Emerging strategies include screening of the ...general athlete population, recommendations of permissible levels of participation by athletes with identified cardiovascular conditions, and preparation for responding to unanticipated cardiac events in athletic venues. The primary focus has been sudden cardiac death and the utility of screening with or without advanced cardiac screening. The National Collegiate Athletic Association convened a multidisciplinary task force to address cardiovascular concerns in collegiate student-athletes and to develop consensus for an interassociation statement. This document summarizes the task force deliberations and follow-up discussions, and includes available evidence on cardiovascular risk, pre-participation evaluation, and the recognition of and response to cardiac arrest. Future recommendations for cardiac research initiatives, education, and collaboration are also provided.
Abstract
We re-examine the UV/optical and X-ray observations of GRB 060218 during the prompt and afterglow phases. We present evidence in the UV/optical spectra that there is a synchrotron component ...contributing to the observed flux in the initial 1350 s. This result suggests that GRB 060218 is produced from a low-luminosity jet, which penetrates through its progenitor envelope after core collapse. The jet interacts with the surrounding medium to generate the UV/optical external shock synchrotron emission. After 1350 s, the thermal radiation in the UV/optical and X-ray becomes the dominant contribution to the observed flux. The UV/optical and X-ray spectra at 1350–10 000 s can be fitted with a spherically outflowing blackbody model, with an additional power-law component to the model at X-ray energies.
We present detailed neutron scattering studies of the static and dynamic stripes in an optimally doped high-temperature superconductor, La_{2}CuO_{4+y}. We observe that the dynamic stripes do not ...disperse towards the static stripes in the limit of vanishing energy transfer. Therefore, the dynamic stripes observed in neutron scattering experiments are not the Goldstone modes associated with the broken symmetry of the simultaneously observed static stripes, and the signals originate from different domains in the sample. These observations support real-space electronic phase separation in the crystal, where the static stripes in one phase are pinned versions of the dynamic stripes in the other, having slightly different periods. Our results explain earlier observations of unusual dispersions in underdoped La_{2-x}Sr_{x}CuO_{4} (x=0.07) and La_{2-x}Ba_{x}CuO_{4} (x=0.095).
Candidate wellbeing is recognised as a continual challenge for doctoral programs, with government mandates requiring an institutional response. This article explores the experiences of candidates ...undertaking intensive writing sessions ('Write-Ins') and their influence on their wellbeing. Exploratory findings demonstrate opportunities for Write-In models to contribute positively to 'Spaces of Wellbeing'. Spaces of Wellbeing theory highlights four dimensions of space that influence wellbeing: capability, security, integrative and therapeutic spaces. Findings show the Write-Ins contributed positively to wellbeing by offering space for candidates to enhance writing productivity, to work to their own pace, to connect with others, and to work flexibly.
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