Repurposing existing drugs for the treatment of COVID-19

The rapid global spread and significant mortality associated with the coronavirus disease (COVID-19) caused by SARS-CoV-2 viral infection has spurred an urgent race to find effective treatments. Repurposing existing drugs is a particularly attractive approach as pharmacokinetic and safety data already exist, thus development can leapfrog straight to clinical trials of efficacy, generating results far more quickly than de novo drug development. This review summarizes the state of play for the principle drugs identified as candidates to be repurposed for treating COVID-19 grouped by broad mechanism of action: antiviral, immune enhancing, and anti-inflammatory or immunomodulatory. Patient selection, particularly with regard to disease stage, is likely to be key. To date only dexamethasone and remedesivir have been shown to be effective, but several other promising candidates are in trials

EXCITATION CONDITIONS IN THE MULTI-COMPONENT SUBMILLIMETER GALAXY SMM J00266+1708

We present multiline CO observations of the complex submillimeter galaxy SMMJ00266+1708. Using the Zpectrometer on the Green Bank Telescope, we provide the first precise spectroscopic measurement of its redshift (z = 2.742). Based on followup CO(1–0), CO(3–2), and CO(5–4) mapping, SMMJ00266+1708 appears to have two distinct components separated by ∼ 500 kms−1 that are nearly coincident along our line of sight. The two components show hints of different kinematics, with the blue-shifted component dispersion-dominated and the red-shifted component showing a clear velocity gradient. CO line ratios differ slightly between the two components, indicating that the physical conditions in their molecular gas may not be alike. We tentatively infer that SMMJ00266+1708 is an on going merger with a mass ratio of (7.8±4.0)/ sin2(i), with its overall size and surface brightness closely resembling that of other merging systems. We perform large velocity gradient modeling of the CO emission from both components and find that each component’s properties are consistent with a single phase of molecular gas (i.e., a single temperatures and density); additional multi-phase modelling of the red-shifted component, although motivated by a CO(1–0) size larger than the CO(3–2) size, is inconclusive. SMMJ00266+1708 provides evidence of early stage mergers within the submillimeter galaxy population. Continuum observations of J00266 at the ∼ 1′′ resolution of our observations could not have distinguished between the two components due to their separation (0.′′73 ± 0.′′06), illustrating that the additional velocity information provided by spectral line studies is important for addressing the prevalence of unresolved galaxy pairs in low-resolution submillimeter surveys

Excitation Conditions in the Multi-component Submillimeter Galaxy SMM J00266+1708

We present multiline CO observations of the complex submillimeter galaxy SMM J00266+1708. Using the Zpectrometer on the Green Bank Telescope, we provide the first precise spectroscopic measurement of its redshift (z=2.742). Based on followup CO(1-0), CO(3-2), and CO(5-4) mapping, SMM J00266+1708 appears to have two distinct components separated by ~500 km/s that are nearly coincident along our line of sight. The two components show hints of different kinematics, with the blue-shifted component dispersion-dominated and the red-shifted component showing a clear velocity gradient. CO line ratios differ slightly between the two components, indicating that the physical conditions in their molecular gas may not be alike. We tentatively infer that SMM J00266+1708 is an ongoing merger with a mass ratio of (7.8+/-4.0)/sin^2(i), with its overall size and surface brightness closely resembling that of other merging systems. We perform large velocity gradient modeling of the CO emission from both components and find that each component's properties are consistent with a single phase of molecular gas (i.e., a single temperatures and density); additional multi-phase modeling of the red-shifted component, although motivated by a CO(1-0) size larger than the CO(3-2) size, is inconclusive. SMM J00266+1708 provides evidence of early stage mergers within the submillimeter galaxy population. Continuum observations of J00266 at the ~1" resolution of our observations could not have distinguished between the two components due to their separation (0.73" +/- 0.06"), illustrating that the additional velocity information provided by spectral line studies is important for addressing the prevalence of unresolved galaxy pairs in low-resolution submillimeter surveys

Podoplanin-positive cancer cells at the edge of esophageal squamous cell carcinomas are involved in invasion

Podoplanin (PDPN) is a well established lymphatic endothelial marker and has frequently been observed in cancer cells at the edge of cancer masses. Previous studies investigating the association between PDPN expression and patient prognosis have had contradictory results. In the present study, it was hypothesized that the different locations of PDPNpositive cells may explain these varying results. The present study aimed to focus on PDPN expression at the edge of esophageal cancer cell nests. In order to analyze the clinical significance of this PDPN expression, immunohistochemistry was performed using esophageal cancer tissue microarrays. PDPN expression at the edge of the cancer cell nest was found to be significantly associated with invasion (P<0.05) and poor prognosis (P<0.001) in patients with cancer. To further investigate the role of PDPN expression in cancer cells, the PDPN gene was cloned and transfected into esophageal squamous cell carcinoma (ESCC) cell lines. PDPN expression was also knocked down using small interfering RNA. PDPNpositive cancer cells were found to exhibit invasion characteristics. Thus, PDPN expression at the edge of a cancer cell nest may indicate invasion and represent a poor prognostic factor for ESCCs.published_or_final_versio

Hopf algebras, coproducts and symbols: an application to Higgs boson amplitudes

We show how the Hopf algebra structure of multiple polylogarithms can be used to simplify complicated expressions for multi-loop amplitudes in perturbative quantum field theory and we argue that, unlike the recently popularized symbol-based approach, the coproduct incorporates information about the zeta values. We illustrate our approach by rewriting the two-loop helicity amplitudes for a Higgs boson plus three gluons in a simplified and compact form involving only classical polylogarithms.Comment: 46 page

Atomic-level structural and chemical analysis of Cr-doped Bi2Se3 thin films

We present a study of the structure and chemical composition of the Cr-doped 3D topological insulator Bi2Se3. Single-crystalline thin films were grown by molecular beam epitaxy on Al2O3 (0001), and their structural and chemical properties determined on an atomic level by aberration-corrected scanning transmission electron microscopy and electron energy loss spectroscopy. A regular quintuple layer stacking of the Bi2Se3 film is found, with the exception of the first several atomic layers in the initial growth. The spectroscopy data gives direct evidence that Cr is preferentially substituting for Bi in the Bi2Se3 host. We also show that Cr has a tendency to segregate at internal grain boundaries of the Bi2Se3 film

Electrically controlled long-distance spin transport through an antiferromagnetic insulator

Spintronics uses spins, the intrinsic angular momentum of electrons, as an alternative for the electron charge. Its long-term goal is in the development of beyond-Moore low dissipation technology devices. Recent progress demonstrated the long-distance transport of spin signals across ferromagnetic insulators. Antiferromagnetically ordered materials are however the most common class of magnetic materials with several crucial advantages over ferromagnetic systems. In contrast to the latter, antiferromagnets exhibit no net magnetic moment, which renders them stable and impervious to external fields. In addition, they can be operated at THz frequencies. While fundamentally their properties bode well for spin transport, previous indirect observations indicate that spin transmission through antiferromagnets is limited to short distances of a few nanometers. Here we demonstrate the long-distance, over tens of micrometers, propagation of spin currents through hematite (\alpha-Fe2O3), the most common antiferromagnetic iron oxide, exploiting the spin Hall effect for spin injection. We control the spin current flow by the interfacial spin-bias and by tuning the antiferromagnetic resonance frequency with an external magnetic field. This simple antiferromagnetic insulator is shown to convey spin information parallel to the compensated moment (N\'eel order) over distances exceeding tens of micrometers. This newly-discovered mechanism transports spin as efficiently as the net magnetic moments in the best-suited complex ferromagnets. Our results pave the way to ultra-fast, low-power antiferromagnet-insulator-based spin-logic devices that operate at room temperature and in the absence of magnetic fields

The Effect of Using an Inappropriate Protein Database for Proteomic Data Analysis

A recent study by Bromenshenk et al., published in PLoS One (2010), used proteomic analysis to identify peptides purportedly of Iridovirus and Nosema origin; however the validity of this finding is controversial. We show here through re-analysis of a subset of this data that many of the spectra identified by Bromenshenk et al. as deriving from Iridovirus and Nosema proteins are actually products from Apis mellifera honey bee proteins. We find no reliable evidence that proteins from Iridovirus and Nosema are present in the samples that were re-analyzed. This article is also intended as a learning exercise for illustrating some of the potential pitfalls of analysis of mass spectrometry proteomic data and to encourage authors to observe MS/MS data reporting guidelines that would facilitate recognition of analysis problems during the review process

Factorization Properties of Soft Graviton Amplitudes

We apply recently developed path integral resummation methods to perturbative quantum gravity. In particular, we provide supporting evidence that eikonal graviton amplitudes factorize into hard and soft parts, and confirm a recent hypothesis that soft gravitons are modelled by vacuum expectation values of products of certain Wilson line operators, which differ for massless and massive particles. We also investigate terms which break this factorization, and find that they are subleading with respect to the eikonal amplitude. The results may help in understanding the connections between gravity and gauge theories in more detail, as well as in studying gravitational radiation beyond the eikonal approximation.Comment: 35 pages, 5 figure

Balancing the dilution and oddity effects: Decisions depend on body size

Background Grouping behaviour, common across the animal kingdom, is known to reduce an individual's risk of predation; particularly through dilution of individual risk and predator confusion (predator inability to single out an individual for attack). Theory predicts greater risk of predation to individuals more conspicuous to predators by difference in appearance from the group (the ‘oddity’ effect). Thus, animals should choose group mates close in appearance to themselves (eg. similar size), whilst also choosing a large group. Methodology and Principal Findings We used the Trinidadian guppy (Poecilia reticulata), a well known model species of group-living freshwater fish, in a series of binary choice trials investigating the outcome of conflict between preferences for large and phenotypically matched groups along a predation risk gradient. We found body-size dependent differences in the resultant social decisions. Large fish preferred shoaling with size-matched individuals, while small fish demonstrated no preference. There was a trend towards reduced preferences for the matched shoal under increased predation risk. Small fish were more active than large fish, moving between shoals more frequently. Activity levels increased as predation risk decreased. We found no effect of unmatched shoal size on preferences or activity. Conclusions and Significance Our results suggest that predation risk and individual body size act together to influence shoaling decisions. Oddity was more important for large than small fish, reducing in importance at higher predation risks. Dilution was potentially of limited importance at these shoal sizes. Activity levels may relate to how much sampling of each shoal was needed by the test fish during decision making. Predation pressure may select for better decision makers to survive to larger size, or that older, larger fish have learned to make shoaling decisions more efficiently, and this, combined with their size relative to shoal-mates, and attractiveness as prey items influences shoaling decisions