Duality between Coronavirus Transmission and Air-based Macroscopic Molecular Communication

This contribution exploits the duality between a viral infection process and macroscopic air-based molecular communication. Airborne aerosol and droplet transmission through human respiratory processes is modeled as an instance of a multiuser molecular communication scenario employing respiratory-event-driven molecular variable-concentration shift keying. Modeling is aided by experiments that are motivated by a macroscopic air-based molecular communication testbed. In artificially induced coughs, a saturated aqueous solution containing a fluorescent dye mixed with saliva is released by an adult test person. The emitted particles are made visible by means of optical detection exploiting the fluorescent dye. The number of particles recorded is significantly higher in test series without mouth and nose protection than in those with a wellfitting medical mask. A simulation tool for macroscopic molecular communication processes is extended and used for estimating the transmission of infectious aerosols in different environments. Towards this goal, parameters obtained through self experiments are taken. The work is inspired by the recent outbreak of the coronavirus pandemic.Comment: 9 pages, 6 figures, submitted to IEEE Transactions on Molecular, Biological, and Multi-Scale Communications for the special issue "Section II: Molecular Communications for Diagnostics and Therapeutic Development of Infectious Diseases

Characterization of novel elongated Parvulin isoforms that are ubiquitously expressed in human tissues and originate from alternative transcription initiation

BACKGROUND: The peptidyl prolyl cis/trans isomerase (PPIase) Parvulin (Par14/PIN4) is highly conserved in all metazoans and is assumed to play a role in cell cycle progression and chromatin remodeling. It is predominantly localized to the nucleus and binds to chromosomal DNA as well as bent oligonucleotides in vitro. RESULTS: In this study we confirm by RT-PCR the existence of a longer Parvulin isoform expressed in all tissues examined so far. This isoform contains a 5' extension including a 75 bp extended open reading frame with two coupled SNPs leading to amino acid substitutions Q16R and R18S. About 1% of all Parvulin mRNAs include the novel extension as quantified by real-time PCR. The human Parvulin promoter is TATA-less and situated in a CpG island typical for house keeping genes. Thus, different Parvulin mRNAs seem to arise by alternative transcription initiation. N-terminally extended Parvulin is protected from rapid proteinaseK degradation. In HeLa and HepG2 cell lysates two protein species of about 17 and 28 KDa are detected by an antibody against an epitope within the N-terminal extension. These two bands are also recognized by an antibody towards the PPIase domain of Parvulin. The longer Parvulin protein is encoded by the human genome but absent from rodent, bovine and non-mammalian genomes. CONCLUSION: Due to its molecular weight of 16.6 KDa we denote the novel Parvulin isoform as Par17 following the E. coli Par10 and human Par14 nomenclature. The N-terminal elongation of Par17-QR and Par17-RS suggests these isoforms to perform divergent functions within the eukaryotic cell than the well characterized Par14

The DNA binding parvulin Par17 is targeted to the mitochondrial matrix by a recently evolved prepeptide uniquely present in Hominidae

<p>Abstract</p> <p>Background</p> <p>The parvulin-type peptidyl prolyl <it>cis/trans </it>isomerase Par14 is highly conserved in all metazoans. The recently identified parvulin Par17 contains an additional N-terminal domain whose occurrence and function was the focus of the present study.</p> <p>Results</p> <p>Based on the observation that the human genome encodes Par17, but bovine and rodent genomes do not, Par17 exon sequences from 10 different primate species were cloned and sequenced. Par17 is encoded in the genomes of Hominidae species including humans, but is absent from other mammalian species. In contrast to Par14, endogenous Par17 was found in mitochondrial and membrane fractions of human cell lysates. Fluorescence of EGFP fusions of Par17, but not Par14, co-localized with mitochondrial staining. Par14 and Par17 associated with isolated human, rat and yeast mitochondria at low salt concentrations, but only the Par17 mitochondrial association was resistant to higher salt concentrations. Par17 was imported into mitochondria in a time and membrane potential-dependent manner, where it reached the mitochondrial matrix. Moreover, Par17 was shown to bind to double-stranded DNA under physiological salt conditions.</p> <p>Conclusion</p> <p>Taken together, the DNA binding parvulin Par17 is targeted to the mitochondrial matrix by the most recently evolved mitochondrial prepeptide known to date, thus adding a novel protein constituent to the mitochondrial proteome of Hominidae.</p

Design of photoactivatable metallodrugs : selective and rapid light-induced ligand dissociation from half-sandwich [Ru([9]aneS3)(N–N′)(py)]2+ complexes

The synthesis of the inert Ru(II) half-sandwich coordination compounds, [Ru([9]aneS3)(bpy)(py)][PF6]2 (1, [9]aneS3 = 1,4,7-trithiacyclononane, bpy = 2,2′-bipyridine, py = pyridine), [Ru([9]aneS3)(en)(py)][PF6]2 (2, en = 1,2-diaminoethane), and [Ru([9]aneN3)(en)(dmso-S)][PF6]2 (3, [9]aneN3 = 1,4,7-triazacyclononane), is reported along with the X-ray crystal structure of 1. We investigated whether these complexes have photochemical properties which might make them suitable for use as pro-drugs in photochemotherapy. Complexes 1 and 2 underwent rapid (minutes) aquation with dissociation of the pyridine ligand in aqueous solution when irradiated with blue light (λ = 420 or 467 nm). The photodecomposition of 3 was much slower. All complexes readily formed adducts with 9-ethylguanine (9-EtG) when this model nucleobase was present in the photolysis solution. Similarly, complex 1 formed adducts with the tripeptide glutathione (GSH), but only when photoactivated. HPLC and MS studies of 1 showed that irradiation promoted rapid formation of 1:1 (major) and 1:2 (minor) adducts of the oligonucleotide d(ATACATGCTACATA) with the fragment {Ru([9]aneS3)(bpy)}2+. Density functional theory (DFT) calculations and time-dependent DFT reproduced the major features of the absorption spectra and suggested that the lowest-lying triplet state with 3MLCT character, which is readily accessible via intersystem crossing, might be responsible for the observed dissociative behavior of the excited states. These complexes are promising for further study as potential photochemotherapeutic agents

Trapping, chemistry, and export of trace gases in the South Asian summer monsoon observed during CARIBIC flights in 2008

The CARIBIC (Civil Aircraft for the Regular Investigation of the Atmosphere Based on an Instrument Container) passenger aircraft observatory performed in situ measurements at 10–12 km altitude in the South Asian summer monsoon anticyclone between June and September 2008. These measurements enable us to investigate this atmospheric region (which so far has mostly been observed from satellites) using the broad suite of trace gases and aerosol particles measured by CARIBIC. Elevated levels of a variety of atmospheric pollutants (e.g. carbon monoxide, total reactive nitrogen oxides, aerosol particles, and several volatile organic compounds) were recorded. The measurements provide detailed information about the chemical composition of air in different parts of the monsoon anticyclone, particularly of ozone precursors. While covering a range of 3500 km inside the monsoon anticyclone, CARIBIC observations show remarkable consistency, i.e. with distinct latitudinal patterns of trace gases during the entire monsoon period. Using the CARIBIC trace gas and aerosol particle measurements in combination with the Lagrangian particle dispersion model FLEXPART, we investigated the characteristics of monsoon outflow and the chemical evolution of air masses during transport. The trajectory calculations indicate that these air masses originated mainly from South Asia and mainland Southeast Asia. Estimated photochemical ages of the air were found to agree well with transport times from a source region east of 90–95° E. The photochemical ages of the air in the southern part of the monsoon anticyclone were systematically younger (less than 7 days) and the air masses were mostly in an ozone-forming chemical mode. In its northern part the air masses were older (up to 13 days) and had unclear ozone formation or destruction potential. Based on analysis of forward trajectories, several receptor regions were identified. In addition to predominantly westward transport, we found evidence for efficient transport (within 10 days) to the Pacific and North America, particularly during June and September, and also of cross-tropopause exchange, which was strongest during June and July. Westward transport to Africa and further to the Mediterranean was the main pathway during July

Liberal market economies, business, and political finance: Britain under New Labour

The extent and nature of business financing of parties is an important feature of political finance. Britain’s transparent and permissive regulatory system provides an excellent opportunity to study business financing of parties. Business donations have been very important to the Conservative party over the last decade, and of only marginal importance to Labour. Unlike other Conservative contributors, business donors are more likely to contribute when the party is popular. In contrast to the previous period of Conservative government, the biggest British businesses tended to abstain from political finance under New Labour. However, their bias towards the Conservatives is affected by the party’s popularity and the closeness of an election. Britain shares the political importance of business financing of parties and its mixture of ideological and pragmatic motivations with other liberal market economies. However, in Britain the bias towards the right is much stronger and the role of big business more marginal

Synthesis, characterisation and photochemistry of PtIV pyridyl azido acetato complexes

PtII azido complexes [Pt(bpy)(N3)2] (1), [Pt(phen)(N3)2] (2) and trans-[Pt(N3)2(py)2] (3) incorporating the bidentate diimine ligands 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen) or the monodentate pyridine (py) respectively, have been synthesised from their chlorido precursors and characterised by X-ray crystallography; complex 3 shows significant deviation from square-planar geometry (N3–Pt–N3 angle 146.7°) as a result of steric congestion at the Pt centre. The novel PtIV complexes trans, cis-[Pt(bpy)(OAc)2(N3)2] (4), trans, cis-[Pt(phen)(OAc)2(N3)2] (5), trans, trans, trans-[Pt(OAc)2(N3)2(py)2] (6), were obtained from 1–3via oxidation with H2O2 in acetic acid followed by reaction of the intermediate with acetic anhydride. Complexes 4–6 exhibit interesting structural and photochemical properties that were studied by X-ray, NMR and UV-vis spectroscopy and TD-DFT (time-dependent density functional theory). These PtIV complexes exhibit greater absorption at longer wavelengths (ε = 9756 M−1 cm−1 at 315 nm for 4; ε = 796 M−1 cm−1 at 352 nm for 5; ε = 16900 M−1 cm−1 at 307 nm for 6, in aqueous solution) than previously reported PtIV azide complexes, due to the presence of aromatic amines, and 4–6 undergo photoactivation with both UVA (365 nm) and visible green light (514 nm). The UV-vis spectra of complexes 4–6 were calculated using TD-DFT; the nature of the transitions contributing to the UV-vis bands provide insight into the mechanism of production of the observed photoproducts. The UV-vis spectra of 1–3 were also simulated by computational methods and comparison between PtII and PtIV electronic and structural properties allowed further elucidation of the photochemistry of 4–6

Identifying and prioritising unanswered research questions for people with hyperacusis: James Lind Alliance Hyperacusis Priority Setting Partnership

Objective To determine research priorities in hyperacusis that key stakeholders agree are the most important. Design/setting A priority setting partnership using two international surveys, and a UK prioritisation workshop, adhering to the six-staged methodology outlined by the James Lind Alliance. Participants People with lived experience of hyperacusis, parents/carers, family and friends, educational professionals and healthcare professionals who support and/or treat adults and children who experience hyperacusis, including but not limited to surgeons, audiologists, psychologists and hearing therapists. Methods The priority setting partnership was conducted from August 2017 to July 2018. An international identification survey asked respondents to submit any questions/uncertainties about hyperacusis. Uncertainties were categorised, refined and rephrased into representative indicative questions using thematic analysis techniques. These questions were verified as ‘unanswered’ through searches of current evidence. A second international survey asked respondents to vote for their top 10 priority questions. A shortlist of questions that represented votes from all stakeholder groups was prioritised into a top 10 at the final prioritisation workshop (UK). Results In the identification survey, 312 respondents submitted 2730 uncertainties. Of those uncertainties, 593 were removed as out of scope, and the remaining were refined into 85 indicative questions. None of the indicative questions had already been answered in research. The second survey collected votes from 327 respondents, which resulted in a shortlist of 28 representative questions for the final workshop. Consensus was reached on the top 10 priorities for future research, including identifying causes and underlying mechanisms, effective management and training for healthcare professionals. Conclusions These priorities were identified and shaped by people with lived experience, parents/carers and healthcare professionals, and as such are an essential resource for directing future research in hyperacusis. Researchers and funders should focus on addressing these priorities.Additional co-authors: Tracey Pollard, Helen Henshaw, Toto A Gronlund, Derek J Hoar

Abyssal food-web model indicates faunal carbon flow recovery and impaired microbial loop 26 years after a sediment disturbance experiment

Due to the predicted future demand for critical metals, abyssal plains covered with polymetallic nodules are currently being prospected for deep-seabed mining. Deep-seabed mining will lead to significant sediment disturbance over large spatial scales and for extended periods of time. The environmental impact of a small-scale sediment disturbance was studied during the ‘DISturbance and reCOLonization’ (DISCOL) experiment in the Peru Basin in 1989 when 10.8 km2 of seafloor were ploughed with a plough harrow. Here, we present a detailed description of carbon-based food-web models constructed from various datasets collected in 2015, 26 years after the experiment. Detailed observations of the benthic food web were made at three distinct sites: inside 26-year old plough tracks (IPT, subjected to direct impact from ploughing), outside the plough tracks (OPT, exposed to settling of resuspended sediment), and at reference sites (REF, no impact). The observations were used to develop highly-resolved food-web models for each site that quantified the carbon (C) fluxes between biotic (ranging from prokaryotes to various functional groups in meio-, macro-, and megafauna) and abiotic (e.g. detritus) compartments. The model outputs were used to estimate total system throughput, i.e., the sum of all C flows in the food web (the ‘ecological size’ of the system), and microbial loop functioning, i.e., the C-cycling through the prokaryotic compartment for each site. Both the estimated total system throughput and the microbial loop cycling were significantly reduced (by 16% and 35%, respectively) inside the plough tracks compared to the other two sites. Site differences in modelled faunal respiration varied among the different faunal compartments. Overall, modelled faunal respiration appeared to have recovered to, or exceeded reference values after 26-years. The model results indicate that food-web functioning, and especially the microbial loop, have not recovered from the disturbance that was inflicted on the abyssal site 26 years ago