Magnetic Reconnection in Extreme Astrophysical Environments

Magnetic reconnection is a basic plasma process of dramatic rearrangement of magnetic topology, often leading to a violent release of magnetic energy. It is important in magnetic fusion and in space and solar physics --- areas that have so far provided the context for most of reconnection research. Importantly, these environments consist just of electrons and ions and the dissipated energy always stays with the plasma. In contrast, in this paper I introduce a new direction of research, motivated by several important problems in high-energy astrophysics --- reconnection in high energy density (HED) radiative plasmas, where radiation pressure and radiative cooling become dominant factors in the pressure and energy balance. I identify the key processes distinguishing HED reconnection: special-relativistic effects; radiative effects (radiative cooling, radiation pressure, and Compton resistivity); and, at the most extreme end, QED effects, including pair creation. I then discuss the main astrophysical applications --- situations with magnetar-strength fields (exceeding the quantum critical field of about 4 x 10^13 G): giant SGR flares and magnetically-powered central engines and jets of GRBs. Here, magnetic energy density is so high that its dissipation heats the plasma to MeV temperatures. Electron-positron pairs are then copiously produced, making the reconnection layer highly collisional and dressing it in a thick pair coat that traps radiation. The pressure is dominated by radiation and pairs. Yet, radiation diffusion across the layer may be faster than the global Alfv\'en transit time; then, radiative cooling governs the thermodynamics and reconnection becomes a radiative transfer problem, greatly affected by the ultra-strong magnetic field. This overall picture is very different from our traditional picture of reconnection and thus represents a new frontier in reconnection research.Comment: Accepted to Space Science Reviews (special issue on magnetic reconnection). Article is based on an invited review talk at the Yosemite-2010 Workshop on Magnetic Reconnection (Yosemite NP, CA, USA; February 8-12, 2010). 30 pages, no figure

Flux-rope twist in eruptive flares and CMEs : due to zipper and main-phase reconnection

Funding: UK Science and Technology Facilities CouncilThe nature of three-dimensional reconnection when a twisted flux tube erupts during an eruptive flare or coronal mass ejection is considered. The reconnection has two phases: first of all, 3D “zipper reconnection” propagates along the initial coronal arcade, parallel to the polarity inversion line (PIL); then subsequent quasi-2D “main phase reconnection” in the low corona around a flux rope during its eruption produces coronal loops and chromospheric ribbons that propagate away from the PIL in a direction normal to it. One scenario starts with a sheared arcade: the zipper reconnection creates a twisted flux rope of roughly one turn (2π radians of twist), and then main phase reconnection builds up the bulk of the erupting flux rope with a relatively uniform twist of a few turns. A second scenario starts with a pre-existing flux rope under the arcade. Here the zipper phase can create a core with many turns that depend on the ratio of the magnetic fluxes in the newly formed flare ribbons and the new flux rope. Main phase reconnection then adds a layer of roughly uniform twist to the twisted central core. Both phases and scenarios are modeled in a simple way that assumes the initial magnetic flux is fragmented along the PIL. The model uses conservation of magnetic helicity and flux, together with equipartition of magnetic helicity, to deduce the twist of the erupting flux rope in terms the geometry of the initial configuration. Interplanetary observations show some flux ropes have a fairly uniform twist, which could be produced when the zipper phase and any pre-existing flux rope possess small or moderate twist (up to one or two turns). Other interplanetary flux ropes have highly twisted cores (up to five turns), which could be produced when there is a pre-existing flux rope and an active zipper phase that creates substantial extra twist.PostprintPublisher PDFPeer reviewe

An Observational Overview of Solar Flares

We present an overview of solar flares and associated phenomena, drawing upon a wide range of observational data primarily from the RHESSI era. Following an introductory discussion and overview of the status of observational capabilities, the article is split into topical sections which deal with different areas of flare phenomena (footpoints and ribbons, coronal sources, relationship to coronal mass ejections) and their interconnections. We also discuss flare soft X-ray spectroscopy and the energetics of the process. The emphasis is to describe the observations from multiple points of view, while bearing in mind the models that link them to each other and to theory. The present theoretical and observational understanding of solar flares is far from complete, so we conclude with a brief discussion of models, and a list of missing but important observations.Comment: This is an article for a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

An antibody developability triaging pipeline exploiting protein language models

Therapeutic monoclonal antibodies (mAbs) are a successful class of biologic drugs that are frequently selected from phage display libraries and transgenic mice that produce fully human antibodies. However, binding affinity to the correct epitope is necessary, but not sufficient, for a mAb to have therapeutic potential. Sequence and structural features affect the developability of an antibody, which influences its ability to be produced at scale and enter trials, or can cause late-stage failures. Using data on paired human antibody sequences, we introduce a pipeline using a machine learning approach that exploits protein language models to identify antibodies which cluster with antibodies that have entered the clinic and are therefore expected to have developability features similar to clinically acceptable antibodies, and triage out those without these features. We propose this pipeline as a useful tool in candidate selection from large libraries, reducing the cost of exploration of the antibody space, and pursuing new therapeutics

Antibody markup language (AbML) — a notation language for antibody-based drug formats and software for creating and rendering AbML (abYdraw)

As interest in antibody-based drug development continues to increase, the biopharmaceutical industry has begun to focus on complex multi-specific antibodies (MsAbs) as an up-and-coming class of biologic that differ from natural monoclonal antibodies through their ability to bind to more than one type of antigen. As techniques to generate such molecules have diversified, so have their formats and the need for standard notation. Previous efforts to develop a notation language for macromolecule drugs have been insufficient, or too complex, for MsAbs. Here, we present Antibody Markup Language (AbML), a new notation language specifically for antibody formats that overcomes the limitations of existing languages and can annotate all current antibody formats, including fusions, fragments, standard antibodies and MsAbs, as well as all currently conceivable future formats. AbML V1.1 also provides explicit support for T-cell receptor domains. To assist users of this language we have also developed a tool, abYdraw, that can draw antibody schematics from AbML strings or generate an AbML string from a drawn antibody schematic. AbML has the potential to become a standardized notation for describing new MsAb formats entering clinical trials.Abbreviations: AbML: Antibody Markup Language; ADC: Antibody-drug conjugate; CAS: Chemical Abstracts Service; CH: Constant heavy; CL: Constant light; Fv: Variable fragment; HELM: Hierarchical Editing Language for Macromolecules; HSA: Human serum albumin; INN: International Nonproprietary Names; KIH: Knobs-into-holes; mAbs: Monoclonal antibodies; MsAb: Multi-specific antibody; WHO: World Health Organization; PEG: Poly-ethylene glycol; scFv: Single-chain variable fragment; SMILES: Simplified Molecular-Input Line-Entry System; VH: Variable heavy; VHH: Single-domain (Camelid) variable heavy; VL: Variable ligh