A review of cytokine-based pathophysiology of Long COVID symptoms

The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production. In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with "brain fog," arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines. There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS

A review of cytokine-based pathophysiology of Long COVID symptoms

The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production. In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with “brain fog,” arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines. There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS

Implementation of Provably Stable MaxNet

MaxNet TCP is a congestion control protocol that uses explicit multi-bit signalling from routers to achieve desirable properties such as high throughput and low latency. In this paper we present an implementation of an extended version of MaxNet. Our contributions are threefold. First, we extend the original algorithm to give both provable stability and rate fairness. Second, we introduce the MaxStart algorithm which allows new MaxNet connections to reach their fair rates quickly. Third, we provide a Linux kernel implementation of the protocol. With no overhead but 24-bit price signals, our implementation scales from 32 bit/s to 1 peta-bit/s with a 0.001% rate accuracy. We confirm the theoretically predicted properties by performing a range of experiments at speeds up to 1 Gbit/sec and delays up to 180 ms on the WAN-in-Lab facility

The pre-inquisitorial career of Bernard Gui

I have tried to provide an account of Bernard Gui's early career, from his birth in 1261 to his appointment as inquisitor of Toulouse in 1307. Biographical accounts of Bernard are few and far between: a short obituary by his nephew in the early 1330s, entries in early-twentieth-century catalogues such as the Histoire littéraire de la France and Dictionnaire d'histoire et de géographie ecclésiastiques, and the sixteenth volume of the Cahiers de Fajeaux in 1981. This dearth belies the essential space Bernard's texts occupy in the modern study of medieval religious orders, the inquisition, and southern France. Bernard himself deserves a study. The worlds around him were changing quickly. Friars who had known Dominic personally were growing old and dying. Burgeoning royal power came into increasingly dramatic conflict with both religious and secular establishments. Southern France was still recovering (financially, politically, and psychologically) from the Albigensian Crusade and its inquisitions. The texts Bernard chose to produce responded to administrative, political, and social realities in dynamic ways. His written record tells modern historians much about contemporary anxieties and the man who faced them. This thesis utilizes Bernard's history of the Dominican Order to learn more about Bernard himself. The boy who will become inquisitor of Toulouse came of age infatuated with the Dominican Order and its attendant personalities, values, and network. The preservation of the order's institutional values and administrative organization animated his first noteworthy historical work. When the friars and their inquisition came under attack in the years immediately preceding his tenure as inquisitor, Bernard suppressed his sense of betrayal to preserve the order's most important relationships. I hope that through this thesis, readers may encounter Bernard and feel more confident in describing his values, anxieties, and personality

How are “Atypical” Sulfite Dehydrogenases Linked to Cell Metabolism? Interactions between the SorT Sulfite Dehydrogenase and Small Redox Proteins

Sulfite dehydrogenases (SDHs) are enzymes that catalyze the oxidation of the toxic and mutagenic compound sulfite to sulfate, thereby protecting cells from adverse effects associated with sulfite exposure. While some bacterial SDHs that have been characterized to date are able to use cytochrome c as an electron acceptor, the majority of these enzymes prefer ferricyanide as an electron acceptor and have therefore been termed “atypical” SDHs. Identifying the natural electron acceptor of these enzymes, however, is crucial for understanding how the “atypical” SDHs are integrated into cell metabolism. The SorT sulfite dehydrogenase from Sinorhizobium meliloti is a representative of this enzyme type and we have investigated the interactions of SorT with two small redox proteins, a cytochrome c and a Cu containing pseudoazurin, that are encoded in the same operon and are co-transcribed with the sorT gene. Both potential acceptor proteins have been purified and characterized in terms of their biochemical and electrochemical properties, and interactions and enzymatic studies with both the purified SorT sulfite dehydrogenase and components of the respiratory chain have been carried out. We were able to show for the first time that an “atypical” sulfite dehydrogenase can couple efficiently to a cytochrome c isolated from the same organism despite being unable to efficiently reduce horse heart cytochrome c, however, at present the role of the pseudoazurin in SorT electron transfer is unclear, but it is possible that it acts as an intermediate electron shuttle between. The SorT system appears to couple directly to the respiratory chain, most likely to a cytochrome oxidase

Dynamic adjustment of receive window utilized by a transmitting device

A method of controlling size of a receive window includes transmitting packets over a communication channel from a transmitting device to a receiver, and receiving acknowledgment packets from the receiver, the received acknowledgement packets from the receiver including an advertised receive window size. The method further includes determining a backlog parameter for the receiver in accordance with the advertised receive window size, determining a queuing delay in accordance the received acknowledgment packets, resetting a size of a congestion window in accordance with a function of a current size of the congestion window and a factor proportional to the queuing delay, and resetting a size of a receive window in accordance with a function of a current size of the receive window and the backlog parameter. A network window is reset in accordance with the smaller of the size of the congestion window and the size of the receive window

Photoionization of High Altitude Gas in a Supernova-Driven Turbulent Interstellar Medium

We investigate models for the photoionization of the widespread diffuse ionized gas in galaxies. In particular we address the long standing question of the penetration of Lyman continuum photons from sources close to the galactic midplane to large heights in the galactic halo. We find that recent hydrodynamical simulations of a supernova-driven interstellar medium have low density paths and voids that allow for ionizing photons from midplane OB stars to reach and ionize gas many kiloparsecs above the midplane. We find ionizing fluxes throughout our simulation grids are larger than predicted by one dimensional slab models, thus allowing for photoionization by O stars of low altitude neutral clouds in the Galaxy that are also detected in Halpha. In previous studies of such clouds the photoionization scenario had been rejected and the Halpha had been attributed to enhanced cosmic ray ionization or scattered light from midplane H II regions. We do find that the emission measure distributions in our simulations are wider than those derived from Halpha observations in the Milky Way. In addition, the horizontally averaged height dependence of the gas density in the hydrodynamical models is lower than inferred in the Galaxy. These discrepancies are likely due to the absence of magnetic fields in the hydrodynamic simulations and we discuss how magnetohydrodynamic effects may reconcile models and observations. Nevertheless, we anticipate that the inclusion of magnetic fields in the dynamical simulations will not alter our primary finding that midplane OB stars are capable of producing high altitude diffuse ionized gas in a realistic three-dimensional interstellar medium.Comment: ApJ accepted. 17 pages, 7 figure

FY 17 Preliminary Education & General Budget Continuing the Discussion Presentation Slides

Slides from presentations regarding the University of Maine\u27s education and general budget for the 2017 fiscal year and fiscal planning. The first set of slides are regarding the preliminary budget, the second are of the final budget discussion, the third are of a multi-year financial analysis FY 2017-2021, and the fourth set are of unified budget with proposed recommendations