Cigarette Smoke Suppresses Type I Interferon-Mediated Antiviral Immunity in Lung Fibroblast and Epithelial Cells

The objective of this study was to investigate the impact of cigarette smoke on innate antiviral defense mechanisms; specifically, we examined the effects of cigarette smoke on the induction of type I interferon (IFN). We observed a dose-dependent decrease in the ability of human lung fibroblast and epithelial cells to elicit an antiviral response against a viral double-strand RNA (dsRNA) mimic, polyI:C, in the presence of cigarette smoke-conditioned medium (SCM). Mechanistically, SCM decreases the expression of IFN-stimulated gene 15 (ISG15) and IFN regulatory factor-7 (IRF-7) transcripts and suppresses the nuclear translocation of key transcription factors, nuclear factor-κB (NF-κB) and IRF-3, after polyI:C stimulation. Furthermore, we provide evidence that the intercellular defense strategy against viral infection is also impaired. We observed a decrease in the ability of fibroblasts to elicit an antiviral state in response to IFN-β stimulation. This was associated with decreased nuclear translocation of phosphorylated Stat1 in response to IFN-β treatment. The effects elicited by SCM are reversible and are almost entirely abrogated in the presence of an antioxidant, such as glutathione. Our findings suggest that cigarette smoke affects the immediate-early, inductive, and amplification phases of the type I IFN response

BlindBuilder : a new encoding to evolve Lego-like structures

This paper introduces a new representation for assemblies of small Lego-like elements: structures are indirectly encoded as construction plans. This representation shows some interesting properties such as hierarchy, modularity and easy constructibility checking by definition. Together with this representation, efficient GP operators are introduced that allow efficient and fast evolution, as witnessed by the results on two construction problems that demonstrate that the proposed approach is able to achieve both compactness and reusability of evolved components

Nodal Project Evaluation Applied to Large-Scale Renewable Energy Procurment: A case analysis of Massachusetts clean energy initiative

Abstract Evaluating a large number of renewable energy project proposals received in response to a single Request for Proposals (RFP) in a consistent manner independent of size and technology and fully cognizant of location and timing is a significant challenge. The current paper presents a methodology and set of tools for preparing a comparative quantitative evaluation of the economic and environmental benefits and costs of the renewable project proposals over a 25-year time horizon. The paper presents a case study of the large-scale renewable energy procurements undertaken in 2018 to comply with Massachusetts energy diversity and greenhouse gas (GHG) emission reduction goals mandated under its “Green Communities Act” of 2008 and Global Warming Solutions Act” of 2008. Section 83D of the Green Communities Act requires Massachusetts electric distribution companies (EDCs) to acquire 9,450 gigawatt hours per year of cost-effective renewable energy. The quantitative evaluation of each proposed renewable project is based on a scenario analysis approach in which a simulation modeling tool calculates energy costs and GHG emissions in the Northeast region (New England and New York) over the evaluation period for a “but for” case without any of the proposed renewable projects and for individual cases for each proposed renewable project. Working from a single database structure, the simulation modeling tool moves from a 30-year, annual resource adequacy module, to an hourly, nodal, 20-year plus SCUC / SCD, to a detailed capacity market valuation model. The simulation modeling system (ENELYTIX) operates with cloud-based technology utilizing user-friendly Excel interfacing with complex data / information transfer from an OLAP cube on the cloud to users’ workstations

Repetitive fracturing during spine extrusion at Unzen volcano, Japan

Rhythmic seismicity associated with spine extrusion is a well-documented phenomenon at a number of dome-forming volcanic systems. At Unzen volcano, Japan, a 4-year dome-forming eruption concluded with the emplacement of a spine from October 1994 to February 1995, offering a valuable opportunity to further investigate seismogenic processes at dome-forming volcanoes. Using continuous data recorded at a seismic station located close to the dome, this study explores trends in the seismic activity during the extrusion of the spine. We identify a total of 12 208 volcano-seismic events in the period between October 1994 and February 1995. Hourly event counts indicate cyclic activity with periods of ∼ 40 to ∼ 100 h, attributed to pulsatory ascent defined by strain localisation and faulting at the conduit margins. Waveform correlation revealed two strong clusters (a.k.a. multiplets, families) which are attributed to fracturing along the margins of the shallow, ascending spine. Further analysis indicates variable seismic velocities during the spine extrusion as well as migration of the cluster sources along the spine margins. Our interpretation of the results from seismic data analyses is supported by previously published field and experimental observations, suggesting that the spine was extruded along an inclined conduit with brittle and ductile deformation occurring along the margins. We infer that changes in stress conditions acting on the upper and lower spine margins led to deepening and shallowing of the faulting sources, respectively. We demonstrate that the combination of geophysical, field and experimental evidence can help improve physical models of shallow conduit processes

High resolution radio observations of the colliding-wind binary WR140

Milli-arcsecond resolution Very Long Baseline Array (VLBA) observations of the archetype WR+O star colliding-wind binary (CWB) system WR140 are presented for 23 epochs between orbital phases 0.74 and 0.97. At 8.4 GHz, the emission in the wind-collision region (WCR) is clearly resolved as a bow-shaped arc that rotates as the orbit progresses. We interpret this rotation as due to the O star moving from SE to approximately E of the WR star, which leads to solutions for the orbit inclination of 122+/-5 deg, the longitude of the ascending node of 353+/-3 deg, and an orbit semi-major axis of 9.0+/-0.5 mas. The distance to WR140 is determined to be 1.85+/-0.16 kpc, which requires the O star to be a supergiant. The inclination implies the mass of the WR and O star to be 20+/-4 and 54+/-10 solar masses respectively. We determine a wind-momentum ratio of 0.22, with an expected half-opening angle for the WCR of 63 deg, consistent with 65+/-10 deg derived from the VLBA observations. Total flux measurements from Very Large Array (VLA) observations show the radio emission from WR140 is very closely the same from one orbit to the next, pointing strongly toward emission, absorption and cooling mechanism(s) that are controlled largely by the orbital motion. The synchrotron spectra evolve dramatically through the orbital phases observed, exhibiting both optically thin and optically thick emission. We discuss a number of absorption and cooling mechanisms that may determine the evolution of the synchrotron spectrum with orbital phase.Comment: Accepted by ApJ, to appear in v623, April 20, 2005. 14 pages, 13 figs, requires emulateapj.cls. A version with full resolution figs can be obtained from http://www.drao.nrc.ca/~smd/preprint/wr140_data.pd

Substance P in the Dorsal Motor Nucleus of the Vagus Evokes Gastric Motor Inhibition via Neurokinin 1 Receptor in Rat 1

ABSTRACT Many gastrointestinal stimuli result in gastric fundic relaxation. This information is integrated at the interface of vagal afferents and efferents in the dorsal vagal complex. Substance P (SP) is present in this region, and the neurokinin 1 receptor (NK 1 R) is highly expressed in preganglionic neurons of the dorsal motor nucleus of the vagus (DMN). However, its functional effects on vagal motor output to the stomach have not been investigated. Therefore, we determined the gastric motor effects of stereotaxic microinjection of SP and selective tachykinin receptor agents into the DMN of anesthetized rats. Dose-related decreases in intragastric pressure and antral motility were obtained on the microinjection of SP (135 and 405 pmol) into the DMN, without cardiovascular changes. Similar decreases in intragastric pressure were noted after the microinjection of [Sar 9 ,Met(O 2 ) 11 ]SP (NK 1 R agonist; 135 pmol) but not senktide (NK 3 R agonist; 135 pmol) or vehicle. The gastric motor inhibition evoked by SP (135 pmol) was attenuated by prior microinjection of 2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-yl)-amine (GR203040; 1 nmol; NK 1 R antagonist). Vagotomy or hexamethonium (15 mg/kg i.v.) completely abolished the gastric relaxation evoked by SP (135 pmol) microinjected into the DMN. We conclude that SP acts on NK 1 R preganglionic cholinergic vagal neurons in the DMN, which control enteric nonadrenergic noncholinergic motor inhibition of the fundus. The potential relevance is that an antiemetic site of action of NK 1 R antagonists may be in the DMN to prevent excitation of neurons controlling fundic relaxation, which is an essential prodromal component of emesis. Many stimuli to the gastrointestinal tract result in hormonal ("endoneurocrine") or neuronal feedback to other regions of the gut, and the vagus nerve is intimately involved in conveying this information to the upper gastrointestinal tract. Integration of "long-loop" vagal afferent-efferent pathways from the gut occurs in the dorsal vagal complex of the hindbrain medulla. This complex comprises the dorsal motor nucleus of the vagus (DMN), where preganglionic motor neurons innervating the gastrointestinal tract are located, and the nucleus tractus solitarius, where primary visceral afferents terminate. Preganglionic neurons in the DMN target the stomach One candidate neurotransmitter in the dorsal vagal complex that could mediate fundic relaxation is substance P (SP). The microinjection of SP into the nucleus tractus solitarius evokes gastric relaxatio

The Value of Rehabilitation Interventions --Integrating Evidence, Clinical Expertise, Critical Assessment, and Patient Needs: A Conference Report

In order to understand issues related to value, outcomes, and cost-effectiveness of rehabilitation interventions, and to explore how scientific evidence, clinical expertise, and patient needs can be integrated, the Rehabilitation Research and Training Center on Developing Optimal Strategies in Exercise and Survival Skills to Increase Health and Function held a State of the Science (SOS) Symposium on “ The Value of Rehabilitation Interventions” at Shirley Ryan AbilityLab in Chicago in 2017. In this conference, the perspectives of 35 invited experts, including people with disabilities, professionals, and consumers, explored the topic of “value” of rehabilitation interventions and discussed their perspectives on the means to integrate best scientific evidence with clinical expertise and patient preferences. This Symposium also resulted in the production of several multifaceted manuscripts providing perspectives on the topic of value and how to use evidence to best determine and demonstrate it. These papers comprise this Supplement. The present paper introduces the key concepts of value, evidence, and knowledge translation, in an effort to provide a context for the papers of the Supplement