Chemical evolution in the early phases of massive star formation II: Deuteration

The chemical evolution in high-mass star-forming regions is still poorly constrained. Studying the evolution of deuterated molecules allows to differentiate between subsequent stages of high-mass star formation regions due to the strong temperature dependence of deuterium isotopic fractionation. We observed a sample of 59 sources including 19 infrared dark clouds, 20 high-mass protostellar objects, 11 hot molecular cores and 9 ultra-compact HII regions in the (3-2) transitions of the four deuterated molecules, DCN, DNC, DCO+ and N2D+ as well as their non-deuterated counterpart. The overall detection fraction of DCN, DNC and DCO+ is high and exceeds 50% for most of the stages. N2D+ was only detected in a few infrared dark clouds and high-mass protostellar objects. It can be related to problems in the bandpass at the frequency of the transition and to low abundances in the more evolved, warmer stages. We find median D/H ratios of ~0.02 for DCN, ~0.005 for DNC, ~0.0025 for DCO+ and ~0.02 for N2D+. While the D/H ratios of DNC, DCO+ and N2D+ decrease with time, DCN/HCN peaks at the hot molecular core stage. We only found weak correlations of the D/H ratios for N2D+ with the luminosity of the central source and the FWHM of the line, and no correlation with the H2 column density. In combination with a previously observed set of 14 other molecules (Paper I) we fitted the calculated column densities with an elaborate 1D physico-chemical model with time-dependent D-chemistry including ortho- and para-H2 states. Good overall fits to the observed data have been obtained the model. It is one of the first times that observations and modeling have been combined to derive chemically based best-fit models for the evolution of high-mass star formation including deuteration.Comment: 26 pages, 16 figures, accepted at A&

Chemical evolution in the early phases of massive star formation. I

Understanding the chemical evolution of young (high-mass) star-forming regions is a central topic in star formation research. Chemistry is employed as a unique tool 1) to investigate the underlying physical processes and 2) to characterize the evolution of the chemical composition. We observed a sample of 59 high-mass star-forming regions at different evolutionary stages varying from the early starless phase of infrared dark clouds to high-mass protostellar objects to hot molecular cores and, finally, ultra-compact HII regions at 1mm and 3mm with the IRAM 30m telescope. We determined their large-scale chemical abundances and found that the chemical composition evolves along with the evolutionary stages. On average, the molecular abundances increase with time. We modeled the chemical evolution, using a 1D physical model where density and temperature vary from stage to stage coupled with an advanced gas-grain chemical model and derived the best-fit chi^2 values of all relevant parameters. A satisfying overall agreement between observed and modeled column densities for most of the molecules was obtained. With the best-fit model we also derived a chemical age for each stage, which gives the timescales for the transformation between two consecutive stages. The best-fit chemical ages are ~10,000 years for the IRDC stage, ~60,000 years for the HMPO stage, ~40,000 years for the HMC stage, and ~10,000 years for the UCHII stage. The total chemical timescale for the entire evolutionary sequence of the high-mass star formation process is on the order of 10^5 years, which is consistent with theoretical estimates. Furthermore, based on the approach of a multiple-line survey of unresolved data, we were able to constrain an intuitive and reasonable physical and chemical model. The results of this study can be used as chemical templates for the different evolutionary stages in high-mass star formation.Comment: 31 pages, 11 figures, 21 tables, accepted by A&A; typos adde

Liquid metal micro heat pipes for space radiator applications

Micromachining is a chemical means of etching three-dimensional structures, typically in single-crystalline silicon. These techniques are leading toward what is coming to be referred to as MEMS (micro electro mechanical systems), where in addition to the ordinary two dimensional (planar) microelectronics, it is possible to build three-dimensional micromotors, electrically-actuated microvalves, hydraulic systems, and much more on the same microchip. These techniques become possible because of differential etching rates of various crystallographic planes and materials used for semiconductor microfabrication. The University of Cincinnati group in collaboration with NASA Lewis formed micro heat pipes in silicon by the above techniques. Work is ongoing at a modest level, but several essential bonding and packaging techniques have been recently developed. Currently, we have constructed and filled water/silicon micro heat pipes. Preliminary thermal tests of arrays of 125 micro heat pipes etched in a 1 inch x 1 inch x 250 micron silicon wafer have been completed. These pipes are instrumented with extremely small P-N junctions to measure their effective conductivity and their maximum operating power. A relatively simple one-dimensional model has been developed in order to predict micro heat pipes' operating characteristics. This information can be used to optimize micro heat pipe design with respect to length, hydraulic diameter, and number of pipes. Work is progressing on the fabrication of liquid-metal micro heat pipes. In order to be compatible with liquid metal (sodium or potassium), the inside of the micro heat pipes will be coated with a refractory metal (such as tungsten, molybdenum, or titanium)

Neuroprotective strategies for ischemic stroke—Future perspectives

Ischemic stroke is the main cause of death and the most common cause of acquired physical disability worldwide. Recent demographic changes increase the relevance of stroke and its sequelae. The acute treatment for stroke is restricted to causative recanalization and restoration of cerebral blood flow, including both intravenous thrombolysis and mechanical thrombectomy. Still, only a limited number of patients are eligible for these time-sensitive treatments. Hence, new neuroprotective approaches are urgently needed. Neuroprotection is thus defined as an intervention resulting in the preservation, recovery, and/or regeneration of the nervous system by interfering with the ischemic-triggered stroke cascade. Despite numerous preclinical studies generating promising data for several neuroprotective agents, successful bench-to-bedside translations are still lacking. The present study provides an overview of current approaches in the research field of neuroprotective stroke treatment. Aside from “traditional” neuroprotective drugs focusing on inflammation, cell death, and excitotoxicity, stem-cell-based treatment methods are also considered. Furthermore, an overview of a prospective neuroprotective method using extracellular vesicles that are secreted from various stem cell sources, including neural stem cells and bone marrow stem cells, is also given. The review concludes with a short discussion on the microbiota–gut–brain axis that may serve as a potential target for future neuroprotective therapies

Preconditioning concepts for the therapeutic use of extracellular vesicles against stroke

Various preclinical stroke models have demonstrated the neuroprotective effects of extracellular vesicles (EVs) obtained from several types of cells, including neurons, astrocytes, microglia, neuronal progenitor cells, bone marrow stem cells, and mesenchymal stem cells. EVs interfere with key mechanisms in stroke pathophysiology such as cell death, neuroinflammation, autophagy, and angiogenesis. The mode of action and efficacy depend on the specific EV content, including miRNAs, proteins, and lipids, which can be modified through (I) bioengineering methods, (II) choice of source cells, and (III) modification of the source cell environment. Indeed, modifying the environment by preconditioning the EV-secreting cells with oxygen-glucose deprivation or medium modification revealed superior neuroprotective effects in stroke models. Although the concept of preconditioned EVs is relatively novel, it holds promise for the future treatment of ischemic stroke. Here, we give a brief overview about the main mechanisms of EV-induced neuroprotection and discuss the current status of preconditioning concepts for EV-treatment of ischemic stroke

A Novel Silicon Micromachined Integrated MCM Thermal Management System

"Micromachining" is a chemical means of etching three-dimensional structures, typically in single- crystalline silicon. These techniques are leading toward what is coming to be referred to as MEMS (Micro Electro Mechanical Systems), where in addition to the ordinary two-dimensional (planar) microelectronics, it is possible to build three-dimensional n-ticromotors, electrically- actuated raicrovalves, hydraulic systems and much more on the same microchip. These techniques become possible because of differential etching rates of various crystallographic planes and materials used for semiconductor n-ticrofabfication. The University of Cincinnati group in collaboration with Karl Baker at NASA Lewis were the first to form micro heat pipes in silicon by the above techniques. Current work now in progress using MEMS technology is now directed towards the development of the next generation in MCM (Multi Chip Module) packaging. Here we propose to develop a complete electronic thermal management system which will allow densifica6on in chip stacking by perhaps two orders of magnitude. Furthermore the proposed technique will allow ordinary conu-nercial integrated chips to be utilized. Basically, the new technique involves etching square holes into a silicon substrate and then inserting and bonding commercially available integrated chips into these holes. For example, over a 100 1/4 in. by 1 /4 in. integrated chips can be placed on a 4 in. by 4 in. silicon substrate to form a Multi-Chip Module (MCM). Placing these MCM's in-line within an integrated rack then allows for three-diniensional stacking. Increased miniaturization of microelectronic circuits will lead to very high local heat fluxes. A high performance thermal management system will be specifically designed to remove the generated energy. More specifically, a compact heat exchanger with milli / microchannels will be developed and tested to remove the heat through the back side of this MCM assembly for moderate and high heat flux applications, respectively. The high heat load application of particular interest in mind is the motor controller developed by Martin Marietta for Nasa to control the thruster's directional actuators on space vechicles. Work is also proposed to develop highly advanced and improved porous wick structures for use in advanced heat loops. The porous wick will be micromachined from silicon using MEMS technology, thus permitting far superior control of pore size and pore distribution (over wicks made from sintered n-ietals), which in turn is expected to led to significantly improved heat loop performance

Cryosectioning Method for Microdissection of Murine Colonic Mucosa.

The colonic mucosal tissue provides a vital barrier to luminal antigens. This barrier is composed of a monolayer of simple columnar epithelial cells. The colonic epithelium is dynamically turned over and epithelial cells are generated in the stem cell containing crypts of Lieberkuhn. Progenitor cells produced in the crypt-bases migrate toward the luminal surface, undergoing a process of cellular differentiation before being shed into the gut lumen. In order to study these processes at the molecular level, we have developed a simple method for the microdissection of two spatially distinct regions of the colonic mucosa; the proliferative crypt zone, and the differentiated surface epithelial cells. Our objective is to isolate specific crypt and surface epithelial cell populations from mouse colonic mucosa for the isolation of RNA and protein

TREM2 regulates microglial lipid droplet formation and represses post-ischemic brain injury

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor protein predominantly expressed in microglia within the central nervous system (CNS). TREM2 regulates multiple microglial functions, including lipid metabolism, immune reaction, inflammation, and microglial phagocytosis. Recent studies have found that TREM2 is highly expressed in activated microglia after ischemic stroke. However, the role of TREM2 in the pathologic response after stroke remains unclear. Herein, TREM2-deficient microglia exhibit an impaired phagocytosis rate and cholesteryl ester (CE) accumulation, leading to lipid droplet formation and upregulation of Perilipin-2 (PLIN2) expression after hypoxia. Knockdown of TREM2 results in increased lipid synthesis (PLIN2, SOAT1) and decreased cholesterol clearance and lipid hydrolysis (LIPA, ApoE, ABCA1, NECH1, and NPC2), further impacting microglial phenotypes. In these lipid droplet-rich microglia, the TGF-β1/Smad2/3 signaling pathway is downregulated, driving microglia towards a pro-inflammatory phenotype. Meanwhile, in a neuron-microglia co-culture system under hypoxic conditions, we found that microglia lost their protective effect against neuronal injury and apoptosis when TREM2 was knocked down. Under in vivo conditions, TREM2 knockdown mice express lower TGF-β1 expression levels and a lower number of anti-inflammatory M2 phenotype microglia, resulting in increased cerebral infarct size, exacerbated neuronal apoptosis, and aggravated neuronal impairment. Our work suggests that TREM2 attenuates stroke-induced neuroinflammation by modulating the TGF-β1/Smad2/3 signaling pathway. TREM2 may play a direct role in the regulation of inflammation and also exert an influence on the post-ischemic inflammation and the stroke pathology progression via regulation of lipid metabolism processes. Thus, underscoring the therapeutic potential of TREM2 agonists in ischemic stroke and making TREM2 an attractive new clinical target for the treatment of ischemic stroke and other inflammation-related diseases.National Natural Science Foundation of China ; Science and Technology Commission of Shanghai Municipality ; China Scholarship Counci

Automating the extraction of essential genes from literature

The construction of repositories with curated information about gene essentiality for organisms of interest in Biotechnology is a very relevant task, mainly in the design of cell factories for the enhanced production of added-value products. However, it requires retrieval and extraction of relevant information from literature, leading to high costs regarding manual curation. Text mining tools implementing methods addressing tasks as information retrieval, named entity recognition and event extraction have been developed to automate and reduce the time required to obtain relevant information from literature in many biomedical fields. However, current tools are not designed or optimized for the purpose of identifying mentions to essential genes in scientific texts.This work is co-funded by the North Portugal Regional Operational Programme, under the “Portugal 2020”, through the European Regional Development Fund (ERDF), within project SISBI- Refa NORTE-01-0247-FEDER-003381. The Centre of Biological Engineering (CEB), University of Minho, sponsored all computational hardware and software required for this work.info:eu-repo/semantics/publishedVersio

Widespread deuteration across the IRDC G035.39-00.33

© 2016 The Authors. Infrared Dark Clouds (IRDCs) are cold, dense regions that are usually found within Giant Molecular Clouds. Ongoing star formation within IRDCs is typically still deeply embedded within the surrounding molecular gas. Characterizing the properties of relatively quiescent IRDCs may therefore help us to understand the earliest phases of the star formation process. Studies of local molecular clouds have revealed that deuterated species are enhanced in the earliest phases of star formation. In this paper, we test this towards IRDC G035.39-00.33. We present an 80 arcsec by 140 arcsec map of the J = 2 → 1 transition of N2D+, obtained with the Institut de Radioastronomie Millimétrique 30 m telescope telescope. We find that N2D+ is widespread throughout G035.39-00.33. Complementary observations of N2H+ (1 - 0) are used to estimate the deuterium fraction, DN2H+ frac ≡ N(N2D+)/N(N2H+). We report a mean DN2H+ frac = 0.04 ± 0.01, with a maximum of DN2H+ frac = 0.09 ± 0.02. The mean deuterium fraction is ~3 orders of magnitude greater than the interstellar [D]/[H] ratio. High angular resolution observations are required to exclude beam dilution effects of compact deuterated cores. Using chemical modelling, we find that the average observed values of DN2H+ frac are in agreement with an equilibrium deuterium fraction, given the general properties of the cloud. This implies that the IRDC is at least ~3 Myr old, which is ~8 times longer than the mean free-fall time of the observed deuterated region