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resting on an uncharged electrode can move towards a charged electrode where droplets will join and merge into one droplet. However, the merged droplet might not always form a circular shape even after the merging process is over due to surface tension. This problem can be solved by implementing a superhydrophobic surface between the droplets and the electrodes. Oil droplets can be merged in the same way as well, but oil droplets will move towards uncharged electrodes unlike aqueous droplets. === Droplet transportation === Discrete droplets can be transported in a highly controlled way using an array of electrodes. In the same way droplets move from an uncharged electrode to a charged electrode, or vice versa, droplets can be continuously transported along the electrodes by sequentially energizing the electrodes. Since droplet transportation involves an array of electrodes, multiple electrodes can be programmed to selectively apply a voltage to each electrode for a better control over transporting multiple droplets. === Displacement by electrostatic actuation === Three-dimensional droplet actuation has been made possible by implementing a closed system; this system contains a μL sized droplet in immiscible fluid medium. The droplet and medium are then sandwiched between two electromagnetic plates, creating an EM field between the two plates. The purpose of this method is to transfer the droplet from a lower planar surface to an upper parallel planar surface and back down via electrostatic forces. The physics behind such particle actuation and perpendicular movement can be understood from early works of N. N. Lebedev and I. P. Skal’skaya. In their research, they attempted to model the Maxwell electrical charge acquired by a perfectly round conducting particle in the presence of a uniform magnetic field caused by a perfectly-conducting and infinitely-stretching surface. Their model helps to predict the Z-direction motion of the microdroplets
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within the device as it points to the magnitude and direction of forces acting upon a micro droplet. This can be used to help accurately predict and correct for unwanted and uncontrollable particle movement. The model explains why failing to employ dielectric coating on one of the two surfaces causes reversal of charge within the droplet upon contact with each electrode and in turn causes the droplets to uncontrollably bounce of between electrodes. Digital microfluidics (DMF), has already been readily adapted in many biological fields. By enabling three-dimensional movement within DMF, the technology can be used even more extensively in biological applications, as it could more accurately mimic 3-D microenvironments. A large benefit of employing this type of method is that it allows for two different environments to be accessible by the droplet, which can be taken advantage of by splitting the microfluidic tasks among the two surfaces. For example, while the lower plane can be used to move droplets, the upper plate can carry out the necessary chemical and/or biological processes. This advantage can be translated into practical experiment protocols in the biological community, such as coupling with DNA amplification. This also allows for the chip to be smaller, and to give researchers more freedom in designing platforms for microdroplet analysis. === All-terrain droplet actuation (ATDA) === All-terrain microfluidics is a method used to transport liquid droplets over non-traditional surface types. Unlike traditional microfluidics platform, which are generally restricted to planar and horizontal surfaces, ATDA enables droplet manipulation over curved, non-horizontal, and inverted surfaces. This is made possible by incorporating flexible thin sheets of copper and polyimide into the surface via a rapid prototyping method. This device works very well with many liquids, including aqueous buffers, solutions of proteins and DNA, and undiluted bovine serum. ATDA is compatible with
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silicone oil or pluronic additives, such as F-68, which reduce non-specific absorption and biofouling when dealing with biological fluids such as proteins, biological serums, and DNA. A drawback of a setup like this is accelerated droplet evaporation. ATDA is a form of open digital microfluidics, and as such the device needs to be encapsulated in a humidified environment in order to minimize droplet evaporation. == Implementation == In one of various embodiments of EWOD-based microfluidic biochips, investigated first by Cytonix in 1987 [1] Archived 2020-09-19 at the Wayback Machine and subsequently commercialized by Advanced Liquid Logic, there are two parallel glass plates. The bottom plate contains a patterned array of individually controllable electrodes and the top plate is coated with a continuous grounding electrode. A dielectric insulator coated with a hydrophobic is added to the plates to decrease the wet-ability of the surface and to add capacitance between the droplet and the control electrode. The droplet containing biochemical samples and the filler medium, such as the silicone oil, a fluorinated oil, or air, are sandwiched between the plates and the droplets travel inside the filler medium. In order to move a droplet, a control voltage is applied to an electrode adjacent to the droplet, and at the same time, the electrode just under the droplet is deactivated. By varying the electric potential along a linear array of electrodes, electrowetting can be used to move droplets along this line of electrodes. == Applications == === Laboratory automation === In research fields such as synthetic biology, where highly iterative experimentation is common, considerable efforts have been made to automate workflows. Digital microfluidics is often touted as a laboratory automation solution, with a number of advantages over alternative solutions such as pipetting robots and droplet microfluidics. These stated advantages often include a reduction
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in the required volume of experimental reagents, a reduction in the likelihood of contamination and cross-contamination, potential improvements in reproducibility, increased throughput, individual droplet addressability, and the ability to integrate with sensor and detector modules to perform end-to-end or even closed loop workflow automation. ==== Reduced experimental footprint ==== One of the core advantages of digital microfluidics, and of microfluidics in general, is the use and actuation of picoliter to microliter scale volumes. Workflows adapted from the bench to a DMF system are miniaturized, meaning working volumes are reduced to fractions of what is normally required for conventional methods. For example, Thaitrong et al. developed a DMF system with a capillary electrophoresis (CE) module with the purpose of automating the process of next generation sequencing (NGS) library characterization. Compared to an Agilent BioAnalyzer (an instrument commonly used to measure sequencing library size distribution), the DMF-CE system consumed ten-fold less sample volume. Reducing volumes for a workflow can be especially beneficial if the reagents are expensive or when manipulating rare samples such as circulating tumor cells and prenatal samples. Miniaturization also means a reduction in waste product volumes. ==== Reduced probability of contamination ==== DMF-based workflows, particularly those using a closed configuration with a top-plate ground electrode, have been shown to be less susceptible to outside contamination compared to some conventional laboratory workflows. This can be attributed to minimal user interaction during automated steps, and the fact that the smaller volumes are less exposed to environmental contaminants than larger volumes which would need to be exposed to open air during mixing. Ruan et al. observed minimal contamination from exogenous nonhuman DNA and no cross-contamination between samples while using their DMF-based digital whole genome sequencing system. ==== Improved reproducibility ==== Overcoming issues of reproducibility has become a topic of growing concern across
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scientific disciplines. Reproducibility can be especially salient when multiple iterations of the same experimental protocol need to be repeated. Using liquid handling robots that can minimize volume loss between experimental steps are often used to reduce error rates and improve reproducibility. An automated DMF system for CRISPR-Cas9 genome editing was described by Sinha et al, and was used to culture and genetically modify H1299 lung cancer cells. The authors noted that no variation in knockout efficiencies across loci was observed when cells were cultured on the DMF device, whereas cells cultured in well-plates showed variability in upstream loci knockout efficiencies. This reduction in variability was attributed to culturing on a DMF device being more homogenous and reproducible compared with well plate methods. ==== Increased throughput ==== While DMF systems cannot match the same throughput achieved by some liquid handling pipetting robots, or by some droplet-based microfluidic systems, there are still throughput advantages when compared to conventional methods carried out manually. ==== Individual droplet addressability ==== DMF allows for droplet level addressability, meaning individual droplets can be treated as spatially distinct microreactors. This level of droplet control is important for workflows where reactions are sensitive to the order of reagent mixing and incubation times, but where the optimal values of these parameters may still need to be determined. These types of workflows are common in cell-free biology, and Liu et al. were able to demonstrate a proof-of-concept DMF-based strategy for carrying out remote-controlled cell-free protein expression on an OpenDrop chip. ==== Detector module integration for end-to-end and closed-loop automation ==== An often cited advantage DMF platforms have is their potential to integrate with on-chip sensors and off-chip detector modules. In theory, real-time and end-point data can be used in conjunction with machine learning methods to automate the process of parameter optimization.
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=== Separation and extraction === Digital microfluidics can be used for separation and extraction of target analytes. These methods include the use of magnetic particles, liquid-liquid extraction, optical tweezers, and hydrodynamic effects. ==== Magnetic particles ==== For magnetic particle separations a droplet of solution containing the analyte of interest is placed on a digital microfluidics electrode array and moved by the changes in the charges of the electrodes. The droplet is moved to an electrode with a magnet on one side of the array with magnetic particles functionalized to bind to the analyte. Then it is moved over the electrode, the magnetic field is removed and the particles are suspended in the droplet. The droplet is swirled on the electrode array to ensure mixing. The magnet is reintroduced and the particles are immobilized and the droplet is moved away. This process is repeated with wash and elution buffers to extract the analyte. Magnetic particles coated with antihuman serum albumin antibodies have been used to isolate human serum albumin, as proof of concept work for immunoprecipitation using digital microfluidics.5 DNA extraction from a whole blood sample has also been performed with digital microfluidics.3 The procedure follows the general methodology as the magnetic particles, but includes pre-treatment on the digital microfluidic platform to lyse the cells prior to DNA extraction. ==== Liquid-liquid extraction ==== Liquid-liquid extractions can be carried out on digital microfluidic device by taking advantage of immiscible liquids.9 Two droplets, one containing the analyte in aqueous phase, and the other an immiscible ionic liquid are present on the electrode array. The two droplets are mixed and the ionic liquid extracts the analyte, and the droplets are easily separable. ==== Optical tweezers ==== Optical tweezers have also been used to separate cells in droplets. Two droplets are mixed on an electrode
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array, one containing the cells, and the other with nutrients or drugs. The droplets are mixed and then optical tweezers are used to move the cells to one side of the larger droplet before it is split. For a more detailed explanation on the underlying principles, see Optical tweezers. ==== Hydrodynamic separation ==== Particles have been applied for use outside of magnetic separation, with hydrodynamic forces to separate particles from the bulk of a droplet. This is performed on electrode arrays with a central electrode and ‘slices’ of electrodes surrounding it. Droplets are added onto the array and swirled in a circular pattern, and the hydrodynamic forces from the swirling cause the particles to aggregate onto the central electrode. === Chemical synthesis === Digital Microfluidics (DMF) allows for precise manipulation and coordination in small-scale chemical synthesis reactions due to its ability to control micro scale volumes of liquid reagents, allowing for overall less reagent use and waste. This technology can be used in the synthesis compounds such as peptidomimetics and PET tracers. PET tracers require nanogram quantities and as such, DMF allows for automated and rapid synthesis of tracers with 90-95% efficiency compared to conventional macro-scale techniques. Organic reagents are not commonly used in DMF because they tend to wet the DMF device and cause flooding; however synthesis of organic reagents can be achieved through DMF techniques by carrying the organic reagents through an ionic liquid droplet, thus preventing the organic reagent from flooding the DMF device. Droplets are combined together by inducing opposite charges thus attracting them to each other. This allows for automated mixing of droplets. Mixing of droplets are also used to deposit MOF crystals for printing by delivering reagents into wells and evaporating the solutions for crystal deposition. This method of MOF crystal deposition is relatively
|
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cheap and does not require extensive robotic equipment. Chemical synthesis using digital microfluidics (DMF) has been applied to many noteworthy biological reactions. These include polymerase chain reaction (PCR), as well as the formation of DNA and peptides. Reduction, alkylation, and enzymatic digestion have also shown robustness and reproducibility utilizing DMF, indicating potential in the synthesis and manipulation of proteomics. Spectra obtained from the products of these reactions are often identical to their library spectra, while only utilizing a small fraction of bench-scale reactants. Thus, conducting these syntheses on the microscale has the benefit of limiting money spent on purchasing reagents and waste products produced while yielding desirable experimental results. However, numerous challenges need to be overcome to push these reactions to completion through DMF. There have been reports of reduced efficiency in chemical reactions as compared to bench-scale versions of the same syntheses, as lower product yields have been observed. Furthermore, since picoliter and nanoliter size samples must be analyzed, any instrument used in analysis needs to be high in sensitivity. In addition, system setup is often difficult due to extensive amounts of wiring and pumps that are required to operate microchannels and reservoirs. Finally, samples are often subject to solvent evaporation which leads to changes in volume and concentration of reactants, and in some cases reactions to not go to completion. The composition and purity of molecules synthesized by DMF are often determined utilizing classic analytical techniques. Nuclear magnetic resonance (NMR) spectroscopy has been successfully applied to analyze corresponding intermediates, products, and reaction kinetics. A potential issue that arises through the use of NMR is low mass sensitivity, however this can be corrected for by employing microcoils that assist in distinguishing molecules of differing masses. This is necessary since the signal-to-noise ratio of sample sizes in the microliter to
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nanoliter range is dramatically reduced compared to bench-scale sample sizes, and microcoils have been shown to resolve this issue. Mass spectrometry (MS) and high-performance liquid chromatography (HPLC) have also been used to overcome this challenge. Although MS is an attractive analytical technique for distinguishing the products of reactions accomplished through DMF, it poses its own weaknesses. Matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) MS have recently been paired with analyzing microfluidic chemical reactions. However, crystallization and dilution associated with these methods often leads to unfavorable side effects, such as sample loss and side reactions occurring. The use of MS in DMF is discussed in more detail in a later section. === Cell culture === Connecting the DMF chip to use in the field or world-to-chip interfaces have been accomplished by means of manual pumps and reservoirs which deliver microbes, cells, and media to the device. The lack of extensive pumps and valves allow for elaborate multi step applications involving cells performed in a simple and compact system. In one application, microbial cultures have been transferred onto the chip and allowed to grow with the use of sterile procedures and temperature required for microbial incubation. To validate that this was a viable space for microbial growth, a transformation assay was carried out in the device. This involves exposing E.coli to a vector and heat shocking the bacteria until they take up the DNA. This is then followed by running a DNA gel to assure that the wanted vector was taken up by the bacteria. This study found that the DNA indeed was taken up by the bacteria and expressed as predicted. Human cells have also been manipulated in Digital Microfluidic Immunocytochemistry in Single Cells (DISC) where DMF platforms were used to culture and use antibodies to label phosphorylated proteins
|
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in the cell. Cultured cells are then removed and taken off chip for screening. Another technique synthesizes hydrogels within DMF platforms. This process uses electrodes to deliver reagents to produce the hydrogel, and delivery of cell culture reagents for absorption into the gel. The hydrogels are an improvement over 2D cell culture because 3D cell culture have increased cell-cell interactions and cel-extracellular matrix interactions. Spherical cell cultures are another method developed around the ability of DMF to deliver droplets to cells. Application of an electric potential allows for automation of droplet transfer directly to the hanging cell culture.] This is beneficial as 3 dimensional cell culture and spheroids better mimic in vivo tissue by allowing for more biologically relevant cultures that have cells growing in an extracellular matrix similarly resembling that in the human body. Another use of DMF platforms in cell culture is its ability to conduct in vitro cell-free cloning using single molecule PCR inside droplets. PCR amplified products are then validated by transfection into yeast cells and a Western blot protein identification. Problems arising from cell culture applications using DMF include protein adsorption to the device floor, and cytotoxicity to cells. To prevent adsorption of protein to the platform's floor, a surfactant stabilized Silicon oil or hexane was used to coat the surface of the device, and droplets were manipulated atop of the oil or hexane. Hexane was later rapidly evaporated from cultures to prevent a toxic effect on cell cultures. Another approach to solve protein adhesion is the addition of Pluronic additives to droplets in the device. Pluronic additives are generally not cytotoxic but some have been shown to be harmful to cell cultures. Bio-compatibility of device set up is important for biological analyses. Along with finding Pluronic additives that are not cytotoxic, creating a device
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whose voltage and disruptive movement would not affect cell viability was accomplished. Through the readout of live/dead assays it was shown that neither voltage required to move droplets, nor the motion of moving cultures affected cell viability. ==== Biological extraction ==== Biological separations usually involve low concentration high volume samples. This can pose an issue for digital microfluidics due to the small sample volume necessary. Digital microfluidic systems can be combined with a macrofluidic system designed to decrease sample volume, in turn increasing analyte concentration. It follows the same principles as the magnetic particles for separation, but includes pumping of the droplet to cycle a larger volume of fluid around the magnetic particles. Extraction of drug analytes from dried urine samples has also been reported. A droplet of extraction solvent, in this case methanol, is repeatedly flowed over a sample of dried urine sample then moved to a final electrode where the liquid is extracted through a capillary and then analyzed using mass spectrometry. ==== Immunoassays ==== The advanced fluid handling capabilities of digital microfluidics (DMF) allows for the adoption of DMF as an immunoassay platform as DMF devices can precisely manipulate small quantities of liquid reagents. Both heterogeneous immunoassays (antigens interacting with immobilized antibodies) and homogeneous immunoassays (antigens interacting with antibodies in solution) have been developed using a DMF platform. With regards to heterogeneous immunoassays, DMF can simplify the extended and intensive procedural steps by performing all delivery, mixing, incubation, and washing steps on the surface of the device (on-chip). Further, existing immunoassay techniques and methods, such as magnetic bead-based assays, ELISAs, and electrochemical detection, have been incorporated onto DMF immunoassay platforms. The incorporation of magnetic bead-based assays onto a DMF immunoassay platform has been demonstrated for the detection of multiple analytes, such as human insulin, IL-6, cardiac marker
|
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Troponin I (cTnI), thyroid stimulating hormone (TSH), sTNF-RI, and 17β-estradiol. For example, a magnetic bead-based approached has been used for the detection of cTnI from whole blood in less than 8 minutes. Briefly, magnetic beads containing primary antibodies were mixed with labeled secondary antibodies, incubated, and immobilized with a magnet for the washing steps. The droplet was then mixed with a chemiluminescent reagent and detection of the accompanying enzymatic reaction was measured on-chip with a photomultiplier tube. The ELISA template, commonly used for performing immunoassays and other enzyme-based biochemical assays, has been adapted for use with the DMF platform for the detection of analytes such as IgE and IgG. In one example, a series of bioassays were conducted to establish the quantification capabilities of DMF devices, including an ELISA-based immunoassay for the detection of IgE. Superparamagnetic nanoparticles were immobilized with anti-IgE antibodies and fluorescently labeled aptamers to quantify IgE using an ELISA template. Similarly, for the detection of IgG, IgG can be immobilized onto a DMF chip, conjugated with horseradish-peroxidase (HRP)-labeled IgG, and then quantified through measurement of the color change associated with product formation of the reaction between HRP and tetramethylbenzidine. To further expand the capabilities and applications of DMF immunoassays beyond colorimetric detection (i.e., ELISA, magnetic bead-based assays), electrochemical detection tools (e.g., microelectrodes) have been incorporated into DMF chips for the detection of analytes such as TSH and rubella virus. For example, Rackus et al. integrated microelectrodes onto a DMF chip surface and substituted a previously reported chemiluminescent IgG immunoassay with an electroactive species, enabling detection of rubella virus. They coated magnetic beads with rubella virus, anti-rubella IgG, and anti-human IgG coupled with alkaline phosphatase, which in turn catalyzed an electron transfer reaction that was detected by the on-chip microelectrodes. === Mass spectrometry === The coupling of digital
|
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microfluidics (DMF) and Mass Spectrometry can largely be categorized into indirect off-line analysis, direct off-line analysis, and in-line analysis and the main advantages of this coupling are decreased solvent and reagent use, as well as decreased analysis times. Indirect off-line analysis is the usage of DMF devices to combine reactants and isolate products, which are then removed and manually transferred to a mass spectrometer. This approach takes advantage of DMF for the sample preparation step but also introduces opportunities for contamination as manual intervention is required to transfer the sample. In one example of this technique, a Grieco three-component condensation was carried out on chip and was taken off the chip by micropipette for quenching and further analysis. Direct off-line analysis is the usage of DMF devices that have been fabricated and incorporated partially or totally into a mass spectrometer. This process is still considered off-line, however as some post-reaction procedures may be carried out manually (but on chip), without the use of the digital capabilities of the device. Such devices are most often used in conjugation with MALDI-MS. In MALDI-based direct off-line devices, the droplet must be dried and recrystallized along with matrix – operations that oftentimes require vacuum chambers. The chip with crystallized analyte is then placed in to the MALDI-MS for analysis. One issue raised with MALDI-MS coupling to DMF is that the matrix necessary for MALDI-MS can be highly acidic, which may interfere with the on-chip reactions Inline analysis is the usage of devices that feed directly into mass spectrometers, thereby eliminating any manual manipulation. Inline analysis may require specially fabricated devices and connecting hardware between the device and the mass spectrometer. Inline analysis is often coupled with electrospray ionization. In one example, a DMF chip was fabricated with a hole that led to a microchannel
|
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This microchannel was, in turn, connected to an electrospray ionizer that emitted directly into a mass spectrometer. Integration ambient ionization techniques where ions are formed outside of the mass spectrometer with little or no treatment pairs well with the open or semi-open microfluidic nature of DMF and allows easy inline couping between DMF and MS systems. Ambient Ionization techniques such as Surface Acoustic Wave (SAW) ionization generate surface waves on a flat piezoelectric surface that imparts enough acoustic energy on the liquid interface to overcome surface tension and desorb ions off the chip into the mass analyzer. Some couplings utilize an external high-voltage pulse source at the physical inlet to the mass spectrometer but the true role of such additions is uncertain. A significant barrier to the widespread integration of DMF with mass spectrometry is biological contamination, often termed bio-fouling. High throughput analysis is a significant advantage in the use of DMF systems, but means that they are particularly susceptible to cross contamination between experiments. As a result, the coupling of DMF with mass spectrometry often requires the integration of a variety of methods to prevent cross contamination such as multiple washing steps, biologically compatible surfactants, and or super hydrophobic surfaces to prevent droplet adsorption. In one example, a reduction in cross contaminant signal during the characterization of an amino acid required 4-5 wash steps between each sample droplet for the contamination intensity to fall below the limit of detection. ==== Miniature Mass Spectrometers ==== Conventional mass spectrometers are often large as well as prohibitively expensive and complex in their operation which has led to the increased attractiveness of miniature mass spectrometers (MMS) for a variety of applications. MMS are optimized towards affordability and simple operation, often forgoing the need for experienced technicians, having a low cost of manufacture, and
|
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being small enough in size to allow for the transfer of data collection from the laboratory into the field. These advantages often come at the cost of reduced performance where MMS resolution, as well as the limits of detection and quantitation, are often barely adequate to perform specialized tasks. The integration of DMF with MMS has the potential for significant improvement of MMS systems by increasing throughput, resolution, and automation, while decreasing solvent cost, enabling lab grade analysis at a much reduced cost. In one example the use of a custom DMF system for urine drug testing enabled the creation of an instrument weighing only 25 kg with performance comparable to standard laboratory analysis. === Nuclear magnetic resonance spectroscopy === Nuclear magnetic resonance (NMR) spectroscopy can be used in conjunction with digital microfluidics (DMF) through the use of NMR microcoils, which are electromagnetic conducting coils that are less than 1 mm in size. Due to their size, these microcoils have several limitations, directly influencing the sensitivity of the machinery they operate within. Microchannel/microcoil interfaces, previous to digital microfluidics, had several drawbacks such as in that many created large amounts of solvent waste and were easily contaminated. In this way, the use of digital microfluidics and its capability to manipulate singlet droplets is promising. The interface between digital microfluidics and NMR relaxometry has led to the creation of systems such as those used to detect and quantify the concentrations of specific molecules on microscales with some such systems using two step processes in which DMF devices guide droplets to the NMR detection site. Introductory systems of high-field NMR and 2D NMR in conjunction with microfluidics have also been developed. These systems use single plate DMF devices with NMR microcoils in place of the second plate. Recently, further modified version of this
|
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interface included pulsed field gradients (PFG) units that enabled this platform to perform more sophisticated NMR measurements (e.g. NMR diffusometry, gradients encoded pulse measurements). This system has been successfully applied into monitoring rapid organic reactions. == References ==
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Conductive metal−organic frameworks are a class of metal–organic frameworks (MOF) with intrinsic ability of electronic conduction. Metal ions and organic linkers assemble to form a framework that are called MOFs. The first conductive MOF, Cu[Cu(2,3-pyrazinedithiol)2] was described in 2009 and exhibited electrical conductivity of 6 × 10−4 S cm−1 at 300 K. The topic has attracted attention from the academic community. == Design and structure == The organic linkers for conductive MOFs are generally conjugated. 2D conductive MOFs have been explored well and several studies of 3D conductive MOFs have also been reported so far. Single crystal structure of a 2D conductive MOF Co(HHTP) [hexahydroxytriphenylene] was reported in 2012. The conductivity of these materials are often tested by two probe method, i.e. a known potential is applied between two probes, the resulting current is measured, and resistance is calculated by using Ohm’s law. A four-probe method employs two wires on the extreme are used to supply a current and the inner two wires measure the drop in potential. This method eliminates the effect of contact resistance. Most MOFs have conductivity less than 10−10 S cm−1 and are considered as Insulator. Based on the literature reports so far, conductivity range in the MOFs can vary from 10−10 to 103 S cm−1. Charge transfer in conductive MOFs have been attributed to three pathways: 1) Through-bond:- when d orbital of transition metal ion overlaps with the p orbital of the organic linker, π electrons are delocalized across all the adjacent p orbitals. 2) Extended conjugation:- When transition metal ions are coupled with the a conjugated organic linker, the d-π conjugation allows delocalization of the charge carriers. 3) Through-space:- Organic linkers in one layer can interact with the one in the adjacent layer via π-π interaction. This will facilitate charge delocalization in the adjacent
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layers. 4) Redox hopping:- Where electrons move between well-separated redox states via self exchange reactions. 5) Guest-Promoted Transport:- Introducing electroactive guest molecules into the MOF pores can contribute to the conductivity of the material. == Synthesis == === Solvothermal synthesis === In 2017 Kimizuka reported a phthalocyanine based conductive MOF Cu-CuPc with an intrinsic conductivity in the range of 10−6 S cm−1. For the solvothermal synthesis of MOF, the organic linker Cu-octahydroxy phthalocyanine (CuPc) and metal ion is dissolved in a DMF/H2O mixture at heated at 130 °C for 48 hours. Afterwards, Mirica and co-workers were able to enhance the conductivity to a range of 10−2 S cm−1 by synthesizing a bimetallic phthalocyanine based MOF NiPc-Cu. === Hydrothermal synthesis === Examples include a series of isoretical catecholate-based MOFs employing hexahudroxytriphenylene (HHTP) as thee organic linker and Ni/Cu/Co as metal nodes. For the hydrothermal synthesis of these MOFs, both organic linker (hexahydroxytriphenylene) and metal ion is dissolved in H2O, aqueous ammonia is added and mixture is heated. Cu3(HHTP) also known as (Cu-CAT-1) showed a conductivity up to 2.1 × 10−1 S cm−1. Another MOF based on hexaaminotriphenylene (HATP) organic linker and Ni metal ion showed an electronic conductivity of 40 S cm−1 when measured by using Van der Pauw method . === Layering method === A Ni-BHT MOF nanosheet has been obtained using liquid-liquid interfacial synthesis. For the synthesis, organic linker is dissolved in dichloromethane upon which H2O is added and then metal salt (Ni(OAc)2) along with sodium bromide is added to the aqueous layer. == Potential applications == Although no conductive MOF has been commercialized, potential applications have been identified. === Electrochemical sensors === Conductive MOF are of interest as a chemiresistive sensors. A 2D conductive MOF Cu3(HITP)2 and bulk conductivity of this MOF was measured to be 0.2 S
|
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cm−1. It was employed for chemiresistive sensing of ammonia vapor and limit of detection of this material was 0.5 ppm. Two isoreticular MOFs based on phthalocyanine and naphthalocyanine organic linkers have been tested for sensing of neurotransmitters. In this study authors were able to get a very low limit of detection, NH3 (0.31–0.33 ppm), H2S (19–32 ppb) and NO (1–1.1 ppb) at a driving voltage of (0.01–1.0 V). Later, same group also reported voltametric detection of neurochemical by isoreticular MOFs based on triphenylene organic linker. Ni3(HHTP)2 (2,3,6,7,10,11-hexahydroxytriphenylene) MOF showed nanomolar limit of detection of Dopamine (63±11 nM) and serotonin (40±17 nM). A 2D conductive MOF based on 2,3,7,8,12,13‐hexahydroxyl truxene linker and copper metal has shown promising electrochemical detection of paraquat. === Electrocatalysis === MOFs have been explored for electrolysis to enhance the rate and selectivity of reactions. Owing to their high surface area they can provide large number of interaction site for the reaction, conductivity of the material allows charge transfer during the electrocatalytic process. Two Cobalt based MOFs Co-BHT (Benzenehexathiol) and Co-HTTP (Hexathioltriphenylene) have been investigated for hydrogen evolution reaction (HER). In this report, overpotential values for Co-BHT and Co-HTTP are found to be 340 mV and 530 mV respectively at pH 1.3. The tafel slopes are between 149 and 189 mV dec−1 at pH 4.2. Ultrathin sheets of Co-HAB MOF have been found to be catalytically active for oxygen evolution reaction (OER). Overpotential for this MOF was 310 mV at 10 mA cm−2 in 1M KOH. Authors claimed that the ultrathin sheets were better than nanoparticles/thick sheets/bulk Co-HAB MOF because of favourable electrode kinetics. A 2-D conductive MOF has also been employed as an electrocatalyst for oxygen reduction reaction (ORR). Ni3(HITP)2 MOF film on glassy carbon electrode in their study showed a potential of 820 mV at 50
|
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"title": "Conductive metal−organic frameworks"
}
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μA in 0.1 M potassium hydroxide (KOH). === Energy storage === MOFs with high surface area, redox active organic linker/metal nodes, intrinsic conductivity have attracted attention as electrode materials for electrochemical energy storage. First Conductive MOF-based electrochemical double layer capacitor (EDLC) was reported by Dinca and co-workers in 2017. They used Ni3(HITP)2 MOF for the fabrication of the device without using conductive additives which are mixed to enhance the conductivity. The resulting electrodes showed a gravimetric capacitance of 111 F g−1 and areal capacitance of 18 μF cm−2 at a discharge rate of 0.05 A g−1. These electrodes also exhibited a capacity retention of 90% after 10000 cycles. A conductive MOFs based on hexaaminobenzene (HAB) organic linker and Cu/Ni metal ions has been tested as electrode for supercapacitor. Ni-HAB and Cu-HAB exhibited gravimetric capacitance of 420 F g−1 and 215 F g−1 respectively. The pellet form of Ni-HAB electrode showed a gravimetric capacitance of 427 F g−1 and volumetric capacitance of 760 F g−1. These MOFs also exhibited a capacitance retention of 90% after 12000 cycles. First conductive MOF based cathode material for Lithium-ion battery was reported by Nishihara and co-workers in 2018. In this study they employed Ni3(HITP)2 MOF, It exhibited a specific capacity of 155 mA h g−1, specific energy density of 434 Wh kg−1 at A current density of 10 mA g−1, and good stability over 300 cycles. In another study, two MOFs based on 2,5‐dichloro‐3,6‐dihydroxybenzoquinone (Cl2dhbqn−) organic linker and Fe metal ions have been employed for Lithium ion battery. (H2NMe2)2Fe2(Cl2dhbq)3 (1) and (H2NMe2)4Fe3(Cl2dhbq)3(SO4)2 (2) showed electrical conductivity of 2.6×10−3 and 8.4×10−5 S cm−1 respectively. (2) exhibited discharge capacity of 165 mA h g−1 at a charging rate of 10 mA g−1) and (1) exhibited 195 mA h g−1 at 20 mA g−1 and a specific energy
|
{
"page_id": 66981695,
"source": null,
"title": "Conductive metal−organic frameworks"
}
|
density of 533 Wh kg−1. == See also == Metal−organic framework Covalent−organic framework Coordination polymer Sensor == References ==
|
{
"page_id": 66981695,
"source": null,
"title": "Conductive metal−organic frameworks"
}
|
This list of research methods in biology is an index to articles about research methodologies used in various branches of biology. == Research design and analysis == === Research designs === === Charts and diagrams === === Statistical analyses === == Laboratory techniques == == Field techniques == == Computational tools == === Mathematical models === === Algorithms === == References == == External links ==
|
{
"page_id": 68292416,
"source": null,
"title": "List of research methods in biology"
}
|
Apache Giraph is an Apache project to perform graph processing on big data. Giraph utilizes Apache Hadoop's MapReduce implementation to process graphs. Facebook used Giraph with some performance improvements to analyze one trillion edges using 200 machines in 4 minutes. Giraph is based on a paper published by Google about its own graph processing system called Pregel. It can be compared to other Big Graph processing libraries such as Cassovary. As of September 2023, it is no longer actively developed. == References == == External links == Official website
|
{
"page_id": 37752641,
"source": null,
"title": "Apache Giraph"
}
|
In developmental biology, von Baer's laws of embryology (or laws of development) are four rules proposed by Karl Ernst von Baer to explain the observed pattern of embryonic development in different species. von Baer formulated the laws in his book On the Developmental History of Animals (German: Über Entwickelungsgeschichte der Thiere), published in 1828, while working at the University of Königsberg. He specifically intended to rebut Johann Friedrich Meckel's 1808 recapitulation theory. According to that theory, embryos pass through successive stages that represent the adult forms of less complex organisms in the course of development, and that ultimately reflects scala naturae (the great chain of being). von Baer believed that such linear development is impossible. He posited that instead of linear progression, embryos started from one or a few basic forms that are similar in different animals, and then developed in a branching pattern into increasingly different organisms. Defending his ideas, he was also opposed to Charles Darwin's 1859 theory of common ancestry and descent with modification, and particularly to Ernst Haeckel's revised recapitulation theory with its slogan "ontogeny recapitulates phylogeny". Darwin was however broadly supportive of von Baer's view of the relationship between embryology and evolution. == The laws == Von Baer described his laws in his book Über Entwickelungsgeschichte der Thiere. Beobachtung und Reflexion published in 1828. They are a series of statements generally summarised into four points, as translated by Thomas Henry Huxley in his Scientific Memoirs: The more general characters of a large group appear earlier in the embryo than the more special characters. From the most general forms the less general are developed, and so on, until finally the most special arises. Every embryo of a given animal form, instead of passing through the other forms, rather becomes separated from them. The embryo of a
|
{
"page_id": 50270017,
"source": null,
"title": "Von Baer's laws (embryology)"
}
|
higher form never resembles any other form, but only its embryo. == Description == Von Baer discovered the blastula (the early hollow ball stage of an embryo) and the development of the notochord (the stiffening rod along the back of all chordates, that forms after the blastula and gastrula stages). From his observations of these stages in different vertebrates, he realised that Johann Friedrich Meckel's recapitulation theory must be wrong. For example, he noticed that the yolk sac is found in birds, but not in frogs. According to the recapitulation theory, such structures should invariably be present in frogs because they were assumed to be at a lower level in the evolutionary tree. Von Baer concluded that while structures like the notochord are recapitulated during embryogenesis, whole organisms are not. He asserted that (as translated): The embryo successively adds the organs that characterize the animal classes in the ascending scale. When the human embryo, for instance, is but a simple vesicle, it is an infusorian; when it has gained a liver, it is a mussel; with the appearance of the osseous system, it enters the class of fishes; and so forth, until it becomes a mammal and then a human being. In terms of taxonomic hierarchy, according to von Baer, characters in the embryo are formed in top-to-bottom sequence, first from those of the largest and oldest taxon, the phylum, then in turn class, order, family, genus, and finally species. == Reception == The laws received a mixed appreciation. While they were criticised in detail, they formed the foundation of modern embryology. === Charles Darwin === The most important supporter of von Baer's laws was Charles Darwin. Darwin came across von Baer's laws from the work of Johannes Peter Müller in 1842, and realised that it was a support for
|
{
"page_id": 50270017,
"source": null,
"title": "Von Baer's laws (embryology)"
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|
his own theory of descent with modification. Darwin was a critique of the recapitulation theory and agreed with von Baer that an adult animal is not reflected by an embryo of another animal, and only embryos of different animals appear similar. He wrote in his Origin of Species (first edition, 1859): [The] adult [animal] differs from its embryo, owing to variations supervening at a not early age, and being inherited at a corresponding age. This process, whilst it leaves the embryo almost unaltered, continually adds, in the course of successive generations, more and more difference to the adult. Thus the embryo comes to be left as a sort of picture, preserved by nature, of the ancient and less modified condition of each animal. This view may be true, and yet it may never be capable of full proof. Darwin also said: It has already been casually remarked that certain organs in the individual, which when mature become widely different and serve for different purposes, are in the embryo exactly alike. The embryos, also, of distinct animals within the same class are often strikingly similar: a better proof of this cannot be given, than a circumstance mentioned by Agassiz, namely, that having forgotten to ticket the embryo of some vertebrate animal, he cannot now tell whether it be that of a mammal, bird, or reptile. Darwin's attribution to Louis Agassiz was a mistake, and was corrected in the third edition as von Baer. He further explained in the later editions of Origin of Species (from third to sixth editions), and wrote: It might be thought that the amount of change which the various parts and organs [of vertebrates] undergo in their development from the embryo to maturity would suffice as a standard of comparison; but there are cases, as with certain
|
{
"page_id": 50270017,
"source": null,
"title": "Von Baer's laws (embryology)"
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|
parasitic crustaceans, in which several parts of the structure become less perfect, so that the mature animal cannot be called higher than its larva. Von Baer's standard seems the most widely applicable and the best, namely, the amount of differentiation of the different parts (in the adult state, as I should be inclined to add) and their specialisation for different functions. Even so, von Baer was a vociferous anti-Darwinist, although he believed in the common ancestry of species. Devoting much of his scholarly effort to criticising natural selection, his criticism culminated with his last work Über Darwins Lehre ("On Darwin's Doctrine"), published in the year of his death in 1876. === Later biologists === The British zoologist Adam Sedgwick studied the developing embryos of dogfish and chicken, and in 1894 noted a series of differences, such as the green yolk in the dogfish and yellow yolk in the chicken, absence of embryonic rim in chick embryos, absence of blastopore in dogfish, and differences in the gill slits and gill clefts. He concluded: There is no stage of development in which the unaided eye would fail to distinguish between them with ease... A blind man could distinguish between them. Modern biologists still debate the validity of the laws. In one line of argument, it is said that although every detail of von Baer's law may not work, the basic assumption that early developmental stages of animals are highly conserved is a biological fact. But an opposition says that there are conserved genetic conditions in embryos, but not the genetic events that govern the development. One example on the problem of von Baer's law is the formation of notochord before heart. This is due to the fact that heart is present in many invertebrates, which never have notochord. == See also ==
|
{
"page_id": 50270017,
"source": null,
"title": "Von Baer's laws (embryology)"
}
|
Evolutionary developmental biology == References ==
|
{
"page_id": 50270017,
"source": null,
"title": "Von Baer's laws (embryology)"
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The pollination of orchids represents a complex aspect of the biology of this plant family, characterized by intricate flower structures and diverse ecological interactions with pollinator. Notably, the topic has garnered significant scientific interest over time, including the attention of Charles Darwin, who is recognized for his contributions to the theory of evolution by natural selection. In 1862, Darwin published his observations on the essential role of insects in orchid pollination in his work The Fertilization of Orchids. He noted that the various strategies employed by orchids to attract their pollinators are complex. == Adaptations of orchids to pollination by animals == Approximately 97% of orchid species rely on pollinator for the transfer of pollen from one plant to the pistils of another, which is essential for fertilization and seed formation. The pollen of orchids is organized into compact masses known as pollinia (singular: "pollinium"), preventing dispersal by wind and necessitating the presence of pollinators for sexual reproduction. These pollinators vary widely and may include flies, mosquitos, bees, wasps, butterflies, coleopterans, and birds, particularly hummingbirds. The phenomenon of zoophily in orchids requires that pollinating animals frequently visit the flowers and remain long enough to contact both the anthers and stigma. For successful pollen transfer, it is crucial that the pollen adheres effectively to the pollinators, enabling it to reach the stigmas of other flowers. The effectiveness of zoophily depends on the ability of these animals to recognize flowers from a distance and their attraction to flowers of the same species. Consequently, zoophilous flowers typically possess "attractive products" such as pollen and nectar, "means of attraction" like scents and colors, and pollen that is viscous or adhesive. Throughout the evolution of angiosperms, there has been significant differentiation in the means of attraction and flower morphology, allowing a broader range of animals
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{
"page_id": 71241537,
"source": null,
"title": "Pollination of orchids"
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to participate in pollination. This evolutionary process has led to the establishment of close relationships between pollinating animals and zoophilous flowers, benefiting both groups. For plants, this relationship has resulted in more precise attraction of specific pollinators, facilitating the transfer of pollen to the stigmas of other plants and reducing the overall production of pollen. In contrast to anemophilous plants, which may produce around one million pollen grains per ovule, orchids typically produce a one-to-one ratio. For specialized pollinators, this mutualism has reduced competition from other anthophilous animals, making targeted pollination advantageous. The evolutionary development of zoophilous angiosperms and their adapting animal partners is best understood as a process of coevolution characterized by reciprocal relationships. In some cases, orchids and their pollinators have become so interdependent that their existence is mutually exclusive. Pollination mechanisms resulting from this coevolution generally benefit both parties: pollinators obtain nectar from the flowers, while orchids gain pollen transfer. However, in numerous instances, the attraction of pollinators to orchids may rely on deceptive strategies that do not offer any rewards. == Orchid flowers == Orchid flowers are predominantly hermaphroditic, with unisexual forms being rare, and they typically exhibit zygomorphic (bilateral) symmetry. Most genera feature three outer elements known as sepals—two lateral and one dorsal—and three inner elements called petals, with the lower petal often modified into a lip or labellum. This labellum is usually larger and more vividly colored than the other petals, often exhibiting a trilobed or uniquely shaped structure, sometimes adorned with fleshy bumps or ridges, and may feature a basal spur with distinct color patterns. The androecium of orchids generally comprises one or two stamens, occasionally three, and is fused with the style and stigma to form a structure known as the column (or gynostema/gynostegium). The pollen is organized into masses called pollinia,
|
{
"page_id": 71241537,
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"title": "Pollination of orchids"
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which can vary in number from one to twelve, though two or four are most common. These pollinia, combined with a sticky stalk derived from the anther or stigma, form the transport unit during pollination. The gynoecium consists of three fused carpels and is situated below the calyx. It features a highly modified style that is solitary and terminal, forming a key component of the column. Near the apex, the stigma has an elongated lobe known as the rostellum, which is typically non-receptive and positioned above the stigmatic region. A part of the rostellum may develop into a sticky platform called the viscidium, which attaches to the pollinium stem. Orchids generally produce nectar as a reward for pollinators, with nectaries varying in their location and type. They may be situated on the lip spur, at the tips of the sepals, or on the septa of the gynoecium. Additionally, some orchid species are capable of self-pollinatings or are apomictics, meaning they can produce seeds without the need for pollinators. == Attraction of pollinators by means of rewards == Many orchid species provide various rewards to pollinators, including nectar, food hairs, oils, and other compounds such as waxes, resins, and fragrances. These rewards serve to reinforce pollinator behavior, enhancing the likelihood of effective pollen transfer. Over time, this specialization on a single type of pollinator has led to increased morphological and structural adaptations in orchid flowers, aimed at attracting specific insect species. This evolutionary aspect of the interspecific relationships between orchids and their pollinators was notably examined by Charles Darwin in his studies of both British and exotic orchid species. A prominent example is the Madagascar species Angraecum sesquipedale, which features a spur exceeding 30 cm in length that contains nectar. Darwin's attempts to extract the pollinia from this flower using needles
|
{
"page_id": 71241537,
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"title": "Pollination of orchids"
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were unsuccessful; he was only able to do so by inserting a cylinder with a diameter of 2.5 mm into the spur and pulling it out, causing the viscidium to adhere to the cylinder. Darwin proposed that when a butterfly reached the bottom of the spur to access the nectar, the pollinia would attach to its head as it withdrew its proboscis. Upon visiting another flower, the butterfly would then transfer the pollinia to its stigma. Based on this reasoning, Darwin suggested that the pollinator of Angraecum sesquipedale would need to have a proboscis longer than 30 cm, an idea that seemed implausible to contemporary biologists. However, this prediction was confirmed in 1903 with the discovery of the moth Xanthopan morganii praedicta in Madagascar, which possesses a proboscis of the predicted length. The subspecific epithet "praedicta" reflects the foretelling of its existence by Darwin. The moth is attracted to Angraecum sesquipedale by its fragrance, particularly during the night. Upon approaching the flower, the moth unrolls its proboscis and inserts it into a crevice of the rostellum that leads to the spur. After accessing the nectar at the base of the spur, the moth lifts its head while withdrawing its proboscis, causing the viscidium to adhere to its head or another part of its body. The viscidium contains a small pedicel, known as the caudicle, which carries the pollinia. When the moth finishes feeding and moves to another flower, the caudicle dehydrates, altering its angle relative to the insect’s body. This positioning ensures that when the moth inserts its proboscis into the next flower, the pollinia are properly aligned to attach to the stigma. After successful pollination, the flowers stop producing fragrance, and their tepals wither shortly thereafter. Nonetheless, the processes of pollen transfer, fertilization, and the formation of numerous new
|
{
"page_id": 71241537,
"source": null,
"title": "Pollination of orchids"
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individuals have already been secured. Many orchids, including Angraecum sesquipedale, are pollinated by nocturnal butterflies and, as a result, tend to have light-colored or nearly white flowers that emit fragrance in the evening or night. Other examples of such orchids include Bonatea speciosa, Habenaria epipactidea, species in the genus Satyrium, Disa cooperi and D. ophrydea. In contrast, some orchid genera have evolved to be pollinated by diurnal butterflies, exhibiting bright colors and providing nectar as a reward. Melitophilous orchids, which are pollinated by bees, typically produce a strong fragrance during the day and are robustly colored. Examples include Satyrium erectum and Disa versicolor. These bee-pollinated orchids often offer not only nectar but also oils—a relatively rare reward in the plant kingdom—used by various bee species to nourish their larvae. Notable genera that provide oil rewards include Disperis, Pterygodium, Corycium, Ceratandra, Evotella, Satyrium, and Pachites. Pollination by flies, known as myophily, is the second most prevalent method of pollination among orchids, involving pollinators from twenty different dipteran families. These flowers typically emit scents reminiscent of decaying organic materials, excrement, or carrion, which attract flies seeking food or suitable sites for egg deposition. Various floral parts produce putrescent or carrion-like odors and often incorporate traps to retain the pollinators, alongside appendages and colors that may mimic flesh or other aspects of rotting matter. For example, species in the genus Bulbophyllum, which are daciniphilous, attract true fruit flies from the Dacini tribe (Tephritidae) using pleasant or spicy scents as floral synomones, establishing mutualistic relationships that confer reproductive benefits to both the orchids and the male flies. Notably, B. hortorum has coevolved with male fruit flies to develop a unique pollination mechanism that selects for optimal-sized individuals as potential pollinators. Stelis hymenantha produces a strong aroma of sweet menthol. It secretes a sticky substance
|
{
"page_id": 71241537,
"source": null,
"title": "Pollination of orchids"
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at the base of the labellum that resembles nectar. Another species, S. immersa, also emits a fragrance, described as melon-like, with its sticky substance located on both the petals and the labellum’s base. The primary visitors to these species are dipterans from various families. Typically, flies remain outside the flowers, investigating the viscous liquid on the petal surfaces. In the case of Stelis immersa, female flies from the genus Megaselia (Phoridae) are specifically adapted for effective pollen transfer. After inspecting the nectar-like substance, these insects enter the flower laterally and land on the downward-facing labellum. When this occurs, the labellum rises, pressing the fly against the viscid pollinium and trapping it. To exit, the fly backs up, causing the viscidium to adhere to its thorax. The labellum then returns to its original position, releasing the fly, which has now facilitated pollination. === Attraction and reward by means of perfumes === The flowers of the subtribes Stanhopeinae and Catasetinae exhibit specialized pollination mechanisms. These species are exclusively pollinated by male euglossine bees, which collect perfumes from the flowers. The reasons behind this behavior are not entirely understood, as the perfumes do not provide nutrition or protection but may play a role in the mating rituals of these bees. The process of scent collection is quite similar across species. The male bee approaches the osmophore, the scent-producing part of the flower, and perches on the labellum. Using the long, dense hairs on its front legs, the bee gathers the aromatic substances, which are typically liquid but can also be found in crystalline form. If the scent compounds are solid, the bee dissolves them with secretions from its salivary glands. Once saturated with the aroma, the bee transfers the scents using its middle legs to storage cavities in its hind legs, where they
|
{
"page_id": 71241537,
"source": null,
"title": "Pollination of orchids"
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can be preserved for extended periods. Different orchid genera attach pollinia to various parts of the bee’s body. Orchids, like many plants, attract specific groups of male euglossine bees by producing species-specific scent mixtures, which likely act as reproductive isolation mechanisms. Some orchids exhibit morphological adaptations that ensure pollinia are only released upon visitation by particular bee species, depending on their size and behavior. Consequently, not all euglossine bees that visit a given orchid species are effective pollinators. Additionally, certain species of Bulbophyllum attract specific male Dacini fruit flies through particular male attractants such as methyl eugenol (ME), raspberry ketone (RK), or zingerone (ZN). Methyl eugenol serves as a sex pheromone precursor for several quarantine pest species of Bactrocera, including the oriental fruit fly (B. dorsalis), B. carambolae, B. occipitalis, and B. umbrosa. Similarly, raspberry ketone and zingerone function as sex pheromone components for male fruit flies like Zeugodacus caudatus, Z. cucurbitae, and Z. tau. == Attraction of pollinators by means of deception == Many orchids employ various deceptive tactics to attract pollinators by mimicking scents, shapes, colors, or movements associated with resources of interest to the pollinators, without providing any actual rewards. The mechanisms of deception are diverse and can be categorized as follows: Generalized Feeding Deception: Flowers mimic the shape and coloration of species that typically offer rewards to pollinators. Feeding Deception Mediated through Floral Mimicry: In this case, flowers closely resemble a specific species that rewards pollinators, cohabiting in the same environment. Mimicry of Nesting Sites: Flowers imitate the egg-laying sites of certain pollinators. Mimicking Shelter Sites: Flowers provide potential shelter for pollinators, a strategy that may not be deceptive but can be mutually beneficial for both the insect and the orchid. Pseudo-Antagonism: This mechanism attracts pollinators by invoking their innate defense responses. Flowers mimic the appearance
|
{
"page_id": 71241537,
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"title": "Pollination of orchids"
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of another insect species that the pollinator may perceive as a threat, prompting the pollinator to attack the flower. In doing so, the insect inadvertently transfers pollen to other flowers. Rendezvous Attraction: Flowers imitate other flowers that are attractive to female pollinators. Sexual Deception: In this scenario, flowers mimic the visual and olfactory mating signals of female pollinators. Among these mechanisms, generalized feeding deception is the most commonly observed in orchids, reported in 38 genera, followed by sexual deception, which has been identified in 18 genera. === Attraction of pollinators by luring them for food === The ability to attract pollinators without offering rewards has evolved independently across several angiosperm lineages, although it typically occurs in only a few species within each family. In contrast, it is estimated that approximately one-third of orchid species employ a food-deceptive mechanism. This strategy involves signaling the presence of food, such as nectar or pollen, to attract pollinators without providing any actual reward. Orchids often achieve this by resembling species that do offer rewards and that cohabit in the same environment. Feeding deception commonly manifests as a general resemblance to rewarding species, with orchids featuring large, brightly colored flowers that exploit pollinators' innate preferences for such floral characteristics. ==== Imitation of other plants ==== Another method employed by orchids to attract pollinators involves mimicking the flowers of other plant species. A notable example is Epidendrum ibaguense, a terrestrial or lithophilous orchid found from Mexico to Bolivia and Brazil. This orchid features orange flowers with an intense yellow labellum, closely resembling the flowers of Asclepias curassavica, a member of the Asclepiadaceae family. The butterfly Agraulis vanillae, which typically visits Asclepias curassavica to collect nectar in exchange for pollen transport, is frequently drawn to the mimetic flowers of Epidendrum ibaguense. When the butterfly approaches the orchid,
|
{
"page_id": 71241537,
"source": null,
"title": "Pollination of orchids"
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it inserts its proboscis into the narrow duct (gynostemium) of the flower. The small diameter of this duct can cause the butterfly's spiracles to become temporarily trapped. In its struggle to escape, the insect inadvertently picks up the orchid's pollinia. After being released, the butterfly may visit another Epidendrum flower, transferring the pollinia and facilitating pollination without receiving nectar for its efforts. === Attraction of pollinators by sexual luring === Certain orchids have evolved deceptive flowers that mimic the shape, hairiness, and scent of female wasps or bees to attract male pollinators. A well-known example is Ophrys insectifera, found in southern Europe, which is exclusively visited by two species of wasps from the genus Argogorytes. Male wasps emerge in spring, weeks before females, and are attracted to the fragrance of Ophrys flowers, which resembles the pheromones secreted by female wasps. Additionally, the labellum of Ophrys insectifera closely resembles the shape, color, and texture of female wasps. This interaction is referred to as pseudocopulation, as male wasps attempt to mate with the flower, during which they come into contact with the anther and transfer pollinia between flowers. The phenomenon of pollination by pseudocopulation was first documented by A. Pouyanne and H. Correvon in 1916 and 1917 while studying the relationship between the orchid Ophrys speculum and the scoliidae wasp Campsoscolia ciliata in Algeria. Their findings initially went unnoticed until Robert Godfrey validated their observations in 1925, prompting increased interest in this area of study. Following this, Australian biologist Edith Coleman published numerous papers on the pollination of orchids from the genus Cryptostylis by males of the ichneumonoidea wasp Lissopimpla excelsa. Several genera of terrestrial orchids employ this pseudocopulation mechanism, including Ophrys, Cryptostylis, Drakaea, Caladenia, Chiloglottis, Geoblasta, Arthrochilus, Calochilus, Leporella, and Spiculaea. Most terrestrial orchid genera utilizing pseudocopulation are found in Australia,
|
{
"page_id": 71241537,
"source": null,
"title": "Pollination of orchids"
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with Ophrys being the largest and best-documented genus in Europe. This mechanism is not limited to a specific continent; it has also been observed in the South American species Geoblasta penicillata and in two South African orchids of the genus Disa. A similar mechanism is found in Tolumnia henekenii, whose flowers mimic the female of the bee species Centris insularis. The resemblance is so convincing that male bees attempt to copulate with the flower, thereby facilitating its pollination. In the genus Caleana, commonly known as the duck orchid due to its labellum resembling the head of a duck and the overall flower resembling a flying duck, a distinct mechanism of pseudocopulation has been observed. This species utilizes a spring mechanism to trap pollinating insects in a pouch, with their only means of escape being through the pollinium and stigma. When male insects land on the labellum, they activate a two-hinged relaxation mechanism involving the labellum-lamellum and the lamina-perianth, which flips the insect into the pouch containing the stigma and pollinia. Pseudocopulation is not limited to pollinators from the Hymenoptera order (such as bees and wasps); it has also been documented in certain Diptera. For instance, male mosquitoes of the genus Bradysia have been observed to pseudocopulate with species of Lepanthes, a large genus of orchids found in neotropical rainforests. In Ophrys orchids, the flowers not only mimic the shape, size, and color of female pollinators but also emit fragrances that include compounds found in female sex pheromones. This reinforces the sexual attraction of males to the flowers. Chemical and electrophysiological comparisons have been made between the volatile compounds emitted by Ophrys iricolor and the female pheromones of its pollinator, Andrena morio. More than 40 compounds have been identified, including alkanes and alkenes with 20 to 29 carbon atoms, aldehydes with
|
{
"page_id": 71241537,
"source": null,
"title": "Pollination of orchids"
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|
9 to 24 carbons, and two esters. Most of these compounds are present in similar proportions in both floral extracts of O. iricolor and extracts from the cuticular surface of A. morio females. The biologically active volatile compounds in Ophrys species are largely similar to those utilized by other Ophrys species that engage in pseudocopulation with males of the genera Andrena and Colletes. == See also == Orchidaceae Orchis == Notes == == References ==
|
{
"page_id": 71241537,
"source": null,
"title": "Pollination of orchids"
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The CD4+/CD8+ ratio is the ratio of T helper cells (with the surface marker CD4) to cytotoxic T cells (with the surface marker CD8). Both CD4+ and CD8+ T cells contain several subsets. The CD4+/CD8+ ratio in the peripheral blood of healthy adults and mice is about 2:1, and an altered ratio can indicate diseases relating to immunodeficiency or autoimmunity. An inverted CD4+/CD8+ ratio (namely, less than 1/1) indicates an impaired immune system. Conversely, an increased CD4+/CD8+ ratio corresponds to increased immune function. Obesity and dysregulated lipid metabolism in the liver leads to loss of CD4+, but not CD8+ cells, contributing to the induction of liver cancer. Regulatory CD4+ cells decline with expanding visceral fat, whereas CD8+ T-cells increase. == Decreased ratio with infection == A reduced CD4+/CD8+ ratio is associated with reduced resistance to infection. Patients with tuberculosis show a reduced CD4+/CD8+ ratio. HIV infection leads to low levels of CD4+ T cells (lowering the CD4+/CD8+ ratio) through a number of mechanisms, including killing of infected CD4+. Acquired immunodeficiency syndrome (AIDS) is (by one definition) a CD4+ T cell count below 200 cells per μL. HIV progresses with declining numbers of CD4+ and expanding number of CD8+ cells (especially CD8+ memory cells), resulting in high morbidity and mortality. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections. Declining CD4+/CD8+ ratio has been found to be a prognostic marker of HIV disease progression. == COVID-19 == In COVID-19 B cell, natural killer cell, and total lymphocyte counts decline, but both CD4+ and CD8+ cells decline to a far greater extent. Low CD4+ predicted greater likelihood of intensive care unit admission, and CD4+ cell count was the only parameter that predicted length of time for viral
|
{
"page_id": 52170563,
"source": null,
"title": "CD4+/CD8+ ratio"
}
|
RNA clearance. == Decreased ratio with aging == A declining CD4+/CD8+ ratio is associated with ageing, and is an indicator of immunosenescence. Compared to CD4+ T-cells, CD8+ T-cells show a greater increase in adipose tissue in obesity and aging, thereby reducing the CD4+/CD8+ ratio. Amplication of numbers of CD8+ cells are required for adipose tissue inflammation and macrophage infiltration, whereas numbers of CD4+ cells are reduced under those conditions. Antibodies against CD8+ T-cells reduces inflammation associated with diet-induced obesity, indicating that CD8+ T-cells are an important cause of the inflammation. CD8+ cell recruitment of macrophages into adipose tissue can initiate a vicious cycle of further recruitment of both cell types. Elderly persons commonly have a CD4+/CD8+ ratio less than one. Obesity is associated with a reduced CD4+/CD8+ ratio, and obesity tends to increase with age. A study of Swedish elderly found that a CD4+/CD8+ ratio less than one was associated with short-term likelihood of death. Immunological aging is characterized by low proportions of naive CD8+ cells and high numbers of memory CD8+ cells, particularly when cytomegalovirus is present. Exercise can reduce or reverse this effect, when not done at extreme intensity and duration. Both effector helper T cells (Th1 and Th2) and regulatory T cells (Treg) cells have a CD4 surface marker, such that although total CD4+ T cells decrease with age, the relative percent of CD4+ T cells increases. The increase in Treg with age results in suppressed immune response to infection, vaccination, and cancer, without suppressing the chronic inflammation associated with aging. == See also == Helper/suppressor ratio List of distinct cell types in the adult human body == References ==
|
{
"page_id": 52170563,
"source": null,
"title": "CD4+/CD8+ ratio"
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Vanesa Gottifredi (born 13 November 1969) is an Argentine chemist and biologist. She works as a researcher in the Principal Investigator category of the Scientific and Technological Researcher Program (CICT) of the National Scientific and Technical Research Council (CONICET). She is also head of the Leloir Institute's Cell Cycle and Genomic Stability Laboratory. She specializes in the mechanisms of tumor cell response to chemotherapy, work for which she was awarded by the Alexander von Humboldt Foundation and L'Oreal-UNESCO. == Career == Vanesa Gottifredi completed her undergraduate studies at the National University of Salta, where she obtained a licentiate in chemistry in 1992. She then studied at the Sapienza University of Rome, where she graduated as a doctor in human biology in 1998. Later she conducted postdoctoral studies in cell biology and cancer at Columbia University in the United States. As head of the Cell Cycle and Genomic Stability Laboratory at the Leloir Institute Foundation, she conducts research on defense mechanisms that both normal and tumor cells use to cope with adverse events, and how malignant cells avoid the effects of chemotherapy. == Awards == Special mention for the Lóreál-UNESCO Award, 2013 Bernardo Houssay Award for Medical Science, 2014 Friedrich Wilhelm Bessel Award from the Alexander von Humboldt Foundation, 2017 Ben Barres Spotlight Award from eLife, 2019 L'Oréal-UNESCO For Women in Science Award (Argentine national edition), in collaboration with CONICET, 2019 == References == == External links == Vanesa Gottifredi at the Leloir Institute
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{
"page_id": 63049540,
"source": null,
"title": "Vanesa Gottifredi"
}
|
Indo-1 is a popular dye that is used as a ratiometric calcium indicator similar to Fura-2. In contrast to Fura-2, Indo-1 has a dual emissions peak and a single excitation. The main emission peak in calcium-free solution is 475 nm while in the presence of calcium the emission is shifted to 400 nm. It is widely used in flow cytometry and laser scanning microscopy, due to its single excitation property. However, its use for confocal microscopy is limited due to its photo-instability caused by photobleaching. Indo-1 is also able to keep possession of its ratiometric emission, dissimilar to Fura-2. The penta potassium salt is commercially available and preferred to the free acid because of its higher solubility in water. While Indo-1 is not cell permeable the penta acetoxymethyl ester Indo-1 AM enters the cell where it is cleaved by intracellular esterases to Indo-1. The synthesis and properties of Indo-1 were presented in 1985 by the group of Roger Y Tsien. In intact heart muscle, Indo-1, in combination with bioluminescent protein aequorin, can be utilized as a tool to distinguish between the internal and exterior inotropic regulation processes. == References ==
|
{
"page_id": 13635394,
"source": null,
"title": "Indo-1"
}
|
A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is mostly of endodermal origin and is continuous with the skin at body openings such as the eyes, eyelids, ears, inside the nose, inside the mouth, lips, the genital areas, the urethral opening and the anus. Some mucous membranes secrete mucus, a thick protective fluid. The function of the membrane is to stop pathogens and dirt from entering the body and to prevent bodily tissues from becoming dehydrated. == Structure == The mucosa is composed of one or more layers of epithelial cells that secrete mucus, and an underlying lamina propria of loose connective tissue. The type of cells and type of mucus secreted vary from organ to organ and each can differ along a given tract. Mucous membranes line the digestive, respiratory and reproductive tracts and are the primary barrier between the external world and the interior of the body; in an adult human the total surface area of the mucosa is about 400 square meters while the surface area of the skin is about 2 square meters.: 1 Along with providing a physical barrier, they also contain key parts of the immune system and serve as the interface between the body proper and the microbiome.: 437 === Examples === Some examples include: Endometrium: the mucosa of the uterus Gastric mucosa Intestinal mucosa Nasal mucosa Olfactory mucosa Oral mucosa Penile mucosa Respiratory mucosa Vaginal mucosa Frenulum of tongue Anal canal Conjunctiva === Development === Developmentally, the majority of mucous membranes are of endodermal origin. Exceptions include the palate, cheeks, floor of the mouth, gums, lips and
|
{
"page_id": 69447,
"source": null,
"title": "Mucous membrane"
}
|
the portion of the anal canal below the pectinate line, which are all ectodermal in origin. == Function == One of its functions is to keep the tissue moist (for example in the respiratory tract, including the mouth and nose).: 480 It also plays a role in absorbing and transforming nutrients.: 5, 813 Mucous membranes also protect the body from itself. For instance, mucosa in the stomach protects it from stomach acid,: 384, 797 and mucosa lining the bladder protects the underlying tissue from urine. In the uterus, the mucous membrane is called the endometrium, and it swells each month and is then eliminated during menstruation.: 1019 === Nutrition === Niacin: 876 and vitamin A are essential nutrients that help maintain mucous membranes. == See also == == References ==
|
{
"page_id": 69447,
"source": null,
"title": "Mucous membrane"
}
|
In ecology, edge effects are changes in population or community structures that occur at the boundary of two or more habitats. Areas with small habitat fragments exhibit especially pronounced edge effects that may extend throughout the range. As the edge effects increase, the boundary habitat allows for greater biodiversity. Urbanization is causing humans to continuously fragment landscapes and thus increase the edge effect. This change in landscape ecology is proving to have consequences. Generalist species, especially invasive ones, have been seen to benefit from this landscape change whilst specialist species are suffering. For example, the alpha diversity of edge-intolerant birds in Lacandona rainforest, Mexico, is decreasing as edge effects increase. == Types == Inherent – Natural features stabilize the border location. Induced – Transient natural disturbances (e.g., fire or flood) or human related activities, subject borders to successional changes over time. Narrow – One habitat abruptly ends and another begins (e.g., an agricultural field.) Wide (ecotone) – A large distance separates the borders of two clearly and purely definable habitats based upon their physical conditions and vegetation, and in between there exists a large transition region. Convoluted – The border is non-linear. Perforated – The border has gaps that host other habitats. Height can create borders between patches as well. == Biodiversity == Environmental conditions enable certain species of plants and animals to colonize habitat borders. Plants that colonize forest edges tend to be shade-intolerant. These plants also tend to be tolerant of dry conditions, such as shrubs and vines. Animals that colonize tend to be those that require two or more habitats, such as white-tailed and mule deer, elk, cottontail rabbits, blue jays, and robins. Some animals travel between habitats, while edge species are restricted to edges. Larger patches have increased native species biodiversity compared to smaller patches. The
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{
"page_id": 69440,
"source": null,
"title": "Edge effects"
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width of the patch also influences diversity: an edge patch must be more pronounced than just a stark border in order to develop gradients of edge effects. Animals traveling between communities can create travel lanes along borders, which in turn increases light reaching plants along the lanes and promotes primary production. As more light reaches the plants, greater numbers and sizes can thrive. Increased primary production can increase numbers of herbivorous insects, followed by nesting birds and so on up the trophic levels. In the case of wide and/or overgrown borders, some species can become restricted to one side of the border despite having the ability to inhabit the other. Sometimes, the edge effects result in abiotic and biotic conditions which diminish natural variation and threaten the original ecosystem. Detrimental edge effects are also seen in physical and chemical conditions of border species. For instance, fertilizer from an agricultural field could invade a bordering forest and contaminate the habitat. The three factors affecting edges can be summarized: Abiotic effect—Changes in the environmental conditions that result from the proximity to a structurally dissimilar matrix Direct biological effects—Changes in species abundance and distribution caused directly by physical conditions near the edge Indirect biological effects which involve changes in species interactions such as predation, brood parasitism, competition, herbivory, and biotic pollination and seed dispersal == Human effects == Human activity creates edges through development and agriculture. Often, the changes are detrimental to both the size of the habitat and to species. Examples of human impacts include: Introduction of invasives/exotics Higher severity and frequency of fires Companion animals (pets) acting as predators and competitors Trails Pollution, erosion Loss of foraging habitats Habitat fragmentation Deforestation and land use change == Examples == When edges divide any natural ecosystem and the area outside the boundary is
|
{
"page_id": 69440,
"source": null,
"title": "Edge effects"
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|
a disturbed or unnatural system, the natural ecosystem can be seriously affected for some distance in from the edge. In 1971, Odum wrote, 'The tendency for increased variety and diversity at community junctions is known as the edge effect... It is common knowledge that the density of songbirds is greater on estates, campuses and similar settings...as compared with tracts of uniform forest.'. In a forest where the adjacent land has been cut, creating an open/forest boundary, sunlight and wind penetrate to a much greater extent, drying out the interior of the forest close to the edge and encouraging growth of opportunistic species there. Air temperature, vapor pressure deficit, soil moisture, light intensity and levels of photosynthetically active radiation (PAR) all change at edges. === Amazon rainforest === One study estimated that the amount of Amazon Basin area modified by edge effects exceeded the area that had been cleared. "In studies of Amazon forest fragments, micro-climate effects were evident up to 100m (330ft.) into the forest interior." The smaller the fragment, the more susceptible it is to fires spreading from nearby cultivated fields. Forest fires are more common close to edges due to increased light availability that leads to increased desiccation and increased understory growth. Increased understory biomass provides fuel that allows pasture fires to spread into the forests. Increased fire frequency since the 1990s is among the edge effects that are slowly transforming Amazonian forests. The changes in temperature, humidity and light levels promote invasion of non-forest species, including invasive species. The overall effect of these fragment processes is that all forest fragments tend to lose native biodiversity depending on fragment size and shape, isolation from other forest areas, and the forest matrix. === North America === The amount of forest edge is orders of magnitude greater now in the
|
{
"page_id": 69440,
"source": null,
"title": "Edge effects"
}
|
United States than when the Europeans first began settling North America. Some species have benefited from this fact, for example, the brown-headed cowbird, which is a brood parasite that lays its eggs in the nests of songbirds nesting in forest near the forest boundary. Another example of a species benefiting from the proliferation of forest edge is poison ivy. Conversely, Dragonflies eat mosquitoes, but have more trouble than mosquitoes surviving around the edges of human habitation. Thus, trails and hiking areas near human settlements often have more mosquitoes than do deep forest habitats. Grasses, huckleberries, flowering currants and shade-intolerant trees such as the Douglas-fir all thrive in edge habitats. In the case of developed lands juxtaposed to wild lands, problems with invasive exotics often result. Species such as kudzu, Japanese honeysuckle and multiflora rose have damaged natural ecosystems. Beneficially, the open spots and edges provide places for species that thrive where there is more light and vegetation that is close to the ground. Deer and elk benefit particularly as their principal diet is that of grass and shrubs which are found only on the edges of forested areas. == Effects on succession == Edge effects also apply to succession, when vegetation spreads rather than losing to competitors. Different species are suited either to the edges or to central sections of the habitat, resulting in a varied distribution. Edges also vary with orientation: edges on the north or south receive less or more sun than the opposite side (depending on hemisphere and convex or concave relief), producing varying vegetation patterns. == Other usage == The phenomenon of increased variety of plants as well as animals at the community junction (ecotone) is also called the edge effect and is essentially due to a locally broader range of suitable environmental conditions or ecological
|
{
"page_id": 69440,
"source": null,
"title": "Edge effects"
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niches. Edge effects in biological assays refer to artifacts in data that are caused by the position of the wells on a screening plate rather than a biological effect. The edge effect in scanning electron microscopy is the phenomenon in which the number of secondary and/or backscattered electrons that escape the sample and reach the detector is higher at an edge than at a surface. The interaction volume spreads far below the surface, but secondary electrons can only escape when close to the surface (generally about 10 nm, although this depends on the material). However, when the electron beam impacts an area close to the edge, electrons that are generated below an impact point that is close to an edge but that is far below the surface may be able to escape through the vertical surface instead. == See also == Ecotone Habitat fragmentation Landscape ecology Ruderal species Spatial ecology Woodland edge == References == == External links == Reducing Edge Effects in biological assays
|
{
"page_id": 69440,
"source": null,
"title": "Edge effects"
}
|
Stability, also known as algorithmic stability, is a notion in computational learning theory of how a machine learning algorithm output is changed with small perturbations to its inputs. A stable learning algorithm is one for which the prediction does not change much when the training data is modified slightly. For instance, consider a machine learning algorithm that is being trained to recognize handwritten letters of the alphabet, using 1000 examples of handwritten letters and their labels ("A" to "Z") as a training set. One way to modify this training set is to leave out an example, so that only 999 examples of handwritten letters and their labels are available. A stable learning algorithm would produce a similar classifier with both the 1000-element and 999-element training sets. Stability can be studied for many types of learning problems, from language learning to inverse problems in physics and engineering, as it is a property of the learning process rather than the type of information being learned. The study of stability gained importance in computational learning theory in the 2000s when it was shown to have a connection with generalization. It was shown that for large classes of learning algorithms, notably empirical risk minimization algorithms, certain types of stability ensure good generalization. == History == A central goal in designing a machine learning system is to guarantee that the learning algorithm will generalize, or perform accurately on new examples after being trained on a finite number of them. In the 1990s, milestones were reached in obtaining generalization bounds for supervised learning algorithms. The technique historically used to prove generalization was to show that an algorithm was consistent, using the uniform convergence properties of empirical quantities to their means. This technique was used to obtain generalization bounds for the large class of empirical risk minimization
|
{
"page_id": 33886025,
"source": null,
"title": "Stability (learning theory)"
}
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(ERM) algorithms. An ERM algorithm is one that selects a solution from a hypothesis space H {\displaystyle H} in such a way to minimize the empirical error on a training set S {\displaystyle S} . A general result, proved by Vladimir Vapnik for an ERM binary classification algorithms, is that for any target function and input distribution, any hypothesis space H {\displaystyle H} with VC-dimension d {\displaystyle d} , and n {\displaystyle n} training examples, the algorithm is consistent and will produce a training error that is at most O ( d n ) {\displaystyle O\left({\sqrt {\frac {d}{n}}}\right)} (plus logarithmic factors) from the true error. The result was later extended to almost-ERM algorithms with function classes that do not have unique minimizers. Vapnik's work, using what became known as VC theory, established a relationship between generalization of a learning algorithm and properties of the hypothesis space H {\displaystyle H} of functions being learned. However, these results could not be applied to algorithms with hypothesis spaces of unbounded VC-dimension. Put another way, these results could not be applied when the information being learned had a complexity that was too large to measure. Some of the simplest machine learning algorithms—for instance, for regression—have hypothesis spaces with unbounded VC-dimension. Another example is language learning algorithms that can produce sentences of arbitrary length. Stability analysis was developed in the 2000s for computational learning theory and is an alternative method for obtaining generalization bounds. The stability of an algorithm is a property of the learning process, rather than a direct property of the hypothesis space H {\displaystyle H} , and it can be assessed in algorithms that have hypothesis spaces with unbounded or undefined VC-dimension such as nearest neighbor. A stable learning algorithm is one for which the learned function does not change much when
|
{
"page_id": 33886025,
"source": null,
"title": "Stability (learning theory)"
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the training set is slightly modified, for instance by leaving out an example. A measure of Leave one out error is used in a Cross Validation Leave One Out (CVloo) algorithm to evaluate a learning algorithm's stability with respect to the loss function. As such, stability analysis is the application of sensitivity analysis to machine learning. == Summary of classic results == Early 1900s - Stability in learning theory was earliest described in terms of continuity of the learning map L {\displaystyle L} , traced to Andrey Nikolayevich Tikhonov. 1979 - Devroye and Wagner observed that the leave-one-out behavior of an algorithm is related to its sensitivity to small changes in the sample. 1999 - Kearns and Ron discovered a connection between finite VC-dimension and stability. 2002 - In a landmark paper, Bousquet and Elisseeff proposed the notion of uniform hypothesis stability of a learning algorithm and showed that it implies low generalization error. Uniform hypothesis stability, however, is a strong condition that does not apply to large classes of algorithms, including ERM algorithms with a hypothesis space of only two functions. 2002 - Kutin and Niyogi extended Bousquet and Elisseeff's results by providing generalization bounds for several weaker forms of stability which they called almost-everywhere stability. Furthermore, they took an initial step in establishing the relationship between stability and consistency in ERM algorithms in the Probably Approximately Correct (PAC) setting. 2004 - Poggio et al. proved a general relationship between stability and ERM consistency. They proposed a statistical form of leave-one-out-stability which they called CVEEEloo stability, and showed that it is a) sufficient for generalization in bounded loss classes, and b) necessary and sufficient for consistency (and thus generalization) of ERM algorithms for certain loss functions such as the square loss, the absolute value and the binary classification loss.
|
{
"page_id": 33886025,
"source": null,
"title": "Stability (learning theory)"
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|
2010 - Shalev Shwartz et al. noticed problems with the original results of Vapnik due to the complex relations between hypothesis space and loss class. They discuss stability notions that capture different loss classes and different types of learning, supervised and unsupervised. 2016 - Moritz Hardt et al. proved stability of gradient descent given certain assumption on the hypothesis and number of times each instance is used to update the model. == Preliminary definitions == We define several terms related to learning algorithms training sets, so that we can then define stability in multiple ways and present theorems from the field. A machine learning algorithm, also known as a learning map L {\displaystyle L} , maps a training data set, which is a set of labeled examples ( x , y ) {\displaystyle (x,y)} , onto a function f {\displaystyle f} from X {\displaystyle X} to Y {\displaystyle Y} , where X {\displaystyle X} and Y {\displaystyle Y} are in the same space of the training examples. The functions f {\displaystyle f} are selected from a hypothesis space of functions called H {\displaystyle H} . The training set from which an algorithm learns is defined as S = { z 1 = ( x 1 , y 1 ) , . . , z m = ( x m , y m ) } {\displaystyle S=\{z_{1}=(x_{1},\ y_{1})\ ,..,\ z_{m}=(x_{m},\ y_{m})\}} and is of size m {\displaystyle m} in Z = X × Y {\displaystyle Z=X\times Y} drawn i.i.d. from an unknown distribution D. Thus, the learning map L {\displaystyle L} is defined as a mapping from Z m {\displaystyle Z_{m}} into H {\displaystyle H} , mapping a training set S {\displaystyle S} onto a function f S {\displaystyle f_{S}} from X {\displaystyle X} to Y {\displaystyle Y} . Here, we
|
{
"page_id": 33886025,
"source": null,
"title": "Stability (learning theory)"
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consider only deterministic algorithms where L {\displaystyle L} is symmetric with respect to S {\displaystyle S} , i.e. it does not depend on the order of the elements in the training set. Furthermore, we assume that all functions are measurable and all sets are countable. The loss V {\displaystyle V} of a hypothesis f {\displaystyle f} with respect to an example z = ( x , y ) {\displaystyle z=(x,y)} is then defined as V ( f , z ) = V ( f ( x ) , y ) {\displaystyle V(f,z)=V(f(x),y)} . The empirical error of f {\displaystyle f} is I S [ f ] = 1 n ∑ V ( f , z i ) {\displaystyle I_{S}[f]={\frac {1}{n}}\sum V(f,z_{i})} . The true error of f {\displaystyle f} is I [ f ] = E z V ( f , z ) {\displaystyle I[f]=\mathbb {E} _{z}V(f,z)} Given a training set S of size m, we will build, for all i = 1....,m, modified training sets as follows: By removing the i-th element S | i = { z 1 , . . . , z i − 1 , z i + 1 , . . . , z m } {\displaystyle S^{|i}=\{z_{1},...,\ z_{i-1},\ z_{i+1},...,\ z_{m}\}} By replacing the i-th element S i = { z 1 , . . . , z i − 1 , z i ′ , z i + 1 , . . . , z m } {\displaystyle S^{i}=\{z_{1},...,\ z_{i-1},\ z_{i}',\ z_{i+1},...,\ z_{m}\}} == Definitions of stability == === Hypothesis Stability === An algorithm L {\displaystyle L} has hypothesis stability β with respect to the loss function V if the following holds: ∀ i ∈ { 1 , . . . , m } , E S , z [ | V (
|
{
"page_id": 33886025,
"source": null,
"title": "Stability (learning theory)"
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f S , z ) − V ( f S | i , z ) | ] ≤ β . {\displaystyle \forall i\in \{1,...,m\},\mathbb {E} _{S,z}[|V(f_{S},z)-V(f_{S^{|i}},z)|]\leq \beta .} === Point-wise Hypothesis Stability === An algorithm L {\displaystyle L} has point-wise hypothesis stability β with respect to the loss function V if the following holds: ∀ i ∈ { 1 , . . . , m } , E S [ | V ( f S , z i ) − V ( f S | i , z i ) | ] ≤ β . {\displaystyle \forall i\in \ \{1,...,m\},\mathbb {E} _{S}[|V(f_{S},z_{i})-V(f_{S^{|i}},z_{i})|]\leq \beta .} === Error Stability === An algorithm L {\displaystyle L} has error stability β with respect to the loss function V if the following holds: ∀ S ∈ Z m , ∀ i ∈ { 1 , . . . , m } , | E z [ V ( f S , z ) ] − E z [ V ( f S | i , z ) ] | ≤ β {\displaystyle \forall S\in Z^{m},\forall i\in \{1,...,m\},|\mathbb {E} _{z}[V(f_{S},z)]-\mathbb {E} _{z}[V(f_{S^{|i}},z)]|\leq \beta } === Uniform Stability === An algorithm L {\displaystyle L} has uniform stability β with respect to the loss function V if the following holds: ∀ S ∈ Z m , ∀ i ∈ { 1 , . . . , m } , sup z ∈ Z | V ( f S , z ) − V ( f S | i , z ) | ≤ β {\displaystyle \forall S\in Z^{m},\forall i\in \{1,...,m\},\sup _{z\in Z}|V(f_{S},z)-V(f_{S^{|i}},z)|\leq \beta } A probabilistic version of uniform stability β is: ∀ S ∈ Z m , ∀ i ∈ { 1 , . . . , m } , P S { sup z ∈ Z
|
{
"page_id": 33886025,
"source": null,
"title": "Stability (learning theory)"
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|
| V ( f S , z ) − V ( f S | i , z ) | ≤ β } ≥ 1 − δ {\displaystyle \forall S\in Z^{m},\forall i\in \{1,...,m\},\mathbb {P} _{S}\{\sup _{z\in Z}|V(f_{S},z)-V(f_{S^{|i}},z)|\leq \beta \}\geq 1-\delta } An algorithm is said to be stable, when the value of β {\displaystyle \beta } decreases as O ( 1 m ) {\displaystyle O({\frac {1}{m}})} . === Leave-one-out cross-validation (CVloo) Stability === An algorithm L {\displaystyle L} has CVloo stability β with respect to the loss function V if the following holds: ∀ i ∈ { 1 , . . . , m } , P S { | V ( f S , z i ) − V ( f S | i , z i ) | ≤ β C V } ≥ 1 − δ C V {\displaystyle \forall i\in \{1,...,m\},\mathbb {P} _{S}\{|V(f_{S},z_{i})-V(f_{S^{|i}},z_{i})|\leq \beta _{CV}\}\geq 1-\delta _{CV}} The definition of (CVloo) Stability is equivalent to Pointwise-hypothesis stability seen earlier. === Expected-leave-one-out error ( === E l o o e r r {\displaystyle Eloo_{err}} ) Stability An algorithm L {\displaystyle L} has E l o o e r r {\displaystyle Eloo_{err}} stability if for each n there exists a β E L m {\displaystyle \beta _{EL}^{m}} and a δ E L m {\displaystyle \delta _{EL}^{m}} such that: ∀ i ∈ { 1 , . . . , m } , P S { | I [ f S ] − 1 m ∑ i = 1 m V ( f S | i , z i ) | ≤ β E L m } ≥ 1 − δ E L m {\displaystyle \forall i\in \{1,...,m\},\mathbb {P} _{S}\{|I[f_{S}]-{\frac {1}{m}}\sum _{i=1}^{m}V(f_{S^{|i}},z_{i})|\leq \beta _{EL}^{m}\}\geq 1-\delta _{EL}^{m}} , with β E L m {\displaystyle \beta _{EL}^{m}} and δ E L m {\displaystyle
|
{
"page_id": 33886025,
"source": null,
"title": "Stability (learning theory)"
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\delta _{EL}^{m}} going to zero for m , → ∞ {\displaystyle m,\rightarrow \infty } == Classic theorems == From Bousquet and Elisseeff (02): For symmetric learning algorithms with bounded loss, if the algorithm has Uniform Stability with the probabilistic definition above, then the algorithm generalizes. Uniform Stability is a strong condition which is not met by all algorithms but is, surprisingly, met by the large and important class of Regularization algorithms. The generalization bound is given in the article. From Mukherjee et al. (06): For symmetric learning algorithms with bounded loss, if the algorithm has both Leave-one-out cross-validation (CVloo) Stability and Expected-leave-one-out error ( E l o o e r r {\displaystyle Eloo_{err}} ) Stability as defined above, then the algorithm generalizes. Neither condition alone is sufficient for generalization. However, both together ensure generalization (while the converse is not true). For ERM algorithms specifically (say for the square loss), Leave-one-out cross-validation (CVloo) Stability is both necessary and sufficient for consistency and generalization. This is an important result for the foundations of learning theory, because it shows that two previously unrelated properties of an algorithm, stability and consistency, are equivalent for ERM (and certain loss functions). The generalization bound is given in the article. == Algorithms that are stable == This is a list of algorithms that have been shown to be stable, and the article where the associated generalization bounds are provided. Linear regression k-NN classifier with a {0-1} loss function. Support Vector Machine (SVM) classification with a bounded kernel and where the regularizer is a norm in a Reproducing Kernel Hilbert Space. A large regularization constant C {\displaystyle C} leads to good stability. Soft margin SVM classification. Regularized Least Squares regression. The minimum relative entropy algorithm for classification. A version of bagging regularizers with the number k {\displaystyle k}
|
{
"page_id": 33886025,
"source": null,
"title": "Stability (learning theory)"
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|
of regressors increasing with n {\displaystyle n} . Multi-class SVM classification. All learning algorithms with Tikhonov regularization satisfies Uniform Stability criteria and are, thus, generalizable. == References == == Further reading ==
|
{
"page_id": 33886025,
"source": null,
"title": "Stability (learning theory)"
}
|
The molecular formula C17H25N3O5S (molar mass: 383.46 g/mol, exact mass: 383.1515 u) may refer to: Meropenem Veralipride
|
{
"page_id": 24710982,
"source": null,
"title": "C17H25N3O5S"
}
|
In chemistry, the equivalent concentration or normality (N) of a solution is defined as the molar concentration ci divided by an equivalence factor or n-factor feq: N = c i f e q {\displaystyle N={\frac {c_{i}}{f_{\rm {eq}}}}} == Definition == Normality is defined as the number of gram or mole equivalents of solute present in one liter of solution. The SI unit of normality is equivalents per liter (Eq/L). N = m s o l E W s o l × V s o l n {\displaystyle N={\frac {m_{\rm {sol}}}{EW_{\rm {sol}}\times V_{\rm {soln}}}}} where N is normality, msol is the mass of solute in grams, EWsol is the equivalent weight of solute, and Vsoln is the volume of the entire solution in liters. == Usage == There are three common types of chemical reaction where normality is used as a measure of reactive species in solution: In acid-base chemistry, normality is used to express the concentration of hydronium ions (H3O+) or hydroxide ions (OH−) in a solution. Here, 1/feq is an integer value. Each solute can produce one or more equivalents of reactive species when dissolved. In redox reactions, the equivalence factor describes the number of electrons that an oxidizing or reducing agent can accept or donate. Here, 1/feq can have a fractional (non-integer) value. In precipitation reactions, the equivalence factor measures the number of ions which will precipitate in a given reaction. Here, 1/feq is an integer value. Normal concentration of an ionic solution is also related to conductivity (electrolytic) through the use of equivalent conductivity. === Medical === Although losing favor in the medical industry, reporting of serum concentrations in units of "eq/L" (= 1 N) or "meq/L" (= 0.001 N) still occurs. == Examples == Normality can be used for acid-base titrations. For example, sulfuric acid (H2SO4)
|
{
"page_id": 9965379,
"source": null,
"title": "Equivalent concentration"
}
|
is a diprotic acid. Since only 0.5 mol of H2SO4 are needed to neutralize 1 mol of OH−, the equivalence factor is: feq(H2SO4) = 0.5 If the concentration of a sulfuric acid solution is c(H2SO4) = 1 mol/L, then its normality is 2 N. It can also be called a "2 normal" solution. Similarly, for a solution with c(H3PO4) = 1 mol/L, the normality is 3 N because phosphoric acid contains 3 acidic H atoms. == Criticism of the term "normality" == The normality of a solution depends on the equivalence factor feq for a particular reaction, which presents two possible sources of ambiguity – namely, feq depends on the choice of reaction as well as which chemical species of the reaction is being discussed (e.g., acid/base species, redox species, precipitating salts, isotopes exchanged, etc.). That is to say, the same solution can possess different normalities for different reactions or potentially even the same reaction in a different context. To avoid ambiguity, IUPAC and NIST discourage the use of the terms "normality" and "normal solution". == See also == Equivalent (chemistry) Normal saline, a solution of NaCl, but not a normal solution. Its normality is about 0.154 N. == References == == External links == Analytical Chemistry 2.1, by David Harvey (Open-source Textboox) | Chapter 16.1: Normality Normality: Definition, formula, equations, type, example,.
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{
"page_id": 9965379,
"source": null,
"title": "Equivalent concentration"
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The International Federation of Digital Seismograph Networks, or FDSN, is a global organization consisting of groups that install and maintain digital, broadband seismic recorders either nationally or globally. Any organizations operating more than one broadband station is eligible for membership. Members agree to coordinate station siting and provide free and open data. This cooperation helps scientists all over the world to further the advancement of earth science and particularly the study of global seismic activity. FDSN is a participant in the Global Earth Observation System of Systems, or GEOSS. == Data specification == The FDSN goals related to station siting and instrumentation are to provide stations with good geographic distribution, recording data with 24 bits of resolution in continuous time series with at least a 20 sample per second sampling rate. The FDSN was also instrumental in development of a universal standard for distribution of broadband waveform data and related parametric information (QuakeML). The Standard for Exchange of Earthquake Data (SEED) format is the result of that effort. == See also == Seismology IRIS Consortium == External links == FDSN – Official website SEED, Chapter 1 – the Standard for the Exchange of Earthquake Data manual
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{
"page_id": 32902986,
"source": null,
"title": "International Federation of Digital Seismograph Networks"
}
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The interstellar medium (ISM) is the matter and radiation that exists in the space between the star systems in a galaxy. This matter includes gas in ionic, atomic, and molecular form, as well as dust and cosmic rays. It fills interstellar space and blends smoothly into the surrounding intergalactic medium. The energy that occupies the same volume, in the form of electromagnetic radiation, is the interstellar radiation field. Although the density of atoms in the ISM is usually far below that in the best laboratory vacuums, the mean free path between collisions is short compared to typical interstellar lengths, so on these scales the ISM behaves as a gas (more precisely, as a plasma: it is everywhere at least slightly ionized), responding to pressure forces, and not as a collection of non-interacting particles. The interstellar medium is composed of multiple phases distinguished by whether matter is ionic, atomic, or molecular, and the temperature and density of the matter. The interstellar medium is composed primarily of hydrogen, followed by helium with trace amounts of carbon, oxygen, and nitrogen. The thermal pressures of these phases are in rough equilibrium with one another. Magnetic fields and turbulent motions also provide pressure in the ISM, and are typically more important, dynamically, than the thermal pressure. In the interstellar medium, matter is primarily in molecular form and reaches number densities of 1012 molecules per m3 (1 trillion molecules per m3). In hot, diffuse regions, gas is highly ionized, and the density may be as low as 100 ions per m3. Compare this with a number density of roughly 1025 molecules per m3 for air at sea level, and 1016 molecules per m3 (10 quadrillion molecules per m3) for a laboratory high-vacuum chamber. Within our galaxy, by mass, 99% of the ISM is gas in any
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form, and 1% is dust. Of the gas in the ISM, by number 91% of atoms are hydrogen and 8.9% are helium, with 0.1% being atoms of elements heavier than hydrogen or helium, known as "metals" in astronomical parlance. By mass this amounts to 70% hydrogen, 28% helium, and 1.5% heavier elements. The hydrogen and helium are primarily a result of primordial nucleosynthesis, while the heavier elements in the ISM are mostly a result of enrichment (due to stellar nucleosynthesis) in the process of stellar evolution. The ISM plays a crucial role in astrophysics precisely because of its intermediate role between stellar and galactic scales. Stars form within the densest regions of the ISM, which ultimately contributes to molecular clouds and replenishes the ISM with matter and energy through planetary nebulae, stellar winds, and supernovae. This interplay between stars and the ISM helps determine the rate at which a galaxy depletes its gaseous content, and therefore its lifespan of active star formation. Voyager 1 reached the ISM on August 25, 2012, making it the first artificial object from Earth to do so. Interstellar plasma and dust will be studied until the estimated mission end date of 2025. Its twin Voyager 2 entered the ISM on November 5, 2018. == Interstellar matter == Table 1 shows a breakdown of the properties of the components of the ISM of the Milky Way. === The three-phase model === Field, Goldsmith & Habing (1969) put forward the static two phase equilibrium model to explain the observed properties of the ISM. Their modeled ISM included a cold dense phase (T < 300 K), consisting of clouds of neutral and molecular hydrogen, and a warm intercloud phase (T ~ 104 K), consisting of rarefied neutral and ionized gas. McKee & Ostriker (1977) added a dynamic third
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phase that represented the very hot (T ~ 106 K) gas that had been shock heated by supernovae and constituted most of the volume of the ISM. These phases are the temperatures where heating and cooling can reach a stable equilibrium. Their paper formed the basis for further study over the subsequent three decades. However, the relative proportions of the phases and their subdivisions are still not well understood. The basic physics behind these phases can be understood through the behaviour of hydrogen, since this is by far the largest constituent of the ISM. The different phases are roughly in pressure balance over most of the Galactic disk, since regions of excess pressure will expand and cool, and likewise under-pressure regions will be compressed and heated. Therefore, since P = n k T, hot regions (high T) generally have low particle number density n. Coronal gas has low enough density that collisions between particles are rare and so little radiation is produced, hence there is little loss of energy and the temperature can stay high for periods of hundreds of millions of years. In contrast, once the temperature falls to O(105 K) with correspondingly higher density, protons and electrons can recombine to form hydrogen atoms, emitting photons which take energy out of the gas, leading to runaway cooling. Left to itself this would produce the warm neutral medium. However, OB stars are so hot that some of their photons have energy greater than the Lyman limit, E > 13.6 eV, enough to ionize hydrogen. Such photons will be absorbed by, and ionize, any neutral hydrogen atom they encounter, setting up a dynamic equilibrium between ionization and recombination such that gas close enough to OB stars is almost entirely ionized, with temperature around 8000 K (unless already in the coronal phase),
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{
"page_id": 69453,
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until the distance where all the ionizing photons are used up. This ionization front marks the boundary between the Warm ionized and Warm neutral medium. OB stars, and also cooler ones, produce many more photons with energies below the Lyman limit, which pass through the ionized region almost unabsorbed. Some of these have high enough energy (> 11.3 eV) to ionize carbon atoms, creating a C II ("ionized carbon") region outside the (hydrogen) ionization front. In dense regions this may also be limited in size by the availability of photons, but often such photons can penetrate throughout the neutral phase and only get absorbed in the outer layers of molecular clouds. Photons with E > 4 eV or so can break up molecules such as H2 and CO, creating a photodissociation region (PDR) which is more or less equivalent to the Warm neutral medium. These processes contribute to the heating of the WNM. The distinction between Warm and Cold neutral medium is again due to a range of temperature/density in which runaway cooling occurs. The densest molecular clouds have significantly higher pressure than the interstellar average, since they are bound together by their own gravity. When stars form in such clouds, especially OB stars, they convert the surrounding gas into the warm ionized phase, a temperature increase of several hundred. Initially the gas is still at molecular cloud densities, and so at vastly higher pressure than the ISM average: this is a classical H II region. The large overpressure causes the ionized gas to expand away from the remaining molecular gas (a Champagne flow), and the flow will continue until either the molecular cloud is fully evaporated or the OB stars reach the end of their lives, after a few millions years. At this point the OB stars explode as
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supernovas, creating blast waves in the warm gas that increase temperatures to the coronal phase (supernova remnants, SNR). These too expand and cool over several million years until they return to average ISM pressure. === The ISM in different kinds of galaxy === Most discussion of the ISM concerns spiral galaxies like the Milky Way, in which nearly all the mass in the ISM is confined to a relatively thin disk, typically with scale height about 100 parsecs (300 light years), which can be compared to a typical disk diameter of 30,000 parsecs. Gas and stars in the disk orbit the galactic centre with typical orbital speeds of 200 km/s. This is much faster than the random motions of atoms in the ISM, but since the orbital motion of the gas is coherent, the average motion does not directly affect structure in the ISM. The vertical scale height of the ISM is set in roughly the same way as the Earth's atmosphere, as a balance between the local gravitation field (dominated by the stars in the disk) and the pressure. Further from the disk plane, the ISM is mainly in the low-density warm and coronal phases, which extend at least several thousand parsecs away from the disk plane. This galactic halo or 'corona' also contains significant magnetic field and cosmic ray energy density. The rotation of galaxy disks influences ISM structures in several ways. Since the angular velocity declines with increasing distance from the centre, any ISM feature, such as giant molecular clouds or magnetic field lines, that extend across a range of radius are sheared by differential rotation, and so tend to become stretched out in the tangential direction; this tendency is opposed by interstellar turbulence (see below) which tends to randomize the structures. Spiral arms are due to
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perturbations in the disk orbits - essentially ripples in the disk, that cause orbits to alternately converge and diverge, compressing and then expanding the local ISM. The visible spiral arms are the regions of maximum density, and the compression often triggers star formation in molecular clouds, leading to an abundance of H II regions along the arms. Coriolis force also influences large ISM features. Irregular galaxies such as the Magellanic Clouds have similar interstellar mediums to spirals, but less organized. In elliptical galaxies the ISM is almost entirely in the coronal phase, since there is no coherent disk motion to support cold gas far from the center: instead, the scale height of the ISM must be comperable to the radius of the galaxy. This is consistent with the observation that there is little sign of current star formation in ellipticals. Some elliptical galaxies do show evidence for a small disk component, with ISM similar to spirals, buried close to their centers. The ISM of lenticular galaxies, as with their other properties, appear intermediate between spirals and ellipticals. Very close to the center of most galaxies (within a few hundred light years at most), the ISM is profoundly modified by the central supermassive black hole: see Galactic Center for the Milky Way, and Active galactic nucleus for extreme examples in other galaxies. The rest of this article will focus on the ISM in the disk plane of spirals, far from the galactic center. === Structures === Astronomers describe the ISM as turbulent, meaning that the gas has quasi-random motions coherent over a large range of spatial scales. Unlike normal turbulence, in which the fluid motions are highly subsonic, the bulk motions of the ISM are usually larger than the sound speed. Supersonic collisions between gas clouds cause shock waves which compress
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and heat the gas, increasing the sounds speed so that the flow is locally subsonic; thus supersonic turbulence has been described as 'a box of shocklets', and is inevitably associated with complex density and temperature structure. In the ISM this is further complicated by the magnetic field, which provides wave modes such as Alfvén waves which are often faster than pure sound waves: if turbulent speeds are supersonic but below the Alfvén wave speed, the behaviour is more like subsonic turbulence. Stars are born deep inside large complexes of molecular clouds, typically a few parsecs in size. During their lives and deaths, stars interact physically with the ISM. Stellar winds from young clusters of stars (often with giant or supergiant HII regions surrounding them) and shock waves created by supernovae inject enormous amounts of energy into their surroundings, which leads to hypersonic turbulence. The resultant structures – of varying sizes – can be observed, such as stellar wind bubbles and superbubbles of hot gas, seen by X-ray satellite telescopes or turbulent flows observed in radio telescope maps. Stars and planets, once formed, are unaffected by pressure forces in the ISM, and so do not take part in the turbulent motions, although stars formed in molecular clouds in a galactic disk share their general orbital motion around the galaxy center. Thus stars are usually in motion relative to their surrounding ISM. The Sun is currently traveling through the Local Interstellar Cloud, an irregular clump of the warm neutral medium a few parsecs across, within the low-density Local Bubble, a 100-parsec radius region of coronal gas. In October 2020, astronomers reported a significant unexpected increase in density in the space beyond the Solar System as detected by the Voyager 1 and Voyager 2 space probes. According to the researchers, this implies that
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"the density gradient is a large-scale feature of the VLISM (very local interstellar medium) in the general direction of the heliospheric nose". === Interaction with interplanetary medium === The interstellar medium begins where the interplanetary medium of the Solar System ends. The solar wind slows to subsonic velocities at the termination shock, 90–100 astronomical units from the Sun. In the region beyond the termination shock, called the heliosheath, interstellar matter interacts with the solar wind. Voyager 1, the farthest human-made object from the Earth (after 1998), crossed the termination shock December 16, 2004 and later entered interstellar space when it crossed the heliopause on August 25, 2012, providing the first direct probe of conditions in the ISM (Stone et al. 2005). === Interstellar extinction === Dust grains in the ISM are responsible for extinction and reddening, the decreasing light intensity and shift in the dominant observable wavelengths of light from a star. These effects are caused by scattering and absorption of photons and allow the ISM to be observed with the naked eye in a dark sky. The apparent rifts that can be seen in the band of the Milky Way – a uniform disk of stars – are caused by absorption of background starlight by dust in molecular clouds within a few thousand light years from Earth. This effect decreases rapidly with increasing wavelength ("reddening" is caused by greater absorption of blue than red light), and becomes almost negligible at mid-infrared wavelengths (> 5 μm). Extinction provides one of the best ways of mapping the three-dimensional structure of the ISM, especially since the advent of accurate distances to millions of stars from the Gaia mission. The total amount of dust in front of each star is determined from its reddening, and the dust is then located along the line
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of sight by comparing the dust column density in front of stars projected close together on the sky, but at different distances. By 2022 it was possible to generate a map of ISM structures within 3 kpc (10,000 light years) of the Sun. Far ultraviolet light is absorbed effectively by the neutral hydrogen gas in the ISM. Specifically, atomic hydrogen absorbs very strongly at about 121.5 nanometers, the Lyman-alpha transition, and also at the other Lyman series lines. Therefore, it is nearly impossible to see light emitted at those wavelengths from a star farther than a few hundred light years from Earth, because most of it is absorbed during the trip to Earth by intervening neutral hydrogen. All photons with wavelength < 91.6 nm, the Lyman limit, can ionize hydrogen and are also very strongly absorbed. The absorption gradually decreases with increasing photon energy, and the ISM begins to become transparent again in soft X-rays, with wavelengths shorter than about 1 nm. == Heating and cooling == The ISM is usually far from thermodynamic equilibrium. Collisions establish a Maxwell–Boltzmann distribution of velocities, and the 'temperature' normally used to describe interstellar gas is the 'kinetic temperature', which describes the temperature at which the particles would have the observed Maxwell–Boltzmann velocity distribution in thermodynamic equilibrium. However, the interstellar radiation field is typically much weaker than a medium in thermodynamic equilibrium; it is most often roughly that of an A star (surface temperature of ~10,000 K) highly diluted. Therefore, bound levels within an atom or molecule in the ISM are rarely populated according to the Boltzmann formula (Spitzer 1978, § 2.4). Depending on the temperature, density, and ionization state of a portion of the ISM, different heating and cooling mechanisms determine the temperature of the gas. === Heating mechanisms === Heating by low-energy
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cosmic rays The first mechanism proposed for heating the ISM was heating by low-energy cosmic rays. Cosmic rays are an efficient heating source able to penetrate in the depths of molecular clouds. Cosmic rays transfer energy to gas through both ionization and excitation and to free electrons through Coulomb interactions. Low-energy cosmic rays (a few MeV) are more important because they are far more numerous than high-energy cosmic rays. Photoelectric heating by grains The ultraviolet radiation emitted by hot stars can remove electrons from dust grains. The photon is absorbed by the dust grain, and some of its energy is used to overcome the potential energy barrier and remove the electron from the grain. This potential barrier is due to the binding energy of the electron (the work function) and the charge of the grain. The remainder of the photon's energy gives the ejected electron kinetic energy which heats the gas through collisions with other particles. A typical size distribution of dust grains is n(r) ∝ r−3.5, where r is the radius of the dust particle. Assuming this, the projected grain surface area distribution is πr2n(r) ∝ r−1.5. This indicates that the smallest dust grains dominate this method of heating. Photoionization When an electron is freed from an atom (typically from absorption of a UV photon) it carries kinetic energy away of the order Ephoton − Eionization. This heating mechanism dominates in H II regions, but is negligible in the diffuse ISM due to the relative lack of neutral carbon atoms. X-ray heating X-rays remove electrons from atoms and ions, and those photoelectrons can provoke secondary ionizations. As the intensity is often low, this heating is only efficient in warm, less dense atomic medium (as the column density is small). For example, in molecular clouds only hard x-rays can penetrate
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{
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and x-ray heating can be ignored. This is assuming the region is not near an x-ray source such as a supernova remnant. Chemical heating Molecular hydrogen (H2) can be formed on the surface of dust grains when two H atoms (which can travel over the grain) meet. This process yields 4.48 eV of energy distributed over the rotational and vibrational modes, kinetic energy of the H2 molecule, as well as heating the dust grain. This kinetic energy, as well as the energy transferred from de-excitation of the hydrogen molecule through collisions, heats the gas. Grain-gas heating Collisions at high densities between gas atoms and molecules with dust grains can transfer thermal energy. This is not important in HII regions because UV radiation is more important. It is also less important in diffuse ionized medium due to the low density. In the neutral diffuse medium grains are always colder, but do not effectively cool the gas due to the low densities. Grain heating by thermal exchange is very important in supernova remnants where densities and temperatures are very high. Gas heating via grain-gas collisions is dominant deep in giant molecular clouds (especially at high densities). Far infrared radiation penetrates deeply due to the low optical depth. Dust grains are heated via this radiation and can transfer thermal energy during collisions with the gas. A measure of efficiency in the heating is given by the accommodation coefficient: α = T 2 − T T d − T {\displaystyle \alpha ={\frac {T_{2}-T}{T_{d}-T}}} where T is the gas temperature, Td the dust temperature, and T2 the post-collision temperature of the gas atom or molecule. This coefficient was measured by (Burke & Hollenbach 1983) as α = 0.35. Other heating mechanisms A variety of macroscopic heating mechanisms are present including: Gravitational collapse of a cloud
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Supernova explosions Stellar winds Expansion of H II regions Magnetohydrodynamic waves created by supernova remnants === Cooling mechanisms === Fine structure cooling The process of fine structure cooling is dominant in most regions of the Interstellar Medium, except regions of hot gas and regions deep in molecular clouds. It occurs most efficiently with abundant atoms having fine structure levels close to the fundamental level such as: C II and O I in the neutral medium and O II, O III, N II, N III, Ne II and Ne III in H II regions. Collisions will excite these atoms to higher levels, and they will eventually de-excite through photon emission, which will carry the energy out of the region. Cooling by permitted lines At lower temperatures, more levels than fine structure levels can be populated via collisions. For example, collisional excitation of the n = 2 level of hydrogen will release a Ly-α photon upon de-excitation. In molecular clouds, excitation of rotational lines of CO is important. Once a molecule is excited, it eventually returns to a lower energy state, emitting a photon which can leave the region, cooling the cloud. == Observations of the ISM == Despite its extremely low density, photons generated in the ISM are prominent in nearly all bands of the electromagnetic spectrum. In fact the optical band, on which astronomers relied until well into the 20th century, is the one in which the ISM is least obvious. Ionized gas radiates at a broad range of energies via bremsstrahlung. For gas in the warm phase (104 K) this is mostly detected in microwaves, while bremsstrahlung from the million-kelvin coronal gas is prominent in soft X-rays. In addition, many spectral lines are produced, including the ones significant for cooling mentioned in the previous section. One of these, a
|
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forbidden line of doubly-ionized oxygen, gives many nebulae their apparent green colour in visual observations, and was once thought to be a new element, nebulium. Spectral lines from highly excited states of hydrogen are detectable at infra-red and longer wavelengths, down to radio recombination lines which, unlike optical lines, are not absorbed by dust and so can trace ionized regions throughout the disk of the Galaxy. Coronal gas emits a different set of lines, since atoms are stripped of a larger fraction of their electrons at its high temperature. The warm neutral medium produces most of the 21-cm line emission from hydrogen detected by radio telescopes, although atomic hydrogen in the cold neutral medium also contributes, both in emission and by absorption of photons from background warm gas ('H I self-absorption', HISA). While not important for cooling, the 21-cm line is easily observable at high spectral and angular resolution, giving us our most detailed view of the WNM. Molecular clouds are detected via spectral lines produced by changes in the rotational quantum state of small molecules, especially carbon monoxide, CO. The most widely used line is at 115 GHz, corresponding to the change from 1 to 0 quanta of angular momentum. Hundreds of other molecules have been detected, each with many lines, which allows physical and chemical processes in molecular clouds to be traced in some detail. These lines are most common at millimetre and sub-mm wavelengths. By far the most common molecule in molecular clouds, H2, is usually not directly observable, as it stays in its ground state except when excited by rare events such as interstellar shock waves. There is some 'dark gas', regions where hydrogen is in molecular form and therefore does not emit the 21-cm line, but CO molecules are broken up so the CO lines
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{
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are also not present. These regions are inferred from the presence of dust grains with no matching line emission from gas. Interstellar dust grains re-emit the energy they absorb from starlight as quasi-blackbody emission in the far infrared, corresponding to typical dust grain temperatures of 20–100 K. Very small grains, essentially fragments of graphene bonded to hydrogen atoms around their edges (polycyclic aromatic hydrocarbons, PAHs), emit numerous spectral lines in the mid-infrared, at wavelengths around 10 micron. Nanometre-sized grains can be spun up to rotate at GHz frequencies by a collision with a single ultraviolet photon, and dipole radiation from such spinning grains is believed to be the source of anomalous microwave emission. Cosmic rays generate gamma-ray photons when they collide with atomic nuclei in ISM clouds. The electrons amongst cosmic ray particles collide with a small fraction of photons in the interstellar radiation field and the cosmic microwave background and bump up the photon energies to X-rays and gamma-rays, via inverse Compton scattering. Due to the galactic magnetic field, charged particles follow spiral paths, and for cosmic-ray electrons this spiralling motion generates synchrotron radiation which is very bright at low radio frequencies. == Radiowave propagation == Radio waves are affected by the plasma properties of the ISM. The lowest frequency radio waves, below ≈ 0.1 MHz, cannot propagate through the ISM since they are below its plasma frequency. At higher frequencies, the plasma has a significant refractive index, decreasing with increasing frequency, and also dependent on the density of free electrons. Random variations in the electron density cause interstellar scintillation, which broadens the apparent size of distant radio sources seen through the ISM, with the broadening decreasing with frequency squared. The variation of refractive index with frequency causes the arrival times of pulses from pulsars and Fast radio bursts
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{
"page_id": 69453,
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to be delayed at lower frequencies (dispersion). The amount of delay is proportional to the column density of free electrons (Dispersion measure, DM), which is useful for both mapping the distribution of ionized gas in the Galaxy and estimating distances to pulsars (more distant ones have larger DM). A second propagation effect is Faraday rotation, which affects linearly polarized radio waves, such as those produced by synchrotron radiation, one of the most common sources of radio emission in astrophysics. Faraday rotation depends on both the electron density and the magnetic field strength, and so is used as a probe of the interstellar magnetic field. The ISM is generally very transparent to radio waves, allowing unimpeded observations right through the disk of the Galaxy. There are a few exceptions to this rule. The most intense spectral lines in the radio spectrum can become opaque, so that only the surface of the line-emitting cloud is visible. This mainly affects the carbon monoxide lines at millimetre wavelengths that are used to trace molecular clouds, but the 21-cm line from neutral hydrogen can become opaque in the cold neutral medium. Such absorption only affects photons at the line frequencies: the clouds are otherwise transparent. The other significant absorption process occurs in dense ionized regions. These emit photons, including radio waves, via thermal bremsstrahlung. At short wavelengths, typically microwaves, these are quite transparent, but their brightness approaches the black body limit as ∝ λ 2.1 {\displaystyle \propto \lambda ^{2.1}} , and at wavelengths long enough that this limit is reached, they become opaque. Thus metre-wavelength observations show H II regions as cool spots blocking the bright background emission from Galactic synchrotron radiation, while at decametres the entire galactic plane is absorbed, and the longest radio waves observed, 1 km, can only propagate 10-50 parsecs through
|
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the Local Bubble. The frequency at which a particular nebula becomes optically thick depends on its emission measure E M = ∫ n e 2 d l {\displaystyle EM=\int n_{e}^{2}\,dl} , the column density of squared electron number density. Exceptionally dense nebulae can become optically thick at centimetre wavelengths: these are just-formed and so both rare and small ('Ultra-compact H II regions') The general transparency of the ISM to radio waves, especially microwaves, may seem surprising since radio waves at frequencies > 10 GHz are significantly attenuated by Earth's atmosphere (as seen in the figure). But the column density through the atmosphere is vastly larger than the column through the entire Galaxy, due to the extremely low density of the ISM. == History of knowledge of interstellar space == The word 'interstellar' (between the stars) was coined by Francis Bacon in the context of the ancient theory of a literal sphere of fixed stars. Later in the 17th century, when the idea that stars were scattered through infinite space became popular, it was debated whether that space was a true vacuum or filled with a hypothetical fluid, sometimes called aether, as in René Descartes' vortex theory of planetary motions. While vortex theory did not survive the success of Newtonian physics, an invisible luminiferous aether was re-introduced in the early 19th century as the medium to carry light waves; e.g., in 1862 a journalist wrote: "this efflux occasions a thrill, or vibratory motion, in the ether which fills the interstellar spaces." In 1864, William Huggins used spectroscopy to determine that a nebula is made of gas. Huggins had a private observatory with an 8-inch telescope, with a lens by Alvan Clark; but it was equipped for spectroscopy, which enabled breakthrough observations. From around 1889, Edward Barnard pioneered deep photography of the
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sky, finding many 'holes in the Milky Way'. At first he compared them to sunspots, but by 1899 was prepared to write: "One can scarcely conceive a vacancy with holes in it, unless there is nebulous matter covering these apparently vacant places in which holes might occur". These holes are now known as dark nebulae, dusty molecular clouds silhouetted against the background star field of the galaxy; the most prominent are listed in his Barnard Catalogue. The first direct detection of cold diffuse matter in interstellar space came in 1904, when Johannes Hartmann observed the binary star Mintaka (Delta Orionis) with the Potsdam Great Refractor. Hartmann reported that absorption from the "K" line of calcium appeared "extraordinarily weak, but almost perfectly sharp" and also reported the "quite surprising result that the calcium line at 393.4 nanometres does not share in the periodic displacements of the lines caused by the orbital motion of the spectroscopic binary star". The stationary nature of the line led Hartmann to conclude that the gas responsible for the absorption was not present in the atmosphere of the star, but was instead located within an isolated cloud of matter residing somewhere along the line of sight to this star. This discovery launched the study of the interstellar medium. Interstellar gas was further confirmed by Slipher in 1909, and then by 1912 interstellar dust was confirmed by Slipher. Interstellar sodium was detected by Mary Lea Heger in 1919 through the observation of stationary absorption from the atom's "D" lines at 589.0 and 589.6 nanometres towards Delta Orionis and Beta Scorpii. In the series of investigations, Viktor Ambartsumian introduced the now commonly accepted notion that interstellar matter occurs in the form of clouds. Subsequent observations of the "H" and "K" lines of calcium by Beals (1936) revealed double and
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asymmetric profiles in the spectra of Epsilon and Zeta Orionis. These were the first steps in the study of the very complex interstellar sightline towards Orion. Asymmetric absorption line profiles are the result of the superposition of multiple absorption lines, each corresponding to the same atomic transition (for example the "K" line of calcium), but occurring in interstellar clouds with different radial velocities. Because each cloud has a different velocity (either towards or away from the observer/Earth), the absorption lines occurring within each cloud are either blue-shifted or red-shifted (respectively) from the lines' rest wavelength through the Doppler Effect. These observations confirming that matter is not distributed homogeneously were the first evidence of multiple discrete clouds within the ISM. The growing evidence for interstellar material led Pickering (1912) to comment: "While the interstellar absorbing medium may be simply the ether, yet the character of its selective absorption, as indicated by Kapteyn, is characteristic of a gas, and free gaseous molecules are certainly there, since they are probably constantly being expelled by the Sun and stars." The same year, Victor Hess's discovery of cosmic rays, highly energetic charged particles that rain onto the Earth from space, led others to speculate whether they also pervaded interstellar space. The following year, the Norwegian explorer and physicist Kristian Birkeland wrote: "It seems to be a natural consequence of our points of view to assume that the whole of space is filled with electrons and flying electric ions of all kinds. We have assumed that each stellar system in evolutions throws off electric corpuscles into space. It does not seem unreasonable therefore to think that the greater part of the material masses in the universe is found, not in the solar systems or nebulae, but in 'empty' space" (Birkeland 1913). Thorndike (1930) noted that "it
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}
|
could scarcely have been believed that the enormous gaps between the stars are completely void. Terrestrial aurorae are not improbably excited by charged particles emitted by the Sun. If the millions of other stars are also ejecting ions, as is undoubtedly true, no absolute vacuum can exist within the galaxy." In September 2012, NASA scientists reported that polycyclic aromatic hydrocarbons (PAHs), subjected to interstellar medium (ISM) conditions, are transformed, through hydrogenation, oxygenation and hydroxylation, to more complex organics, "a step along the path toward amino acids and nucleotides, the raw materials of proteins and DNA, respectively". Further, as a result of these transformations, the PAHs lose their spectroscopic signature, which could be one of the reasons "for the lack of PAH detection in interstellar ice grains, particularly the outer regions of cold, dense clouds or the upper molecular layers of protoplanetary disks." In February 2014, NASA announced a greatly upgraded database for tracking polycyclic aromatic hydrocarbons (PAHs) in the universe. According to scientists, more than 20% of the carbon in the universe may be associated with PAHs, possible starting materials for the formation of life. PAHs seem to have been formed shortly after the Big Bang, are widespread throughout the universe, and are associated with new stars and exoplanets. In April 2019, scientists, working with the Hubble Space Telescope, reported the confirmed detection of the large and complex ionized molecules of buckminsterfullerene (C60) (also known as "buckyballs") in the interstellar medium spaces between the stars. In September 2020, evidence was presented of solid-state water in the interstellar medium, and particularly, of water ice mixed with silicate grains in cosmic dust grains. == See also == == References == === Citations === === Sources === == External links == Freeview Video 'Chemistry of Interstellar Space' William Klemperer, Harvard University. A Royal
|
{
"page_id": 69453,
"source": null,
"title": "Interstellar medium"
}
|
Institution Discourse by the Vega Science Trust. The interstellar medium: an online tutorial
|
{
"page_id": 69453,
"source": null,
"title": "Interstellar medium"
}
|
Conjugate eye movement refers to motor coordination of the eyes that allows for bilateral fixation on a single object. A conjugate eye movement is a movement of both eyes in the same direction to maintain binocular gaze (also referred to as “yoked” eye movement). This is in contrast to vergence eye movement, where binocular gaze is maintained by moving eyes in opposite directions, such as going “cross eyed” to view an object moving towards the face. Conjugate eye movements can be in any direction, and can accompany both saccadic eye movements and smooth pursuit eye movements. Conjugate eye movements are used to change the direction of gaze without changing the depth of gaze. This can be used to either follow a moving object, or change focus entirely. When following a moving object, conjugate eye movements allow individuals to stabilize their perception of the moving object, and focus on the object rather than the rest of the visual world. When changing focus, conjugate eye movements allow for the perception of a stabilized world relative to an individual, rather than the perception of the world “jumping” as the individual’s gaze shifts. Without conjugate eye movements, there would be no synchronicity of the information obtained by each eye, so an individual would not be able to willingly move their eyes around a scene while still maintaining depth perception and scene or object stability. Several centers in the brainstem are involved. Horizontal conjugate gaze is controlled by the nuclei of the Ocular Nerve, CN III, and the Abducens nerve, CN VI, the paramedian pontine reticular formation, and the nucleus prepositus hypoglossi-medial vestibular nucleus. Vertical conjugate gaze is controlled by the nuclei of CN III and the Trochlear nerve, CN IV, the rostral interstitial nucleus of medial longitudinal fasciculus (riMLF), and the interstitial nucleus of
|
{
"page_id": 20451156,
"source": null,
"title": "Conjugate eye movement"
}
|
Cajal. Disorders of conjugate gaze typically consist of the inability to move one or both eyes in the desired direction, or the inability to prevent eyes from making vergence movements. Conjugate gaze palsy: Conjugate gaze palsies typically affect horizontal gaze, although some affect upward gaze. Few affect downward gaze. These effects can range in severity from a complete lack of voluntary eye movement to mild impairments in speed, accuracy or range of eye movement. Internuclear ophthalmoplegia: Internuclear ophthalmoplegia affects horizontal gaze, such that one eye is capable of full horizontal movement, while the other is incapable of gazing in the direction contralateral to the affected eye. One and a half syndrome: “One and a half syndrome” also affects horizontal gaze. One eye is completely incapable of horizontal movement, while the other eye is capable of horizontal movement only in one direction away from the midline. == See also == Gaze (physiology) == References ==
|
{
"page_id": 20451156,
"source": null,
"title": "Conjugate eye movement"
}
|
Mister Sinister (Dr. Nathaniel Essex) is a supervillain appearing in American comic books published by Marvel Comics. Created by writer Chris Claremont, the character was first mentioned as the employer behind the team of assassins known as the Marauders in The Uncanny X-Men #212 (December 1986), and later seen in silhouette in The Uncanny X-Men #213, with both issues serving as chapters of the 1986 "Mutant Massacre" crossover. Mr. Sinister then made his first full appearance in The Uncanny X-Men #221 (September 1987). His appearance was designed by artist Marc Silvestri. A villain who usually prefers to act through agents and manipulation, Mr. Sinister was born Nathaniel Essex in Victorian London. A human scientist, Essex is inspired by the work of his contemporary Charles Darwin and becomes obsessed with engineering humanity into a perfect race of superhumans. As he learns about mutants (superhuman beings born with the X-gene), Essex encounters the mutant villain Apocalypse. The two become allies and Apocalypse uses alien Celestial technology to transform the British scientist into Mr. Sinister, an ageless man with super-powers. Later on, Sinister increases his power through self-experimentation. In the modern day, Sinister develops a great interest and protective attitude towards the mutant heroes Cyclops and Jean Grey, believing their DNA can create the ultimate mutant. This and other factors lead him to have repeated clashes with the X-Men (a group Cyclops and Jean Grey helped found) and related teams. Through clones, Sinister has managed to cheat his death repeatedly and even acquire a mutant gene. Later, the Krakoan Age storyline revealed that the original Mr Sinister was one of several clones of the original Nathaniel Essex, each with a distinctive scientific specialism and playing card theme. Making frequent appearances in the X-Men comics and related spin-off titles, Mr. Sinister has also featured
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
in associated Marvel merchandise including animated television series, toys, trading cards, and video games. IGN's list of the "Top 100 Comic Book Villains of All Time" ranked Sinister as #29. The character was exposed to a wider audience with his television debut on X-Men: The Animated Series voiced by Christopher Britton, as well as an appearance in Wolverine and the X-Men voiced by Clancy Brown. == Publication history == Writer Chris Claremont conceived Sinister as a new villain for the X-Men. Having felt "tired of just going back to Magneto and the Brotherhood of Evil Mutants and the same old same old" Claremont recalled: Dave Cockrum and I went over ideas, and what we were coming towards was a mysterious young boy—apparently an 11-year-old—at the orphanage where Scott (Cyclops) was raised, who turned out to be the secret master of the place. In effect what we were setting up was a guy who was aging over a lifespan of roughly a thousand years. Even though he looked like an 11-year-old, he'd actually been alive since the mid-century at this point—he was actually about 50 [...] He had all the grown-up urges. He's growing up in his mind but his body isn't capable of handling it, which makes him quite cranky. And, of course, looking like an 11-year-old, who'd take him seriously in the criminal community? [...] So he built himself an agent in a sense, which was Mister Sinister, that was, in effect, the rationale behind Sinister's rather—for want of a better word—childish or kid-like appearance. The costume... the look... the face... it's what would scare a child. Even when he was designed, he wasn't what you'd expect in a guy like that. Mister Sinister was first mentioned by the assassin Sabretooth as the employer behind the team of assassins
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
known as the Marauders in The Uncanny X-Men #212 (December 1986), which was part of the 1986 "Mutant Massacre" storyline, in which Sinister ordered the Marauders to kill the Morlocks living beneath New York City. In the next issue, drawn by Alan Davis, Mr. Sinister is first glimpsed as a generic silhouette when the telepathic X-Man Psylocke scans Sabretooth's mind. Mister Sinister appeared unobscured for the first time on the opening splash page of issue #221 (September 1987), drawn by Marc Silvestri. The character is one of the major antagonists in the 1989 "Inferno" storyline, where it is revealed he created the character Madelyne Pryor, estranged wife of Scott Summers (the mutant hero Cyclops), by cloning Scott's former lover Jean Grey, who was believed dead at the time. Sinister sent Madelyne into Scott's life in the hopes that the combined DNA of Grey and Summers would result in the birth of a powerful mutant. Soon after "Inferno", Sinister is also revealed to have manipulated Cyclops' life since early childhood and who at times has influenced his behavior from afar. After a battle with the X-Men and X-Factor, the villain is apparently destroyed by Cyclops' optic beam, leaving behind only bones. Months after his apparent death, backup stories by Claremont published in the reprint series Classic X-Men #41–42 (December 1989) detailed the role Mister Sinister played in Cyclops' early life at an orphanage in Nebraska. The stories feature a boy named Nate who is roommates with the young Scott Summers. Despite Scott saying he does not particularly like Nate, the boy appears to be unhealthily attached to him and is aggressively protective, blocking Scott from having other friends. Claremont intended Nate to actually be Mister Sinister, revealing this was his true form and the armored villain was an illusion he used
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
to threaten others. However, Claremont left the X-Men comics before this origin was revealed to readers. Fans later considered "Nate" to be Sinister in disguise as a boy, whereas his adult, armored appearance was his true form. The 2009 series X-Men Forever (vol. 2) showed an alternate timeline, beginning at roughly the same point where Chris Claremont left as head writer of the X-Men years before. Written by Claremont, the series revealed how he would have continued the stories and what revelations he would have made about different characters. The 2010 sequel series, X-Men Forever 2 features Mr. Sinister as a character who is over a century old yet still physically an adolescent boy, using a robot called Mr. Sinister to act as a proxy. Despite his apparent death in 1989, Sinister appeared again in X-Factor in 1992, now leader of the Nasty Boys team and displaying the ability to regenerate from damage. He played a major role in the 1992-1993 crossover storyline "X-Cutioner's Song", unwittingly helping to unleash the Legacy Virus on the world. In X-Men (vol. 2) #22-23 (1993), Sinister reveals his seeming death in 1989 was a "ruse" so he could retreat rather than fight the combined X-Men and X-Factor teams. The same story depicts Sinister willing to protect Cyclops from other villains. By 1994 Mister Sinister was popular enough that Chef Boyardee used him to advertise its pasta. In X-Men (vol. 2) Annual 1995, flashbacks reveal Sinister living in Los Angeles in the 1930s as "Nathan Essex" and depict him as an adult man during that era. In the 1996 limited series The Further Adventures of Cyclops and Phoenix, writer Peter Milligan (with artists John Paul Leon and Klaus Janson) establishes Sinister's origin, revealing he was originally a Victorian-era scientist named Nathaniel Essex who later gained
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
superhuman powers from Apocalypse, thus abandoning Claremont's idea that he was an immortal trapped in the form of a child. The 2006 mini-series X-Men: Colossus Bloodline revealed that Mr. Sinister's powers were weakening and he hoped to restore them. Before he can restore his full power, Sinister is killed in New X-Men (vol. 2) #46 (2008). The same year, a contingency plan in X-Men: Legacy #214-215 involves him attempting to take a new host body, but fails. In X-23 (vol. 3) #5-6 (2011), another resurrection contingency plan led to the creation of Miss Sinister and to Mr. Sinister's mind inhabiting a clone body of himself. In The Uncanny X-Men #544 (2011), it is revealed that Sinister is now an entire colony of Sinister clones co-existing, each with minor differences. In subsequent battles, the leader Sinister and other clones were killed, only to be replaced by new clones with the same consciousness and improved genetics. The community of Sinister clones is destroyed in The Uncanny X-Men (vol. 2) #16 (2012). In issue #17 (2012), reveals that one copy of Mr. Sinister's mind survived, however, planting himself in the mind of X-Men public relations manager Kate Kildare. The surviving Sinister mind kills her and creates a new clone body to inhabit. In the 2019 mini-series Powers of X, it is revealed that several years before the present-day, one of the Sinister clones created possessed an X-gene, making him a mutant like the X-Men. This mutant Sinister assumed leadership of the community of Sinister clones and seems to be the surviving version who operates today. The same mini-series involved Mr. Sinister joining the new mutant community of the island Krakoa, and joining its ruling Quiet Council alongside Magneto, Professor X, Apocalypse, and others. The 2023 series Immortal X-Men established that the original Nathaniel
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
Essex died in 1895 on being murdered by Sherlock Holmes / Mystique. Before his death he created four clones to research paths to Machine Dominionhood independent of one another, whom Mystique's wife Destiny (Irene Adler) ensured would survive to adulthood. The clone branded with (♦️) continued to operate as Minister Sinister, while two others, branded with (♣️) and (♠️) respectively, became Doctor Stasis who researched various ways to post-Humanity and Orbis Stellaris who abandoned Earth and ventured into space to research alien technologies. The fourth clone with the (♥️) was of his late wife Rebecca who became a magical user called Mother Righteous. The male clones were unaware of one another for a long time, and each believed themselves to be the original Nathaniel, with no memory of dying and being cloned. In different possible futures, each had eventually succeeded in ascending to categorical godhood as a Dominion, only to be blocked and had their progress harvested by the A.I. imprint of the original Essex, who thus retroactively brought itself into existence as Enigma, a universal-level godlike intelligence existing outside space and time. == Fictional character biography == === 19th century === Born in Milbury House in Victorian London, Nathaniel Essex is the son of Admiral Erasmus Essex and Mary Essex. Earning a full scholarship to the University of Oxford, Essex becomes a biologist in 1859 and marries his wife Rebecca. A contemporary of Charles Darwin, Essex becomes highly interested in research regarding evolution and "survival of the fittest." He concludes humanity is undergoing increasing mutation due to what he calls "Essex Factors" in the human genome. After the loss of his four-year-old son Adam due to birth defects, Essex becomes more obsessed with his research in perfecting and improving the human race. Arguing that science is beyond morality, his
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
questionable research methods and ideas lead to suspicion, mockery, and finally ousting from the Royal Society and the scientific community. Angry and bitter, Essex accepts that being a "monster" in the eyes of others may be necessary to achieve his goals. Essex later hires the criminal Cootie Tremble and his gang, known as the Marauders. The Marauders kidnap homeless people off the streets of London as test subjects for Essex's experiments, including a man named Daniel Summers (whose descendant Scott Summers will one day be the hero called Cyclops). Two years after Adam Essex's death, Nathaniel Essex learns that some humans are born with mutant genetics that make them superhuman and discovers that one called En Sabah Nur ("The First One," known in later years as Apocalypse) is in hibernation. The Marauders awaken En Sabah Nur who then offers Essex an alliance, believing they have similar goals in perfecting the world and humanity. Nur then intends to conquer 19th-century England but is confronted by Cyclops and Phoenix, heroes from the future who arrive via time travel. Nur defeats the two heroes, leaving them for Essex to experiment on. Hoping to stop Apocalypse and possibly the origin of Mr. Sinister, Phoenix tells Essex that continuing his work with Nur will lead to worldwide destruction. Sensing truth in her words, Essex releases the heroes and decides to rededicate himself to family, as his wife Rebecca is pregnant again. Meanwhile, Rebecca Essex discovers Nathaniel's imprisoned human test subjects and his lab where he has experimented on the remains of their son. After freeing the prisoners and reburying her son, Rebecca goes into premature labor and her second child dies in stillbirth. Nathaniel then finds Rebecca, who is now dying from blood loss, and asks for forgiveness. Rebecca refuses, saying with her dying breath,
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
"To me, you are... utterly... and contemptibly... sinister!" Following Rebecca's death, Essex continues his alliance with En Sabah Nur, becoming the villain's first "prelate." Apocalypse reveals he has alien technology belonging to the Celestials (god-like beings who manipulated humanity in the past, resulting in the creation of the Eternals and the Deviants, as well as humanity's genetic potential for superhumans). With the Celestial machines, Apocalypse subjects Essex to a painful genetic transformation, turning him into an ageless being with chalk-white skin and a form of telekinesis. En Sabah Nur tells the transformed scientist to shed his past identity and choose another, and Essex renames himself "Sinister." Although he claims his humanity is gone, Essex continues to carry Rebecca's photo until 1882. When Apocalypse demands Sinister create a plague that will wipe out much of humanity, leaving only "the strong" alive, the scientist refuses, arguing that cruelty without purpose is ignorance and the enemy of science. Appreciating Sinister has shown strength through defiance, Apocalypse returns to his hibernation state, promising that when he returns he and Sinister will reshape the world. Following the death of Charles Darwin, Sinister travels to America and assumes the identity of obstetrician "Nathan Milbury" (taking the name of his ancestral home), head of the Essex Clinic in New York in the 1890s. There he continues secret experiments on people. He comes to understand more and more that mutants are human beings born with an "X-factor gene" or "X-gene", causing powers, traits, and abilities that often manifest during puberty or trauma. One early test subject is a mutant with a long lifespan named Amanda Mueller. To study how the X-gene may pass on to children in different ways, Sinister arranges for Amanda to marry his former test subject Daniel Summers (who recently became the first of his
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
family to immigrate to America). On several occasions when Amanda is pregnant, Sinister pays her to feign miscarriage and then secretly bring him the child for study. Seeing great potential in the Summers genetic line, Sinister decides to monitor the family. Around this same time, Sinister encounters two other mutants traveling from the future: Gambit and Courier. After experimenting with a cell sample from the latter man, Sinister gains complete control over his physical form, allowing him regenerative abilities and shape-shifting, while leaving Courier trapped in the form of a woman. Before the two time travelers leave, Sinister sees evidence of his own surgical techniques on Gambit. In 1899, Apocalypse emerges from hibernation again and is pleased with Sinister's work, including the development of a deadly techno-organic virus. Sinister then injects the virus into Apocalypse, but it only weakens the villain. As Apocalypse returns to hibernation to heal, he promises to kill Sinister when next they meet. Sinister decides to engineer a mutant who can kill Apocalypse. === 20th century === In 1907, Sinister works at the Ravencroft Institute and employs the mutant killer and mercenary Sabretooth as an agent. Sabretooth brings him the mutant called Logan for experimentation, but the man is then freed by coworker Dr. Claudia Russell (ancestor of the werewolf Jack Russell). Sinister leaves Ravencroft afterward. In 1912, Sinister encounters Grigori Rasputin and encourages him to father many children, promising they will have superhuman potential. Rasputin's descendants later include siblings Colossus, Magik, and Mikhail Rasputin. A few years after meeting Rasputin, Sinister grants shape-shifting abilities to Jacob Shaw (father of the X-Men villain Sebastian Shaw). It is possible that during the 1920s, Sinister also gave Dr. Herbert Edgar Wyndham information regarding how to map and break the human genetic code. Wyndam, a student of the Inhuman
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
scientist Phaeder, later becomes the master geneticist called the High Evolutionary. During the 1920s, Sinister lives in Los Angeles as "Nathan Essex" and befriends radio comedian Faye Livingstone. Realizing Faye's potential to have mutant children, Sinister temporarily imprisons and experiments on her. After her release, Faye never has children and develops cancer. As her mind and health deteriorate, she becomes a hospital patient in San Diego for the rest of her life, her treatment provided by Sinister himself, who visits annually in his human guise of Nathan Essex. During World War II, Sinister works with the Nazi Josef Mengele. Several Nazis who encounter Sinister nickname him "Nosferatu." A young Max Eisenhardt (who will grow to be Magneto) encounters him at this time and realizes Sinister is experimenting on children, killing those he deems failures or no longer needed. During these experiments, Sinister sometimes plays a favorite piece by Franz Schubert. During his work with the Nazis, Sinister creates a clone of Namor named N2. This clone is defeated by Captain America. Soon afterward, Sinister leaves the Nazis, concluding they will lose the war. Mr. Sinister's research during World War II is later recovered and used by the Weapon X project. Following World War II, Sinister adopts the name "Dr. Nathan Milbury" again and works on Project: Black Womb with Dr. Kurt Marko (the father of Juggernaut), Dr. Alexander Ryking (who, like Marko, is a friend and colleague of Brian Xavier, father of Charles Xavier), and the precognitive mutant Irene Adler. They conduct research on many mutant children and take note of several families that may produce mutant children later, allowing Sinister to monitor these bloodlines for decades. Concerned his own physical death may be inevitable, Sinister uses the Cronus Device to implant his own hidden cells of his genetic information
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
into the DNA strands of the Marko, Ryking, Shaw, and Xavier family lines. In time, their descendants can act as hosts for Sinister's consciousness. During the Vietnam War, Mr. Sinister sets up a lab in Saigon and has his agent Scalphunter bring him soldiers and civilians for experimentation. Locals refer to Sinister as the "White Devil." In 1968, Sabretooth investigates Sinister's operation but is then bribed and blackmailed to not interfere. He is told Sinister may have use for him in the future. Some years later, as "Dr. Milbury", Mr. Sinister becomes a professor at the University of Oxford. His students include Moira MacTaggert and the mutant telepath Charles Xavier, who realizes he cannot sense Milbury's thoughts. Years after Sinister's time back at Oxford, and during the time that Charles Xavier is first befriending Magneto while both are living in Israel, a version of the heroic mutant Hank McCoy from an alternate timeline (known as the "Age of Apocalypse") enters the mainstream Marvel reality. Known as the Dark Beast, this corrupt version of McCoy is former student and employee of his reality's Sinister. Dark Beast eventually makes his way to New York City and experiments on many mutants, using techniques his Sinister taught him. Several of his surviving test subjects become deformed or disabled by their own abilities as a result, choosing to hide underground and join a sewer-dwelling mutant community known as the "Morlocks" (taking the name from the subterranean race of the novel The Time Machine). Years later, Dark Beast's experiments indirectly lead to Sinister ordering the "Mutant Massacre." === Jean Grey and Scott Summers === Returning to America, Sinister creates an orphanage to monitor some of the children of families he first observed during Project: Black Womb. The State Home for Foundlings in Omaha, Nebraska hides a
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
high-tech, underground laboratory. Later, young Jean Grey's mutant telepathy prematurely activates when she witnesses the death of her best friend. Becoming aware of Jean's power, Mr. Sinister plans to kill her parents and bring her to the orphanage, only to learn the Greys have already contacted the now adult Charles Xavier for help, due to his background as a leading geneticist and psychological expert in trauma cases. Not wishing to be detected by Xavier, who at this point has already fought terrorists and superhuman menaces, Sinister decides to keep his distance after acquiring a DNA sample from Jean. Soon afterward, Sinister discovers a recently orphaned mutant boy named Scott Summers (descendant of Daniel Summers) released the same type of optic blasts displayed by the time-traveling hero Cyclops. Sinister tracks down Scott and his younger brother Alex, both of whom survived an airplane explosion that seemingly killed their parents. Scott awakens in the hospital and accidentally releases another optic blast, unable to shut off his power (perhaps due to brain-damage suffered during the fall). To experiment on the boy in a controlled environment, Sinister causes Scott to slip into a coma then arranges for him and his brother to be entrusted to the State Home for Foundlings. Mr. Sinister allows Alex to be adopted by people he can easily monitor, then spends the next year conducting experiments on the comatose Scott. Concluding the boy will never be able to fully control his power, Sinister learns the kinetic force blasts can be blocked by ruby quartz lenses. After placing temporary mental blocks in Scott, Sinister allows the boy to awaken. Scott experiences migraines until he is given ruby quartz glasses. Scott spends a few years in the care of the State Home for Foundlings. Hoping to make Cyclops an isolated warrior who
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
can be easily manipulated, Sinister takes on the guise of Nate, another orphan who acts as Scott's overly territorial friend while sometimes bullying him. As part of his long-term plan, Sinister allows Scott Summers to be adopted by a criminal named Jack Winters who abuses the boy and forces him to help with crimes. Rather than bend to his abusive guardian, Scott resists and is discovered by Professor Charles Xavier and his ally FBI agent Fred Duncan. With Duncan's help, Scott becomes Xavier's ward and the first official recruit of the original X-Men, a team of mutant heroes trained to stop mutant terrorists. Jean Grey joins this same team weeks later. Sinister continues to monitor Scott somewhat but keeps his distance so the telepathic Xavier and the other X-Men don't become aware of and interfere with his plans. Not long afterward, Mr. Sinister hires the villains Blob and Kraven the Hunter to fight and wound each of the X-Men. This results in a battle that draws the attention of the teenage hero Spider-Man. Kraven then brings the blood samples of the X-Men and Spider-Man back to Sinister for study, even providing a sample of his own DNA. Mr. Sinister concludes that offspring of Jean Grey and Scott Summers could represent the ultimate stage of mutant potential, possibly a mutant capable of destroying Apocalypse. Using Jean Grey's cell sample, Mr. Sinister creates a clone who is rapidly aged. When the clone shows no sign of the X-gene, Sinister leaves her in a hibernation chamber. Years later, Jean Grey suffers catastrophic radiation poisoning but is saved by the cosmic Phoenix Force, who desires her to be a host. With her increased power, Jean creates a new body for her consciousness and the cosmic Phoenix Force to occupy, while creating a healing cocoon
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
to repair the damage done to her original body. As "Phoenix", Jean becomes a more powerful hero. She is later temporarily corrupted, causing the Phoenix Force itself to become a corrupt and deadly entity. The new "Dark Phoenix" asserts control, burying Jean's personality. Jean's personality later resumes control and she eventually kills herself rather than allow Dark Phoenix to rise again and destroy more lives. Without a host, the Phoenix Force reverts to its original nature and feels remorse for its role in Jean's death. To make amends, it restores Jean's consciousness to her original body, now fully healed. Simultaneously, the Phoenix Force causes a spark of life in the Jean Grey clone Sinister created. === Madelyne Pryor and Nathan Summers === Deciding his clone may be useful after all, Sinister names her Madelyne Pryor (a joke on the fact that she was birthed from a "prior existence", a cell sample taken from a previously existing person). Mr. Sinister gives "Maddie" false memories and documentation of a life where she is a pilot who survived a plane crash that occurred at the same time Jean Grey killed herself. After influencing her personality to be one that will appeal to Scott Summers and will also fall in love with him, Sinister arranges for Maddie to have a job working alongside Scott's grandfather in Alaska. Unaware of her own true nature, Maddie meets Scott at a Summers family reunion. Seeing Maddie's resemblance to Jean and hearing about the timing of her experience in a plane crash, Scott wonders if Pryor is somehow his first love reborn. Maddie admits to having feelings for Cyclops but insists she is her own person and must be seen as such rather than as a copy of Jean Grey. Scott concedes and over time the two fall
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
in love, deciding to marry soon afterward. They have a son, Nathan Summers. While Christopher was Scott's father's name and Charles was Professor Xavier's first name, it is later said that Sinister influenced Scott and Maddie to name their son Nathan Summers after him as well. Scott decides to leave behind the dangerous world of the X-Men so he can raise his family in peace in Anchorage, Alaska, nearby his own grandparents. Studying the sewer-dwelling community known as the Morlocks, Mr. Sinister decides these mutants should not be allowed the chance to mix with the gene pool of other mutants and humans. His studies also reveal that several Morlocks bear signs of genetic manipulation based on his own research (due to Dark Beast's experiments). Enraged that someone has used his "signature" without his permission, Sinister decides to wipe out the mutant Morlocks living beneath Manhattan. He hires the mutant thief Gambit (who has not yet time traveled and so considers this to be his first meeting with Sinister) to recruit a new team of Marauders who will work with Sabretooth and Scalphunter. In exchange, Mr. Sinister performs surgery on Gambit to correct a defect that would have ensured the mutant thief would one day lose control of his powers. Before sending his Marauders against the Morlocks, Sinister learns the Avengers have discovered Jean Grey is alive and well in her cocoon. Sinister decides to seize the opportunity and at last kidnap Nathan Summers for experimentation. When Scott Summers learns of Jean's reappearance, Sinister mentally influences him to immediately leave Alaska to see for himself that it's actually her, leaving his family behind and without protection. Sinister then continues his mental influence, causing Scott to abandon his family and remain in New York City with Jean and the other original X-Men
|
{
"page_id": 528214,
"source": null,
"title": "Mister Sinister"
}
|
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