UFO (UnFold Operator) computer program abstract
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kissel, L.; Biggs, F.
UFO (UnFold Operator) is an interactive user-oriented computer program designed to solve a wide range of problems commonly encountered in physical measurements. This document provides a summary of the capabilities of version 3A of UFO.
Verification of unfold error estimates in the UFO code
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fehl, D.L.; Biggs, F.
Spectral unfolding is an inverse mathematical operation which attempts to obtain spectral source information from a set of tabulated response functions and data measurements. Several unfold algorithms have appeared over the past 30 years; among them is the UFO (UnFold Operator) code. In addition to an unfolded spectrum, UFO also estimates the unfold uncertainty (error) induced by running the code in a Monte Carlo fashion with prescribed data distributions (Gaussian deviates). In the problem studied, data were simulated from an arbitrarily chosen blackbody spectrum (10 keV) and a set of overlapping response functions. The data were assumed to have anmore » imprecision of 5% (standard deviation). 100 random data sets were generated. The built-in estimate of unfold uncertainty agreed with the Monte Carlo estimate to within the statistical resolution of this relatively small sample size (95% confidence level). A possible 10% bias between the two methods was unresolved. The Monte Carlo technique is also useful in underdetemined problems, for which the error matrix method does not apply. UFO has been applied to the diagnosis of low energy x rays emitted by Z-Pinch and ion-beam driven hohlraums.« less
Verification of unfold error estimates in the unfold operator code
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fehl, D.L.; Biggs, F.
Spectral unfolding is an inverse mathematical operation that attempts to obtain spectral source information from a set of response functions and data measurements. Several unfold algorithms have appeared over the past 30 years; among them is the unfold operator (UFO) code written at Sandia National Laboratories. In addition to an unfolded spectrum, the UFO code also estimates the unfold uncertainty (error) induced by estimated random uncertainties in the data. In UFO the unfold uncertainty is obtained from the error matrix. This built-in estimate has now been compared to error estimates obtained by running the code in a Monte Carlo fashionmore » with prescribed data distributions (Gaussian deviates). In the test problem studied, data were simulated from an arbitrarily chosen blackbody spectrum (10 keV) and a set of overlapping response functions. The data were assumed to have an imprecision of 5{percent} (standard deviation). One hundred random data sets were generated. The built-in estimate of unfold uncertainty agreed with the Monte Carlo estimate to within the statistical resolution of this relatively small sample size (95{percent} confidence level). A possible 10{percent} bias between the two methods was unresolved. The Monte Carlo technique is also useful in underdetermined problems, for which the error matrix method does not apply. UFO has been applied to the diagnosis of low energy x rays emitted by Z-pinch and ion-beam driven hohlraums. {copyright} {ital 1997 American Institute of Physics.}« less
UFO (UnFold Operator) user guide
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kissel, L.; Biggs, F.; Marking, T.R.
UFO is a collection of interactive utility programs for estimating unknown functions of one variable using a wide-ranging class of information as input, for miscellaneous data-analysis applications, for performing feasibility studies, and for supplementing our other software. Inverse problems, which include spectral unfolds, inverse heat-transfer problems, time-domain deconvolution, and unusual or difficult curve-fit problems, are classes of applications for which UFO is well suited. Extensive use of B-splines and (X,Y)-datasets is made to represent functions. The (X,Y)-dataset representation is unique in that it is not restricted to equally-spaced data. This feature is used, for example, in a table-generating algorithm thatmore » evaluates a function to a user-specified interpolation accuracy while minimizing the number of points stored in the corresponding dataset. UFO offers a variety of miscellaneous data-analysis options such as plotting, comparing, transforming, scaling, integrating; and adding, subtracting, multiplying, and dividing functions together. These options are often needed as intermediate steps in analyzing and solving difficult inverse problems, but they also find frequent use in other applications. Statistical options are available to calculate goodness-of-fit to measurements, specify error bands on solutions, give confidence limits on calculated quantities, and to point out the statistical consequences of operations such as smoothing. UFO is designed to do feasibility studies on a variety of engineering measurements. It is also tailored to supplement our Test Analysis and Design codes, SRAD Test-Data Archive software, and Digital Signal Analysis routines.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fehl, D.L.; Chandler, G.A.; Biggs, F.
X-ray-producing hohlraums are being studied as indirect drives for inertial confinement fusion targets. In a 1994 target series on the PBFAII accelerator, cylindrical hohlraum targets were heated by an intense Li{sup +} ion beam and viewed by an array of 13 time-resolved, filtered x-ray detectors (XRDs). The unfold operator (UFO) code and its suite of auxiliary functions were used extensively in obtaining time-resolved x-ray spectra and radiation temperatures from this diagnostic. The UFO was also used to obtain fitted response functions from calibration data, to simulate data from blackbody x-ray spectra of interest, to determine the suitability of various unfoldingmore » parameters (e.g., energy domain, energy partition, smoothing conditions, and basis functions), to interpolate the XRD signal traces, and to unfold experimental data. The simulation capabilities of the code were useful in understanding an anomalous feature in the unfolded spectra at low photon energies ({le}100 eV). Uncertainties in the differential and energy-integrated unfolded spectra were estimated from uncertainties in the data. The time{endash}history of the radiation temperature agreed well with independent calculations of the wall temperature in the hohlraum. {copyright} {ital 1997 American Institute of Physics.}« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fehl, D.L.; Chandler, G.A.; Biggs, F.
X-ray-producing hohlraums are being studied as indirect drives for Inertial Confinement Fusion targets. In a 1994 target series on the PBFAII accelerator, cylindrical hohlraum targets were heated by an intense Li{sup +} ion beam and viewed by an array of 13 time-resolved, filtered x-ray detectors (XRDs). The UFO unfold code and its suite of auxiliary functions were used extensively in obtaining time- resolved x-ray spectra and radiation temperatures from this diagnostic. UFO was also used to obtain fitted response functions from calibration data, to simulate data from blackbody x-ray spectra of interest, to determine the suitability of various unfolding parametersmore » (e.g., energy domain, energy partition, smoothing conditions, and basis functions), to interpolate the XRD signal traces, and to unfold experimental data. The simulation capabilities of the code were useful in understanding an anomalous feature in the unfolded spectra at low photon energies ({le} 100 eV). Uncertainties in the differential and energy-integrated unfolded spectra were estimated from uncertainties in the data. The time-history of the radiation temperature agreed well with independent calculations of the wall temperature in the hohlraum.« less
UFO (UnFold Operator) default data format
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kissel, L.; Biggs, F.; Marking, T.R.
The default format for the storage of x,y data for use with the UFO code is described. The format assumes that the data stored in a file is a matrix of values; two columns of this matrix are selected to define a function of the form y = f(x). This format is specifically designed to allow for easy importation of data obtained from other sources, or easy entry of data using a text editor, with a minimum of reformatting. This format is flexible and extensible through the use of inline directives stored in the optional header of the file. Amore » special extension of the format implements encoded data which significantly reduces the storage required as compared wth the unencoded form. UFO supports several extensions to the file specification that implement execute-time operations, such as, transformation of the x and/or y values, selection of specific columns of the matrix for association with the x and y values, input of data directly from other formats (e.g., DAMP and PFF), and a simple type of library-structured file format. Several examples of the use of the format are given.« less
Family of Beyond Line-of-Sight - Terminals (FAB-T)
2013-12-01
Inter- operable with the AEHF, APS, Milstar, and UFO -E/EE Inter- operable with the AEHF, APS, Milstar, and UFO -E/EE Inter- operable with the...AEHF, APS, Milstar, and UFO -E/EE Milstar connectivity has been extensively tested; partial AEHF on-orbit testing has been conducted...Program SR-3300. This performance parameter only applies to the CPT configuration. 8. Interoperability with UFO /E and UFO /EE is predicated on
Filter-fluorescer measurement of low-voltage simulator x-ray energy spectra
DOE Office of Scientific and Technical Information (OSTI.GOV)
Baldwin, G.T.; Craven, R.E.
X-ray energy spectra of the Maxwell Laboratories MBS and Physics International Pulserad 737 were measured using an eight-channel filter-fluorescer array. The PHOSCAT computer code was used to calculate channel response functions, and the UFO code to unfold spectrum.
Time-resolved hard x-ray spectrometer
NASA Astrophysics Data System (ADS)
Moy, Kenneth; Cuneo, Michael; McKenna, Ian; Keenan, Thomas; Sanford, Thomas; Mock, Ray
2006-08-01
Wired array studies are being conducted at the SNL Z accelerator to maximize the x-ray generation for inertial confinement fusion targets and high energy density physics experiments. An integral component of these studies is the characterization of the time-resolved spectral content of the x-rays. Due to potential spatial anisotropy in the emitted radiation, it is also critical to diagnose the time-evolved spectral content in a space-resolved manner. To accomplish these two measurement goals, we developed an x-ray spectrometer using a set of high-speed detectors (silicon PIN diodes) with a collimated field-of-view that converged on a 1-cm-diameter spot at the pinch axis. Spectral discrimination is achieved by placing high Z absorbers in front of these detectors. We built two spectrometers to permit simultaneous different angular views of the emitted radiation. Spectral data have been acquired from recent Z shots for the radial and axial (polar) views. UNSPEC 1 has been adapted to analyze and unfold the measured data to reconstruct the x-ray spectrum. The unfold operator code, UFO2, is being adapted for a more comprehensive spectral unfolding treatment.
Defense Acquisitions: Assessments of Selected Weapon Programs
2013-03-01
UHF) Follow-On ( UFO ) satellite system currently in operation and provide interoperability with legacy terminals. MUOS consists of a network of...MUOS satellites remain important due to the past operational failures of two UFO satellites and predicted end-of-life of on-orbit UFO satellites...Despite the delay and earlier, unexpected failures of two UFO satellites, the required availability level of UHF communication capabilities has been
Defense Acquisitions: Assessments of Selected Weapon Programs
2011-03-01
Frequency (UHF) Follow-On ( UFO ) satellite system currently in operation and provide interoperability with legacy terminals. MUOS consists of a...delivery of MUOS capabilities is time-critical due to the operational failures of two UFO satellites. The MUOS program has taken several steps to...launch increased due to the unexpected failures of two UFO satellites. Based on the current health of on-orbit satellites, UHF communication
Defense Acquisitions: Assessments of Selected Weapon Programs
2010-03-01
improved availability for small terminals. It is to replace the Ultra High Frequency (UHF) Follow-On ( UFO ) satellite system currently in operation...of MUOS capabilities is time-critical due to the operational failures of two UFO satellites. The MUOS program has taken several steps to address...failures of two UFO satellites. Based on the current health of on-orbit satellites, UHF communication capabilities are predicted to fall below the
Defense Acquisitions: Assessments of Selected Weapon Programs
2014-03-01
Frequency (UHF) Follow-On ( UFO ) satellite system currently in operation and provide interoperability with legacy terminals. MUOS consists of a...failures of two UFO satellites and predicted end-of-life of on-orbit UFO satellites, one of which was taken off-line in November 2012. A...needed because most on-orbit UFO satellites are past their design lives. Two of these unexpectedly failed—one in June 2005 and another in
MUOS: Application in Naval Helicopter Operations
2015-03-01
increase in voice and data. capacity over legacy UFO systelllS. Leveraging current WCDMA technology used by cormnercial cellular companies, the MUOS...and data capacity over legacy UFO systems. Leveraging current WCDMA technology used by commercial cellular companies, the MUOS system will allow...17 1. FLTSAT ..............................................................................................18 2. UFO
High Frontier: The Journal for Space and Missile Professionals. Volume 6, Number 2, February 2010
2010-02-01
congressional testimony, MUOS, which was supposed to provide continuity for the nearly defunct ultrahigh frequency follow-on ( UFO ) satellites, is now about...of Leasat satellites provided UHF capac- ity in the period between FLTSATCOM’s end of life and the first UHF UFO system launch in 1993. The UFO ...Harris, the deputy chief of naval operations for communications Networks, told a Senate subcommittee this spring that by May 2010, the UFO
Global Broadcast Service (GBS)
2014-12-01
Frequency Follow-On ( UFO ) satellites, leased commercial satellite transponders, and the Wideband Global SATCOM constellation. Theater Injection Point...each IOC: IOC 1: - PIPs operational on UFO satellites 8, 9, 10. - Full Satellite Broadcast Manager capability. - Field 20% of JPO Receive Suites (19...Independently assess system capabilities. - Augment UFO GBS with leased commercial satellite services to cover gaps over CONUS. - Demonstrate smart push and
2009-12-01
Tactical Imaging Nano-sat Yielding Small-Cost Operations and Persistent Earth-coverage UFO UHF Follow On UHF Ultra-High Frequency USCG United...replaced by UHF Follow On ( UFO ) satellites in the 1990s. The UFO satellites are being updated and scheduled for replacement by the Mobile User
Global Broadcast Service (GBS)
2013-12-01
as to be unusable by smaller and more mobile units. To this end, GBS currently uses broadcast payloads on two Ultra-High Frequency Follow-On ( UFO ...operational on UFO satellites 8, 9, 10. - Full Satellite Broadcast Manager capability. - Field 20% of JPO Receive Suites (19 units). - Personnel training...capabilities. - Augment UFO GBS with leased commercial satellite services to cover gaps over CONUS. - Demonstrate smart push and user pull capability
2013-05-29
support, products, and services, as required. US Tenth Fleet is the SSE for fleet satellite (FLTSAT) and ultrahigh frequency follow-on ( UFO ). b...direct support of Navy and joint forces. These systems include FLTSAT, UFO , MUOS, and varied payloads (Interim Polar and GBS). 10. Air Force Component...33-50 GHz S S-band, 2-4 GHz SHF super high frequency UFO ultrahigh frequency (UHF) follow-on WGS Wideband Global Satellite Communications System X
Optimizing the Navy’s Investment in Space Professionals
2011-09-01
UFO Ultra High Frequency Follow-On UHF Ultra High Frequency URL Unrestricted Line USA United States Army USAF United States Air Force USCYBERCOM...LEASAT), and eight UHF Follow-On ( UFO ) satellites all flying in geostationary orbit (GEO). NAVSOC is the principle Navy command that operates, manages...and maintains the DoD’s narrowband UHF capability from five different ground stations. The replacement satellite for the aging UFO system is the
2015-06-01
System UFG Ulchi Freedom Guardian UFO UHF Follow-On System UHF Ultra-High Frequency URE User Range Error VTC Video Teleconference WGS Wideband...in the UHF band; two legacy systems, Fleet Satellite Communication System (FLTSATCOM) and UHF Follow-on ( UFO ), and the new constellation being
Differential expression of the ufo/axl oncogene in human leukemia-lymphoma cell lines.
Challier, C; Uphoff, C C; Janssen, J W; Drexler, H G
1996-05-01
The ufo protein (also termed axl) is a member of a new family of receptor tyrosine kinases and is encoded by a transforming gene that was initially isolated from primary human myeloid leukemia cells by DNA-mediated transformation of NIH/3T3 cells. The ligand, Gas6, a protein S-related molecule lacking any known function yet, has recently been identified. We report the expression pattern of ufo mRNA in a panel of 76 human continuous leukemia-lymphoma cell lines. The gene was not expressed in cell lines derived from lymphoid malignancies (n=28), but transcription was seen in 3/11 myeloid, 0/6 monocytic, 9/13 erythroid and 11/18 megakaryocytic cell lines. Several cell lines were treated with phorbol ester leading to significant upregulation of the ufo message in constitutively positive cells. An apparent ufo mRNA overexpression was not found in any of the positive leukemia cell lines, but was identified in the drug-resistant subclones of the cervix carcinoma cell line HeLa. Southern blot analysis of restriction enzyme-digested genomic DNA did not provide evidence for gene amplification, but the HeLa subclones showed banding patterns suggestive of gene rearrangement. Two main ufo mRNA bands of 3.2 and 5.0 kb were identified; no differences in the half-lives (t1/2 = 2.5 h) of these two mRNA species could be identified. In summary, ufo, representing a novel type of receptor tyrosine kinase, is expressed solely in myeloid and erythro-megakaryocytic leukemias but not in lymphoid malignancies. These and previous data suggest an involvement of the ufo receptor tyrosine kinase in normal and malignant myelopoiesis; however, its exact role, if any, and mode of operation in leukemogenesis remains to be determined.
UFO: A THREE-DIMENSIONAL NEUTRON DIFFUSION CODE FOR THE IBM 704
DOE Office of Scientific and Technical Information (OSTI.GOV)
Auerbach, E.H.; Jewett, J.P.; Ketchum, M.A.
A description of UFO, a code for the solution of the fewgroup neutron diffusion equation in three-dimensional Cartesian coordinates on the IBM 704, is given. An accelerated Liebmann flux iteration scheme is used, and optimum parameters can be calculated by the code whenever they are required. The theory and operation of the program are discussed. (auth)
Ultrafast Outflows: Galaxy-scale Active Galactic Nucleus Feedback
NASA Astrophysics Data System (ADS)
Wagner, A. Y.; Umemura, M.; Bicknell, G. V.
2013-01-01
We show, using global three-dimensional grid-based hydrodynamical simulations, that ultrafast outflows (UFOs) from active galactic nuclei (AGNs) result in considerable feedback of energy and momentum into the interstellar medium (ISM) of the host galaxy. The AGN wind interacts strongly with the inhomogeneous, two-phase ISM consisting of dense clouds embedded in a tenuous, hot, hydrostatic medium. The outflow floods through the intercloud channels, sweeps up the hot ISM, and ablates and disperses the dense clouds. The momentum of the UFO is primarily transferred to the dense clouds via the ram pressure in the channel flow, and the wind-blown bubble evolves in the energy-driven regime. Any dependence on UFO opening angle disappears after the first interaction with obstructing clouds. On kpc scales, therefore, feedback by UFOs operates similarly to feedback by relativistic AGN jets. Negative feedback is significantly stronger if clouds are distributed spherically rather than in a disk. In the latter case, the turbulent backflow of the wind drives mass inflow toward the central black hole. Considering the common occurrence of UFOs in AGNs, they are likely to be important in the cosmological feedback cycles of galaxy formation.
ULTRAFAST OUTFLOWS: GALAXY-SCALE ACTIVE GALACTIC NUCLEUS FEEDBACK
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wagner, A. Y.; Umemura, M.; Bicknell, G. V., E-mail: ayw@ccs.tsukuba.ac.jp
We show, using global three-dimensional grid-based hydrodynamical simulations, that ultrafast outflows (UFOs) from active galactic nuclei (AGNs) result in considerable feedback of energy and momentum into the interstellar medium (ISM) of the host galaxy. The AGN wind interacts strongly with the inhomogeneous, two-phase ISM consisting of dense clouds embedded in a tenuous, hot, hydrostatic medium. The outflow floods through the intercloud channels, sweeps up the hot ISM, and ablates and disperses the dense clouds. The momentum of the UFO is primarily transferred to the dense clouds via the ram pressure in the channel flow, and the wind-blown bubble evolves inmore » the energy-driven regime. Any dependence on UFO opening angle disappears after the first interaction with obstructing clouds. On kpc scales, therefore, feedback by UFOs operates similarly to feedback by relativistic AGN jets. Negative feedback is significantly stronger if clouds are distributed spherically rather than in a disk. In the latter case, the turbulent backflow of the wind drives mass inflow toward the central black hole. Considering the common occurrence of UFOs in AGNs, they are likely to be important in the cosmological feedback cycles of galaxy formation.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
De Doncker, Rik W. A. A.
The direct (d) and quadrature (q) components of flux, as sensed by flux sensors or determined from voltage and current measurements in a direct field orientation scheme, are processed rapidly and accurately to provide flux amplitude and angular position values for use by the vector rotator of a universal field-oriented (UFO) controller. Flux amplitude (linear or squared) is provided as feedback to tune the UFO controller for operation in direct and indirect field orientation modes and enables smooth transitions from one mode to the other.
DOE Office of Scientific and Technical Information (OSTI.GOV)
De Doncker, R.W.A.A.
The direct (d) and quadrature (q) components of flux, as sensed by flux sensors or determined from voltage and current measurements in a direct field orientation scheme, are processed rapidly and accurately to provide flux amplitude and angular position values for use by the vector rotator of a universal field-oriented (UFO) controller. Flux amplitude (linear or squared) is provided as feedback to tune the UFO controller for operation in direct and indirect field orientation modes and enables smooth transitions from one mode to the other. 3 figs.
De Doncker, R.W.A.A.
1992-09-01
The direct (d) and quadrature (q) components of flux, as sensed by flux sensors or determined from voltage and current measurements in a direct field orientation scheme, are processed rapidly and accurately to provide flux amplitude and angular position values for use by the vector rotator of a universal field-oriented (UFO) controller. Flux amplitude (linear or squared) is provided as feedback to tune the UFO controller for operation in direct and indirect field orientation modes and enables smooth transitions from one mode to the other. 3 figs.
Laufs, Patrick; Coen, Enrico; Kronenberger, Jocelyne; Traas, Jan; Doonan, John
2003-02-01
The UNUSUAL FLORAL ORGANS (UFO) gene is required for several aspects of floral development in Arabidopsis including specification of organ identity in the second and third whorls and the proper pattern of primordium initiation in the inner three whorls. UFO is expressed in a dynamic pattern during the early phases of flower development. Here we dissect the role of UFO by ubiquitously expressing it in ufo loss-of-function flowers at different developmental stages and for various durations using an ethanol-inducible expression system. The previously known functions of UFO could be separated and related to its expression at specific stages of development. We show that a 24- to 48-hour period of UFO expression from floral stage 2, before any floral organs are visible, is sufficient to restore normal petal and stamen development. The earliest requirement for UFO is during stage 2, when the endogenous UFO gene is transiently expressed in the centre of the wild-type flower and is required to specify the initiation patterns of petal, stamen and carpel primordia. Petal and stamen identity is determined during stages 2 or 3, when UFO is normally expressed in the presumptive second and third whorl. Although endogenous UFO expression is absent from the stamen whorl from stage 4 onwards, stamen identity can be restored by UFO activation up to stage 6. We also observed floral phenotypes not observed in loss-of-function or constitutive gain-of-function backgrounds, revealing additional roles of UFO in outgrowth of petal primordia.
Holloway, Ryan W; Regnery, Julia; Nghiem, Long D; Cath, Tzahi Y
2014-09-16
A hybrid ultrafiltration-osmotic membrane bioreactor (UFO-MBR) was investigated for over 35 days for nutrient and trace organic chemical (TOrC) removal from municipal wastewater. The UFO-MBR system uses both ultrafiltration (UF) and forward osmosis (FO) membranes in parallel to simultaneously extract clean water from an activated sludge reactor for nonpotable (or environmental discharge) and potable reuse, respectively. In the FO stream, water is drawn by osmosis from activated sludge through an FO membrane into a draw solution (DS), which becomes diluted during the process. A reverse osmosis (RO) system is then used to reconcentrate the diluted DS and produce clean water suitable for direct potable reuse. The UF membrane extracts water, dissolved salts, and some nutrients from the system to prevent their accumulation in the activated sludge of the osmotic MBR. The UF permeate can be used for nonpotable reuse purposes (e.g., irrigation and toilet flushing). Results from UFO-MBR investigation illustrated that the chemical oxygen demand, total nitrogen, and total phosphorus removals were greater than 99%, 82%, and 99%, respectively. Twenty TOrCs were detected in the municipal wastewater that was used as feed to the UFO-MBR system. Among these 20 TOrCs, 15 were removed by the hybrid UFO-MBR system to below the detection limit. High FO membrane rejection was observed for all ionic and nonionic hydrophilic TOrCs and lower rejection was observed for nonionic hydrophobic TOrCs. With the exceptions of bisphenol A and DEET, all TOrCs that were detected in the DS were well rejected by the RO membrane. Overall, the UFO-MBR can operate sustainably and has the potential to be utilized for direct potable reuse applications.
UFO: an Arabidopsis gene involved in both floral meristem and floral organ development.
Levin, J Z; Meyerowitz, E M
1995-05-01
We describe the role of the UNUSUAL FLORAL ORGANS (UFO) gene in Arabidopsis floral development based on a genetic and molecular characterization of the phenotypes of nine ufo alleles. UFO is required for the proper identity of the floral meristem and acts in three different aspects of the process that distinguishes flowers from shoots. UFO is involved in establishing the whorled pattern of floral organs, controlling the determinacy of the floral meristem, and activating the APETALA3 and PISTILLATA genes required for petal and stamen identity. In many respects, UFO acts in a manner similar to LEAFY, but the ufo mutant phenotype also suggests an additional role for UFO in defining boundaries within the floral primordia or controlling cell proliferation during floral organ growth. Finally, genetic interactions that prevent flower formation and lead to the generation of filamentous structures implicate UFO as a member of a new, large, and diverse class of genes in Arabidopsis necessary for flower formation.
Ingram, G C; Goodrich, J; Wilkinson, M D; Simon, R; Haughn, G W; Coen, E S
1995-09-01
The unusual floral organs (ufo) mutant of Arabidopsis has flowers with variable homeotic organ transformations and inflorescence-like characteristics. To determine the relationship between UFO and previously characterized meristem and organ identity genes, we cloned UFO and determined its expression pattern. The UFO gene shows extensive homology with FIMBRIATA (FIM), a gene mediating between meristem and organ identity genes in Antirrhinum. All three UFO mutant alleles that we sequenced are predicted to produce truncated proteins. UFO transcripts were first detected in early floral meristems, before organ identity genes had been activated. At later developmental stages, UFO expression is restricted to the junction between sepal and petal primordia. Phenotypic, genetic, and expression pattern comparisons between UFO and FIM suggest that they are cognate homologs and play a similar role in mediating between meristem and organ identity genes. However, some differences in the functions and genetic interactions of UFO and FIM were apparent, indicating that changes in partially redundant pathways have occurred during the evolutionary divergence of Arabidopsis and Antirrhinum.
Physical Conditions in Ultra-fast Outflows in AGN
NASA Astrophysics Data System (ADS)
Kraemer, S. B.; Tombesi, F.; Bottorff, M. C.
2018-01-01
XMM-Newton and Suzaku spectra of Active Galactic Nuclei (AGN) have revealed highly ionized gas, in the form of absorption lines from H-like and He-like Fe. Some of these absorbers, ultra-fast outflows (UFOs), have radial velocities of up to 0.25c. We have undertaken a detailed photoionization study of high-ionization Fe absorbers, both UFOs and non-UFOs, in a sample of AGN observed by XMM-Newton. We find that the heating and cooling processes in UFOs are Compton-dominated, unlike the non-UFOs. Both types are characterized by force multipliers on the order of unity, which suggest that they cannot be radiatively accelerated in sub-Eddington AGN, unless they were much less ionized at their point of origin. However, such highly ionized gas can be accelerated via a magneto-hydrodynamic (MHD) wind. We explore this possibility by applying a cold MHD flow model to the UFO in the well-studied Seyfert galaxy, NGC 4151. We find that the UFO can be accelerated along magnetic streamlines anchored in the accretion disk. In the process, we have been able to constrain the magnetic field strength and the magnetic pressure in the UFO and have determined that the system is not in magnetic/gravitational equipartition. Open questions include the variability of the UFOs and the apparent lack of non-UFOs in UFO sources.
UNUSUAL FLORAL ORGANS Controls Meristem Identity and Organ Primordia Fate in Arabidopsis.
Wilkinson, M. D.; Haughn, G. W.
1995-09-01
A novel gene that is involved in regulating flower initiation and development has been identified in Arabidopsis. This gene has been designated UNUSUAL FLORAL ORGANS (UFO), with five corresponding nuclear recessive alleles designated ufo[middot]1 to ufo[middot]5. Under short day-length conditions, ufo homozygotes generate more coflorescences than do the wild type, and coflorescences often appear apical to the first floral shoot, resulting in a period of inflorescence development in which regions of floral and coflorescence shoots are produced alternately. ufo enhances the phenotype of weak leafy alleles, and the double mutant Ufo-1 Apetala1-1 produces only coflorescence-like shoots, suggesting that these two genes control different aspects of floral initiation. Floral development was also altered in Ufo plants. Ufo flowers have an altered organ number in all whorls, and organs in the first, second, and third whorls exhibit variable homeotic transformations. Ufo single and double mutant phenotypes suggest that the floral changes result from reduction in class B floral homeotic gene expression and fluctuations in the expression boundaries of class C function and FLO10. Surprisingly, in situ hybridization analysis revealed no obvious differences in expression pattern or level in developing Ufo flowers compared with that of the wild type for any class B or C gene studied. We propose that UFO acts in concert with known floral initiation genes and regulates the domains of floral homeotic gene function.
Towards a Low-Cost Quadrotor Research Platform
2010-03-01
FIGURES Figure 1. Quadrotor schematic showing rotor direction of rotation (From [2])................3 Figure 2. Toy quadrotor: Walkera UFO (from...Some examples are the Walkera UFO #5, Walkera UFO #8, Dragonfly, and Alien Air Jump Jet. Figure 2. Toy quadrotor: Walkera UFO (from Walkera...the X- UFO made by Silverlit Electronics used small mechanical gyros. These were relatively cheap due to low-cost labor, but suffered from mechanical
UNUSUAL FLORAL ORGANS Controls Meristem Identity and Organ Primordia Fate in Arabidopsis.
Wilkinson, M. D.; Haughn, G. W.
1995-01-01
A novel gene that is involved in regulating flower initiation and development has been identified in Arabidopsis. This gene has been designated UNUSUAL FLORAL ORGANS (UFO), with five corresponding nuclear recessive alleles designated ufo[middot]1 to ufo[middot]5. Under short day-length conditions, ufo homozygotes generate more coflorescences than do the wild type, and coflorescences often appear apical to the first floral shoot, resulting in a period of inflorescence development in which regions of floral and coflorescence shoots are produced alternately. ufo enhances the phenotype of weak leafy alleles, and the double mutant Ufo-1 Apetala1-1 produces only coflorescence-like shoots, suggesting that these two genes control different aspects of floral initiation. Floral development was also altered in Ufo plants. Ufo flowers have an altered organ number in all whorls, and organs in the first, second, and third whorls exhibit variable homeotic transformations. Ufo single and double mutant phenotypes suggest that the floral changes result from reduction in class B floral homeotic gene expression and fluctuations in the expression boundaries of class C function and FLO10. Surprisingly, in situ hybridization analysis revealed no obvious differences in expression pattern or level in developing Ufo flowers compared with that of the wild type for any class B or C gene studied. We propose that UFO acts in concert with known floral initiation genes and regulates the domains of floral homeotic gene function. PMID:12242408
Potential of used frying oil in paving material: solution to environmental pollution problem.
Singh-Ackbarali, Dimple; Maharaj, Rean; Mohamed, Nazim; Ramjattan-Harry, Vitra
2017-05-01
The improper disposal of used frying oil (UFO) presents numerous ecological, environmental and municipal problems. Of great concern is the resultant blockage of municipal drainage systems and water treatment facilities, harm to wildlife when they become coated in it and detriment to aquatic life and ecosystems due to the depletion of the oxygen content in water bodies such as rivers and lakes that have become contaminated. Statistics show that in Trinidad and Tobago, in excess of one million liters of used cooking oil is collected annually from various restaurant chains. This paper investigated the potential of using UFO as a performance enhancing additive for road paving applications utilizing Trinidad Lake Asphalt (TLA) and Trinidad Petroleum Bitumen (TPB) as a mitigation strategy for improper UFO disposal. Modified blends containing various additions of UFO (2-10% wt) were prepared for the TLA and TPB asphaltic binders. Results demonstrated in terms of stiffness, increasing the dosage of UFO in TLA and TPB base binders resulted in a gradual decrease in stiffness (G* value decreased). In terms of elasticity, increasing the dosage of the UFO additive in TLA resulted in a general decrease in the elasticity of the blends indicated by an increase in phase angle or phase lag (δ). Increasing dosages of the UFO additive in TPB resulted in a significant decrease in δ where the most elastic blend was at the 6% UFO level. TLA and UFO-TLA modified blends exhibited significantly lower values of δ and higher values of G* confirming the superiority of the TLA material. Incorporation of the UFO in the blends led to a decrease in the rutting resistance and increase in the fatigue cracking resistance (decrease in G*/sinδ and G*sinδ, respectively). This study highlighted the potential for the reuse of UFO as an asphalt modifier capable of producing customized UFO modified asphaltic blends for special applications and confirms its feasibility as an environmentally attractive means of reusing the waste/hazardous UFO material locally.
ERIC Educational Resources Information Center
Coleman, William
1980-01-01
This article is in response to the Scientific-Study of Unidentified Flying Objects (UFOs) by the University of Colorado which stated that miseducation was taking place in schools that allowed children to read UFO books. The author encourages the aerospace teacher to allow UFO studies to take place. (SA)
Faust, M; Ebensperger, C; Schulz, A S; Schleithoff, L; Hameister, H; Bartram, C R; Janssen, J W
1992-07-01
We have cloned the mouse homologue of the ufo oncogene. It encodes a novel tyrosine kinase receptor characterized by a unique extracellular domain containing two immunoglobulin-like and two fibronectin type III repeats. Comparison of the predicted ufo amino acid sequences of mouse and man revealed an overall identity of 87.6%. The ufo locus maps to mouse chromosome 7A3-B1 and thereby extends the known conserved linkage group between mouse chromosome 7 and human chromosome 19. RNA in situ hybridization analysis established the onset of specific ufo expression in the late embryogenesis at day 12.5 post coitum (p.c.) and localized ufo transcription to distinct substructures of a broad spectrum of developing tissues (e.g. subepidermal cells of the skin, mesenchymal cells of the periosteum). In adult animals ufo is expressed in cells forming organ capsules as well as in connective tissue structures. ufo may function as a signal transducer between specific cell types of mesodermal origin.
Persinger, M A; Derr, J S
1985-02-01
A strong temporal correlation was found between the numbers of reports of UFOs (unidentified flying objects) and nearby seismic activity within the Uinta Basin for the year 1967. The numbers of UFO reports per month during this classic UFO flap were correlated 0.80 with the sum of the earthquake magnitudes per month for events within 150 km of the report area. Numbers of UFO reports were not correlated significantly with earthquake activity at distances greater than 150 km but less than 250 km away. The strongest correlation occurred between UFO reports and nearby seismic activity within the same month but not for previous or consequent months. Close scrutiny of daily shifts in epicenters and reports of UFOs indicate that they occurred when the locus of successive epicenters shifted across the area. These analyses were interpreted as support for the existence of strain fields whose movements generate natural phenomena that are reported as UFOs.
Sasaki, Katsutomo; Yamaguchi, Hiroyasu; Aida, Ryutaro; Shikata, Masahito; Abe, Tomoko; Ohtsubo, Norihiro
2012-09-01
We identified a Torenia fournieri Lind. mutant (no. 252) that exhibited a sepaloid phenotype in which the second whorls were changed to sepal-like organs. This mutant had no stamens, and the floral organs consisted of sepals and carpels. Although the expression of a torenia class B MADS-box gene, GLOBOSA (TfGLO), was abolished in the 252 mutant, no mutation of TfGLO was found. Among torenia homologs such as APETALA1 (AP1), LEAFY (LFY), and UNUSUAL FLORAL ORGANS (UFO), which regulate expression of class B genes in Arabidopsis, only accumulation of the TfUFO transcript was diminished in the 252 mutant. Furthermore, a missense mutation was found in the coding region of the mutant TfUFO. Intact TfUFO complemented the mutant phenotype whereas mutated TfUFO did not; in addition, the transgenic phenotype of TfUFO-knockdown torenias coincided with the mutant phenotype. Yeast two-hybrid analysis revealed that the mutated TfUFO lost its ability to interact with TfLFY protein. In situ hybridization analysis indicated that the transcripts of TfUFO and TfLFY were partially accumulated in the same region. These results clearly demonstrate that the defect in TfUFO caused the sepaloid phenotype in the 252 mutant due to the loss of interaction with TfLFY. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.
Recent Developments in the Scientific Study of UFO's
ERIC Educational Resources Information Center
Salisbury, Frank B.
1975-01-01
Reviews the interest of the last few years, both inside and outside the scientific community, in unidentified flying objects (UFO), placing special emphasis on the extraterrestrial intelligence hypothesis. Cites numerous examples of UFO sightings and urges that the investigation of UFO's proceed in a scientific manner, despite skeptical public…
Durfee, Tim; Roe, Judith L; Sessions, R Allen; Inouye, Carla; Serikawa, Kyle; Feldmann, Kenneth A; Weigel, Detlef; Zambryski, Patricia C
2003-07-08
The UNUSUAL FLORAL ORGANS (UFO) gene is required for multiple processes in the developing Arabidopsis flower, including the proper patterning and identity of both petals and stamens. The gene encodes an F-box-containing protein, UFO, which interacts physically and genetically with the Skp1 homolog, ASK1. In this report, we describe four ufo alleles characterized by the absence of petals, which uncover another role for UFO in promoting second whorl development. This UFO-dependent pathway is required regardless of the second whorl organ to be formed, arguing that it affects a basic process acting in parallel with those establishing organ identity. However, the pathway is dispensable in the absence of AGAMOUS (AG), a known inhibitor of petal development. In situ hybridization results argue that AG is not transcribed in the petal region, suggesting that it acts non-cell-autonomously to inhibit second whorl development in ufo mutants. These results are combined into a genetic model explaining early second whorl initiation/proliferation, in which UFO functions to inhibit an AG-dependent activity.
Roy, Soumendra K; Jian, Tian; Lopez, Gary V; Li, Wei-Li; Su, Jing; Bross, David H; Peterson, Kirk A; Wang, Lai-Sheng; Li, Jun
2016-02-28
The observation of the gaseous UFO(-) anion is reported, which is investigated using photoelectron spectroscopy and relativisitic ab initio calculations. Two strong photoelectron bands are observed at low binding energies due to electron detachment from the U-7sσ orbital. Numerous weak detachment bands are also observed due to the strongly correlated U-5f electrons. The electron affinity of UFO is measured to be 1.27(3) eV. High-level relativistic quantum chemical calculations have been carried out on the ground state and many low-lying excited states of UFO to help interpret the photoelectron spectra and understand the electronic structure of UFO. The ground state of UFO(-) is linear with an O-U-F structure and a (3)H4 spectral term derived from a U 7sσ(2)5fφ(1)5fδ(1) electron configuration, whereas the ground state of neutral UFO has a (4)H(7/2) spectral term with a U 7sσ(1)5fφ(1)5fδ(1) electron configuration. Strong electron correlation effects are found in both the anionic and neutral electronic configurations. In the UFO neutral, a high density of electronic states with strong configuration mixing is observed in most of the scalar relativistic and spin-orbit coupled states. The strong electron correlation, state mixing, and spin-orbit coupling of the electronic states make the excited states of UFO very challenging for accurate quantum chemical calculations.
NASA Astrophysics Data System (ADS)
Roy, Soumendra K.; Jian, Tian; Lopez, Gary V.; Li, Wei-Li; Su, Jing; Bross, David H.; Peterson, Kirk A.; Wang, Lai-Sheng; Li, Jun
2016-02-01
The observation of the gaseous UFO- anion is reported, which is investigated using photoelectron spectroscopy and relativisitic ab initio calculations. Two strong photoelectron bands are observed at low binding energies due to electron detachment from the U-7sσ orbital. Numerous weak detachment bands are also observed due to the strongly correlated U-5f electrons. The electron affinity of UFO is measured to be 1.27(3) eV. High-level relativistic quantum chemical calculations have been carried out on the ground state and many low-lying excited states of UFO to help interpret the photoelectron spectra and understand the electronic structure of UFO. The ground state of UFO- is linear with an O-U-F structure and a 3H4 spectral term derived from a U 7sσ25fφ15fδ1 electron configuration, whereas the ground state of neutral UFO has a 4H7/2 spectral term with a U 7sσ15fφ15fδ1 electron configuration. Strong electron correlation effects are found in both the anionic and neutral electronic configurations. In the UFO neutral, a high density of electronic states with strong configuration mixing is observed in most of the scalar relativistic and spin-orbit coupled states. The strong electron correlation, state mixing, and spin-orbit coupling of the electronic states make the excited states of UFO very challenging for accurate quantum chemical calculations.
Voloshin, Olga; Bakhrat, Anya; Herrmann, Sharon; Raveh, Dina
2012-01-01
The F-box protein, Ufo1, recruits Ho endonuclease to the SCFUfo1 complex for ubiquitylation. Both ubiquitylated Ho and Ufo1 are transferred by the UbL-UbA protein, Ddi1, to the 19S Regulatory Particle (RP) of the proteasome for degradation. The Ddi1-UbL domain binds Rpn1 of the 19S RP, the Ddi1-UbA domain binds ubiquitin chains on the degradation substrate. Here we used complex reconstitution in vitro to identify stages in the transfer of Ho and Ufo1 from the SCFUfo1 complex to the proteasome. We report SCFUfo1 complex at the proteasome formed in the presence of Ho. Subsequently Ddi1 is recruited to this complex by interaction between the Ddi1-UbL domain and Ufo1. The core of Ddi1 binds both Ufo1 and Rpn1; this interaction confers specificity of SCFUfo1 for Ddi1. The substrate-shield model predicts that Ho would protect Ufo1 from degradation and we find that Ddi1 binds Ho, Ufo1, and Rpn1 simultaneously forming a complex for transfer of Ho to the 19S RP. In contrast, in the absence of Ho, Rpn1 displaces Ufo1 from Ddi1 indicating a higher affinity of the Ddi1-UbL for the 19S RP. However, at high Rpn1 levels there is synergistic binding of Ufo1 to Ddi1 that is dependent on the Ddi1-UbA domain. Our interpretation is that in the absence of substrate, the Ddi1-UbL binds Rpn1 while the Ddi1-UbA binds ubiquitin chains on Ufo1. This would promote degradation of Ufo1 and disassembly of SCFUfo1 complexes. PMID:22815701
First results on video meteors from Crete, Greece
NASA Astrophysics Data System (ADS)
Maravelias, G.
2012-01-01
This work presents the first systematic video meteor observations from a, forthcoming permanent, station in Crete, Greece, operating as the first official node within the International Meteor Organization's Video Network. It consists of a Watec 902 H2 Ultimate camera equipped with a Panasonic WV-LA1208 (focal length 12mm, f/0.8) lens running MetRec. The system operated for 42 nights during 2011 (August 19-December 30, 2011) recording 1905 meteors. It is significantly more performant than a previous system used by the author during the Perseids 2010 (DMK camera 21AF04.AS by The Imaging Source, CCTV lens of focal length 2.8 mm, UFO Capture v2.22), which operated for 17 nights (August 4-22, 2010) recording 32 meteors. Differences - according to the author's experience - between the two softwares (MetRec, UFO Capture) are discussed along with a small guide to video meteor hardware.
Hypothesis on the nature of atmospheric UFOs
NASA Astrophysics Data System (ADS)
Mukharev, L. A.
1991-08-01
A hypothesis is developed according to which the atmospheric UFO phenomenon has an electromagnetic nature. It is suggested that an atmospheric UFO is an agglomeration of charged atmospheric dust within which there exists a slowly damped electromagnetic field. This field is considered to be the source of the observed optical effects and the motive force of the UFO.
UFO Literature for the Serious Ufologist.
ERIC Educational Resources Information Center
Eberhart, George M.
1980-01-01
Discusses the differences between the serious ufologist and the interested novice, reviews essential reference works and journals dealing with UFOs, and addresses problems that libraries have in collecting UFO literature. (FM)
Untrained Forward Observer (UFO) Translator for Call for Fire
2013-09-01
release; distribution is unlimited UNTRAINED FORWARD OBSERVER ( UFO ) TRANSLATOR FOR CALL FOR FIRE by Regan R. King September 2013 Thesis...DATE September 2013 3. REPORT TYPE AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE UNTRAINED FORWARD OBSERVER ( UFO ) TRANSLATOR FOR CALL...application, which we call the Untrained Forward Observer ( UFO ) Translator, capable of assisting untrained observers in performing Call for Fire by asking a
Close encounters: an examination of UFO experiences.
Spanos, N P; Cross, P A; Dickson, K; DuBreuil, S C
1993-11-01
Ss who reported UFO experiences were divided into those whose experiences were nonintense (e.g., seeing lights and shapes in the sky) and those whose experiences were intense (e.g., seeing and communicating with aliens or missing time). On a battery of objective tests Ss in these 2 groups did not score as more psychopathological, less intelligent, or more fantasy prone and hypnotizable than a community comparison group or a student comparison group. However, Ss in the UFO groups believed more strongly in space alien visitation than did comparison Ss. The UFO experiences of Ss in the intense group were more frequently sleep-related than the experiences of Ss in the nonintense group. Among the combined UFO Ss, intensity of UFO experiences correlated significantly with inventories that assessed proneness toward fantasy and unusual sensory experiences. Implications are discussed.
The ASK1 gene regulates B function gene expression in cooperation with UFO and LEAFY in Arabidopsis.
Zhao, D; Yu, Q; Chen, M; Ma, H
2001-07-01
The Arabidopsis floral regulatory genes APETALA3 (AP3) and PISTILLATA (PI) are required for the B function according to the ABC model for floral organ identity. AP3 and PI expression are positively regulated by the LEAFY (LFY) and UNUSUAL FLORAL ORGANS (UFO) genes. UFO encodes an F-box protein, and we have shown previously that UFO genetically interacts with the ASK1 gene encoding a SKP1 homologue; both the F-box containing protein and SKP1 are subunits of ubiquitin ligases. We show here that the ask1-1 mutation can enhance the floral phenotypes of weak lfy and ap3 mutants; therefore, like UFO, ASK1 also interacts with LFY and AP3 genetically. Furthermore, our results from RNA in situ hybridizations indicate that ASK1 regulates early AP3 and PI expression. These results support the idea that UFO and ASK1 together positively regulate AP3 and PI expression. We propose that the UFO and ASK1 proteins are components of a ubiquitin ligase that mediates the proteolysis of a repressor of AP3 and PI expression. Our genetic studies also indicate that ASK1 and UFO play a role in regulating the number of floral organ primordia, and we discuss possible mechanisms for such a regulation.
The genomic structure of the human UFO receptor.
Schulz, A S; Schleithoff, L; Faust, M; Bartram, C R; Janssen, J W
1993-02-01
Using a DNA transfection-tumorigenicity assay we have recently identified the UFO oncogene. It encodes a tyrosine kinase receptor characterized by the juxtaposition of two immunoglobulin-like and two fibronectin type III repeats in its extracellular domain. Here we describe the genomic organization of the human UFO locus. The UFO receptor is encoded by 20 exons that are distributed over a region of 44 kb. Different isoforms of UFO mRNA are generated by alternative splicing of exon 10 and differential usage of two imperfect polyadenylation sites resulting in the presence or absence of 1.5-kb 3' untranslated sequences. Primer extension and S1 nuclease analyses revealed multiple transcriptional initiation sites including a major site 169 bp upstream of the translation start site. The promoter region is GC rich, lacks TATA and CAAT boxes, but contains potential recognition sites for a variety of trans-acting factors, including Sp1, AP-2 and the cyclic AMP response element-binding protein. Proto-UFO and its oncogenic counterpart exhibit identical cDNA and promoter regions sequences. Possible modes of UFO activation are discussed.
First UFO Incident for Our Country
1983-09-09
researchers abroad still have obtained nothing rela- tive to this kind of UFO or aliens . Nor do they include in their large collection of photos of flying...FTD-ID(RS)T-1019-83 M FOREIGN TECHNOLOGY DIVISION FIRST UFO INCIDENT FOR OUR COUNTRY by Long Ruyi :DOO OCT 71983 Li. -Approved for public release...extracted from the best quality copy available. ’* CO • -.i o ° - .- - - - - • - ° • • . • • ° ° I . . . ... . .- , . • - - ° , . FIRST UFO INCIDENT
Probing the Physical Properties and Origins of Ultra-fast Outflows in AGN
NASA Astrophysics Data System (ADS)
Kraemer, Steven B.; Tombesi, Francesco; Bottorff, Mark
2017-01-01
Approximately half of Type 1 AGN possess intrinsic absorption and high resolution UV and X-ray spectroscopy have revealed that the absorbing gas is radially outflowing, with velocities of 100s to 1000s km/sec. X-ray ("warm") absorbers, originally revealed by the presence of bound-free edges of O~VII and O~VIII, are more highly ionized than their UV counterparts, and photo-ionization modeling studies have determined that they have ionization parameters of logU ~ -1 to 1. Recently, muchmore highly ionized gas, with logU > 2, has been detected in XMM-Newton spectra, as evidenced by absorption lines from H- and He-like Fe. Some of these absorbers, ``Ultra Fast Outlows (UFOs)'', have radial velocities up to 0.2c. We have undertaken a detailed photo-ionization study of high-ionization Fe absorbers, both UFOs and non-UFOs, in a sample of AGN observed by XMM-Newton. We find that the UFOs are completely Compton-cooled, unlike the non-UFOS. Both types are too highly ionized to be radiatively accelerated, hence they are more likely driven via Magneto-Hydrodynamic processes. Their large column densities and velocity gradients are consistent with flows along magnetic streamlines emanating from accretion disks. Open questions include: the temporal stability of the UFOs, the apparent lack of non-UFOs in UFO sources, and their relationship to warm absorbers.
Improving DLA Aviation Engineering’s Support to its Customers and the DoD Supply Chain
2014-10-01
costs and first article test costs) and (2) DLA supply chain responsiveness as measured in terms of the days required to satisfy unfilled orders ( UFOs ...135,000 UFOs or requisitions at any time. This number of UFOs overstates the magnitude of the backorder problem since many of these backorders are...backorders or long term unfilled orders ( UFOs ). This can have serious implications for the materiel readiness of those weapon systems that utilize
A LEAFY co-regulator encoded by UNUSUAL FLORAL ORGANS.
Lee, I; Wolfe, D S; Nilsson, O; Weigel, D
1997-02-01
. Development of petals and stamens in Arabidopsis flowers requires the function of the organ-identity gene APETALA3 (AP3), whose RNA is expressed specifically in petal and stamen primordia. AP3 expression is positively regulated by the meristem-identity gene LEAFY (LFY), which is expressed ubiquitously in young flowers. It is unknown how the transition from ubiquitous expression of LFY to region-specific expression of AP3 is made. It has previously been proposed for Antirrhinum that another gene, FIMBRIATA (FIM), mediates between the LFY and AP3 orthologs, with the three genes acting in a simple regulatory hierarchy. FIM is activated later than the LFY ortholog, and its expression is more restricted than that of the LFY ortholog. . We have tested whether the model proposed for Antirrhinum applies to Arabidopsis, by creating transgenic plants in which the FIM ortholog UNUSUAL FLORAL ORGANS (UFO) was expressed constitutively from the promoter of the cauliflower mosaic virus 35S gene. In 35S::UFO flowers, AP3 was expressed precociously and ectopically, confirming that UFO is an upstream regulator of AP3. However, 35S::UFO could not restore petal and stamen development in lfy mutants, indicating that UFO can only function in the presence of LFY activity. The failure of 35S::UFO to rescue lfy mutants is consistent with our observation that UFO expression levels are not markedly changed in lfy mutants. . We conclude that UFO is not a simple mediator between meristem- and organ-identity genes, but is likely to be a partially dispensable co-regulator that acts together with LFY. The interplay between LFY and UFO provides a paradigm for how a global regulator such as LFY activates selected target genes only in restricted regions within its expression domain.
Tan, Jin; Li, Rong; Jiang, Zi-Tao; Tang, Shu-Hua; Wang, Ying; Shi, Meng; Xiao, Yi-Qian; Jia, Bin; Lu, Tian-Xiang; Wang, Hao
2017-02-15
Synchronous front-face fluorescence spectroscopy has been developed for the discrimination of used frying oil (UFO) from edible vegetable oil (EVO), the estimation of the using time of UFO, and the determination of the adulteration of EVO with UFO. Both the heating time of laboratory prepared UFO and the adulteration of EVO with UFO could be determined by partial least squares regression (PLSR). To simulate the EVO adulteration with UFO, for each kind of oil, fifty adulterated samples at the adulterant amounts range of 1-50% were prepared. PLSR was then adopted to build the model and both full (leave-one-out) cross-validation and external validation were performed to evaluate the predictive ability. Under the optimum condition, the plots of observed versus predicted values exhibited high linearity (R(2)>0.96). The root mean square error of cross-validation (RMSECV) and root mean square error of prediction (RMSEP) were both lower than 3%. Copyright © 2016 Elsevier Ltd. All rights reserved.
Braunger, J; Schleithoff, L; Schulz, A S; Kessler, H; Lammers, R; Ullrich, A; Bartram, C R; Janssen, J W
1997-06-05
Ufo/Axl belongs to a new family of receptor tyrosine kinases with an extracellular structure similar to that of neural cell adhesion molecules. In order to elucidate intracellular signaling, the cytoplasmic moiety of Ufo/Axl was used to screen an expression library according to the CORT (cloning of receptor targets) method. Three putative Ufo substrates were identified: phospholipase Cgamma1 (PLCgamma), as well as p85alpha and p85beta subunits of phosphatidylinositol 3'-kinase (PI3-kinase). Subsequently, chimeric EGFR/Ufo receptors consisting of the extracellular domains of the epidermal growth factor receptor (EGFR) and the transmembrane and intracellular moiety of Ufo were engineered. Using different far-Western blot analyses and coimmunoprecipitation assays, receptor binding of PLCgamma and p85 proteins as well as GRB2, c-src and lck was examined in vitro and in vivo. Competitive inhibition of substrate binding and mutagenesis experiments with EGFR/Ufo constructs revealed C-terminal tyrosine 821 (EILpYVNMDEG) as a docking site for multiple effectors, namely PLCgamma, p85 proteins, GRB2, c-src and lck. Tyrosine 779 (DGLpYALMSRC) demonstrated an additional, but lower binding affinity for the p85 proteins in vitro. In addition, binding of PLCgamma occurred through tyrosine 866 (AGRpYVLCPST). Moreover, our in vivo data indicate that further direct or indirect binding sites for PLCgamma, GRB2, c-src and lck on the human Ufo receptor may exist.
Risseeuw, Eddy; Venglat, Prakash; Xiang, Daoquan; Komendant, Kristina; Daskalchuk, Tim; Babic, Vivijan; Crosby, William; Datla, Raju
2013-01-01
Plants are unique in their ability to continuously produce new meristems and organ primordia. In Arabidopsis, the transcription factor LEAFY (LFY) functions as a master regulator of a gene network that is important for floral meristem and organ specification. UNUSUAL FLORAL ORGANS (UFO) is a co-activator of LEAFY and is required for proper activation of APETALA3 in the floral meristem during the specification of stamens and petals. The ufo mutants display defects in other parts of the flower and the inflorescence, suggestive of additional roles. Here we show that the normal determinacy of the developing Arabidopsis leaves is affected by the expression of a gain-of-function UFO fusion protein with the VP16 transcriptional activator domain. In these lines, the rosette and cauline leaf primordia exhibit reiterated serration, and upon flowering produce ectopic meristems that develop into flowers, bract leaves and inflorescences. These striking phenotypes reveal that developing leaves maintain the competency to initiate flower and inflorescence programs. Furthermore, the gain-of-function phenotypes are dependent on LFY and the SEPALLATA (SEP) MADS-box transcription factors, indicative of their functional interactions with UFO. The findings of this study also suggest that UFO promotes the establishment of the lateral meristems and primordia in the peripheral zone of the apical and floral meristems by enhancing the activity of LFY. These novel phenotypes along with the mutant phenotypes of UFO orthologs in other plant species suggest a broader function for UFO in plants. PMID:24376756
Risseeuw, Eddy; Venglat, Prakash; Xiang, Daoquan; Komendant, Kristina; Daskalchuk, Tim; Babic, Vivijan; Crosby, William; Datla, Raju
2013-01-01
Plants are unique in their ability to continuously produce new meristems and organ primordia. In Arabidopsis, the transcription factor LEAFY (LFY) functions as a master regulator of a gene network that is important for floral meristem and organ specification. UNUSUAL FLORAL ORGANS (UFO) is a co-activator of LEAFY and is required for proper activation of APETALA3 in the floral meristem during the specification of stamens and petals. The ufo mutants display defects in other parts of the flower and the inflorescence, suggestive of additional roles. Here we show that the normal determinacy of the developing Arabidopsis leaves is affected by the expression of a gain-of-function UFO fusion protein with the VP16 transcriptional activator domain. In these lines, the rosette and cauline leaf primordia exhibit reiterated serration, and upon flowering produce ectopic meristems that develop into flowers, bract leaves and inflorescences. These striking phenotypes reveal that developing leaves maintain the competency to initiate flower and inflorescence programs. Furthermore, the gain-of-function phenotypes are dependent on LFY and the SEPALLATA (SEP) MADS-box transcription factors, indicative of their functional interactions with UFO. The findings of this study also suggest that UFO promotes the establishment of the lateral meristems and primordia in the peripheral zone of the apical and floral meristems by enhancing the activity of LFY. These novel phenotypes along with the mutant phenotypes of UFO orthologs in other plant species suggest a broader function for UFO in plants.
Benefits of a Space-Based Group System Architecture
2015-06-01
Relay Satellite TRL Technology Readiness Level TT&C Telemetry, Tracking, and Control UFO UHF Follow-On xv ACKNOWLEDGMENTS I would like to...replacement with more advanced systems. An example of this addition was adding UHF Follow-On ( UFO ) satellite F11, as a gap filler between the UFO
The Dtk receptor tyrosine kinase, which binds protein S, is expressed during hematopoiesis.
Crosier, P S; Freeman, S A; Orlic, D; Bodine, D M; Crosier, K E
1996-02-01
Dtk (Tyro 3/Sky/Rse/Brt/Tif) belongs to a recently recognized subfamily of receptor tyrosine kinases that also includes Ufo (Axl/Ark) and Mer (Eyk). Ligands for Dtk and Ufo have been identified as protein S and the related molecule Gas6, respectively. This study examined expression of Dtk during ontogeny of the hematopoietic system and compared the pattern of expression with that of Ufo. Both receptors were abundantly expressed in differentiating embryonic stem cells, yolk sac blood islands, para-aortic splanchnopleural mesoderm, fractionated AA4+ fetal liver cells, and fetal thymus from day 14 until birth. Although Ufo was expressed at moderate levels in adult bone marrow, expression of Dtk in this tissue was barely detectable. In adult bone marrow subpopulations fractionated using counterflow centrifugal elutriation, immunomagnetic bead selection for lineage-depletion and FACS sorting for c-kit expression, very low levels of Dtk and/or Ufo were detected in some cell fractions. These results suggest that Dtk and Ufo are likely to be involved in the regulation of hematopoiesis, particularly during the embryonic stages of blood cell development.
Hepworth, Shelley R; Klenz, Jennifer E; Haughn, George W
2006-03-01
The UNUSUAL FLORAL ORGANS (UFO) gene of Arabidopsis encodes an F-box protein required for the determination of floral-organ and floral-meristem identity. Mutation of UFO leads to dramatic changes in floral-organ type which are well-characterized whereas inflorescence defects are more subtle and less understood. These defects include an increase in the number of secondary inflorescences, nodes that alternate between forming flowers and secondary inflorescences, and nodes in which a single flower is subtended by a bract. Here, we show how inflorescence defects correlate with the abnormal development of floral primordia and establish a temporal requirement for UFO in this process. At the inflorescence apex of ufo mutants, newly formed primordia are initially bract-like. Expression of the floral-meristem identity genes LFY and AP1 are confined to a relatively small adaxial region of these primordia with expression of the bract-identity marker FIL observed in cells that comprise the balance of the primordia. Proliferation of cells in the adaxial region of these early primordia is delayed by several nodes such that primordia appear "chimeric" at several nodes, having visible floral and bract components. However, by late stage 2 of floral development, growth of the bract generally ceases and is overtaken by development of the floral primordium. This abnormal pattern of floral meristem development is not rescued by expression of UFO from the AP1 promoter, indicating that UFO is required prior to AP1 activation for normal development of floral primordia. We propose that UFO and LFY are jointly required in the inflorescence meristem to both promote floral meristem development and inhibit, in a non-cell autonomous manner, growth of the bract.
Distance Estimation Using Handheld Devices
2013-06-01
each and all centered in the pin that marks the location of the device. ................................47 Figure 21. Form interface where the UFO ...SIFT Scale-invariant feature transform SURF Speed up Robust Features SAD Sum of Absolute Distance UFOs Untrained Forward Observers WHATWG Web...Forward Observers ( UFOs ) to make a successful call for fire. This chapter presents the solution from different aspects and is organized as follows
Mobile User Objective System (MUOS)
2015-12-01
the current UHF Follow-On ( UFO ) constellation. MUOS includes the satellite constellation, a ground control and network management system, and a new...MUOS CAI. Each MUOS satellite carries a legacy payload similar to that flown on UFO -11. These legacy payloads will continue to support legacy...Antecedent Information The antecedent system to MUOS was the Ultra High Frequency (UHF) Follow-on ( UFO ) satellite communications program. Comparisons
A Highly Expressed High-Molecular-Weight S-Layer Complex of Pelosinus sp. Strain UFO1 Binds Uranium
Thorgersen, Michael P.; Lancaster, W. Andrew; Rajeev, Lara; Ge, Xiaoxuan; Vaccaro, Brian J.; Poole, Farris L.; Arkin, Adam P.; Mukhopadhyay, Aindrila
2016-01-01
ABSTRACT Cell suspensions of Pelosinus sp. strain UFO1 were previously shown, using spectroscopic analysis, to sequester uranium as U(IV) complexed with carboxyl and phosphoryl group ligands on proteins. The goal of our present study was to characterize the proteins involved in uranium binding. Virtually all of the uranium in UFO1 cells was associated with a heterodimeric protein, which was termed the uranium-binding complex (UBC). The UBC was composed of two S-layer domain proteins encoded by UFO1_4202 and UFO1_4203. Samples of UBC purified from the membrane fraction contained 3.3 U atoms/heterodimer, but significant amounts of phosphate were not detected. The UBC had an estimated molecular mass by gel filtration chromatography of 15 MDa, and it was proposed to contain 150 heterodimers (UFO1_4203 and UFO1_4202) and about 500 uranium atoms. The UBC was also the dominant extracellular protein, but when purified from the growth medium, it contained only 0.3 U atoms/heterodimer. The two genes encoding the UBC were among the most highly expressed genes within the UFO1 genome, and their expressions were unchanged by the presence or absence of uranium. Therefore, the UBC appears to be constitutively expressed and is the first line of defense against uranium, including by secretion into the extracellular medium. Although S-layer proteins were previously shown to bind U(VI), here we showed that U(IV) binds to S-layer proteins, we identified the proteins involved, and we quantitated the amount of uranium bound. IMPORTANCE Widespread uranium contamination from industrial sources poses hazards to human health and to the environment. Herein, we identified a highly abundant uranium-binding complex (UBC) from Pelosinus sp. strain UFO1. The complex makes up the primary protein component of the S-layer of strain UFO1 and binds 3.3 atoms of U(IV) per heterodimer. While other bacteria have been shown to bind U(VI) on their S-layer, we demonstrate here an example of U(IV) bound by an S-layer complex. The UBC provides a potential tool for the microbiological sequestration of uranium for the cleaning of contaminated environments. PMID:27913415
A Highly Expressed High-Molecular-Weight S-Layer Complex of Pelosinus sp. Strain UFO1 Binds Uranium
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thorgersen, Michael P.; Lancaster, W. Andrew; Rajeev, Lara
Cell suspensions of Pelosinus sp. strain UFO1 were previously shown, using spectroscopic analysis, to sequester uranium as U(IV) complexed with carboxyl and phosphoryl group ligands on proteins. The goal of our present study was to characterize the proteins involved in uranium binding. Virtually all of the uranium in UFO1 cells was associated with a heterodimeric protein, which was termed the uranium-binding complex (UBC). The UBC was composed of two S-layer domain proteins encoded by UFO1_4202 and UFO1_4203. Samples of UBC purified from the membrane fraction contained 3.3 U atoms/heterodimer, but significant amounts of phosphate were not detected. The UBC hadmore » an estimated molecular mass by gel filtration chromatography of 15 MDa, and it was proposed to contain 150 heterodimers (UFO1_4203 and UFO1_4202) and about 500 uranium atoms. The UBC was also the dominant extracellular protein, but when purified from the growth medium, it contained only 0.3 U atoms/heterodimer. The two genes encoding the UBC were among the most highly expressed genes within the UFO1 genome, and their expressions were unchanged by the presence or absence of uranium. Therefore, the UBC appears to be constitutively expressed and is the first line of defense against uranium, including by secretion into the extracellular medium. Although S-layer proteins were previously shown to bind U(VI), here we showed that U(IV) binds to S-layer proteins, we identified the proteins involved, and we quantitated the amount of uranium bound. Widespread uranium contamination from industrial sources poses hazards to human health and to the environment. Here in this paper, we identified a highly abundant uranium-binding complex (UBC) from Pelosinus sp. strain UFO1. The complex makes up the primary protein component of the S-layer of strain UFO1 and binds 3.3 atoms of U(IV) per heterodimer. Finally, while other bacteria have been shown to bind U(VI) on their S-layer, we demonstrate here an example of U(IV) bound by an S-layer complex. The UBC provides a potential tool for the microbiological sequestration of uranium for the cleaning of contaminated environments.« less
A Highly Expressed High-Molecular-Weight S-Layer Complex of Pelosinus sp. Strain UFO1 Binds Uranium.
Thorgersen, Michael P; Lancaster, W Andrew; Rajeev, Lara; Ge, Xiaoxuan; Vaccaro, Brian J; Poole, Farris L; Arkin, Adam P; Mukhopadhyay, Aindrila; Adams, Michael W W
2017-02-15
Cell suspensions of Pelosinus sp. strain UFO1 were previously shown, using spectroscopic analysis, to sequester uranium as U(IV) complexed with carboxyl and phosphoryl group ligands on proteins. The goal of our present study was to characterize the proteins involved in uranium binding. Virtually all of the uranium in UFO1 cells was associated with a heterodimeric protein, which was termed the uranium-binding complex (UBC). The UBC was composed of two S-layer domain proteins encoded by UFO1_4202 and UFO1_4203. Samples of UBC purified from the membrane fraction contained 3.3 U atoms/heterodimer, but significant amounts of phosphate were not detected. The UBC had an estimated molecular mass by gel filtration chromatography of 15 MDa, and it was proposed to contain 150 heterodimers (UFO1_4203 and UFO1_4202) and about 500 uranium atoms. The UBC was also the dominant extracellular protein, but when purified from the growth medium, it contained only 0.3 U atoms/heterodimer. The two genes encoding the UBC were among the most highly expressed genes within the UFO1 genome, and their expressions were unchanged by the presence or absence of uranium. Therefore, the UBC appears to be constitutively expressed and is the first line of defense against uranium, including by secretion into the extracellular medium. Although S-layer proteins were previously shown to bind U(VI), here we showed that U(IV) binds to S-layer proteins, we identified the proteins involved, and we quantitated the amount of uranium bound. Widespread uranium contamination from industrial sources poses hazards to human health and to the environment. Herein, we identified a highly abundant uranium-binding complex (UBC) from Pelosinus sp. strain UFO1. The complex makes up the primary protein component of the S-layer of strain UFO1 and binds 3.3 atoms of U(IV) per heterodimer. While other bacteria have been shown to bind U(VI) on their S-layer, we demonstrate here an example of U(IV) bound by an S-layer complex. The UBC provides a potential tool for the microbiological sequestration of uranium for the cleaning of contaminated environments. Copyright © 2017 American Society for Microbiology.
Tavakoli, Javad; Estakhr, Parviz; Jelyani, Aniseh Zarei
2017-08-01
The present study was carried out to investigate the improvement of oxidative stability of refined olive oil using various concentrations of unsaponifiable matters extracted from Pistacia khinjuk fruit oil (UFO). For further elucidation of UFO antioxidative power, tertbutylhydroquinone (TBHQ) was used in an olive oil sample, too. Oxidative stability of olive oil samples without and with different levels of UFO (50, 100, 250, 500, 750 and 1000 ppm) and TBHQ (100 ppm) were studied via evaluation of conjugated diene value, carbonyl value, oil/oxidative stability index, acid value and total tocopherol (TT) contents through 8 h thermal process at 170 °C. Results obtained by oxidative stability assays revealed that the highest antioxidative activity of olive oil was obtained by 100 ppm of UFO, followed using 100, 250, 500, 750, and 1000 ppm of UFO and 100 ppm TBHQ, respectively. Evaluation of the relationship between oxidative stability indexes and TT changes indicated a strong correlation (R 2 = 0.9718) between mean relative resistance to oxidation and relative resistance to TT reduction during thermal process. By promotion of relative resistance to TT reduction, olive oil samples' relative resistance to oxidation was enhanced exponentially; implying importance of TT in promotion of oxidative stability of edible oils. The results obtained in this study showed that UFO has higher antioxidative activity compared to TBHQ; thus UFO can be considered as a natural antioxidant with ideal antioxidative activity.
Mobile User Objective System (MUOS)
2013-12-01
system capacity of the current UHF Follow-On ( UFO ) constellation. MUOS includes the satellite constellation, a ground control and network management...terminals able to support the MUOS CAI. Each MUOS satellite carries a legacy payload similar to that flown on UFO -11. These legacy payloads will...Antecedent Information: The antecedent system to MUOS was the Ultra High Frequency (UHF) Follow-on ( UFO ) satellite communications program. Comparisons of O
Flight and abduction in witchcraft and UFO lore.
Musgrave, J B; Houran, J
2000-04-01
The lore surrounding the mythical Witches' Sabbat and contemporary reports of UFO abductions share three main characteristics: the use of masks, the appearance of "Men in Black," and references to flight and abduction. We review these three commonalities with particular focus on the aspect of flight and abduction. We argue that narratives of the Witches' Sabbat and UFO abductions share the same basic structure, common symbolism, and serve the same psychological needs of providing a coherent explanation for anomalous (ambiguous) experiences while simultaneously giving the experient a sense of freedom, release, and escape from the self. This pattern of similarities suggests the possibility that UFO abductions are a modern version of tales of flight to the Sabbat.
Space and Airborne Communications for the Future Force
2010-03-01
Existing - Military Strategic and Tactical Relay (MILSTAR); Defense Satellite Communication System (DSCS); UHF Follow-On ( UFO )); Global Broadcast...System (GBS)) is an ad-on package to the UFO satellites. 7 Figure 2: SATCOM Current and Future Figure 3: Existing SATCOM 8 Future Future...decade. UFO and MUOS are for individuals or moving platforms. But they are low data rate and quickly saturate with number of users. All of
2010 Defense Logistics Agency Enterprise Supplier Conference and Exhibition
2010-08-25
into safety stock and if unfilled will cause safety stock depletion and UFOs . NOT CUSTOMER FOCUSED Processing/Reporting against Required Delivery...Date allows for full ALT and PLT, resulting in UFOs . WARFIGHTER FOCUSED, GLOBALLY RESPONSIVE SUPPLY CHAIN LEADERSHIP 5 ATP Overview • Definition of...Need Arrival Date – Limits impact to UFOs and SS depletion ATP Goal = Materiel receipt by the “Need Arrival Date” … period ADMINISTRATIVE LEAD TIME
Ultra-fast outflows (aka UFOs) in AGNs and their relevance for feedback
NASA Astrophysics Data System (ADS)
Cappi, Massimo; Tombesi, F.; Giustini, M.; Dadina, M.; Braito, V.; Kaastra, J.; Reeves, J.; Chartas, G.; Gaspari, M.; Vignali, C.; Gofford, J.; Lanzuisi, G.
2012-09-01
During the last decade, several observational evidences have been accumulated for the existence of massive, high velocity winds/outflows (aka UFOs) in nearby AGNs and, possibly, distant quasars. I will review here such evidences, present some of the latest results in this field, and discuss the relevance of UFOs for both understanding the physics of accretion/ejection flows on supermassive black holes, and for quantifying the amount of AGN feedback.
BAL QSOs AND EXTREME UFOs: THE EDDINGTON CONNECTION
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zubovas, Kastytis; King, Andrew, E-mail: kastytis.zubovas@ftmc.lt
We suggest a common physical origin connecting the fast, highly ionized winds (UFOs) seen in nearby active galactic nuclei (AGNs), and the slower and less ionized winds of broad absorption line (BAL) QSOs. The primary difference is the mass-loss rate in the wind, which is ultimately determined by the rate at which mass is fed toward the central supermassive black hole (SMBH) on large scales. This is below the Eddington accretion rate in most UFOs, and slightly super-Eddington in extreme UFOs such as PG1211+143, but ranges up to {approx}10-50 times this in BAL QSOs. For UFOs this implies black holemore » accretion rates and wind mass-loss rates which are at most comparable to Eddington, giving fast, highly ionized winds. In contrast, BAL QSO black holes have mildly super-Eddington accretion rates, and drive winds whose mass-loss rates are significantly super-Eddington, and so are slower and less ionized. This picture correctly predicts the velocities and ionization states of the observed winds, including the recently discovered one in SDSS J1106+1939. We suggest that luminous AGNs may evolve through a sequence from BAL QSO through LoBAL to UFO-producing Seyfert or quasar as their Eddington factors drop during the decay of a bright accretion event. LoBALs correspond to a short-lived stage in which the AGN radiation pressure largely evacuates the ionization cone, but before the large-scale accretion rate has dropped to the Eddington value. We show that sub-Eddington wind rates would produce an M-{sigma} relation lying above that observed. We conclude that significant SMBH mass growth must occur in super-Eddington phases, either as BAL QSOs, extreme UFOs, or obscured from direct observation.« less
Searching for the UV counterpart of the extraordinary X-ray UFO in the NLSy1 IRAS17020+4544
NASA Astrophysics Data System (ADS)
Krongold, Yair
2017-08-01
We recently reported the first unambiguous discovery in high resolution X-ray data of an ultra fast outflow (UFO) with velocity .1c. This wind, in Narrow Line Seyfert 1 galaxy IRAS17020+4544, represents so far the most compelling detection of an UFO, with many different absorption lines that give rise to very high significance detections. The charge states that form the wind clearly indicate a large range of ionization states in the gas, and significant absorption by Ly alpha, C IV, Si IV and N V (among other ions) is expected in the UV band. The goal of our proposed program is to observe an characterize the best X-ray detected UFO in the UV. These observations are crucial to study in great detail the UFO phenomenon, and understand its nature and its relation to the narrow absorption line low velocity systems. Only through detection of Ly alpha absorption in the UV data, measurements of the metallicity of these winds will be possible. The proposed program will help guide new theoretical models of UFOs origins, beyond the simple actual picture that predicts only very high ionization Fe absorption. UV data are required to understand the wind nature and launching mechanism (whether due to radiation pressure via line or continuum opacity, or magnetic forces). Fully characterizing the wind properties will put stronger constraints in the mass outflow and kinetic outflow rates of these systems, as well as in their geometry. Such estimates will give a much clearer picture of UFOs feedback potential, and will provide clues on the feedback mode in action (e.g. energy conserving vs. momentum conserving).
BAL QSOs and Extreme UFOs: The Eddington Connection
NASA Astrophysics Data System (ADS)
Zubovas, Kastytis; King, Andrew
2013-05-01
We suggest a common physical origin connecting the fast, highly ionized winds (UFOs) seen in nearby active galactic nuclei (AGNs), and the slower and less ionized winds of broad absorption line (BAL) QSOs. The primary difference is the mass-loss rate in the wind, which is ultimately determined by the rate at which mass is fed toward the central supermassive black hole (SMBH) on large scales. This is below the Eddington accretion rate in most UFOs, and slightly super-Eddington in extreme UFOs such as PG1211+143, but ranges up to ~10-50 times this in BAL QSOs. For UFOs this implies black hole accretion rates and wind mass-loss rates which are at most comparable to Eddington, giving fast, highly ionized winds. In contrast, BAL QSO black holes have mildly super-Eddington accretion rates, and drive winds whose mass-loss rates are significantly super-Eddington, and so are slower and less ionized. This picture correctly predicts the velocities and ionization states of the observed winds, including the recently discovered one in SDSS J1106+1939. We suggest that luminous AGNs may evolve through a sequence from BAL QSO through LoBAL to UFO-producing Seyfert or quasar as their Eddington factors drop during the decay of a bright accretion event. LoBALs correspond to a short-lived stage in which the AGN radiation pressure largely evacuates the ionization cone, but before the large-scale accretion rate has dropped to the Eddington value. We show that sub-Eddington wind rates would produce an M-σ relation lying above that observed. We conclude that significant SMBH mass growth must occur in super-Eddington phases, either as BAL QSOs, extreme UFOs, or obscured from direct observation.
Investigating a New Approach to Space-Based Information Networks
2012-09-01
Tracking and Communications UAV Unmanned Aerial Vehicle UFO UHF Follow On UHF Ultra High Frequency VBR...Follow on ( UFO ) and most recently the Mobile User Objective System (MUOS) Protected MILSATCOM is intended to support mobile users with very small...where it is needed. Ultra High Frequency Follow on ( UFO ) is currently the primary provider of narrowband communications for the military. The current
Leveraging an SNMP Agent in Terminal Equipment for Network Monitoring of U.S. Navy SATCOM
2011-09-01
Network Topology TWT Traveling-wave Tube TX Transmitter UCD Uplink Channel Descriptor UDP User Datagram Protocol UFO UHF Follow-On UHF Ultra High...through DSCS III, UFO , and Milstar” (Martin, n.d.a). “Capabilities have grown dramatically with the development of satellite and electronics...Communication Systems (DSCS) II and III and the Global Broadcast Service (GBS) payload on the UHF Follow-On ( UFO ) satellite In 1971, the DSCS II
Ultra-fast outflows (aka UFOs) from AGNs and QSOs
NASA Astrophysics Data System (ADS)
Cappi, M.; Tombesi, F.; Giustini, M.
During the last decade, strong observational evidence has been accumulated for the existence of massive, high velocity winds/outflows (aka Ultra Fast Outflows, UFOs) in nearby AGNs and in more distant quasars. Here we briefly review some of the most recent developments in this field and discuss the relevance of UFOs for both understanding the physics of accretion disk winds in AGNs, and for quantifying the global amount of AGN feedback on the surrounding medium.
An Arabidopsis F-box protein acts as a transcriptional co-factor to regulate floral development.
Chae, Eunyoung; Tan, Queenie K-G; Hill, Theresa A; Irish, Vivian F
2008-04-01
Plants flower in response to both environmental and endogenous signals. The Arabidopsis LEAFY (LFY) transcription factor is crucial in integrating these signals, and acts in part by activating the expression of multiple floral homeotic genes. LFY-dependent activation of the homeotic APETALA3 (AP3) gene requires the activity of UNUSUAL FLORAL ORGANS (UFO), an F-box component of an SCF ubiquitin ligase, yet how this regulation is effected has remained unclear. Here, we show that UFO physically interacts with LFY both in vitro and in vivo, and this interaction is necessary to recruit UFO to the AP3 promoter. Furthermore, a transcriptional repressor domain fused to UFO reduces endogenous LFY activity in plants, supporting the idea that UFO acts as part of a transcriptional complex at the AP3 promoter. Moreover, chemical or genetic disruption of proteasome activity compromises LFY-dependent AP3 activation, indicating that protein degradation is required to promote LFY activity. These results define an unexpected role for an F-box protein in functioning as a DNA-associated transcriptional co-factor in regulating floral homeotic gene expression. These results suggest a novel mechanism for promoting flower development via protein degradation and concomitant activation of the LFY transcription factor. This mechanism may be widely conserved, as homologs of UFO and LFY have been identified in a wide array of plant species.
Samach, A; Klenz, J E; Kohalmi, S E; Risseeuw, E; Haughn, G W; Crosby, W L
1999-11-01
Genetic and molecular studies have suggested that the UNUSUAL FLORAL ORGANS (UFO) gene, from Arabidopsis thaliana, is expressed in all shoot apical meristems, and is involved in the regulation of a complex set of developmental events during floral development, including floral meristem and floral organ identity. Results from in situ hybridization using genes expressed early in floral development as probes indicate that UFO controls growth of young floral primordia. Transgenic constructs were used to provide evidence that UFO regulates floral organ identity by activating or maintaining transcription of the class B organ-identity gene APETALA 3, but not PISTILLATA. In an attempt to understand the biochemical mode of action of the UFO gene product, we show here that UFO is an F-box protein that interacts with Arabidopsis SKP1-like proteins, both in the yeast two-hybrid system and in vitro. In yeast and other organisms both F-box proteins and SKP1 homologues are subunits of specific ubiquitin E3 enzyme complexes that target specific proteins for degradation. The protein selected for degradation by the complex is specified by the F-box proteins. It is therefore possible that the role of UFO is to target for degradation specific proteins controlling normal growth patterns in the floral primordia, as well as proteins that negatively regulate APETALA 3 transcription.
Ultrafast outflows disappear in high-radiation fields
NASA Astrophysics Data System (ADS)
Pinto, C.; Alston, W.; Parker, M. L.; Fabian, A. C.; Gallo, L. C.; Buisson, D. J. K.; Walton, D. J.; Kara, E.; Jiang, J.; Lohfink, A.; Reynolds, C. S.
2018-05-01
Ultrafast outflows (UFOs) are the most extreme winds launched by active galactic nuclei (AGN) due to their mildly relativistic speeds (˜0.1-0.3c) and are thought to significantly contribute to galactic evolution via AGN feedback. Their nature and launching mechanism are however not well understood. Recently, we have discovered the presence of a variable UFO in the narrow-line Seyfert 1 IRAS 13224-3809. The UFO varies in response to the brightness of the source. In this work we perform flux-resolved X-ray spectroscopy to study the variability of the UFO and found that the ionization parameter is correlated with the luminosity. In the brightest states the gas is almost completely ionized by the powerful radiation field and the UFO is hardly detected. This agrees with our recent results obtained with principal component analysis. We might have found the tip of the iceberg: the high ionization of the outflowing gas may explain why it is commonly difficult to detect UFOs in AGN and possibly suggest that we may underestimate their actual feedback. We have also found a tentative correlation between the outflow velocity and the luminosity, which is expected from theoretical predictions of radiation-pressure-driven winds. This trend is rather marginal due to the Fe XXV-XXVI degeneracy. Further work is needed to break such degeneracy through time-resolved spectroscopy.
Extraterrestrial beliefs and experiences: an application of the theory of reasoned action.
Patry, A L; Pelletier, L G
2001-04-01
The authors expanded the applicability of I. Ajzen and M. Fishbein's (1980) theory of reasoned action by assessing the participants' beliefs, attitudes, and experiences related to sightings of unidentified flying objects (UFOs) and to alien abductions. The authors designed and administered a survey on UFO phenomena to 398 Canadian students. The survey contains items relating to each component of Ajzen and Fishbein's model, as well as scales that evaluate paranormal beliefs and social desirability. A majority of the sample believed in UFOs, although most had never seen one. However, only a minority believed in alien abductions--again, most without having had any reported experience. According to path analyses, UFO beliefs originated from societal forces rather than from personal experiences as the model would predict.
White, Jocelyn; Fromme, Erik K
2013-11-01
Quality standards no longer allow physicians to delay discussing goals of care and resuscitation. We propose 2 novel strategies for discussing goals and resuscitation on admission. The first, SPAM (determine Surrogate decision maker, determine resuscitation Preferences, Assume full care, and advise them to expect More discussion especially with clinical changes), helps clinicians discover patient preferences and decision maker during routine admissions. The second, UFO-UFO (Understand what they know, Fill in knowledge gaps, ask about desired Outcomes, Understand their reasoning, discuss the spectrum Feasible Outcomes), helps patients with poor or uncertain prognosis or family-team conflict. Using a challenging case example, this article illustrates how SPAM and UFO-UFO can help clinicians have patient-centered resuscitation and goals of care discussions at the beginning of care.
Compositional Verification with Abstraction, Learning, and SAT Solving
2015-05-01
arithmetic, and bit-vectors (currently, via bit-blasting). The front-end is based on an existing tool called UFO [8] which converts C programs to the Horn...supports propositional logic, linear arithmetic, and bit-vectors (via bit-blasting). The front-end is based on the tool UFO [8]. It encodes safety of...tool UFO [8]. The encoding in Horn-SMT only uses the theory of Linear Rational Arithmetic. All experiments were carried out on an Intel R© CoreTM2 Quad
Automated Discovery of Simulation Between Programs
2014-10-18
relation. These relations enable the refinement-step of SimAbs. We have implemented SimAbs using UFO framework and Z3 SMT-solver and applied it to...step of SimAbs. We implemented SimAbs and AE-VAL on the top of the UFO framework [1, 15] and an SMT-solver Z3 [8], respectively. We have evaluated SimAbs...ut 6 Evaluation We have implemented SimAbs in the UFO framework, and evaluated it on the Software Verification Competition (SVCOMP’14) benchmarks and
2011-06-01
designed to augment and eventually replace the currently oversubscribed UHF Follow- On ( UFO ) System. MUOS adapts a commercial third generation (3G...towers) with the goal of providing a more capable UHF SATCOM system. This research aims at investigating the differences between the legacy UFO and...improvements. The study finds that MUOS can tolerate a traffic demand rate of about 83 calls/messages per second whereas UFO saturates at roughly 4 calls
Air Force Research Laboratory Sensors Directorate Communications Branch History from 1960-2011
2011-12-01
transponders on three UHF Follow-On ( UFO ) satellites to provide high data rate (i.e. up to 23.5 Mbps) broadcast service to ground and shipboard users...Luneberg Lens antenna. The Milstar system was also used as a reach-back channel to Norfolk to request changes in the test sequence. Figure 5 UFO ...UHF SATCOM use a pair of Raytheon ARC- 231 radios through the UHF Follow-On ( UFO ) satellites into military ground entry stations to provide secure
Zhao, D; Yang, M; Solava, J; Ma, H
1999-09-01
Normal flower development likely requires both specific and general regulators. We have isolated an Arabidopsis mutant ask1-1 (for -Arabidopsis skp1-like1-1), which exhibits defects in both vegetative and reproductive development. In the ask1-1mutant, rosette leaf growth is reduced, resulting in smaller than normal rosette leaves, and internodes in the floral stem are shorter than normal. Examination of cell sizes in these organs indicates that cell expansion is normal in the mutant, but cell number is reduced. In the mutant, the numbers of petals and stamens are reduced, and many flowers have one or more petals with a reduced size. In addition, all mutant flowers have short stamen filaments. Furthermore, petal/stamen chimeric organs are found in many flowers. These results indicate that the ASK1 gene affects the size of vegetative and floral organs. The ask1 floral phenotype resembles somewhat that of the Arabidopsis ufo mutants in that both genes affect whorls 2 and 3. We therefore tested for possible interactions between ASK1 and UFO by analyzing the phenotypes of ufo-2 ask1-1 double mutant plants. In these plants, vegetative development is similar to that of the ask1-1 single mutant, whereas the floral defects are more severe than those in either single mutant. Interior to the first whorl, the double mutant flowers have more sepals or sepal-like organs than are found in ufo-2, and less petals than ask1-1. Our results suggest that ASK1 interacts with UFO to control floral organ identity in whorls 2 and 3. This is very intriguing because ASK1 is very similar in sequence to the yeast SKP1 protein and UFO contains an F-box, a motif known to interact with SKP1 in yeast. Although the precise mechanism of ASK1 and UFO action is unknown, our results support the hypothesis that these two proteins physically interact in vivo. Copyright 1999 Wiley-Liss, Inc.
Aliens or the SR-71 Blackbird?
NASA Astrophysics Data System (ADS)
Ruiz, Michael J.
2006-04-01
Unidentified flying objects (UFOs) capture the interest of our students and the general public.1,2 Here is a UFO story I tell my students to illustrate the workings of science. Science, at its most fundamental level, is observation and an attempt to analyze what is observed. But what happens when an observation cannot be explained with the available knowledge at the time? What do we do? The UFO sighting of my story could not be explained until disclosure of a top-secret military aircraft, the SR-71, also known as the "Blackbird."
Yet another UFO in the X-ray spectrum of a high-z lensed QSO
NASA Astrophysics Data System (ADS)
Dadina, M.; Vignali, C.; Cappi, M.; Lanzuisi, G.; Ponti, G.; Torresi, E.; De Marco, B.; Chartas, G.; Giustini, M.
2018-02-01
Aim. Ultra-fast outflows (UFO) appear to be common in local active galactic nuclei (AGN) and may be powerful enough (Ėkin ≥ 1% of Lbol) to effectively quench the star formation in their host galaxies. To test feedback models based on AGN outflows, it is mandatory to investigate UFOs near the peak of AGN activity, that is, at high-z where only a few studies are available to date. Methods: UFOs produce Fe resonant absorption lines measured above ≈7 keV. The most critical problem in detecting such features in distant objects is the difficulty in obtaining X-ray data with sufficient signal-to-noise. We therefore selected a distant QSO that gravitational lensing made bright enough for these purposes, the z = 2.64 QSO MG J0414+0534, and observed it with XMM-Newton for ≈78 ks. Results: The X-ray spectrum of MG J0414+0534 is complex and shows signatures of cold absorption (NH ≈ 4 × 1022 cm-2) and of the presence of an iron emission line (E ≈ 6.4 keV, EW = 95 ± 53 eV) consistent with it originating in the cold absorber. Our main result, however, is the robust detection (more than 5σ) of an absorption line at Eint ≈ 9.2 keV (Eobs ≈ 2.5 keV observer frame). If interpreted as due to FeXXVI, it implies gas outflowing at vout ≈ 0.3c. To our knowledge, this is the first detection of an UFO in a radio-loud quasar at z ≥ 1.5. We estimated that the UFO mechanical output is Ėkin ≈ 2.5Lbol with ṗout/ṗrad ≈ 17 indicating that it is capable of installing significant feedback between the super-massive black hole and the bulge of the host galaxy. We argue that this also suggests a magnetic driving origin of the UFO.
Introducing the LHC in the Classroom: An Overview of Education Resources Available
ERIC Educational Resources Information Center
Wiener, Gerfried J.; Woithe, Julia; Brown, Alexander; Jende, Konrad
2016-01-01
In the context of the recent re-start of CERN's Large Hadron Collider (LHC) and the challenge presented by unidentified falling objects (UFOs), we seek to facilitate the introduction of high energy physics in the classroom. Therefore, this paper provides an overview of the LHC and its operation, highlighting existing education resources, and…
ERIC Educational Resources Information Center
Lockwood, Jeffrey F.
1990-01-01
Described is an interdisciplinary unit on pseudoscience which combines interest in unidentified flying objects (UFO's), physics, astronomy, art, and english composition. The different phases of the lesson, assignments, and evaluation are discussed. A list of books available on UFOs is provided. (CW)
Jacob, A N; Kalapurakal, J; Davidson, W R; Kandpal, G; Dunson, N; Prashar, Y; Kandpal, R P
1999-01-01
We have used a modified differential display PCR protocol for isolating 3' restriction fragments of cDNAs specifically expressed or overexpressed in metastatic prostate carcinoma cell line DU145. Several cDNA fragments were identified that matched to milk fat globule protein, UFO/Axl, a receptor tyrosine kinase, human homologue of a Xenopus maternal transcript, laminin and laminin receptor, human carcinoma-associated antigen, and some expressed sequence tags. The transcript for milk fat globule protein, a marker protein shown to be overexpressed in breast tumors, was elevated in DU145 cells. The expression of UFO/Axl, a receptor tyrosine kinase, was considerably higher in DU145 cells as compared to normal prostate cells and prostatic carcinoma cell line PC-3. The overexpression of UFO oncogene in DU145 cells is discussed in the context of prostate cancer metastasis.
A comparison of the UHF Follow-On and MILSTAR satellite communication systems
NASA Astrophysics Data System (ADS)
Perkins, Clifton E., Jr.
1991-09-01
The author compares the UHF Follow-On and MILSTAR satellite communication systems. The comparison uses an analytical hierarchy process. Although the two systems have been tasked with different missions, a comparison of cost, capability, and orbit is conducted. UFO provides many of the same capabilities as MILSTAR, but on a smaller scale. Since UFO is also a new space system acquisition, it is used to compare dollars spent to field a viable communication system. A review of frequency bands, losses, and problems is conducted to establish the relationship. Cost data is provided to establish the major difference in the systems. While MILSTAR does possess more total capability than UFO, it is 10 times more costly. Additionally, UFO is a satellite that will evolve with new technology while MILSTAR is built to full capability immediately. In the author's opinion, the incremental performance of MILSTAR does not justify its incremental cost.
The COP9 signalosome interacts with SCF UFO and participates in Arabidopsis flower development.
Wang, Xiping; Feng, Suhua; Nakayama, Naomi; Crosby, W L; Irish, Vivian; Deng, Xing Wang; Wei, Ning
2003-05-01
The COP9 signalosome (CSN) is involved in multiple developmental processes. It interacts with SCF ubiquitin ligases and deconjugates Nedd8/Rub1 from cullins (deneddylation). CSN is highly expressed in Arabidopsis floral tissues. To investigate the role of CSN in flower development, we examined the expression pattern of CSN in developing flowers. We report here that two csn1 partially deficient Arabidopsis strains exhibit aberrant development of floral organs, decline of APETALA3 (AP3) expression, and low fertility in addition to defects in shoot and inflorescence meristems. We show that UNUSUAL FLORAL ORGANS (UFO) forms a SCF(UFO) complex, which is associated with CSN in vivo. Genetic interaction analysis indicates that CSN is necessary for the gain-of-function activity of the F-box protein UFO in AP3 activation and in floral organ transformation. Compared with the previously reported csn5 antisense and csn1 null mutants, partial deficiency of CSN1 causes a reduction in the level of CUL1 in the mutant flowers without an obvious defect in CUL1 deneddylation. We conclude that CSN is an essential regulator of Arabidopsis flower development and suggest that CSN regulates Arabidopsis flower development in part by modulating SCF(UFO)-mediated AP3 activation.
Black hole feedback in a multiphase interstellar medium
NASA Astrophysics Data System (ADS)
Bourne, Martin A.; Nayakshin, Sergei; Hobbs, Alexander
2014-07-01
Ultrafast outflows (UFOs) from supermassive black holes (SMBHs) are thought to regulate the growth of SMBHs and host galaxies, resulting in a number of observational correlations. We present high-resolution numerical simulations of the impact of a thermalized UFO on the ambient gas in the inner part of the host galaxy. Our results depend strongly on whether the gas is homogeneous or clumpy. In the former case all of the ambient gas is driven outward rapidly as expected based on commonly used energy budget arguments, while in the latter the flows of mass and energy de-couple. Carrying most of the energy, the shocked UFO escapes from the bulge via paths of least resistance, taking with it only the low-density phase of the host. Most of the mass is however in the high-density phase, and is affected by the UFO much less strongly, and may even continue to flow inwards. We suggest that the UFO energy leakage through the pores in the multiphase interstellar medium (ISM) may explain why observed SMBHs are so massive despite their overwhelmingly large energy production rates. The multiphase ISM effects reported here are probably under-resolved in cosmological simulations but may be included in prescriptions for active galactic nuclei feedback in future simulations and in semi-analytical models.
Souer, Erik; Rebocho, Alexandra B; Bliek, Mattijs; Kusters, Elske; de Bruin, Robert A M; Koes, Ronald
2008-08-01
Angiosperms display a wide variety of inflorescence architectures differing in the positions where flowers or branches arise. The expression of floral meristem identity (FMI) genes determines when and where flowers are formed. In Arabidopsis thaliana, this is regulated via transcription of LEAFY (LFY), which encodes a transcription factor that promotes FMI. We found that this is regulated in petunia (Petunia hybrida) via transcription of a distinct gene, DOUBLE TOP (DOT), a homolog of UNUSUAL FLORAL ORGANS (UFO) from Arabidopsis. Mutation of DOT or its tomato (Solanum lycopersicum) homolog ANANTHA abolishes FMI. Ubiquitous expression of DOT or UFO in petunia causes very early flowering and transforms the inflorescence into a solitary flower and leaves into petals. Ectopic expression of DOT or UFO together with LFY or its homolog ABERRANT LEAF AND FLOWER (ALF) in petunia seedlings activates genes required for identity or outgrowth of organ primordia. DOT interacts physically with ALF, suggesting that it activates ALF by a posttranslational mechanism. Our findings suggest a wider role than previously thought for DOT and UFO in the patterning of flowers and indicate that the different roles of LFY and UFO homologs in the spatiotemporal control of floral identity in distinct species result from their divergent expression patterns.
Closed-loop torque feedback for a universal field-oriented controller
DOE Office of Scientific and Technical Information (OSTI.GOV)
De Doncker, R.W.A.A.; King, R.D.; Sanza, P.C.
A torque feedback system is employed in a universal field-oriented (UFO) controller to tune a torque-producing current command and a slip frequency command in order to achieve robust torque control of an induction machine even in the event of current regulator errors and during transitions between pulse width modulated (PWM) and square wave modes of operation. 1 figure.
Closed-loop torque feedback for a universal field-oriented controller
De Doncker, R.W.A.A.; King, R.D.; Sanza, P.C.; Haefner, K.B.
1992-11-24
A torque feedback system is employed in a universal field-oriented (UFO) controller to tune a torque-producing current command and a slip frequency command in order to achieve robust torque control of an induction machine even in the event of current regulator errors and during transitions between pulse width modulated (PWM) and square wave modes of operation. 1 figure.
Closed-loop torque feedback for a universal field-oriented controller
DOE Office of Scientific and Technical Information (OSTI.GOV)
De Doncker, Rik W. A. A.; King, Robert D.; Sanza, Peter C.
A torque feedback system is employed in a universal field-oriented (UFO) controller to tune a torque-producing current command and a slip frequency command in order to achieve robust torque control of an induction machine even in the event of current regulator errors and during transitions between pulse width modulated (PWM) and square wave modes of operation.
Activation of the Arabidopsis B class homeotic genes by APETALA1.
Ng, M; Yanofsky, M F
2001-04-01
Proper development of petals and stamens in Arabidopsis flowers requires the activities of APETALA3 (AP3) and PISTILLATA (PI), whose transcripts can be detected in the petal and stamen primordia. Localized expression of AP3 and PI requires the activities of at least three genes: APETALA1 (AP1), LEAFY (LFY), and UNUSUAL FLORAL ORGANS (UFO). It has been proposed that UFO provides spatial cues and that LFY specifies competence for AP3 and PI expression in the developing flower. To understand the epistatic relationship among AP1, LFY, and UFO in regulating AP3 and PI expression, we generated two versions of AP1 that have strong transcriptional activation potential. Genetic and molecular analyses of transgenic plants expressing these activated AP1 proteins show that the endogenous AP1 protein acts largely as a transcriptional activator in vivo and that AP1 specifies petals by regulating the spatial domains of AP3 and PI expression through UFO.
Nigerian Unity: In the Balance
2013-06-01
Religious Conflict Resolution in Nigeria. Lanham, MD: Lexington Books, 1999, pp. 70-87. Allen, Fidelis and Ufo Okeke-Uzodike. “Oil, Politics, and Conflict...Allen and Ufo Okeke-Uzodike, “Oil, Politics, and Conflict in the Niger Delta: A Nonkilling Analysis,” Africa Peace and Conflict Journal, Vol. 3, No
Imprecision and Uncertainty in the UFO Database Model.
ERIC Educational Resources Information Center
Van Gyseghem, Nancy; De Caluwe, Rita
1998-01-01
Discusses how imprecision and uncertainty are dealt with in the UFO (Uncertainty and Fuzziness in an Object-oriented) database model. Such information is expressed by means of possibility distributions, and modeled by means of the proposed concept of "role objects." The role objects model uncertain, tentative information about objects,…
Network Management System for Tactical Mobile Ad Hoc Network Segments
2011-09-01
Protocol UFO UHF Follow-On UHF Ultra High Frequency USB Universal Serial Bus VHF Very High Frequency VIRT Valuable Information at the Right Time...military satellite system known as the UHF Follow-on system ( UFO ) only provides capacity for 600 concurrent users. DoD users also have commercial
Single-cycle Optical Pulses and Isolated Attosecond Pulse Generation
2012-02-29
picosecond green light from a frequency-doubled hybrid cryogenic Yb:YAG laser system,” 36 UFO /HFSW 2009 (Arcachon, France, Aug. 31-Sept. 4, 2009...High Fields Short Wavelength,” ( UFO VII – HFSW XIII), Arcachon, France, August 31 – September 4, 2009 (invited). 25) Kyung-Han Hong, Juliet Gopinath
UFO - The Universal FEYNRULES Output
NASA Astrophysics Data System (ADS)
Degrande, Céline; Duhr, Claude; Fuks, Benjamin; Grellscheid, David; Mattelaer, Olivier; Reiter, Thomas
2012-06-01
We present a new model format for automatized matrix-element generators, the so-called Universal FEYNRULES Output (UFO). The format is universal in the sense that it features compatibility with more than one single generator and is designed to be flexible, modular and agnostic of any assumption such as the number of particles or the color and Lorentz structures appearing in the interaction vertices. Unlike other model formats where text files need to be parsed, the information on the model is encoded into a PYTHON module that can easily be linked to other computer codes. We then describe an interface for the MATHEMATICA package FEYNRULES that allows for an automatic output of models in the UFO format.
Exploring the Powerful Ionised Wind in the Seyfert Galaxy PG1211+143
NASA Astrophysics Data System (ADS)
Pounds, Ken
2013-10-01
Highly-ionised high-speed winds in AGN (UFOs) were first detected with XMM-Newton a decade ago, and are now established as a key factor in the study of SMBH accretion, and in the growth and metal enrichment of their host galaxies. However, information on the ionisation and dynamical structure, and the ultimate fate of UFOs remains very limited. We request a 600ks extended XMM-Newton study of the prototype UFO PG1211+143 in AO-13, to obtain high quality EPIC and RGS spectra, to map the flow structure and variability, while seeking evidence for the anticipated interaction with the ISM and possible conversion of the energetic wind to a momentum-driven flow.
The Mechanisms and Value of Competition for Major Weapon Systems
2011-04-01
technology. MUOS is intended to replace the Ultra-High Frequency Follow-On system ( UFO ), which was fielded between 1993 and 2003. Launch of the first......performance on the UFO system was considered an outstanding success. Based on rather limited evidence, Scearce concludes that Boeing’s bid for MUOS was based
Unidentified Flying Objects (UFOs). LC Science Tracer Bullet.
ERIC Educational Resources Information Center
Library of Congress, Washington, DC. Science and Technology Div.
This guide lists information sources dealing with unidentified flying objects (UFOs). Not meant to be a comprehensive bibliography, this compilation is designed--as the name of the series implies--to put the reader "on target." Included are: (1) subject headings used by the Library of Congress, under which publications on this subject…
A method for detecting the presence of organic fraction in nucleation mode sized particles
NASA Astrophysics Data System (ADS)
Vaattovaara, P.; Räsänen, M.; Kühn, T.; Joutsensaari, J.; Laaksonen, A.
2005-12-01
New particle formation and growth has a very important role in many climate processes. However, the overall knowlegde of the chemical composition of atmospheric nucleation mode (particle diameter, d<20 nm) and the lower end of Aitken mode particles (d≤50 nm) is still insufficient. In this work, we have applied the UFO-TDMA (ultrafine organic tandem differential mobility analyzer) method to shed light on the presence of an organic fraction in the nucleation mode size class in different atmospheric environments. The basic principle of the organic fraction detection is based on our laboratory UFO-TDMA measurements with organic and inorganic compounds. Our laboratory measurements indicate that the usefulness of the UFO-TDMA in the field experiments would arise especially from the fact that atmospherically the most relevant inorganic compounds do not grow in subsaturated ethanol vapor, when particle size is 10 nm in diameter and saturation ratio is about 86% or below it. Furthermore, internally mixed particles composed of ammonium bisulfate and sulfuric acid with sulfuric acid mass fraction ≤33% show no growth at 85% saturation ratio. In contrast, 10 nm particles composed of various oxidized organic compounds of atmospheric relevance are able to grow in those conditions. These discoveries indicate that it is possible to detect the presence of organics in atmospheric nucleation mode sized particles using the UFO-TDMA method. In the future, the UFO-TDMA is expected to be an important aid to describe the composition of atmospheric newly-formed particles.
Allen, S; Barlow, S; Halasyamani, P S; Mosselmans, J F; O'Hare, D; Walker, S M; Walton, R I
2000-08-21
A new hybrid organic-inorganic mixed-valent uranium oxyfluoride, (C6N2H14)2(U3O4F12), UFO-17, has been synthesized under hydrothermal conditions using uranium dioxide as the uranium source, hydrofluoric acid as mineralizer, and 1,4-diazabicyclo[2.2.2]octane as template. The single-crystal X-ray structure was determined. Crystals of UFO-17 belonged to the orthorhombic space group Cmcm (no. 63), with a = 14.2660(15) A, b = 24.5130(10) A, c = 7.201(2) A, and Z = 4. The structure reveals parallel uranium-containing chains of two types: one type is composed of edge-sharing UO2F5 units; the other has a backbone of edge-sharing UF8 units, each sharing an edge with a pendant UO2F5 unit. Bond-valence calculations suggest the UF8 groups contain UIV, while the UO2F5 groups contain UVI. EXAFS data give results consistent with the single-crystal X-ray structure determination, while comparison of the uranium LIII-edge XANES of UFO-17 with that of related UIV and UVI compounds supports the oxidation-state assignment. Variable-temperature magnetic susceptibility measurements on UFO-17 and a range of related hybrid organic-inorganic uranium(IV) and uranium(VI) fluorides and oxyfluorides further support the formulation of UFO-17 as a mixed-valent UIV/UVI compound.
A method for detecting the presence of organic fraction in nucleation mode sized particles
NASA Astrophysics Data System (ADS)
Vaattovaara, P.; Räsänen, M.; Kühn, T.; Joutsensaari, J.; Laaksonen, A.
2005-06-01
New particle formation and growth has a very important role in many climate processes. However, the overall knowlegde of the chemical composition of atmospheric nucleation mode (particle diameter, d<20 nm) and the lower end of Aitken mode particles (d≤50 nm) is still insufficient. In this work, we have applied the UFO-TDMA (ultrafine organic tandem differential mobility analyzer) method to shed light on the presence of organic fraction in the nucleation mode size class in different atmospheric environments. The basic principle of the organic fraction detection is based on our laboratory UFO-TDMA measurements with organic and inorganic compounds. Our laboratory measurements indicate that the usefulness of the UFO-TDMA in the field experiments would arise especially from the fact that atmospherically the most relevant inorganic compounds do not grow in subsaturated ethanol vapor, when particle size is 10nm in diameter and saturation ratio is about 86% or below it. Furthermore, internally mixed particles composed of ammonium bisulfate and sulfuric acid with sulfuric acid mass fraction ≤33% show no growth at 85% saturation ratio. In contrast, 10 nm particles composed of various organic compounds of atmospheric relevance are able to grow in those conditions. These discoveries indicate that it is possible to detect the presence of organics in atmospheric nucleation mode sized particles using the UFO-TDMA method. In the future, the UFO-TDMA is expected to be an important aid to describe the composition of atmospheric newly-formed particles.
Introducing the LHC in the classroom: an overview of education resources available
NASA Astrophysics Data System (ADS)
Wiener, Gerfried J.; Woithe, Julia; Brown, Alexander; Jende, Konrad
2016-05-01
In the context of the recent re-start of CERN’s Large Hadron Collider (LHC) and the challenge presented by unidentified falling objects (UFOs), we seek to facilitate the introduction of high energy physics in the classroom. Therefore, this paper provides an overview of the LHC and its operation, highlighting existing education resources, and linking principal components of the LHC to topics in physics curricula.
Media Impact on Fright Reactions and Belief in UFOs: The Potential Role of Mental Imagery.
ERIC Educational Resources Information Center
Sparks, Glenn G.; And Others
1995-01-01
Explores the potential role of mental imagery for media effects in emotional responses to frightening mass media, and in the effects of the media on beliefs in UFOs. Finds that individual differences in vividness of mental imagery may play a crucial role in moderating both types of media impact. (SR)
Insects as unidentified flying objects.
Callahan, P S; Mankin, R W
1978-11-01
Five species of insects were subjected to a large electric field. Each of the insects stimulated in this manner emitted visible glows of various colors and blacklight (uv). It is postulated that the Uintah Basin, Utah, nocturnal UFO display (1965-1968) was partially due to mass swarms of spruce budworms, Choristoneura fumiferana (Clemens), stimulated to emit this type of St. Elmo's fire by flying into high electric fields caused by thunderheads and high density particulate matter in the air. There was excellent time and spatial correlation between the 1965-1968 UFO nocturnal sightings and spruce budworm infestation. It is suggested that a correlation of nocturnal UFO sightings throughout the U.S. and Canada with spruce budworm infestations might give some insight into nocturnal insect flight patterns.
Persinger, M A
1985-04-01
The tectonic strain hypothesis for many reports of UFOs (UFORs), primarily odd luminosities and metallic-looking phenomena, has been criticized on the basis of inadequate data. This reply begins with the distinction between the empirical basis for the association between UFORs and seismic activity, the hypothesis, and laboratory experiments. It is emphasized that criticisms of data should be based upon empirical criteria rather than value judgments about scientific credibility. Multivariate and bivariate analyses have indicated systematic relationships between UFORs and earthquake measures within several different areas and for different historical periods. However, the physical mechanisms for the generation of individual UFO events and their relationship to UFORs require closer examination.
OPERATOR NORM INEQUALITIES BETWEEN TENSOR UNFOLDINGS ON THE PARTITION LATTICE
Wang, Miaoyan; Duc, Khanh Dao; Fischer, Jonathan; Song, Yun S.
2017-01-01
Interest in higher-order tensors has recently surged in data-intensive fields, with a wide range of applications including image processing, blind source separation, community detection, and feature extraction. A common paradigm in tensor-related algorithms advocates unfolding (or flattening) the tensor into a matrix and applying classical methods developed for matrices. Despite the popularity of such techniques, how the functional properties of a tensor changes upon unfolding is currently not well understood. In contrast to the body of existing work which has focused almost exclusively on matricizations, we here consider all possible unfoldings of an order-k tensor, which are in one-to-one correspondence with the set of partitions of {1, …, k}. We derive general inequalities between the lp-norms of arbitrary unfoldings defined on the partition lattice. In particular, we demonstrate how the spectral norm (p = 2) of a tensor is bounded by that of its unfoldings, and obtain an improved upper bound on the ratio of the Frobenius norm to the spectral norm of an arbitrary tensor. For specially-structured tensors satisfying a generalized definition of orthogonal decomposability, we prove that the spectral norm remains invariant under specific subsets of unfolding operations. PMID:28286347
OPERATOR NORM INEQUALITIES BETWEEN TENSOR UNFOLDINGS ON THE PARTITION LATTICE.
Wang, Miaoyan; Duc, Khanh Dao; Fischer, Jonathan; Song, Yun S
2017-05-01
Interest in higher-order tensors has recently surged in data-intensive fields, with a wide range of applications including image processing, blind source separation, community detection, and feature extraction. A common paradigm in tensor-related algorithms advocates unfolding (or flattening) the tensor into a matrix and applying classical methods developed for matrices. Despite the popularity of such techniques, how the functional properties of a tensor changes upon unfolding is currently not well understood. In contrast to the body of existing work which has focused almost exclusively on matricizations, we here consider all possible unfoldings of an order- k tensor, which are in one-to-one correspondence with the set of partitions of {1, …, k }. We derive general inequalities between the l p -norms of arbitrary unfoldings defined on the partition lattice. In particular, we demonstrate how the spectral norm ( p = 2) of a tensor is bounded by that of its unfoldings, and obtain an improved upper bound on the ratio of the Frobenius norm to the spectral norm of an arbitrary tensor. For specially-structured tensors satisfying a generalized definition of orthogonal decomposability, we prove that the spectral norm remains invariant under specific subsets of unfolding operations.
UV and arsenate toxicity: a specific and sensitive yeast bioluminescence assay.
Bakhrat, Anya; Eltzov, Evgeni; Finkelstein, Yishay; Marks, Robert S; Raveh, Dina
2011-06-01
We describe a Saccharomyces cerevisiae bioluminescence assay for UV and arsenate in which bacterial luciferase genes are regulated by the promoter of the yeast gene, UFO1. UFO1 encodes the F-box subunit of the Skp1–Cdc53–F-box protein ubiquitin ligase complex and is induced by DNA damage and by arsenate. We engineered the UFO1 promoter into an existing yeast bioreporter that employs human genes for detection of steroid hormone-disrupting compounds in water bodies. Our analysis indicates that use of an endogenous yeast promoter in different mutant backgrounds allows discrimination between different environmental signals. The UFO1-engineered yeast give a robust bioluminescence response to UVB and can be used for evaluating UV protective sunscreens. They are also effective in detecting extremely low concentrations of arsenate, particularly in pdr5Δ mutants that lack a mechanism to extrude toxic chemicals; however, they do not respond to cadmium or mercury. Combined use of endogenous yeast promoter elements and mutants of stress response pathways may facilitate development of high-specificity yeast bioreporters able to discriminate between closely related chemicals present together in the environment.
NASA Astrophysics Data System (ADS)
Pressel, Phil
2014-12-01
This project was to design and build a protective weapon for a group of associations that believed in aliens and UFO's. They collected enough contributions from societies and individuals to be able to sponsor and totally fund the design, fabrication and testing of this equipment. The location of this facility is classified. It also eventually was redesigned by the Quartus Engineering Company for use at a major amusement park as a "shoot at targets facility." The challenge of this project was to design a "smart rock," namely an infrared bullet (the size of a gallon can of paint) that could be shot from the ground to intercept a UFO or any incoming suspicious item heading towards the earth. Some of the challenges to design this weapon were to feed cryogenic helium at 5 degrees Kelvin from an inair environment through a unique rotary coupling and air-vacuum seal while spinning the bullet at 1500 rpm and maintain its dynamic stability (wobble) about its spin axis to less than 10 micro-radians (2 arc seconds) while it operated in a vacuum. Precision optics monitored the dynamic motion of the "smart rock."
UFO-a multi-analyser option for IN12
NASA Astrophysics Data System (ADS)
Schmidt, Wolfgang; Rheinstädter, Maikel C.; Raymond, Stephane; Ohl, Michael
2004-07-01
The IN12 instrument is operated by FZ Jülich in collaboration with CEA Grenoble as a CRG-B instrument at the Institut Laue Langevin in Grenoble. As a three-axis spectrometer for cold neutrons it is dedicated for high-resolution studies of low-energy excitations. In the past years the instrument has been continuously improved and it has demonstrated its excellent performance for neutron scattering research. To meet further challenges as a state-of-the-art instrument in the next funding period we will propose to upgrade IN12 with a multi-analyser option similar to planned or existing RITA-type instruments. IN12 will then be optionally equipped with an array of individual analyser blades which can be positioned separately in order to map the scattered beam on a user-chosen path in (Q,ω)-space. We refer to this set-up as IN12-UFO (universal focusing option). Both, the feasibility and the scientific case are currently being studied. On the conference we will show details of the planned instrumental set-up and demonstrate its flexibility and multiplex advantages for specific physical applications.
An Approach to Understanding Psychotronics
1976-06-01
a biological system, psi, consciousness, inception, telepathy psychokinesis, UFO’s, God, and the collective unconscious can be taken. Materialization...consciousness, inception, telepathy , tpsychkinesis, UFO’s,, God, and the collective unconscious can be taken. Materialization, demat rializaticn, and...8217the first three laws, then the four law system is indeed closed, and the logician’s dream of a closed metalogic is realized. Further, anything which
ERIC Educational Resources Information Center
Chen, Mei-Yung; Hong, Jon-Chao; Hwang, Ming-Yueh; Wong, Wan-Tzu
2013-01-01
The venerable aphorism "an old dog cannot learn new tricks" implies that the elderly rarely learn anything new--in particular, scientific knowledge. On the basis of "learning by doing," the present study emphasized knowledge application (KA) as elderly subjects collaborated on the design of a toy flying saucer (UFO). Three…
Sartori, R; Sartor-Bergfelt, R; Mertens, S A; Guenther, J N; Parrish, J J; Wiltbank, M C
2002-11-01
Two experiments in two seasons evaluated fertilization rate and embryonic development in dairy cattle. Experiment 1 (summer) compared lactating Holstein cows (n = 27; 97.3 +/- 4.1 d postpartum [dppl; 40.0 +/- 1.5 kg milk/d) to nulliparous heifers (n = 28; 11 to 17 mo old). Experiment 2 (winter) compared lactating cows (n = 27; 46.4 +/- 1.6 dpp; 45.9 +/- 1.4 kg milk/d) to dry cows (n = 26). Inseminations based on estrus included combined semen from four high-fertility bulls. Embryos and oocytes recovered 5 d after ovulation were evaluated for fertilization, embryo quality (1 = excellent to 5 = degenerate), nuclei/embryo, and accessory sperm. In experiment 1, 21 embryos and 17 unfertilized oocytes (UFO) were recovered from lactating cows versus 32 embryos and no UFO from heifers (55% vs. 100% fertilization). Embryos from lactating cows had inferior quality scores (3.8 +/- 0.4 vs. 2.2 +/- 0.3), fewer nuclei/embryo (19.3 +/- 3.7 vs. 36.8 +/- 3.0) but more accessory sperm (37.3 +/- 5.8 vs. 22.4 +/- 5.5/embryo) than embryos from heifers. Sperm were attached to 80% of UFO (17.8 +/- 12.1 sperm/UFO). In experiment 2, lactating cows yielded 36 embryos and 5 UFO versus 34 embryos and 4 UFO from dry cows (87.8 vs. 89.5% fertilization). Embryo quality from lactating cows was inferior to dry cows (3.1 +/- 0.3 vs. 2.2 +/- 0.3), but embryos had similar numbers of nuclei (27.2 +/- 2.7 vs. 30.6 +/- 2.1) and accessory sperm (42.0 +/- 9.4 vs. 36.5 +/- 6.3). From 53% of the flushings from lactating cows and 28% from dry cows, only nonviable embryos were collected. Thus, embryos of lactating dairy cows were detectably inferior to embryos from nonlactating females as early as 5 d after ovulation, with a surprisingly high percentage of nonviable embryos. In addition, fertilization rate was reduced only in summer, apparently due to an effect of heat stress on the oocyte.
Comparison of Ejection Events in the Jet and Accretion Disc Outflows in 3C 111
NASA Technical Reports Server (NTRS)
Tombesi, F.; Sambruna, R. M.; Marscher, A. P.; Jorstad, S. G.; Reynolds, C. S.; Markowtiz, A.
2012-01-01
We present a comparison of the parameters of accretion disc outflows and the jet of the broad-line radio galaxy 3C 111 on sub-pc scales. We make use of published X-ray observations of ultra-fast outflows (UFOs) and new 43 GHz VLBA images to track the jet knots ejection. We find that the superluminal jet coexists with the mildly relativistic outflows on sub-pc scales, possibly indicating a transverse stratification of a global flow. The two are roughly in pressure equilibrium, with the UFOs potentially providing additional support for the initial jet collimation. The UFOs are much more massive than the jet, but their kinetic power is probably about an order of magnitude lower, at least for the observations considered here. However, their momentum flux is equivalent and both of them are powerful enough to exert a concurrent feedback impact on the surrounding environment. A link between these components is naturally predicted in the context of MHD models for jet/outflow formation. However, given the high radiation throughput of AGNs, radiation pressure should also be taken into account. From the comparison with the long-term 2-10 keV RXTE light curve we find that the UFOs are preferentially detected during periods of increasing flux. We also find the possibility to place the UFOs within the known X-ray dips-jet ejection cycles, which has been shown to be a strong proof of the disc-jet connection, in analogue with stellar-mass black holes. However, given the limited number of observations presently available, these relations are only tentative and additional spectral monitoring is needed to test them conclusively.
NASA Astrophysics Data System (ADS)
Contenta, Filippo; Gieles, Mark; Balbinot, Eduardo; Collins, Michelle L. M.
2017-04-01
In the last decade, several ultra faint objects (UFOs, MV ≳ -3.5) have been discovered in the outer halo of the Milky Way. For some of these objects, it is not clear whether they are star clusters or (ultra faint) dwarf galaxies. In this work, we quantify the contribution of star clusters to the population of UFOs. We extrapolated the mass and Galactocentric radius distribution of the globular clusters using a population model, finding that the Milky Way contains about 3.3^{+7.3}_{-1.6} star clusters with MV ≳ -3.5 and Galactocentric radius ≥20 kpc. To understand whether dissolving clusters can appear as UFOs, we run a suite of direct N-body models, varying the orbit, the Galactic potential, the binary fraction and the black hole (BH) natal kick velocities. In the analyses, we consider observational biases such as luminosity limit, field stars and line-of-sight projection. We find that star clusters contribute to both the compact and the extended population of UFOs: clusters without BHs appear compact with radii ˜5 pc, while clusters that retain their BHs after formation have radii ≳ 20 pc. The properties of the extended clusters are remarkably similar to those of dwarf galaxies: high-inferred mass-to-light ratios due to binaries, binary properties mildly affected by dynamical evolution, no observable mass segregation and flattened stellar mass function. We conclude that the slope of the stellar mass function as a function of Galactocentric radius and the presence/absence of cold streams can discriminate between dark matter-free and dark matter-dominated UFOs.
Comparison of ejection events in the jet and accretion disc outflows in 3C 111
NASA Astrophysics Data System (ADS)
Tombesi, F.; Sambruna, R. M.; Marscher, A. P.; Jorstad, S. G.; Reynolds, C. S.; Markowitz, A.
2012-07-01
We present a comparison of the parameters of accretion disc outflows and the jet of the broad-line radio galaxy 3C 111 on subparsec (sub-pc) scales. We make use of published X-ray observations of ultra-fast outflows (UFOs) and new 43-GHz Very Long Baseline Array images to track the jet knot ejection. We find that the superluminal jet coexists with the mildly relativistic outflows on sub-pc scales, possibly indicating a transverse stratification of a global flow. The two are roughly in pressure equilibrium, with the UFOs potentially providing additional support for the initial jet collimation. The UFOs are much more massive than the jet, but their kinetic power is probably about an order of magnitude lower, at least for the observations considered here. However, their momentum flux is equivalent and both of them are powerful enough to exert a concurrent feedback impact on the surrounding environment. A link between these components is naturally predicted in the context of magnetohydrodynamic models for jet/outflow formation. However, given the high radiation throughput of active galactic nuclei, radiation pressure should also be taken into account. From the comparison with the long-term 2-10 keV Rossi X-ray Timing Explorer light curve, we find that the UFOs are preferentially detected during periods of increasing flux. We also find the possibility to place the UFOs within the known X-ray dips-jet ejection cycles, which has been shown to be a strong proof of the disc-jet connection, in analogue with stellar mass black holes. However, given the limited number of observations presently available, these relations are only tentative and additional spectral monitoring is needed to test them conclusively.
Levin, J Z; Fletcher, J C; Chen, X; Meyerowitz, E M
1998-06-01
In a screen to identify novel genes required for early Arabidopsis flower development, we isolated four independent mutations that enhance the Ufo phenotype toward the production of filamentous structures in place of flowers. The mutants fall into three complementation groups, which we have termed FUSED FLORAL ORGANS (FFO) loci. ffo mutants have specific defects in floral organ separation and/or positioning; thus, the FFO genes identify components of a boundary formation mechanism(s) acting between developing floral organ primordia. FFO1 and FFO3 have specific functions in cauline leaf/stem separation and in first- and third-whorl floral organ separation, with FFO3 likely acting to establish and FFO1 to maintain floral organ boundaries. FFO2 acts at early floral stages to regulate floral organ number and positioning and to control organ separation within and between whorls. Plants doubly mutant for two ffo alleles display additive phenotypes, indicating that the FFO genes may act in separate pathways. Plants doubly mutant for an ffo gene and for ufo, lfy, or clv3 reveal that the FFO genes play roles related to those of UFO and LFY in floral meristem initiation and that FFO2 and FFO3 may act to control cell proliferation late in inflorescence development.
Investigation of UFO defect on DUV CAR and BARC process
NASA Astrophysics Data System (ADS)
Yet, Siew Ing; Ko, Bong Sang; Lee, Soo Man; May, Mike
2004-05-01
Photo process defect reduction is one of the most important factors to improve the process stability and yield in sub-0.18um DUV process. In this paper, a new approach to minimize the Deep-UV (DUV) Chemically Amplified Resist (CAR) and Bottom Anti-Reflective Coating (BARC) induced defect known as UFO (UnidentiFied Object) defect will be introduced. These defects have mild surface topography difference on BARC; it only exists on the wide exposed area where there is no photoresist pattern. In this test, Nikon KrF Stepper & Scanner and TEL Clean track were used. Investigation was carried out on the defect formulation on both Acetal and ESCAP type of photoresist while elemental analysis was done by Atomic Force Microscope (AFM) & Auger Electron Spectroscopy (AES). Result indicated that both BARC and photoresist induce this UFO defect; total defect quantity is related with Post Exposure Bake (PEB) condition. Based on the elemental analysis and process-split test, we can conclude that this defect is caused by lack of acid amount and low diffusivity which is related to PAG (Photo Acid Generator) and TAG (Thermal Acid Generator) in KrF photoresist and BARC material. By optimizing photoresist bake condition, this UFO defect as well as other related defect such as Satellite defect could be eliminated.
SARAH 3.2: Dirac gauginos, UFO output, and more
NASA Astrophysics Data System (ADS)
Staub, Florian
2013-07-01
SARAH is a Mathematica package optimized for the fast, efficient and precise study of supersymmetric models beyond the MSSM: a new model can be defined in a short form and all vertices are derived. This allows SARAH to create model files for FeynArts/FormCalc, CalcHep/CompHep and WHIZARD/O'Mega. The newest version of SARAH now provides the possibility to create model files in the UFO format which is supported by MadGraph 5, MadAnalysis 5, GoSam, and soon by Herwig++. Furthermore, SARAH also calculates the mass matrices, RGEs and 1-loop corrections to the mass spectrum. This information is used to write source code for SPheno in order to create a precision spectrum generator for the given model. This spectrum-generator-generator functionality as well as the output of WHIZARD and CalcHep model files has seen further improvement in this version. Also models including Dirac gauginos are supported with the new version of SARAH, and additional checks for the consistency of the implementation of new models have been created. Program summaryProgram title:SARAH Catalogue identifier: AEIB_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEIB_v2_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 3 22 411 No. of bytes in distributed program, including test data, etc.: 3 629 206 Distribution format: tar.gz Programming language: Mathematica. Computer: All for which Mathematica is available. Operating system: All for which Mathematica is available. Classification: 11.1, 11.6. Catalogue identifier of previous version: AEIB_v1_0 Journal reference of previous version: Comput. Phys. Comm. 182 (2011) 808 Does the new version supersede the previous version?: Yes, the new version includes all known features of the previous version but also provides the new features mentioned below. Nature of problem: To use Madgraph for new models it is necessary to provide the corresponding model files which include all information about the interactions of the model. However, the derivation of the vertices for a given model and putting those into model files which can be used with Madgraph is usually very time consuming. Dirac gauginos are not present in the minimal supersymmetric standard model (MSSM) or many extensions of it. Dirac mass terms for vector superfields lead to new structures in the supersymmetric (SUSY) Lagrangian (bilinear mass term between gaugino and matter fermion as well as new D-terms) and modify also the SUSY renormalization group equations (RGEs). The Dirac character of gauginos can change the collider phenomenology. In addition, they come with an extended Higgs sector for which a precise calculation of the 1-loop masses has not happened so far. Solution method: SARAH calculates the complete Lagrangian for a given model whose gauge sector can be any direct product of SU(N) gauge groups. The chiral superfields can transform as any, irreducible representation with respect to these gauge groups and it is possible to handle an arbitrary number of symmetry breakings or particle rotations. Also the gauge fixing is automatically added. Using this information, SARAH derives all vertices for a model. These vertices can be exported to model files in the UFO which is supported by Madgraph and other codes like GoSam, MadAnalysis or ALOHA. The user can also study models with Dirac gauginos. In that case SARAH includes all possible terms in the Lagrangian stemming from the new structures and can also calculate the RGEs. The entire impact of these terms is then taken into account in the output of SARAH to UFO, CalcHep, WHIZARD, FeynArts and SPheno. Reasons for new version: SARAH provides, with this version, the possibility of creating model files in the UFO format. The UFO format is supposed to become a standard format for model files which should be supported by many different tools in the future. Also models with Dirac gauginos were not supported in earlier versions. Summary of revisions: Support of models with Dirac gauginos. Output of model files in the UFO format, speed improvement in the output of WHIZARD model files, CalcHep output supports the internal diagonalization of mass matrices, output of control files for LHPC spectrum plotter, support of generalized PDG numbering scheme PDG.IX, improvement of the calculation of the decay widths and branching ratios with SPheno, the calculation of new low energy observables are added to the SPheno output, the handling of gauge fixing terms has been significantly simplified. Restrictions: SARAH can only derive the Lagrangian in an automatized way for N=1 SUSY models, but not for those with more SUSY generators. Furthermore, SARAH supports only renormalizable operators in the output of model files in the UFO format and also for CalcHep, FeynArts and WHIZARD. Also color sextets are not yet included in the model files for Monte Carlo tools. Dimension 5 operators are only supported in the calculation of the RGEs and mass matrices. Unusual features: SARAH does not need the Lagrangian of a model as input to calculate the vertices. The gauge structure, particle and content and superpotential as well as rotations stemming from gauge symmetry breaking are sufficient. All further information is derived by SARAH on its own. Therefore, the model files are very short and the implementation of new models is fast and easy. In addition, the implementation of a model can be checked for physical and formal consistency. In addition, SARAH can generate Fortran code for a full 1-loop analysis of the mass spectrum in the context for Dirac gauginos. Running time: Measured CPU time for the evaluation of the MSSM using a Lenovo Thinkpad X220 with i7 processor (2.53 GHz). Calculating the complete Lagrangian: 9 s. Calculating all vertices: 51 s. Output of the UFO model files: 49 s.
Persinger, M A
1988-12-01
Luminous phenomena and anomalous physical forces have been hypothesized to be generated by focal tectonic strain fields that precede earthquakes. If these geophysical processes exist, then their spatial and temporal density should be greatest during periods of protracted, localized UFO reports; they might be used as dosimetric indicators. Contemporary epidemiological data concerning the health risks of power frequency electromagnetic fields and radon gas levels (expected correlates of certain tectonic strain fields), suggest that increased incidence (odds ratios greater 1:3) of brain tumors and leukemia should be evident within "flap" areas. In addition the frequency of variants of temporal lobe lability, psychological depression and posttraumatic stress should be significantly elevated. UFO field investigators, because they have repeated, intermittent close proximity to these fields, are considered to be a particularly high risk population for these disorders.
Probing the connection between the accretion disk, outflows and the jet in 3C111
NASA Astrophysics Data System (ADS)
Tombesi, Francesco
2011-10-01
Recent XMM-Newton and Suzaku observations of 3C111 demonstrated the presence of ultra-fast outflows (UFOs) with v~0.1c and their relation with the accretion disk. Independent studies found that X-ray dips are followed by ejection of superluminal radio knots, therefore providing a proof of the disk-jet connection. We acquired evidence that UFOs are preferentially present between X-ray dips and new knots, possibly indicating also a link between disk outflows and the jet. The goal of this XMM-Newton proposal is to confirm this evidence. Given the strong correlation with X-rays, we will use an ongoing optical monitoring campaign to trigger a 90ks observation within two days of a dip to detect a UFO and we request a possible additional 60ks >15 days after to compare with the non-dipped state.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Persinger, M.A.
Luminous phenomena and anomalous physical forces have been hypothesized to be generated by focal tectonic strain fields that precede earthquakes. If these geophysical processes exist, then their spatial and temporal density should be greatest during periods of protracted, localized UFO reports; they might be used as dosimetric indicators. Contemporary epidemiological data concerning the health risks of power frequency electromagnetic fields and radon gas levels (expected correlates of certain tectonic strain fields), suggest that increased incidence (odds ratios greater 1:3) of brain tumors and leukemia should be evident within flap areas. In addition the frequency of variants of temporal lobe lability,more » psychological depression and posttraumatic stress should be significantly elevated. UFO field investigators, because they have repeated, intermittent close proximity to these fields, are considered to be a particularly high risk population for these disorders. 22 references.« less
Rice ABERRANT PANICLE ORGANIZATION 1, encoding an F-box protein, regulates meristem fate.
Ikeda, Kyoko; Ito, Momoyo; Nagasawa, Nobuhiro; Kyozuka, Junko; Nagato, Yasuo
2007-09-01
Inflorescence architecture is one of the most important agronomical traits. Characterization of rice aberrant panicle organization 1 (apo1) mutants revealed that APO1 positively controls spikelet number by suppressing the precocious conversion of inflorescence meristems to spikelet meristems. In addition, APO1 is associated with the regulation of the plastchron, floral organ identity, and floral determinacy. Phenotypic analyses of apo1 and floral homeotic double mutants demonstrate that APO1 positively regulates class-C floral homeotic genes, but not class-B genes. Molecular studies revealed that APO1 encodes an F-box protein, an ortholog of Arabidopsis UNUSUAL FLORAL ORGAN (UFO), which is a positive regulator of class-B genes. Overexpression of APO1 caused an increase in inflorescence branches and spikelets. As the mutant inflorescences and flowers differed considerably between apo1 and ufo, the functions of APO1 and UFO appear to have diverged during evolution.
NASA Astrophysics Data System (ADS)
Ailleris, P.
2011-10-01
We present the website's extensive and well illustrated list of misidentifications and describe how people can further check details and develop their knowledge (e.g. satellite paths, stars/planets charts, characteristics of meteors, pictures of sprites, clouds classification). A short illustrated list of cases will be featured, both explained and inexplicable; and outreach activities and partnerships with relevant astronomical projects (e.g. Astronomers without Borders, The World at Night) will be described. We will underline that the project definitely fulfills a need in relation to demystifying UFO events, providing education on pseudo-scientific information, while keeping an attitude of scientific openmindedness. For these reasons, we will encourage the planetary scientists community to further advertise the project's existence and the amateur astronomers and societies who receive questions about UFOs to redirect those queries to the websit.
Unifying X-ray winds in radio galaxies with Chandra HETG
NASA Astrophysics Data System (ADS)
Tombesi, Francesco
2013-09-01
X-ray winds are routinely observed in the spectra of Seyfert galaxies. They can be classified as warm absorbers (WAs), with v~100-1,000km/s, and ultra-fast outflows (UFOs), with v>10,000km/s. In stark contrast, the lack of sensitive enough observations allowed the detection of WAs or UFOs only in very few radio galaxies. Therefore, we propose to observe a small sample of three radio galaxies with the Chandra HETG - 3C111 for 150ks, 3C390.3 for 150ks and 3C120 for 200ks - to detect and study in detail their WAs. We will quantify the importance of mechanical feedback from winds in radio galaxies and compare them to the radio jet power. We will also test whether WAs and UFOs can be unified in a single, multi-phase and multi-scale outflow, as recently reported for Seyferts.
Levin, J Z; Fletcher, J C; Chen, X; Meyerowitz, E M
1998-01-01
In a screen to identify novel genes required for early Arabidopsis flower development, we isolated four independent mutations that enhance the Ufo phenotype toward the production of filamentous structures in place of flowers. The mutants fall into three complementation groups, which we have termed FUSED FLORAL ORGANS (FFO) loci. ffo mutants have specific defects in floral organ separation and/or positioning; thus, the FFO genes identify components of a boundary formation mechanism(s) acting between developing floral organ primordia. FFO1 and FFO3 have specific functions in cauline leaf/stem separation and in first- and third-whorl floral organ separation, with FFO3 likely acting to establish and FFO1 to maintain floral organ boundaries. FFO2 acts at early floral stages to regulate floral organ number and positioning and to control organ separation within and between whorls. Plants doubly mutant for two ffo alleles display additive phenotypes, indicating that the FFO genes may act in separate pathways. Plants doubly mutant for an ffo gene and for ufo, lfy, or clv3 reveal that the FFO genes play roles related to those of UFO and LFY in floral meristem initiation and that FFO2 and FFO3 may act to control cell proliferation late in inflorescence development. PMID:9611175
Iterative Repair Planning for Spacecraft Operations Using the Aspen System
NASA Technical Reports Server (NTRS)
Rabideau, G.; Knight, R.; Chien, S.; Fukunaga, A.; Govindjee, A.
2000-01-01
This paper describes the Automated Scheduling and Planning Environment (ASPEN). ASPEN encodes complex spacecraft knowledge of operability constraints, flight rules, spacecraft hardware, science experiments and operations procedures to allow for automated generation of low level spacecraft sequences. Using a technique called iterative repair, ASPEN classifies constraint violations (i.e., conflicts) and attempts to repair each by performing a planning or scheduling operation. It must reason about which conflict to resolve first and what repair method to try for the given conflict. ASPEN is currently being utilized in the development of automated planner/scheduler systems for several spacecraft, including the UFO-1 naval communications satellite and the Citizen Explorer (CX1) satellite, as well as for planetary rover operations and antenna ground systems automation. This paper focuses on the algorithm and search strategies employed by ASPEN to resolve spacecraft operations constraints, as well as the data structures for representing these constraints.
[Harm reduction policies in Brazil: contributions of a North American program].
Inglez-Dias, Aline; Ribeiro, José Mendes; Bastos, Francisco I; Page, Kimberly
2014-01-01
Given the rapid spread of the HIV epidemic and the need to control its transmission among intravenous drug users (IDU), harm reduction strategies have been incorporated in many countries, including Brazil. Considering these aspects and taking into account the emergence of drugs as a core concern on the government's agenda, especially crack cocaine, this article presents some of the contributions acquired from observing and recording the practices of an American model of research and care for IDUs, namely the UFO (You Find Out) Study. Issues such as participants' access and adherence, financing difficulties, sustainability and outcome evaluation were considered. The study involved documental research, systematic observation and interviews with key informants. Some of the UFO features that could contribute to the formulation of harm reduction policies in Brazil are highlighted. The UFO appears to be a successful example of harm reduction initiatives that successfully contact and guarantee the commitment of that risk group, ensuring its access to health services and reducing risks associated with drug use.
UFO: a web server for ultra-fast functional profiling of whole genome protein sequences.
Meinicke, Peter
2009-09-02
Functional profiling is a key technique to characterize and compare the functional potential of entire genomes. The estimation of profiles according to an assignment of sequences to functional categories is a computationally expensive task because it requires the comparison of all protein sequences from a genome with a usually large database of annotated sequences or sequence families. Based on machine learning techniques for Pfam domain detection, the UFO web server for ultra-fast functional profiling allows researchers to process large protein sequence collections instantaneously. Besides the frequencies of Pfam and GO categories, the user also obtains the sequence specific assignments to Pfam domain families. In addition, a comparison with existing genomes provides dissimilarity scores with respect to 821 reference proteomes. Considering the underlying UFO domain detection, the results on 206 test genomes indicate a high sensitivity of the approach. In comparison with current state-of-the-art HMMs, the runtime measurements show a considerable speed up in the range of four orders of magnitude. For an average size prokaryotic genome, the computation of a functional profile together with its comparison typically requires about 10 seconds of processing time. For the first time the UFO web server makes it possible to get a quick overview on the functional inventory of newly sequenced organisms. The genome scale comparison with a large number of precomputed profiles allows a first guess about functionally related organisms. The service is freely available and does not require user registration or specification of a valid email address.
Radiation hydrodynamic simulations of line-driven disk winds for ultra-fast outflows
NASA Astrophysics Data System (ADS)
Nomura, Mariko; Ohsuga, Ken; Takahashi, Hiroyuki R.; Wada, Keiichi; Yoshida, Tessei
2016-02-01
Using two-dimensional radiation hydrodynamic simulations, we investigate the origin of the ultra-fast outflows (UFOs) that are often observed in luminous active galactic nuclei (AGNs). We found that the radiation force due to the spectral lines generates strong winds (line-driven disk winds) that are launched from the inner region of accretion disks (˜30 Schwarzschild radii). A wide range of black hole masses (MBH) and Eddington ratios (ε) was investigated to study the conditions causing the line-driven winds. For MBH = 106-109 M⊙ and ε = 0.1-0.7, funnel-shaped disk winds appear, in which dense matter is accelerated outward with an opening angle of 70°-80° and with 10% of the speed of light. If we observe the wind along its direction, the velocity, the column density, and the ionization state are consistent with those of the observed UFOs. As long as obscuration by the torus does not affect the observation of X-ray bands, the UFOs could be statistically observed in about 13%-28% of the luminous AGNs, which is not inconsistent with the observed ratio (˜40%). We also found that the results are insensitive to the X-ray luminosity and the density of the disk surface. Thus, we can conclude that UFOs could exist in any luminous AGNs, such as narrow-line Seyfert 1s and quasars with ε > 0.1, with which fast line-driven winds are associated.
NASA Astrophysics Data System (ADS)
Feruglio, C.; Fiore, F.; Carniani, S.; Piconcelli, E.; Zappacosta, L.; Bongiorno, A.; Cicone, C.; Maiolino, R.; Marconi, A.; Menci, N.; Puccetti, S.; Veilleux, S.
2015-11-01
Mrk 231 is a nearby ultra-luminous IR galaxy exhibiting a kpc-scale, multi-phase AGN-driven outflow. This galaxy represents the best target to investigate in detail the morphology and energetics of powerful outflows, as well as their still poorly-understood expansion mechanism and impact on the host galaxy. In this work, we present the best sensitivity and angular resolution maps of the molecular disk and outflow of Mrk 231, as traced by CO(2-1) and (3-2) observations obtained with the IRAM/PdBI. In addition, we analyze archival deep Chandra and NuSTAR X-ray observations. We use this unprecedented combination of multi-wavelength data sets to constrain the physical properties of both the molecular disk and outflow, the presence of a highly-ionized ultra-fast nuclear wind, and their connection. The molecular CO(2-1) outflow has a size of 1 kpc, and extends in all directions around the nucleus, being more prominent along the south-west to north-east direction, suggesting a wide-angle biconical geometry. The maximum projected velocity of the outflow is nearly constant out to 1 kpc, thus implying that the density of the outflowing material must decrease from the nucleus outwards as r-2. This suggests that either a large part of the gas leaves the flow during its expansion or that the bulk of the outflow has not yet reached out to 1 kpc, thus implying a limit on its age of 1 Myr. Mapping the mass and energy rates of the molecular outflow yields dot {M} OF = [500-1000] M⊙ yr-1 and Ėkin,OF = [7-10] × 1043 erg s-1. The total kinetic energy of the outflow is Ekin,OF is of the same order of the total energy of the molecular disk, Edisk. Remarkably, our analysis of the X-ray data reveals a nuclear ultra-fast outflow (UFO) with velocity -20 000 km s-1, dot {M}UFO = [0.3-2.1] M⊙ yr-1, and momentum load dot {P}UFO/ dot {P}rad = [0.2-1.6]. We find Ėkin,UFO Ėkin,OF as predicted for outflows undergoing an energy conserving expansion. This suggests that most of the UFO kinetic energy is transferred to mechanical energy of the kpc-scale outflow, strongly supporting that the energy released during accretion of matter onto super-massive black holes is the ultimate driver of giant massive outflows. The momentum flux dot {P}OF derived for the large scale outflows in Mrk 231 enables us to estimate a momentum boost dot {P}OF/ dot {P} UFO ≈ [30-60]. The ratios Ėkin,UFO/Lbol,AGN = [1-5] % and Ėkin,OF/Lbol,AGN = [1-3] % agree with the requirements of the most popular models of AGN feedback. Based on observations carried out with the IRAM Plateau de Bure Interferometer. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain), and with Chandra and NuSTAR observatories.
"Need to Know" vs. "Need to Believe" in UFOlogy
NASA Astrophysics Data System (ADS)
Teodorani, Massimo
2009-09-01
How authentic is UFO documentation? A lot of factors demonstrate -- doing a simple analysis -- that most of UFO photographic material, in particular the one that circulates on the web, is totally unreliable. It is not only a matter of lack of scientific method; it is mostly a simple matter of lack of common sense. The common sense of people is constantly made a fun of and the reasons of this are many, the most important of which is the emotional effect caused by the imaginary collective. UFO iconography is a drug at all effects, and can be used to switch minds in many ways, also to collect proselytes to make up new fanatic religions, but more generally to give people a sort of psychological medicine with which people can escape from the hard reality of everyday, where the continuous competitions of present society often obscure the human and spiritual dimension: people need to retrieve the very nucleus of their soul. This intimate need is clearly legitimate, but it is also risky: in fact persons who are not well rationally grounded are very easily subject to manipulation: it seems that most persons in the world are just in this condition, especially at our epoch. When critical thinking starts to lack, who leads this society has at his disposal a huge mass of sheep, ready to follow alleged miracles, saviour aliens and related gurus. The less people think in a grounded way the least this people are conscious of what is happening at their shoulders. This is the effect of UFO iconography.
Broholm, Suvi K.; Tähtiharju, Sari
2016-01-01
The evolutionary success of Asteraceae, the largest family of flowering plants, has been attributed to the unique inflorescence architecture of the family, which superficially resembles an individual flower. Here, we show that Asteraceae inflorescences (flower heads, or capitula) resemble solitary flowers not only morphologically but also at the molecular level. By conducting functional analyses for orthologs of the flower meristem identity genes LEAFY (LFY) and UNUSUAL FLORAL ORGANS (UFO) in Gerbera hybrida, we show that GhUFO is the master regulator of flower meristem identity, while GhLFY has evolved a novel, homeotic function during the evolution of head-like inflorescences. Resembling LFY expression in a single flower meristem, uniform expression of GhLFY in the inflorescence meristem defines the capitulum as a determinate structure that can assume floral fate upon ectopic GhUFO expression. We also show that GhLFY uniquely regulates the ontogeny of outer, expanded ray flowers but not inner, compact disc flowers, indicating that the distinction of different flower types in Asteraceae is connected with their independent evolutionary origins from separate branching systems. PMID:27382139
Constraining physical parameters of ultra-fast outflows in PDS 456 with Monte Carlo simulations
NASA Astrophysics Data System (ADS)
Hagino, K.; Odaka, H.; Done, C.; Gandhi, P.; Takahashi, T.
2014-07-01
Deep absorption lines with extremely high velocity of ˜0.3c observed in PDS 456 spectra strongly indicate the existence of ultra-fast outflows (UFOs). However, the launching and acceleration mechanisms of UFOs are still uncertain. One possible way to solve this is to constrain physical parameters as a function of distance from the source. In order to study the spatial dependence of parameters, it is essential to adopt 3-dimensional Monte Carlo simulations that treat radiation transfer in arbitrary geometry. We have developed a new simulation code of X-ray radiation reprocessed in AGN outflow. Our code implements radiative transfer in 3-dimensional biconical disk wind geometry, based on Monte Carlo simulation framework called MONACO (Watanabe et al. 2006, Odaka et al. 2011). Our simulations reproduce FeXXV and FeXXVI absorption features seen in the spectra. Also, broad Fe emission lines, which reflects the geometry and viewing angle, is successfully reproduced. By comparing the simulated spectra with Suzaku data, we obtained constraints on physical parameters. We discuss launching and acceleration mechanisms of UFOs in PDS 456 based on our analysis.
Does the X-ray outflow quasar PDS 456 have a UV outflow at 0.3c?
NASA Astrophysics Data System (ADS)
Hamann, Fred; Chartas, George; Reeves, James; Nardini, Emanuele
2018-05-01
The quasar PDS 456 (at redshift ˜0.184) has a prototype ultra-fast outflow (UFO) measured in X-rays. This outflow is highly ionized with relativistic speeds, large total column densities log NH(cm-2) > 23, and large kinetic energies that could be important for feedback to the host galaxy. A UV spectrum of PDS 456 obtained with the Hubble Space Telescope in 2000 contains one well-measured broad absorption line (BAL) at ˜1346 Å (observed) that might be Ly α at v ≈ 0.06c or N V λ1240 at v ≈ 0.08c. However, we use photoionization models and comparisons to other outflow quasars to show that these BAL identifications are problematic because other lines that should accompany them are not detected. We argue that the UV BAL is probably C IV at v ≈ 0.30c. This would be the fastest UV outflow ever reported, but its speed is similar to the X-ray outflow and its appearance overall is similar to relativistic UV BALs observed in other quasars. The C IV BAL identification is also supported indirectly by the tentative detection of another broad C IV line at v ≈ 0.19c. The high speeds suggest that the UV outflow originates with the X-ray UFO crudely 20-30 rg from the central black hole. We speculate that the C IV BAL might form in dense clumps embedded in the X-ray UFO, requiring density enhancements of only ≳0.4 dex compared to clumpy structures already inferred for the soft X-ray absorber in PDS 456. The C IV BAL might therefore be the first detection of low-ionization clumps proposed previously to boost the opacities in UFOs for radiative driving.
NASA Astrophysics Data System (ADS)
Nomura, M.; Ohsuga, K.
2017-03-01
In order to reveal the origin of the ultrafast outflows (UFOs) that are frequently observed in active galactic nuclei (AGNs), we perform two-dimensional radiation hydrodynamics simulations of the line-driven disc winds, which are accelerated by the radiation force due to the spectral lines. The line-driven winds are successfully launched for the range of MBH = 106-9 M⊙ and ε = 0.1-0.5, and the resulting mass outflow rate (dot{M_w}), momentum flux (dot{p_w}), and kinetic luminosity (dot{E_w}) are in the region containing 90 per cent of the posterior probability distribution in the dot{M}_w-Lbol plane, dot{p}_w-Lbol plane, and dot{E}_w-Lbol plane shown in Gofford et al., where MBH is the black hole mass, ε is the Eddington ratio, and Lbol is the bolometric luminosity. The best-fitting relations in Gofford et al., d log dot{M_w}/d log {L_bol}˜ 0.9, d log dot{p_w}/d log {L_bol}˜ 1.2, and d log dot{E_w}/d log {L_bol}˜ 1.5, are roughly consistent with our results, d log dot{M_w}/d log {L_bol}˜ 9/8, d log dot{p_w}/d log {L_bol}˜ 10/8, and d log dot{E_w}/d log {L_bol}˜ 11/8. In addition, our model predicts that no UFO features are detected for the AGNs with ε ≲ 0.01, since the winds do not appear. Also, only AGNs with MBH ≲ 108 M⊙ exhibit the UFOs when ε ∼ 0.025. These predictions nicely agree with the X-ray observations. These results support that the line-driven disc wind is the origin of the UFOs.
Unification of X-ray Winds in Seyfert Galaxies: From Ultra-fast Outflows to Warm Absorbers
NASA Astrophysics Data System (ADS)
Tombesi, Francesco; Cappi, M.; Reeves, J.; Nemmen, R.; Braito, V.; Gaspari, M.; Reynolds, C. S.
2013-04-01
The existence of ionized X-ray absorbing layers of gas along the line of sight to the nuclei of Seyfert galaxies is a well established observational fact. This material is systematically outflowing and shows a large range in parameters. However, its actual nature and dynamics are still not clear. In order to gain insights into these important issues we performed a literature search for papers reporting the parameters of the soft X-ray warm absorbers (WAs) in 35 type 1 Seyferts and compared their properties to those of the ultra-fast outflows (UFOs) detected in the same sample. The fraction of sources with WAs is >60%, consistent with previous studies. The fraction of sources with UFOs is >34%, >67% of which also show WAs. The large dynamic range obtained when considering all the absorbers together allows us, for the first time, to investigate general relations among them. In particular, we find significant correlations indicating that the closer the absorber is to the central black hole, the higher the ionization, column, outflow velocity and consequently the mechanical power. The absorbers continuously populate the whole parameter space, with the WAs and the UFOs lying always at the two ends of the distribution. This strongly suggest that these absorbers, often considered of different types, could actually represent parts of a single large-scale stratified outflow observed at different locations from the black hole. The observed parameters and correlations are consistent with both radiation pressure through Compton scattering and MHD processes contributing to the outflow acceleration, the latter playing a major role. Most of the absorbers, especially the UFOs, have a sufficiently high mechanical power to significantly contribute to the AGN feedback.
Past-life identities, UFO abductions, and satanic ritual abuse: the social construction of memories.
Spanos, N P; Burgess, C A; Burgess, M F
1994-10-01
People sometimes fantasize entire complex scenarios and later define these experiences as memories of actual events rather than as imaginings. This article examines research associated with three such phenomena: past-life experiences, UFO alien contact and abduction, and memory reports of childhood ritual satanic abuse. In each case, elicitation of the fantasy events is frequently associated with hypnotic procedures and structured interviews which provide strong and repeated demands for the requisite experiences, and which then legitimate the experiences as "real memories." Research associated with these phenomena supports the hypothesis that recall is reconstructive and organized in terms of current expectations and beliefs.
Persinger, M A
1985-02-01
The contribution of geomagnetic variation to the occurrence of UFORs (reports of UFOs) within the New Madrid States during the 6-mo. increments before increases in the numbers of IV-V or less intensity earthquakes within the central USA was determined. Although statistically significant zero-order correlations existed between measures of earthquakes, UFORs and geomagnetic variability, the association between the latter two deteriorated markedly when their shared variance with earthquakes was held constant. These outcomes are compatible with the hypothesis that geomagnetic variability (or phenomena associated with it) may enhance UFORs but only if tectonic stress and strain are increasing within the region.
Di Vaio, Claudio; Marallo, Nadia; Graziani, Giulia; Ritieni, Alberto; Di Matteo, Antonio
2015-08-15
Fruit quality traits (fresh weight, dry weight, soluble solids content, titratable acidity and firmness) as well as the content of bioactive compounds (phenolic compounds) and total antioxidant activity were evaluated in four commercial cultivars of peach (Greta, Ufo 4, Rome Star and Ufo 6) and four of nectarine (Neve, Planet 1, Maria Carla and Mesembrina) differing in fruit shape (standard or flat) and flesh colour (white or yellow), important cultivars of the Italian and foreign market. The higher fruit organoleptic quality and nutritional profile of flat peach and nectarine cultivars make them candidates for exploiting new market opportunities and the chance to improve profits of farmers. The results showed that assayed quality parameters differed greatly among cultivars. In particular, flesh color and fruit shape accounted for most of the variation in traits underlying organoleptic and nutritional quality. Overall data suggested that the flat white-fleshed nectarine Planet 1, the yellow-fleshed nectarine Mesembrina and the yellow-fleshed peach Ufo 6, because of their profiles in terms of soluble solids content, titratable acidity and bioactive compounds, have the greatest potential to meet current consumer requirements. © 2014 Society of Chemical Industry.
XMM-Newton, powerful AGN winds and galaxy feedback
NASA Astrophysics Data System (ADS)
Pounds, K.; King, A.
2016-06-01
The discovery that ultra-fast ionized winds - sufficiently powerful to disrupt growth of the host galaxy - are a common feature of luminous AGN is major scientific breakthrough led by XMM-Newton. An extended observation in 2014 of the prototype UFO, PG1211+143, has revealed an unusually complex outflow, with distinct and persisting velocities detected in both hard and soft X-ray spectra. While the general properties of UFOs are consistent with being launched - at the local escape velocity - from the inner disc where the accretion rate is modestly super-Eddington (King and Pounds, Ann Rev Astron Astro- phys 2015), these more complex flows have raised questions about the outflow geometry and the importance of shocks and enhanced cooling. XMM-Newton seems likely to remain the best Observatory to study UFOs prior to Athena, and further extended observations, of PG1211+143 and other bright AGN, have the exciting potential to establish the typical wind dynamics, while providing new insights on the accretion geometry and continuum source structure. An emphasis on such large, coordinated observing programmes with XMM-Newton over the next decade will continue the successful philosophy pioneered by EXOSAT, while helping to inform the optimum planning for Athena
Zhao, Yafei; Zhang, Teng; Broholm, Suvi K; Tähtiharju, Sari; Mouhu, Katriina; Albert, Victor A; Teeri, Teemu H; Elomaa, Paula
2016-09-01
The evolutionary success of Asteraceae, the largest family of flowering plants, has been attributed to the unique inflorescence architecture of the family, which superficially resembles an individual flower. Here, we show that Asteraceae inflorescences (flower heads, or capitula) resemble solitary flowers not only morphologically but also at the molecular level. By conducting functional analyses for orthologs of the flower meristem identity genes LEAFY (LFY) and UNUSUAL FLORAL ORGANS (UFO) in Gerbera hybrida, we show that GhUFO is the master regulator of flower meristem identity, while GhLFY has evolved a novel, homeotic function during the evolution of head-like inflorescences. Resembling LFY expression in a single flower meristem, uniform expression of GhLFY in the inflorescence meristem defines the capitulum as a determinate structure that can assume floral fate upon ectopic GhUFO expression. We also show that GhLFY uniquely regulates the ontogeny of outer, expanded ray flowers but not inner, compact disc flowers, indicating that the distinction of different flower types in Asteraceae is connected with their independent evolutionary origins from separate branching systems. © 2016 American Society of Plant Biologists. All rights reserved.
X-ray Evidence for Ultra-Fast Outflows in Local AGNs
NASA Astrophysics Data System (ADS)
Tombesi, F.; Cappi, M.; Sambruna, R. M.; Reeves, J. N.; Reynolds, C. S.; Braito, V.; Dadina, M.
2012-08-01
X-ray evidence for ultra-fast outflows (UFOs) has been recently reported in a number of local AGNs through the detection of blue-shifted Fe XXV/XXVI absorption lines. We present the results of a comprehensive spectral analysis of a large sample of 42 local Seyferts and 5 Broad-Line Radio Galaxies (BLRGs) observed with XMM-Newton and Suzaku. We detect UFOs in ga 40% of the sources. Their outflow velocities are in the range ˜ 0.03-0.3c, with a mean value of ˜ 0.14c. The ionization is high, in the range logℰ ˜3-6rm erg s-1 cm, and also the associated column densities are large, in the interval ˜ 1022-1024rm cm-2. Overall, these results point to the presence of highly ionized and massive outflowing material in the innermost regions of AGNs. Their variability and location on sub-pc scales favor a direct association with accretion disk winds/outflows. This also suggests that UFOs may potentially play a significant role in the AGN cosmological feedback besides jets, and their study can provide important clues on the connection between accretion disks, winds, and jets.
Unification of X-ray Winds in Seyfert Galaxies: From Ultra-fast Outflows to Warm Absorbers
NASA Technical Reports Server (NTRS)
Tombesi, F.; Cappi, M.; Reeves, J. N.; Nemmen, R. S.; Braito, V.; Gaspari, M.; Reynolds, C. S.
2013-01-01
The existence of ionized X-ray absorbing layers of gas along the line of sight to the nuclei of Seyfert galaxies is a well established observational fact. This material is systematically outflowing and shows a large range in parameters. However, its actual nature and dynamics are still not clear. In order to gain insights into these important issues we performed a literature search for papers reporting the parameters of the soft X-ray warm absorbers (WAs) in 35 type 1 Seyferts and compared their properties to those of the ultra-fast outflows (UFOs) detected in the same sample. The fraction of sources with WAs is >60 per cent, consistent with previous studies. The fraction of sources with UFOs is >34 per cent, >67 per cent of which also show WAs. The large dynamic range obtained when considering all the absorbers together, spanning several orders of magnitude in ionization, column, velocity and distance allows us, for the first time, to investigate general relations among them. In particular, we find significant correlations indicating that the closer the absorber is to the central black hole, the higher the ionization, column, outflow velocity and consequently the mechanical power. In all the cases, the absorbers continuously populate the whole parameter space, with the WAs and the UFOs lying always at the two ends of the distribution. These evidence strongly suggest that these absorbers, often considered of different types, could actually represent parts of a single large-scale stratified outflow observed at different locations from the black hole. The UFOs are likely launched from the inner accretion disc and the WAs at larger distances, such as the outer disc and/or torus. We argue that the observed parameters and correlations are, to date, consistent with both radiation pressure through Compton scattering and magnetohydrodynamic processes contributing to the outflow acceleration, the latter playing a major role. Most of the absorbers, especially the UFOs, show a sufficiently high mechanical power (at least approx 0.5 per cent of the bolometric luminosity) to provide a significant contribution to active galactic nuclei (AGN) feedback and thus to the evolution of the host galaxy. In this regard, we find possible evidence for the interaction of the AGN wind with the surrounding environment on large scales.
Unification of X-ray winds in Seyfert galaxies: from ultra-fast outflows to warm absorbers
NASA Astrophysics Data System (ADS)
Tombesi, F.; Cappi, M.; Reeves, J. N.; Nemmen, R. S.; Braito, V.; Gaspari, M.; Reynolds, C. S.
2013-04-01
The existence of ionized X-ray absorbing layers of gas along the line of sight to the nuclei of Seyfert galaxies is a well established observational fact. This material is systematically outflowing and shows a large range in parameters. However, its actual nature and dynamics are still not clear. In order to gain insights into these important issues we performed a literature search for papers reporting the parameters of the soft X-ray warm absorbers (WAs) in 35 type 1 Seyferts and compared their properties to those of the ultra-fast outflows (UFOs) detected in the same sample. The fraction of sources with WAs is >60 per cent, consistent with previous studies. The fraction of sources with UFOs is >34 per cent, >67 per cent of which also show WAs. The large dynamic range obtained when considering all the absorbers together, spanning several orders of magnitude in ionization, column, velocity and distance allows us, for the first time, to investigate general relations among them. In particular, we find significant correlations indicating that the closer the absorber is to the central black hole, the higher the ionization, column, outflow velocity and consequently the mechanical power. In all the cases, the absorbers continuously populate the whole parameter space, with the WAs and the UFOs lying always at the two ends of the distribution. These evidence strongly suggest that these absorbers, often considered of different types, could actually represent parts of a single large-scale stratified outflow observed at different locations from the black hole. The UFOs are likely launched from the inner accretion disc and the WAs at larger distances, such as the outer disc and/or torus. We argue that the observed parameters and correlations are, to date, consistent with both radiation pressure through Compton scattering and magnetohydrodynamic processes contributing to the outflow acceleration, the latter playing a major role. Most of the absorbers, especially the UFOs, show a sufficiently high mechanical power (at least ˜0.5 per cent of the bolometric luminosity) to provide a significant contribution to active galactic nuclei (AGN) feedback and thus to the evolution of the host galaxy. In this regard, we find possible evidence for the interaction of the AGN wind with the surrounding environment on large scales.
NASA Astrophysics Data System (ADS)
Tombesi, F.; Cappi, M.; Reeves, J. N.; Palumbo, G. G. C.; Braito, V.; Dadina, M.
2011-11-01
X-ray absorption line spectroscopy has recently shown evidence for previously unknown Ultra-fast Outflows (UFOs) in radio-quiet active galactic nuclei (AGNs). These have been detected essentially through blueshifted Fe XXV/XXVI K-shell transitions. In the previous paper of this series we defined UFOs as those highly ionized absorbers with an outflow velocity higher than 10,000 km s-1 and assessed the statistical significance of the associated blueshifted absorption lines in a large sample of 42 local radio-quiet AGNs observed with XMM-Newton. The present paper is an extension of that work. First, we report a detailed curve of growth analysis of the main Fe XXV/XXVI transitions in photoionized plasmas. Then, we estimate an average spectral energy distribution for the sample sources and directly model the Fe K absorbers in the XMM-Newton spectra with the detailed Xstar photoionization code. We confirm that the frequency of sources in the radio-quiet sample showing UFOs is >35% and that the majority of the Fe K absorbers are indeed associated with UFOs. The outflow velocity distribution spans from ~10,000 km s-1 (~0.03c) up to ~100,000 km s-1 (~0.3c), with a peak and mean value of ~42,000 km s-1 (~0.14c). The ionization parameter is very high and in the range log ξ ~ 3-6 erg s-1 cm, with a mean value of log ξ ~ 4.2 erg s-1 cm. The associated column densities are also large, in the range N H ~ 1022-1024 cm-2, with a mean value of N H ~ 1023 cm-2. We discuss and estimate how selection effects, such as those related to the limited instrumental sensitivity at energies above 7 keV, may hamper the detection of even higher velocities and higher ionization absorbers. We argue that, overall, these results point to the presence of extremely ionized and possibly almost Compton-thick outflowing material in the innermost regions of AGNs. This also suggests that UFOs may potentially play a significant role in the expected cosmological feedback from AGNs and their study can provide important clues on the connection between accretion disks, winds, and jets.
NASA Astrophysics Data System (ADS)
Teodorani, M.
1999-03-01
The psycho-sociological reasons why the academic science is not willing to face operatively and officially a hard problem such as the 'UFO phenomenon', are introduced in the ambit of an episthemological discussion. It is shown how such a phenomenon, due to his peculiar nature, might impose a drastic revision of the laws of physics which are commonly accepted. It is demonstrated how a strict application of the measurement methods which are normally adopted by physics can permit to obtain relevant quantitative results, whatever they are. As an example of such a procedure, the anomalous light phenomenology which reoccurs in the Hessdalen valley in Norway is presented, by showing that it represents so far the ideal worldly physical laboratory for the study of luminous phenomena in the low atmosphere. After describing the multiform morphologic and dynamic characteristics of the luminous component of the phenomenon as they are deduced from visual and photographic reports, the results coming out from the magnetometric, radiometric and radar monitoring operations which were carried out by Project Hessdalen in 1984, are presented in detail. Subsequently, the postumous analysis carried out by the author is shown, by pointing out the clear cohexistence of the magnetic and the optical phenomenology and the apparent correlation of the magnetic component of the phenomenon with maxima of solar activity. In a subsequent phase, the most credited physical theories, which have been proposed so far in order to interpret the phenomenon, are described and discussed, together with 'non-canonical hypotheses'. Finally, it is pointed out how the physical parameters which are expected to be measured with the proper instrumented equipment and aimed tactics and strategies, resemble strictly the methodology which is normally used during astrophysical observations.
[Trauma and accident documentation in Germany compared with elsewhere in Europe].
Probst, C; Richter, M; Haasper, C; Lefering, R; Otte, D; Oestern, H J; Krettek, C; Hüfner, T
2008-07-01
The role of trauma documentation has grown continuously since the 1970s. Prevention and management of injuries were adapted according to the results of many analyses. Since 1993 there have been two different trauma databases in Germany: the German trauma registry (TR) and the database of the Accident Research Unit (UFO). Modern computer applications improved the data processing. Our study analysed the pros and cons of each system and compared them with those of our European neighbours. We compared the TR and the UFO databases with respect to aims and goals, advantages and disadvantages, and current status. Results were reported as means +/- standard errors of the mean. The level of significance was set at P<0.05. There were differences between the two databases concerning number and types of items, aims and goals, and demographics. The TR documents care for severely injured patients and the clinical course of different types of accidents. The UFO describes traffic accidents, accident conditions, and interrelations. The German and British systems are similar, and the French system shows interesting differences. The German trauma documentation systems focus on different points. Therefore both can be used for substantiated analyses of different hypotheses. Certain intersections of both databases may help to answer very special questions in the future.
Ectopic expression of SUPERMAN suppresses development of petals and stamens.
Yun, Jae-Young; Weigel, Detlef; Lee, Ilha
2002-01-01
The floral regulatory gene SUPERMAN (SUP) encodes a C2H2 type zinc finger protein that is required for maintaining boundaries between floral organs in Arabidopsis. It has been proposed that the main function of SUP is to balance cell proliferation in the third and fourth whorl of developing flowers, thereby maintaining the boundaries between the two whorls. To gain further insight into the function of SUP, we have ectopically expressed SUP using the promoter of APETALA1 (AP1), a gene that is initially expressed throughout floral meristems and later becomes restricted to the first and second whorls. Flowers of AP1::SUP plants have fewer floral organs, consistent with an effect of SUP on cell proliferation. In addition, the AP1::SUP transgene caused the conversion of petals to sepals and suppressed the development of stamens. The expression of the B function homeotic gene APETALA3 (AP3) and its regulator UNUSUAL FLORAL ORGANS (UFO) were delayed and reduced in AP1::SUP flowers. However, SUP does not act merely through UFO, as constitutive expression of UFO did not rescue the defects in petal and stamen development in AP1::SUP flowers. Together, these results suggest that SUP has both indirect and direct effects on the expression of B function homeotic genes.
Kusters, Elske; Della Pina, Serena; Castel, Rob; Souer, Erik; Koes, Ronald
2015-08-15
Higher plant species diverged extensively with regard to the moment (flowering time) and position (inflorescence architecture) at which flowers are formed. This seems largely caused by variation in the expression patterns of conserved genes that specify floral meristem identity (FMI), rather than changes in the encoded proteins. Here, we report a functional comparison of the promoters of homologous FMI genes from Arabidopsis, petunia, tomato and Antirrhinum. Analysis of promoter-reporter constructs in petunia and Arabidopsis, as well as complementation experiments, showed that the divergent expression of leafy (LFY) and the petunia homolog aberrant leaf and flower (ALF) results from alterations in the upstream regulatory network rather than cis-regulatory changes. The divergent expression of unusual floral organs (UFO) from Arabidopsis, and the petunia homolog double top (DOT), however, is caused by the loss or gain of cis-regulatory promoter elements, which respond to trans-acting factors that are expressed in similar patterns in both species. Introduction of pUFO:UFO causes no obvious defects in Arabidopsis, but in petunia it causes the precocious and ectopic formation of flowers. This provides an example of how a change in a cis-regulatory region can account for a change in the plant body plan. © 2015. Published by The Company of Biologists Ltd.
X-ray evidence for ultra-fast outflows in Seyfert galaxies
NASA Astrophysics Data System (ADS)
Tombesi, Francesco; Braito, Valentina; Reeves, James; Cappi, Massimo; Dadina, Mauro
2012-07-01
X-ray evidence for massive, highly ionized, ultra-fast outflows (UFOs) has been recently reported in a number of AGNs through the detection of blue-shifted Fe XXV/XXVI absorption lines. We present the results of a comprehensive spectral analysis of a large sample of 42 local Seyferts observed with XMM-Newton. Similar results are also obtained from a Suzaku analysis of 5 radio galaxies. We find that UFOs are common phenomena, being present in >40% of the sources. Their outflow velocity distribution is in the range ˜0.03--0.3c, with mean value of ˜0.14c. The ionization parameter is very high, in the range logξ˜3--6 erg~s^{-1}~cm, and the associated column densities are also large, in the range ˜10^{22}--10^{24} cm^{-2}. Their location is constrained at ˜0.0003--0.03pc (˜10^2--10^4 r_s) from the central black hole, consistent with what is expected for accretion disk winds/outflows. The mass outflow rates are in the interval ˜0.01--1M_{⊙}~yr^{-1}. The associated mechanical power is also high, in the range ˜10^{43}--10^{45} erg/s, which indicates that UFOs are capable to provide a significant contribution to the AGN cosmological feedback.
NuSTAR View of the Black Hole Wind in the Galaxy Merger IRAS F11119+3257
NASA Astrophysics Data System (ADS)
Tombesi, F.; Veilleux, S.; Meléndez, M.; Lohfink, A.; Reeves, J. N.; Piconcelli, E.; Fiore, F.; Feruglio, C.
2017-12-01
Galactic winds driven by active galactic nuclei (AGNs) have been invoked to play a fundamental role in the co-evolution between supermassive black holes and their host galaxies. Finding observational evidence of such feedback mechanisms is of crucial importance and it requires a multi-wavelength approach in order to compare winds at different scales and phases. In Tombesi et al., we reported the detection of a powerful ultra-fast outflow (UFO) in the Suzaku X-ray spectrum of the ultra-luminous infrared galaxy IRAS F11119+3257. The comparison with a galaxy-scale OH molecular outflow observed with Herschel in the same source supported the energy-conserving scenario for AGN feedback. The main objective of this work is to perform an independent check of the Suzaku results using the higher sensitivity and wider X-ray continuum coverage of NuSTAR. We clearly detect a highly ionized Fe K UFO in the 100 ks NuSTAR spectrum with parameters N H = (3.2 ± 1.5) × 1024 cm-2, log ξ = {4.0}-0.3+1.2 erg s-1 cm, and {v}{out}={0.253}-0.118+0.061c. The launching radius is likely at a distance of r ≥ 16r s from the black hole. The mass outflow rate is in the range of {\\dot{M}}{out} ≃ 0.5-2 M ⊙ yr-1. The UFO momentum rate and power are {\\dot{P}}{out} ≃ 0.5-2 L AGN/c and {\\dot{E}}{out} ≃ 7%-27% L AGN, respectively. The UFO parameters are consistent between the 2013 Suzaku and the 2015 NuSTAR observations. Only the column density is found to be variable, possibly suggesting a clumpy wind. The comparison with the energetics of molecular outflows estimated in infrared and millimeter wavelengths support a connection between the nuclear and galaxy-scale winds in luminous AGNs.
NASA Technical Reports Server (NTRS)
Tombesi, Francesco; Clapp, M.; Reeves, J. N.; Palumbo, G. G. C.; Braito, V.; Dadina, M.
2011-01-01
X-ray absorption line spectroscopy has recently shown evidence for previously unknown Ultra-fast Outflows (UFOs) in radio-quiet AGNs. In the previous paper of this series we defined UFOs as those absorbers with an outflow velocity higher than 10,000km/s and assessed the statistical significance of the associated blue shifted FeK absorption lines in a large sample of 42 local radio-quiet AGNs observed with XMM-Newton. In the present paper we report a detailed curve of growth analysis and directly model the FeK absorbers with the Xstar photo-ionization code. We confirm that the frequency of sources in the radio-quiet sample showing UFOs is >35%. The outflow velocity distribution spans from \\sim10,000km/s (\\sim0.03c) up to \\siml00,000kmis (\\sim0.3c), with a peak and mean value of\\sim42,000km/s (\\sim0.14c). The ionization parameter is very high and in the range log\\xi 3-6 erg s/cm, with a mean value of log\\xi 4.2 erg s/cm. The associated column densities are also large, in the range N_H\\siml0(exp 22)-10(exp 24)/sq cm, with a mean value of N_H\\siml0(exp23)/sq cm. We discuss and estimate how selection effects, such as those related to the limited instrumental sensitivity at energies above 7keV, may hamper the detection of even higher velocities and higher ionization absorbers. We argue that, overall, these results point to the presence of extremely ionized and possibly almost Compton thick outflowing material in the innermost regions of AGNs. This also suggests that UFOs may potentially play a significant role in the expected cosmological feedback from AGNs and their study can provide important clues on the connection between accretion disks, winds and jets.
IN12-UFO: new frontiers for cold triple-axis spectroscopy
NASA Astrophysics Data System (ADS)
Schmidt, Wolfgang; Ohl, Michael
2006-11-01
The IN12 instrument is operated by the Research Centre at Jülich in collaboration with CEA Grenoble as a CRG-B instrument at the Institute Laue Langevin in Grenoble. As a triple-axis spectrometer for cold neutrons it is dedicated for high-resolution studies of low-energy excitations. To meet further challenges as a state-of-the-art instrument we will now upgrade IN12 with a multi-analyzer option. IN12 will then be equipped with a large 2-dimensional position sensitive detector and an array of 15 individual analyser blades which can be rotated and positioned separately in order to map the scattered beam on a user-chosen path in Q- ω-space. We refer to this set-up as IN12-UFO (Universal Focusing Option). The innovative flexibility of the analyzer array is realized by completely non-magnetic drive mechanisms where all relevant parameters are controlled by an absolute encoding system. This mechanics allows to position the individual analyzers so that (a) there are no gaps or overlaps as seen from the sample (optimum coverage) and (b) all reflected beams from the analyzers meet at one single focus point on their way to different spots on the detector surface. The focus point is controlled by a movable diaphragm and provides the only opening between analyzer and detector shielding to prevent cross-talk and to keep the background low. We will present further details of this set-up and demonstrate its flexibility and multiplex advantages for specific physical applications.
NASA Astrophysics Data System (ADS)
Fraknoi, A.
2008-11-01
During IYA educators and scientists will interact with the public in many ways. There will likely be public questions at IYA events about pseudo-scientific topics. While the particular pseudo-sciences that are in vogue change with time, these days popular astronomical pseudo-science includes creationism and intelligent design (and their denial of the age of the universe), astrology, UFO's as extra-terrestrial spaceships, selling star names, the ``face'' on Mars, the claim that the moon landings were a hoax, etc. We discuss some of the recent surveys of belief in pseudo-science and some ways to respond to questions about these topics. A separate resource guide to help answer questions about astronomical pseudoscience is also included in this volume.
AGN feedback through UFO and galaxy-wide winds in the early Universe
NASA Astrophysics Data System (ADS)
Feruglio, C.; Piconcelli, E.; Bischetti, M.; Zappacosta, L.; Fiore, F.
2017-10-01
AGN feedback through massive molecular winds is today routinely observed in local AGN host galaxies, but not as such in the early universe. I will present the first evidence for a massive, AGN-driven molecular wind in the z 4 QSO APM08279, which also hosts the most well studied and persistent nuclear semi-raltivistic wind (UFO). This observation directly probes the expansion mechanism of a nuclear wind into the ISM on galaxy wide scales, that so far was constrained by a couple of other objects only (Feruglio et al. 2015, Tombesi et al. 2015). This result also opens the path toward the exploration of molecular AGN-driven winds at early epochs, close after the end of the Epoch of Reionisation (EoR).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Renzi, N.E.; Roseberry, R.J.
>The experimental measurements and nuclear analysis of a uniformly loaded, unpoisoned slab core with a partially insented hafnium rod are described. Comparisons of experimental data with calculated results of the UFO code and flux synthesis techniques are given. It was concluded that one of the flux synthesis techniques and the UFO code are able to predict flux distributions to within approximately 5% of experiment for most cases. An error of approximately 10% was found in the synthesis technique for a channel near the partially inserted rod. The various calculations were able to predict neutron pulsed shutdowns to only approximately 30%.more » (auth)« less
The KNOXI Transcription Factor SHOOT MERISTEMLESS Regulates Floral Fate in Arabidopsis.
Roth, Ohad; Alvarez, John; Levy, Matan; Bowman, John L; Ori, Naomi; Shani, Eilon
2018-05-09
Plants have evolved a unique and conserved developmental program that enables the conversion of leaves into floral organs. Elegant genetic and molecular work has identified key regulators of flower meristem identity. However, further understanding of flower meristem specification has been hampered by redundancy and by pleiotropic effects. The KNOXI transcription factor SHOOT MERISTEMLESS (STM) is a well-characterized regulator of shoot apical meristem maintenance. Arabidopsis thaliana stm loss-of-function mutants arrest shortly after germination, and therefore the knowledge on later roles of STM in later processes, including flower development, is limited. Here, we uncover a role for STM in the specification of flower meristem identity. Silencing STM in the APETALA1 (AP1) expression domain in the ap1-4 mutant background resulted in a leafy-flower phenotype, and an intermediate stm-2 allele enhanced the flower meristem identity phenotype of ap1-4. Transcriptional profiling of STM perturbation suggested that STM activity affects multiple floral fate genes, among them the F-Box protein-encoding gene UNUSUAL FLORAL ORGANS (UFO). In agreement with this notion, stm-2 enhanced the ufo-2 floral fate phenotype, and ectopic UFO expression rescued the leafy flowers in genetic backgrounds with compromised AP1 and STM activities. This work suggests a genetic mechanism that underlies the activity of STM in the specification of flower meristem identity. © 2018 American Society of Plant Biologists. All rights reserved.
Modeling X-ray Absorbers in AGNs with MHD-Driven Accretion-Disk Winds
NASA Astrophysics Data System (ADS)
Fukumura, Keigo; Kazanas, D.; Shrader, C. R.; Tombesi, F.; Contopoulos, J.; Behar, E.
2013-04-01
We have proposed a systematic view of the observed X-ray absorbers, namely warm absorbers (WAs) in soft X-ray and highly-ionized ultra-fast outflows (UFOs), in the context of magnetically-driven accretion-disk wind models. While potentially complicated by variability and thermal instability in these energetic outflows, in this simplistic model we have calculated 2D kinematic field as well as density and ionization structure of the wind with density profile of 1/r corresponding to a constant column distribution per decade of ionization parameter. In particular we show semi-analytically that the inner layer of the disk-wind manifests itself as the strongly-ionized fast outflows while the outer layer is identified as the moderately-ionized absorbers. The computed characteristics of these two apparently distinct absorbers are consistent with X-ray data (i.e. a factor of ~100 difference in column and ionization parameters as well as low wind velocity vs. near-relativistic flow). With the predicted contour curves for these wind parameters one can constrain allowed regions for the presence of WAs and UFOs.The model further implies that the UFO's gas pressure is comparable to that of the observed radio jet in 3C111 suggesting that the magnetized disk-wind with density profile of 1/r is a viable agent to help sustain such a self-collimated jet at small radii.
Coal Technology Program progress report for April 1976
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
In the Hydrocarbonization Research program, two successful experiments were completed in the bench-scale hydrocarbonizer. A settling test at a lower temperature (390/sup 0/F) using 20 percent toluene in Solvent Refined Coal (SRC) Unfiltered Oil (UFO) produced a 30 percent clarified product in 2 hr. Characterization tests include distillation curves for Wilsonville's SRC-UFO and a particle size distribution of Pittsburg and Midway Coal Mining Company's (PAMCO) SRC-UFO. Studies of intermediate-temperature pyrolysis of large blocks have been maintained with char samples continuing to demonstrate pyrophoricity, even after heating to 700/sup 0/C. Simulated distillation analysis of tars produced by the last eight experimentsmore » are being compared with those performed at Laramie upon tars produced by the Hanna No. 2 experiment. In Coal-Fueled MIUS, stainless steel tubing to be used in one of the furnace tube bundles was ordered and the bid package for the furnace completed. Tests continued on the coal feed system and with the cold flow fluidized bed model. For the Synthoil process, flow diagrams, material balances, and utilities requirements were completed for the entire facility. For the Hydrocarbonization process, flowsheets were reviewed for compatibility; equipment lists were brought up to date; and utilities requirements were compiled from the individual flowsheets. The char recovery and storage subsystem flowsheet was completed. (auth)« less
Inverse Compton X-ray signature of AGN feedback
NASA Astrophysics Data System (ADS)
Bourne, Martin A.; Nayakshin, Sergei
2013-12-01
Bright AGN frequently show ultrafast outflows (UFOs) with outflow velocities vout ˜ 0.1c. These outflows may be the source of AGN feedback on their host galaxies sought by galaxy formation modellers. The exact effect of the outflows on the ambient galaxy gas strongly depends on whether the shocked UFOs cool rapidly or not. This in turn depends on whether the shocked electrons share the same temperature as ions (one-temperature regime, 1T) or decouple (2T), as has been recently suggested. Here we calculate the inverse Compton spectrum emitted by such shocks, finding a broad feature potentially detectable either in mid-to-high energy X-rays (1T case) or only in the soft X-rays (2T). We argue that current observations of AGN do not seem to show evidence for the 1T component. The limits on the 2T emission are far weaker, and in fact it is possible that the observed soft X-ray excess of AGN is partially or fully due to the 2T shock emission. This suggests that UFOs are in the energy-driven regime outside the central few pc, and must pump considerable amounts of not only momentum but also energy into the ambient gas. We encourage X-ray observers to look for the inverse Compton components calculated here in order to constrain AGN feedback models further.
Shah, Syed Imran Hussain; Lim, Sungjoon
2017-11-20
In this paper, a novel dual band frequency reconfigurable antenna using an origami magic cube is proposed for wireless sensor network (WSN) applications. The proposed origami antenna consists of a meandered monopole folded onto three sides of the magic cube. A microstrip open-ended stub is loaded on the meandered monopole. The proposed origami magic cube can be mechanically folded and unfolded. The proposed antenna operates at 1.57 GHZ and 2.4 GHz in the folded state. In the unfolded state, the proposed antenna operates at 900 MHz and 2.3 GHz. The resonant frequency of the second band can be tunable by varying the length and position of the open stub. The origami magic cube is built on paper. Its performance is numerically and experimentally demonstrated from S-parameters and radiation patterns. The measured 10 dB impedance bandwidth of the proposed origami antenna is 18% (900-1120 MHz) and 15% (2.1-2.45 GHz) for the unfolded state and 20% (1.3-1.6 GHz) and 14% (2.3-2.5 GHz) for the folded state. The measured peak gain at 900 MHz and 2.3 GHz are 1.1 dBi and 2.32 dBi, respectively, in the unfolded state. The measured peak gain at 1.5 GHz and 2.4 GHz are 3.28 dBi and 1.98 dBi, respectively, in the folded state.
NASA Astrophysics Data System (ADS)
Gaina, Alex
1996-08-01
Critical analysis is given of some paranormal phenomena events (UFO, healers, psychokinesis (telekinesis))reported in Moldova. It is argued that correct analysis of paranormal phenomena should be made in the framework of electromagnetism.
Deiana, Antonio; Giansanti, Andrea
2010-04-21
Natively unfolded proteins lack a well defined three dimensional structure but have important biological functions, suggesting a re-assignment of the structure-function paradigm. To assess that a given protein is natively unfolded requires laborious experimental investigations, then reliable sequence-only methods for predicting whether a sequence corresponds to a folded or to an unfolded protein are of interest in fundamental and applicative studies. Many proteins have amino acidic compositions compatible both with the folded and unfolded status, and belong to a twilight zone between order and disorder. This makes difficult a dichotomic classification of protein sequences into folded and natively unfolded ones. In this work we propose an operational method to identify proteins belonging to the twilight zone by combining into a consensus score good performing single predictors of folding. In this methodological paper dichotomic folding indexes are considered: hydrophobicity-charge, mean packing, mean pairwise energy, Poodle-W and a new global index, that is called here gVSL2, based on the local disorder predictor VSL2. The performance of these indexes is evaluated on different datasets, in particular on a new dataset composed by 2369 folded and 81 natively unfolded proteins. Poodle-W, gVSL2 and mean pairwise energy have good performance and stability in all the datasets considered and are combined into a strictly unanimous combination score SSU, that leaves proteins unclassified when the consensus of all combined indexes is not reached. The unclassified proteins: i) belong to an overlap region in the vector space of amino acidic compositions occupied by both folded and unfolded proteins; ii) are composed by approximately the same number of order-promoting and disorder-promoting amino acids; iii) have a mean flexibility intermediate between that of folded and that of unfolded proteins. Our results show that proteins unclassified by SSU belong to a twilight zone. Proteins left unclassified by the consensus score SSU have physical properties intermediate between those of folded and those of natively unfolded proteins and their structural properties and evolutionary history are worth to be investigated.
2010-01-01
Background Natively unfolded proteins lack a well defined three dimensional structure but have important biological functions, suggesting a re-assignment of the structure-function paradigm. To assess that a given protein is natively unfolded requires laborious experimental investigations, then reliable sequence-only methods for predicting whether a sequence corresponds to a folded or to an unfolded protein are of interest in fundamental and applicative studies. Many proteins have amino acidic compositions compatible both with the folded and unfolded status, and belong to a twilight zone between order and disorder. This makes difficult a dichotomic classification of protein sequences into folded and natively unfolded ones. In this work we propose an operational method to identify proteins belonging to the twilight zone by combining into a consensus score good performing single predictors of folding. Results In this methodological paper dichotomic folding indexes are considered: hydrophobicity-charge, mean packing, mean pairwise energy, Poodle-W and a new global index, that is called here gVSL2, based on the local disorder predictor VSL2. The performance of these indexes is evaluated on different datasets, in particular on a new dataset composed by 2369 folded and 81 natively unfolded proteins. Poodle-W, gVSL2 and mean pairwise energy have good performance and stability in all the datasets considered and are combined into a strictly unanimous combination score SSU, that leaves proteins unclassified when the consensus of all combined indexes is not reached. The unclassified proteins: i) belong to an overlap region in the vector space of amino acidic compositions occupied by both folded and unfolded proteins; ii) are composed by approximately the same number of order-promoting and disorder-promoting amino acids; iii) have a mean flexibility intermediate between that of folded and that of unfolded proteins. Conclusions Our results show that proteins unclassified by SSU belong to a twilight zone. Proteins left unclassified by the consensus score SSU have physical properties intermediate between those of folded and those of natively unfolded proteins and their structural properties and evolutionary history are worth to be investigated. PMID:20409339
Computer simulation and high level virial theory of Saturn-ring or UFO colloids.
Bates, Martin A; Dennison, Matthew; Masters, Andrew
2008-08-21
Monte Carlo simulations are used to map out the complete phase diagram of hard body UFO systems, in which the particles are composed of a concentric sphere and thin disk. The equation of state and phase behavior are determined for a range of relative sizes of the sphere and disk. We show that for relatively large disks, nematic and solid phases are observed in addition to the isotropic fluid. For small disks, two different solid phases exist. For intermediate sizes, only a disordered fluid phase is observed. The positional and orientational structure of the various phases are examined. We also compare the equations of state and the nematic-isotropic coexistence densities with those predicted by an extended Onsager theory using virial coefficients up to B(8).
Computer simulation and high level virial theory of Saturn-ring or UFO colloids
NASA Astrophysics Data System (ADS)
Bates, Martin A.; Dennison, Matthew; Masters, Andrew
2008-08-01
Monte Carlo simulations are used to map out the complete phase diagram of hard body UFO systems, in which the particles are composed of a concentric sphere and thin disk. The equation of state and phase behavior are determined for a range of relative sizes of the sphere and disk. We show that for relatively large disks, nematic and solid phases are observed in addition to the isotropic fluid. For small disks, two different solid phases exist. For intermediate sizes, only a disordered fluid phase is observed. The positional and orientational structure of the various phases are examined. We also compare the equations of state and the nematic-isotropic coexistence densities with those predicted by an extended Onsager theory using virial coefficients up to B8.
Electroweak Higgs production with HiggsPO at NLO QCD
NASA Astrophysics Data System (ADS)
Greljo, Admir; Isidori, Gino; Lindert, Jonas M.; Marzocca, David; Zhang, Hantian
2017-12-01
We present the HiggsPO UFO model for Monte Carlo event generation of electroweak VH and VBF Higgs production processes at NLO in QCD in the formalism of Higgs pseudo-observables (PO). We illustrate the use of this tool by studying the QCD corrections, matched to a parton shower, for several benchmark points in the Higgs PO parameter space. We find that, while being sizable and thus important to be considered in realistic experimental analyses, the QCD higher-order corrections largely factorize. As an additional finding, based on the NLO results, we advocate to consider 2D distributions of the two-jet azimuthal-angle difference and the leading jet p_T for new physics searches in VBF Higgs production. The HiggsPO UFO model is publicly available.
Brown, Steven D.; Utturkar, Sagar M.; Magnuson, Timothy S.; ...
2014-09-04
Pelosinus fermentans strain R7 was isolated from Russian kaolin clays as the type strain and it can reduce Fe(III) during fermentative growth (1). Draft genome sequences for P. fermentans R7 and four strains from Hanford, Washington, USA, have been published (2–4). The P. fermentans 16S rRNA sequence dominated the lactate-based enrichment cultures from three geochemically contrasting soils from the Melton Branch Watershed, Oak Ridge, Tennessee, USA (5) and also at another stimulated, uraniumcontaminated field site near Oak Ridge (6). For the current work, strain UFO1 was isolated from pristine sediments at a background field site in Oak Ridge and characterizedmore » as facilitating U(VI) reduction and precipitation with phosphate (7).« less
Coal technology program progress report, February 1976
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
Final testing of the 20-atm bench-scale system is underway in preparation for experiments with hydrogen. Laboratory-scale testing of a number of inexpensive pure compounds to improve the settling rate of solids in Solvent Refined Coal (SRC) unfiltered oil (UFO), bench-scale testing of the effect of the Tretolite additive on settling, and characterization tests on a new sample of UFO from the PAMCO-SRC process are reported. Experimental engineering support of an in situ gasification process include low-temperature pyrolyses at exceptionally low heating rates (0.3/sup 0/C/min). Highly pyrophoric chars were consistently produced. Aqueous by-products from coal conversion technologies and oil shale retortingmore » have been analyzed directly to determine major organic components. A report is being prepared discussing various aspects of the engineering evaluations of nuclear process heat for coal. A bench-scale test program on thermochemical water splitting for hydrogen production is under consideration. In the coal-fueled MIUS program, preparations for procurement of tubing for the matrix in the fluidized-bed furnace and for fabrication of the furnace continued. Analyses of the AiResearch gas turbine and recuperator under coal-fueled MIUS operating conditions are near completion. Process flow diagrams and heat and material balances were completed for most of the units in the synthoil process. Overall utilities requirements were calculated and the coal preparation flowsheets were finalized. For hydrocarbonization, the flowsheet was revised to include additional coal data. Flowsheets were finalized for the acid gas separation and recycle, and the oil-solids separation. (LTN)« less
Shah, Syed Imran Hussain
2017-01-01
In this paper, a novel dual band frequency reconfigurable antenna using an origami magic cube is proposed for wireless sensor network (WSN) applications. The proposed origami antenna consists of a meandered monopole folded onto three sides of the magic cube. A microstrip open-ended stub is loaded on the meandered monopole. The proposed origami magic cube can be mechanically folded and unfolded. The proposed antenna operates at 1.57 GHZ and 2.4 GHz in the folded state. In the unfolded state, the proposed antenna operates at 900 MHz and 2.3 GHz. The resonant frequency of the second band can be tunable by varying the length and position of the open stub. The origami magic cube is built on paper. Its performance is numerically and experimentally demonstrated from S-parameters and radiation patterns. The measured 10 dB impedance bandwidth of the proposed origami antenna is 18% (900–1120 MHz) and 15% (2.1–2.45 GHz) for the unfolded state and 20% (1.3–1.6 GHz) and 14% (2.3–2.5 GHz) for the folded state. The measured peak gain at 900 MHz and 2.3 GHz are 1.1 dBi and 2.32 dBi, respectively, in the unfolded state. The measured peak gain at 1.5 GHz and 2.4 GHz are 3.28 dBi and 1.98 dBi, respectively, in the folded state. PMID:29156654
The lure of local SETI: Fifty years of field experiments
NASA Astrophysics Data System (ADS)
Ailleris, Philippe
2011-01-01
With the commemoration in October 2007 of the Sputnik launch, space exploration celebrated its 50th anniversary. Despite impressive technological and scientific achievements the fascination for space has weakened during the last decades. One contributing factor has been the gradual disappearance of mankind's hope of discovering extraterrestrial life within its close neighbourhood. In striking contrast and since the middle of the 20th century, a non-negligible proportion of the population have already concluded that intelligent beings from other worlds do exist and visit Earth through space vehicles popularly called Unidentified Flying Objects (UFOs). In light of the continuous public interest for the UFO enigma symbolized by the recent widely diffused media announcements on the release of French and English governmental files; and considering the approach of broadening the strategies of the "Active SETI" approach and the existence of a rich multi-disciplinary UFO documentation of potential interest for SETI; this paper describes some past scientific attempts to demonstrate the physical reality of the phenomena and potentially the presence on Earth of probes of extraterrestrial origin. Details of the different instrumented field studies deployed by scientists and organizations during the period 1950-1990 in the USA, Canada and Europe are provided. In conclusion it will be argued that while continuing the current radio/optical SETI searches, there is the necessity to maintain sustaining attention to the topic of anomalous aerospace phenomena and to develop new rigorous research approaches.
Taylor, S; Hofer, J; Murfet, I
2001-01-01
Isolation and characterization of two severe alleles at the Stamina pistilloida (Stp) locus reveals that Stp is involved in a wide range of developmental processes in the garden pea. The most severe allele, stp-4, results in flowers consisting almost entirely of sepals and carpels. Production of ectopic secondary flowers in stp-4 plants suggests that Stp is involved in specifying floral meristem identity in pea. The stp mutations also reduce the complexity of the compound pea leaf, and primary inflorescences often terminate prematurely in an aberrant sepaloid flower. In addition, stp mutants were shorter than their wild-type siblings due to a reduction in cell number in their internodes. Fewer cells were also found in the epidermis of the leaf rachis of stp mutants. Examination of the effects of stp-4 in double mutant combinations with af, tl, det, and veg2-2-mutations known to influence leaf, inflorescence, and flower development in pea-suggests that Stp function is independent of these genes. A synergistic interaction between weak mutant alleles at Stp and Uni indicated that these two genes act together, possibly to regulate primordial growth. Molecular analysis revealed that Stp is the pea homolog of the Antirrhinum gene Fimbriata (Fim) and of UNUSUAL FLORAL ORGANS (UFO) from Arabidopsis. Differences between Fim/UFO and Stp mutant phenotypes and expression patterns suggest that expansion of Stp activity into the leaf was an important step during evolution of the compound leaf in the garden pea.
X-ray evidence for ultra-fast outflows in AGNs
NASA Astrophysics Data System (ADS)
Tombesi, Francesco; Sambruna, Rita; Braito, Valentina; Reeves, James; Reynolds, Christopher; Cappi, Massimo
2012-07-01
X-ray evidence for massive, highly ionized, ultra-fast outflows (UFOs) has been recently reported in a number of AGNs through the detection of blue-shifted Fe XXV/XXVI absorption lines. We present the results of a comprehensive spectral analysis of a large sample of 42 local Seyferts and 5 radio galaxies observed with XMM-Newton and Suzaku. We assessed the global detection significance of the absorption lines and performed a detailed photo-ionization modeling. We find that UFOs are common phenomena, being present in >40% of the sources. Their outflow velocity distribution is in the range ˜0.03--0.3c, with mean value of ˜0.14c. The ionization parameter is very high, in the range logξ˜3--6 erg~s^{-1}~cm, and the associated column densities are also large, in the range ˜10^{22}--10^{24} cm^{-2}. Their location is constrained at ˜0.0003--0.03pc (˜10^2--10^4 r_s) from the central black hole, consistent with what is expected for accretion disk winds/outflows. The mass outflow rates are in the interval ˜0.01--1M_{⊙}~yr^{-1} and the associated mechanical power is high, in the range ˜10^{43}--10^{45} erg/s. Therefore, UFOs are capable to provide a significant contribution to the AGN cosmological feedback and their study can provide important clues on the connection between accretion disks, winds and jets.
An Automatic Video Meteor Observation Using UFO Capture at the Showa Station
NASA Astrophysics Data System (ADS)
Fujiwara, Y.; Nakamura, T.; Ejiri, M.; Suzuki, H.
2012-05-01
The goal of our study is to clarify meteor activities in the southern hemi-sphere by continuous optical observations with video cameras with automatic meteor detection and recording at Syowa station, Antarctica.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lewis, P.M.; Crosier, K.E.; Crosier, P.S.
The receptor tyrosine kinase Dtk/Tyro 3/Sky/rse/brt/tif is a member of a new subfamily of receptors that also includes Axl/Ufo/Ark and Eyk/Mer. These receptors are characterized by the presence of two immunoglobulin-like loops and two fibronectin type III repeats in their extracellular domains. The structure of the murine Dtk gene has been determined. The gene consists of 21 exons that are distributed over 21 kb of genomic DNA. An isoform of Dtk is generated by differential splicing of exons from the 5{prime} region of the gene. The overall genomic structure of Dtk is virtually identical to that determined for the humanmore » UFO gene. This particular genomic organization is likely to have been duplicated and closely maintained throughout evolution. 38 refs., 3 figs., 1 tab.« less
Revealing the ultrafast outflow in IRAS 13224-3809 through spectral variability
NASA Astrophysics Data System (ADS)
Parker, M. L.; Alston, W. N.; Buisson, D. J. K.; Fabian, A. C.; Jiang, J.; Kara, E.; Lohfink, A.; Pinto, C.; Reynolds, C. S.
2017-08-01
We present an analysis of the long-term X-ray variability of the extreme narrow-line Seyfert 1 galaxy IRAS 13224-3809 using principal component analysis (PCA) and fractional excess variability (Fvar) spectra to identify model-independent spectral components. We identify a series of variability peaks in both the first PCA component and Fvar spectrum which correspond to the strongest predicted absorption lines from the ultrafast outflow (UFO) discovered by Parker et al. (2017). We also find higher order PCA components, which correspond to variability of the soft excess and reflection features. The subtle differences between RMS and PCA results argue that the observed flux-dependence of the absorption is due to increased ionization of the gas, rather than changes in column density or covering fraction. This result demonstrates that we can detect outflows from variability alone and that variability studies of UFOs are an extremely promising avenue for future research.
Chandra and Swift Observations of Unidentified Fermi-LAT Objects
NASA Astrophysics Data System (ADS)
Donato, Davide; Cheung, T.; Gehrels, N.
2010-03-01
In the last year we targeted some of the unidentified Fermi-LAT objects (UFOs) at high Galactic latitude with Chandra and Swift in order to determine the basic properties (positions, fluxes, hardness ratios) of all X-ray sources within the Fermi-LAT localization circles. These satellites enable us to detect the X-ray conterparts with a flux limit that is at least an order of magnitude lower than achieved in extant RASS data and to further follow-up at other wavelengths, with the ultimate goal to reveal the nature of these enigmatic gamma-ray sources. Here we present the results obtained with 5 Chandra pointings of high Galactic latitude UFOs in the Fermi-LAT 3-months bright source list. The association of detected X-ray sources within the improved 11-months Fermi-LAT localization circles with available optical and radio observations is discussed.
Sanders, Geoff; Sinclair, Kamila
2011-12-01
We report two Internet studies that investigated sex differences in the accuracy and precision of judging time to arrival. We used accuracy to mean the ability to match the actual time to arrival and precision to mean the consistency with which each participant made their judgments. Our task was presented as a computer game in which a toy UFO moved obliquely towards the participant through a virtual three-dimensional space on route to a docking station. The UFO disappeared before docking and participants pressed their space bar at the precise moment they thought the UFO would have docked. Study 1 showed it was possible to conduct quantitative studies of spatiotemporal judgments in virtual reality via the Internet and confirmed reports that men are more accurate because women underestimate, but found no difference in precision measured as intra-participant variation. Study 2 repeated Study 1 with five additional presentations of one condition to provide a better measure of precision. Again, men were more accurate than women but there were no sex differences in precision. However, within the coincidence-anticipation timing (CAT) literature, of those studies that report sex differences, a majority found that males are both more accurate and more precise than females. Noting that many CAT studies report no sex differences, we discuss appropriate interpretations of such null findings. While acknowledging that CAT performance may be influenced by experience we suggest that the sex difference may have originated among our ancestors with the evolutionary selection of men for hunting and women for gathering.
Taylor, Scott; Hofer, Julie; Murfet, Ian
2001-01-01
Isolation and characterization of two severe alleles at the Stamina pistilloida (Stp) locus reveals that Stp is involved in a wide range of developmental processes in the garden pea. The most severe allele, stp-4, results in flowers consisting almost entirely of sepals and carpels. Production of ectopic secondary flowers in stp-4 plants suggests that Stp is involved in specifying floral meristem identity in pea. The stp mutations also reduce the complexity of the compound pea leaf, and primary inflorescences often terminate prematurely in an aberrant sepaloid flower. In addition, stp mutants were shorter than their wild-type siblings due to a reduction in cell number in their internodes. Fewer cells were also found in the epidermis of the leaf rachis of stp mutants. Examination of the effects of stp-4 in double mutant combinations with af, tl, det, and veg2-2—mutations known to influence leaf, inflorescence, and flower development in pea—suggests that Stp function is independent of these genes. A synergistic interaction between weak mutant alleles at Stp and Uni indicated that these two genes act together, possibly to regulate primordial growth. Molecular analysis revealed that Stp is the pea homolog of the Antirrhinum gene Fimbriata (Fim) and of UNUSUAL FLORAL ORGANS (UFO) from Arabidopsis. Differences between Fim/UFO and Stp mutant phenotypes and expression patterns suggest that expansion of Stp activity into the leaf was an important step during evolution of the compound leaf in the garden pea. PMID:11158527
ERIC Educational Resources Information Center
Scott, Alan J.; Barnhart, Carolyn M.; Parejko, Ken S.; Schultz, Forrest S.; Schultz, Steven E.
2001-01-01
Discusses the legitimacy of teaching about astrology, extrasensory perception, UFOs, touch therapy, cloning dinosaurs, or any other unusual claims in the classroom. Suggests that bringing unusual claims to the science classroom is an opportunity to motivate students in the principles of scientific thought. (SAH)
U.S. EPA, Pesticide Product Label, , 12/11/1986
2011-04-21
... (lI",/ .. r 1110' F, ,f,-r." In'(-. ,I,,, F""(;I( ufo'. ,,/1./ f.:,,, 11/" ,d. ,\\, I ..... lfl.' IId"d) /. ', 1'. r .:! t":'- 01 -,' ",j~.'" ' l)i"l ~\\ll'l ,"~ ~I'·';' If:. "Ii Yilli '1,11' ~ ...
A New Look at Speeding Outflows
NASA Astrophysics Data System (ADS)
Kohler, Susanna
2018-02-01
The compact centers of active galaxies known as active galactic nuclei, or AGN are known for the dynamic behavior they exhibit as the supermassive black holes at their centers accrete matter. New observations of outflows from a nearby AGN provide a more detailed look at what happens in these extreme environments.Outflows from GiantsThe powerful radio jets of Cygnus A, which extend far beyond the galaxy. [NRAO/AUI]AGN consist of a supermassive black hole of millions to tens of billions of solar masses surrounded by an accretion disk of in-falling matter. But not all the material falling toward the black hole accretes! Some of it is flung from the AGN via various types of outflows.The most well-known of these outflows are powerful radio jets collimated and incredibly fast-moving streams of particles that blast their way out of the host galaxy and into space. Only around 10% of AGN are observed to host such jets, however and theres another outflow thats more ubiquitous.Fast-Moving AbsorbersPerhaps 30% of AGN both those with and without observed radio jets host wider-angle, highly ionized gaseous outflows known as ultra-fast outflows (UFOs). Ultraviolet and X-ray radiation emitted from the AGN is absorbed by the UFO, revealing the outflows presence: absorption lines appear in the ultraviolet and X-ray spectra of the AGN, blue-shifted due to the high speeds of the absorbing gas in the outflow.Quasar PG 1211+143, indicated by the crosshairs at the center of the image, in the color context of its surroundings. [SDSS/S. Karge]But what is the nature of UFOs? Are they disk winds? Or are they somehow related to the radio jets? And what impact do they have on the AGNs host galaxy?X-ray and Ultraviolet CooperationNew observations are now providing fresh information about one particular UFO. A team of scientists led by Ashkbiz Danehkar (Harvard-Smithsonian Center for Astrophysics) recently used the Chandra and Hubble space telescopes to make the first simultaneous observations of the same outflow a UFO in quasar PG 1211+143 in both X-rays and in ultraviolet.Danehkar and collaborators found absorption lines in both sets of data revealing an outflow moving at 17,000 km/s (for reference, thats 5.6% of the speed of light, and more than 1,500 times faster than Elon Musks roadster will be traveling at its maximum speed in the orbit it was launched onto yesterday by the Falcon Heavy). Having the information both from the X-ray and the ultraviolet data provides the opportunity to better asses the UFOs physical characteristics.The X-ray spectrum for PG 1211+143 was obtained by Chandra HETGS (top); the ultraviolet spectrum was obtained by HST-COS G130M (bottom). [Adapted from Danehkar et al. 2018]A Link Between Black Holes and Galaxies?The authors use models of the data to demonstrate the plausibility of a scenario in which a shock driven by the radio jet gives rise to the fast bulk outflows detected in the X-ray and ultraviolet spectra.They also estimate the impact that the outflows might have on the AGNs host galaxy, demonstrating that the energy injected into the galaxy could be somewhere between 0.02% and 0.6% of the AGNs total luminosity. At the higher end of this range, this could have an evolutionary impact on the host galaxy, suggesting a possible link between the black holes behavior and how its host galaxy evolves.In order to draw definitive conclusions, we will need higher-resolution observations that can determine the total size and extent of these outflows. For that, we may need to wait for 2023, when a proposed X-ray spectrometer that might fit the bill, Arcus, may be launched.CitationAshkbiz Danehkar et al 2018 ApJ 853 165. doi:10.3847/1538-4357/aaa427
Cognitive Pathways: Analysis of Students' Written Texts for Science Understanding
ERIC Educational Resources Information Center
Grimberg, Bruna Irene; Hand, Brian
2009-01-01
The purpose of this study was to reconstruct writers' reasoning process as reflected in their written texts. The codes resulting from the text analysis were related to cognitive operations, ranging from simple to more sophisticated ones. The sequence of the cognitive operations as the text unfolded represents the writer's cognitive pathway at the…
Marshall Blinks: Operational Art and Strategic Vision
2014-12-04
speaks of his fear that at the outset of World War II “our officers were too theoretical.” By this he meant that the officers did not have concrete ...Marshall viewed the various conflagrations unfolding in China in the mid-1920s and, more importantly, the operational considerations for the 15th
Investigating Interdimensional Relationships
ERIC Educational Resources Information Center
Valentine, Keri Duncan
2017-01-01
The phrase "interdimensional relationships" may conjure images of UFOs, alien beings, wormholes, and even mystical powers. These notions of interdimensionality were not out of bounds in the middle school learners' experiences described in this article. However, these notions do not entirely capture the mathematical relationships…
The Chelyabinsk Meteorite Hits an Anomalous Zone in the Urals
NASA Astrophysics Data System (ADS)
Kochemasov, G. G.
2013-09-01
The Chelyabinsk meteorite is "strange" because it hits an area in the Urals where anomalous events are observed: shining skies, light balls, UFOs, electrphonic bolids. The area tectonically occurs at the intersection of two fold belts: Urals and Timan.
Wang, Jihua; Zhao, Liling; Dou, Xianghua; Zhang, Zhiyong
2008-06-01
Forty nine molecular dynamics simulations of unfolding trajectories of the segment B1 of streptococcal protein G (GB1) provide a direct demonstration of the diversity of unfolding pathway and give a statistically utmost unfolding pathway under the physical property space. Twelve physical properties of the protein were chosen to construct a 12-dimensional property space. Then the 12-dimensional property space was reduced to a 3-dimensional principle component property space. Under the property space, the multiple unfolding trajectories look like "trees", which have some common characters. The "root of the tree" corresponds to the native state, the "bole" homologizes the partially unfolded conformations, and the "crown" is in correspondence to the unfolded state. These unfolding trajectories can be divided into three types. The first one has the characters of straight "bole" and "crown" corresponding to a fast two-state unfolding pathway of GB1. The second one has the character of "the standstill in the middle tree bole", which may correspond to a three-state unfolding pathway. The third one has the character of "the circuitous bole" corresponding to a slow two-state unfolding pathway. The fast two-state unfolding pathway is a statistically utmost unfolding pathway or preferred pathway of GB1, which occupies 53% of 49 unfolding trajectories. In the property space all the unfolding trajectories construct a thermal unfolding pathway ensemble of GB1. The unfolding pathway ensemble resembles a funnel that is gradually emanative from the native state ensemble to the unfolded state ensemble. In the property space, the thermal unfolded state distribution looks like electronic cloud in quantum mechanics. The unfolded states of the independent unfolding simulation trajectories have substantial overlaps, indicating that the thermal unfolded states are confined by the physical property values, and the number of protein unfolded state are much less than that was believed before.
ERIC Educational Resources Information Center
Online-Offline, 1999
1999-01-01
This theme issue on anomalies includes Web sites, CD-ROMs and software, videos, books, and additional resources for elementary and junior high school students. Pertinent activities are suggested, and sidebars discuss UFOs, animal anomalies, and anomalies from nature; and resources covering unexplained phenonmenas like crop circles, Easter Island,…
A Deficiency of Credulousness.
ERIC Educational Resources Information Center
Brewer, Richard
1992-01-01
Asks the question: how does society assist citizens to stop deluding themselves with ESP, UFOs, astrology, polygraphy, water dowsing, channeling, and all manner of New Age gimcrackery? Supplies an answer: educators should emphasize instruction in probability models and scientific inference, while imparting an appropriate, scientific skepticism to…
Physical activity in middle-aged women and hip fracture risk: the UFO study.
Englund, U; Nordström, P; Nilsson, J; Bucht, G; Björnstig, U; Hallmans, G; Svensson, O; Pettersson, U
2011-02-01
In a population-based case-control study, we demonstrate that middle-aged women who were active with walking or in different physical spare time activities were at lower risk of later sustaining a hip fracture compared to more sedentary women. In middle-aged women participating in the Umeå Fracture and Osteoporosis (UFO) study, we investigated whether physical activity is associated with a subsequent decreased risk of sustaining a hip fracture. The UFO study is a nested case-control study investigating associations between bone markers, lifestyle, and osteoporotic fractures. We identified 81 female hip fracture cases that had reported lifestyle data before they sustained their fracture. Each case was compared with two female controls who were identified from the same cohort and matched for age and week of reporting data, yielding a total cohort of 237 subjects. Mean age at baseline was 57.2 ± 5.0 years, and mean age at fracture was 65.4 ± 6.4 years. Conditional logistic regression analysis with adjustments for height, weight, smoking, and menopausal status showed that subjects who were regularly active with walking or had a moderate or high frequency of physical spare time activities (i.e. berry/mushroom picking and snow shovelling) were at reduced risk of sustaining a hip fracture (OR 0.14; 95% CI; 0.05-0.53 for walking and OR 0.19; 95% CI; 0.08-0.46, OR 0.17, 95% CI; 0.05-0.64 for moderate and high frequency of spare time activities, respectively) compared to more sedentary women. An active lifestyle in middle age seems to reduce the risk of future hip fracture. Possible mechanisms may include improved muscle strength, coordination, and balance resulting in a decreased risk of falling and perhaps also direct skeletal benefits.
Regulation of flower development in Arabidopsis by SCF complexes.
Ni, Weimin; Xie, Daoxin; Hobbie, Lawrence; Feng, Baomin; Zhao, Dazhong; Akkara, Joseph; Ma, Hong
2004-04-01
SCF complexes are the largest and best studied family of E3 ubiquitin protein ligases that facilitate the ubiquitylation of proteins targeted for degradation. The SCF core components Skp1, Cul1, and Rbx1 serve in multiple SCF complexes involving different substrate-specific F-box proteins that are involved in diverse processes including cell cycle and development. In Arabidopsis, mutations in the F-box gene UNUSUAL FLORAL ORGANS (UFO) result in a number of defects in flower development. However, functions of the core components Cul1 and Rbx1 in flower development are poorly understood. In this study we analyzed floral phenotypes caused by altering function of Cul1 or Rbx1, as well as the effects of mutations in ASK1 and ASK2. Plants homozygous for a point mutation in the AtCUL1 gene showed reduced floral organ number and several defects in each of the four whorls. Similarly, plants with reduced AtRbx1 expression due to RNA interference also exhibited floral morphological defects. In addition, compared to the ask1 mutant, plants homozygous for ask1 and heterozygous for ask2 displayed enhanced reduction of B function, as well as other novel defects of flower development, including carpelloid sepals and an inhibition of petal development. Genetic analyses demonstrate that AGAMOUS (AG) is required for the novel phenotypes observed in the first and second whorls. Furthermore, the genetic interaction between UFO and AtCUL1 supports the idea that UFO regulates multiple aspects of flower development as a part of SCF complexes. These results suggest that SCF complexes regulate several aspects of floral development in Arabidopsis.
Evidence for a Variable Ultrafast Outflow in the Newly Discovered Ultraluminous Pulsar NGC 300 ULX-1
NASA Astrophysics Data System (ADS)
Kosec, P.; Pinto, C.; Walton, D. J.; Fabian, A. C.; Bachetti, M.; Brightman, M.; Fürst, F.; Grefenstette, B. W.
2018-06-01
Ultraluminous pulsars are a definite proof that persistent super-Eddington accretion occurs in nature. They support the scenario according to which most Ultraluminous X-ray Sources (ULXs) are super-Eddington accretors of stellar mass rather than sub-Eddington intermediate mass black holes. An important prediction of theories of supercritical accretion is the existence of powerful outflows of moderately ionized gas at mildly relativistic speeds. In practice, the spectral resolution of X-ray gratings such as RGS onboard XMM-Newton is required to resolve their observational signatures in ULXs. Using RGS, outflows have been discovered in the spectra of 3 ULXs (none of which are currently known to be pulsars). Most recently, the fourth ultraluminous pulsar was discovered in NGC 300. Here we report detection of an ultrafast outflow (UFO) in the X-ray spectrum of the object, with a significance of more than 3σ, during one of the two simultaneous observations of the source by XMM-Newton and NuSTAR in December 2016. The outflow has a projected velocity of 65000 km/s (0.22c) and a high ionisation factor with a log value of 3.9. This is the first direct evidence for a UFO in a neutron star ULX and also the first time that this its evidence in a ULX spectrum is seen in both soft and hard X-ray data simultaneously. We find no evidence of the UFO during the other observation of the object, which could be explained by either clumpy nature of the absorber or a slight change in our viewing angle of the accretion flow.
Discovery of Ultra-fast Outflows in a Sample of Broad-line Radio Galaxies Observed with Suzaku
NASA Astrophysics Data System (ADS)
Tombesi, F.; Sambruna, R. M.; Reeves, J. N.; Braito, V.; Ballo, L.; Gofford, J.; Cappi, M.; Mushotzky, R. F.
2010-08-01
We present the results of a uniform and systematic search for blueshifted Fe K absorption lines in the X-ray spectra of five bright broad-line radio galaxies observed with Suzaku. We detect, for the first time in radio-loud active galactic nuclei (AGNs) at X-rays, several absorption lines at energies greater than 7 keV in three out of five sources, namely, 3C 111, 3C 120, and 3C 390.3. The lines are detected with high significance according to both the F-test and extensive Monte Carlo simulations. Their likely interpretation as blueshifted Fe XXV and Fe XXVI K-shell resonance lines implies an origin from highly ionized gas outflowing with mildly relativistic velocities, in the range v ~= 0.04-0.15c. A fit with specific photoionization models gives ionization parameters in the range log ξ ~= 4-5.6 erg s-1 cm and column densities of N H ~= 1022-1023 cm-2. These characteristics are very similar to those of the ultra-fast outflows (UFOs) previously observed in radio-quiet AGNs. Their estimated location within ~0.01-0.3 pc of the central super-massive black hole suggests a likely origin related with accretion disk winds/outflows. Depending on the absorber covering fraction, the mass outflow rate of these UFOs can be comparable to the accretion rate and their kinetic power can correspond to a significant fraction of the bolometric luminosity and is comparable to their typical jet power. Therefore, these UFOs can play a significant role in the expected feedback from the AGN to the surrounding environment and can give us further clues on the relation between the accretion disk and the formation of winds/jets in both radio-quiet and radio-loud AGNs.
Suzaku Discovery of Ultra-fast Outflows in Radio-loud AGN
NASA Astrophysics Data System (ADS)
Sambruna, Rita M.; Tombesi, F.; Reeves, J.; Braito, V.; Gofford, J.; Cappi, M.
2010-03-01
We present the results of an analysis of the 3.5--10.5 keV spectra of five bright Broad-Line Radio Galaxies (BLRGs) using proprietary and archival Suzaku observations. In three sources -- 3C 111, 3C 120, and 3C 390.3 -- we find evidence, for the first time in a radio-loud AGN, for absorption features at observed energies 7 keV and 8--9 keV, with high significance according to both the F-test and extensive Monte Carlo simulations (99% or larger). In the remaining two BLRGs, 3C 382 and 3C 445, there is no evidence for such absorption features in the XIS spectra. If interpreted as due to Fe XXV and/or Fe XXVI K-shell resonance lines, the absorption features in 3C 111, 3C 120, and 3C 390.3 imply an origin from an ionized gas outflowing with velocities in the range v 0.04-0.15c, reminiscent of Ultra-Fast Outflows (UFOs) previously observed in radio-quiet Seyfert galaxies. A fit with specific photoionization models gives ionization parameters log ξ 4--5.6 erg s-1 cm and column densities of NH 1022-23 cm-2, similar to the values observed in Seyferts. Based on light travel time arguments, we estimate that the UFOs in the three BLRGs are located within 20--500 gravitational radii from the central black hole, and thus most likely are connected to disk winds/outflows. Our estimates show that the UFOs mass outflow rate is comparable to the accretion rate and their kinetic energy a significant fraction of the AGN bolometric luminosity, making these outflows significant for the global energetic of these systems, in particular for mechanisms of jet formation.
The One Human Problem, Its Solution, and Its Relation to UFO Phenomen
1977-01-01
spirit, stages of evolution, technological species, telepathy , time, tobiscope, tulpa, ultraviolet, unidentified flying objects. Block20. (Continued...manner undreamed of in his present wildest imagination. And indeed there are stranger things in ultimate reality than are dreamed of in our
UFOs, NGOs, or IGOs: Using International Documents for General Reference.
ERIC Educational Resources Information Center
Shreve, Catherine
1997-01-01
Discusses accessing and using documents from international (intergovernmental) organizations. Profiles the United Nations, the European Union and other Intergovernmental Organizations (IGOs). Discusses the librarian as "Web detective," notes questions to focus on, and presents examples to demonstrate navigation of IGO sites. Lists basic…
The Paranormal: A Selected Bibliography of Serials and Reference Works, with Commentary.
ERIC Educational Resources Information Center
Smith, Charles H.
1997-01-01
Provides bibliography of references and serials to assist acquisitions librarians in selection of the paranormal. Topics include alchemy, astrology, magic, conjuring, witchcraft, paganism, demonology, satanism, voodooism, sorcery, cults, shamanism, UFOs, exobiology, curious physical and biological phenomena, ghosts, poltergeists, haunted places,…
Etcheverry, M Florencia; Lum, Paula J; Evans, Jennifer L; Sanchez, Emilia; de Lazzari, Elisa; Mendez-Arancibia, Eva; Sierra, Ernesto; Gatell, José M; Page, Kimberly; Joseph, Joan
2011-02-24
Being able to recruit high-risk volunteers who are also willing to consider future participation in vaccine trials are critical features of vaccine preparedness studies. We described data from two cohorts of injection- and non-injection drug users in Barcelona, Spain [Red Cross centre] and in San Francisco, USA, [UFO-VAX study] at high risk of HIV/HCV infection to assess behaviour risk exposure and willingness to participate in future preventive HIV vaccine trials. We successfully identified drug-using populations that would be eligible for future HIV vaccine efficacy trials, based on reported levels of risk during screening and high levels of willingness to participate. In both groups, Red Cross and UFO-VAX respectively, HCV infection was highly prevalent at baseline (41% and 34%), HIV baseline seroprevalence was 4.2% and 1.5%, and high levels of willingness were seen (83% and 78%). Copyright © 2011 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Roseberry, R.J.
The experimental measurements and nuclear analysis of a uniformly loaded, unpoisoned slab core with a partially inserted hafnium rod and/or a partially inserted water gap are described. Comparisons of experimental data with calculated results of the UFO core and flux synthesis techniques are given. It is concluded that one of the flux synthesis techniques and the UFO code are able to predict flux distributions to within approximately -5% of experiment for most cases, with a maximum error of approximately -10% for a channel at the core- reflector boundary. The second synthesis technique failed to give comparable agreement with experiment evenmore » when various refinements were used, e.g. increasing the number of mesh points, performing the flux synthesis technique of iteration, and spectrum-weighting the appropriate calculated fluxes through the use of the SWAKRAUM code. These results are comparable to those reported in Part I of this study. (auth)« less
Fung, Erik; Hui, Elsie; Yang, Xiaobo; Lui, Leong T; Cheng, King F; Li, Qi; Fan, Yiting; Sahota, Daljit S; Ma, Bosco H M; Lee, Jenny S W; Lee, Alex P W; Woo, Jean
2018-01-01
Heart failure and frailty are clinical syndromes that present with overlapping phenotypic characteristics. Importantly, their co-presence is associated with increased mortality and morbidity. While mechanical and electrical device therapies for heart failure are vital for select patients with advanced stage disease, the majority of patients and especially those with undiagnosed heart failure would benefit from early disease detection and prompt initiation of guideline-directed medical therapies. In this article, we review the problematic interactions between heart failure and frailty, introduce a focused cardiac screening program for community-living elderly initiated by a mobile communication device app leading to the Undiagnosed heart Failure in frail Older individuals (UFO) study, and discuss how the knowledge of pre-frailty and frailty status could be exploited for the detection of previously undiagnosed heart failure or advanced cardiac disease. The widespread use of mobile devices coupled with increasing availability of novel, effective medical and minimally invasive therapies have incentivized new approaches to heart failure case finding and disease management.
Computing decay rates for new physics theories with FEYNRULES and MADGRAPH 5_AMC@NLO
NASA Astrophysics Data System (ADS)
Alwall, Johan; Duhr, Claude; Fuks, Benjamin; Mattelaer, Olivier; Öztürk, Deniz Gizem; Shen, Chia-Hsien
2015-12-01
We present new features of the FEYNRULES and MADGRAPH 5_AMC@NLO programs for the automatic computation of decay widths that consistently include channels of arbitrary final-state multiplicity. The implementations are generic enough so that they can be used in the framework of any quantum field theory, possibly including higher-dimensional operators. We extend at the same time the conventions of the Universal FEYNRULES Output (or UFO) format to include decay tables and information on the total widths. We finally provide a set of representative examples of the usage of the new functions of the different codes in the framework of the Standard Model, the Higgs Effective Field Theory, the Strongly Interacting Light Higgs model and the Minimal Supersymmetric Standard Model and compare the results to available literature and programs for validation purposes.
High-irradiance reactor design with practical unfolded optics
NASA Astrophysics Data System (ADS)
Feuermann, Daniel; Gordon, Jeffrey M.
2008-08-01
In the design of high-temperature chemical reactors and furnaces, as well as high-radiance light projection applications, reconstituting the ultra-high radiance of short-arc discharge lamps at maximum radiative efficiency constitutes a significant challenge. The difficulty is exacerbated by the high numerical aperture necessary at both the source and the target. Separating the optic from both the light source and the target allows practical operation, control, monitoring, diagnostics and maintenance. We present near-field unfolded aplanatic optics as a feasible solution. The concept is illustrated with a design customized to a high-temperature chemical reactor for nano-material synthesis, driven by an ultra-bright xenon short-arc discharge lamp, with near-unity numerical aperture for both light input and light output. We report preliminary optical measurements for the first prototype, which constitutes a double-ellipsoid solution. We also propose compound unfolded aplanats that collect the full angular extent of lamp emission (in lieu of light recycling optics) and additionally permit nearly full-circumference irradiation of the reactor.
ERIC Educational Resources Information Center
Todor, John I.
The author presents an overview of Pascual-Leone's Theory of Constructive Operators, a process-structural theory based upon Piagetian constructs which has evolved to both explain and predict the temporal unfolding of behavior. An application is made of the theory to the demands of a discrete motor task and prediction of (a) the minimal age…
Filtration of micron-sized particles for coal liquids: carbonaceous precoats. [5 refs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rodgers, B.R.
Carbonaceous precoats, such as bituminous coal and char from hydrocarbonization, are shown to be effective, inexpensive substitutes for traditional diatomaceous earth materials, both at laboratory-scale and bench-scale. Model equations are developed for filtration of Solvent Refined Coal-Unfiltered Oil (SRC-UFO).
Unidentified Flying Objects, A Selected Bibliography.
ERIC Educational Resources Information Center
Rodgers, Kay, Comp.
This bibliography, intended for the general reader, provides selective coverage of the unidentified flying object (UFO) literature that has appeared since 1969. The coverage is limited to English language works, but does include translations and materials published abroad. Other bibliographies are listed, as are books, congressional and other…
Ultra-Fast Outflows in Radio-Loud AGN: New Constraints on Jet-Disk Connection
NASA Astrophysics Data System (ADS)
Sambruna, Rita
There is strong observational and theoretical evidence that outflows/jets are coupled to accretion disks in black hole accreting systems, from Galactic to extragalactic sizes. While in radio-quiet AGN there is ample evidence for the presence of Ultra-Fast Outflows (UFOs) from the presence of blue-shifted absorption features in their 4-10~keV spectra, sub-relativistic winds are expected on theoretical basis in radio-loud AGN but have not been observed until now. Our recent Suzaku observations of 5 bright Broad- Line Radio Galaxies (BLRGs, the radio-loud counterparts of Seyferts) has started to change this picture. We found strong evidence for UFOs in 3 out of 5 BLRGs, with ionization parameters, column densities, and velocities of the absorber similar to Seyferts. Moreover, the outflows in BLRGs are likely to be energetically very significant: from the Suzaku data of the three sources, outflow masses similar to the accretion masses and kinetic energies of the wind similar to the X-ray luminosity and radio power of the jet are inferred. Clearly, UFOs in radio-loud AGN represent a new key ingredient to understand their central engines and in particular, the jet-disk linkage. Our discovery of UFOs in a handful of BLRGs raises the questions of how common disk winds are in radio-loud AGN, what the absorber physical and dynamical characteristics are, and what is the outflow role in broader picture of galaxy-black hole connection for radio sources, i.e., for large-scale feedback models. To address these and other issues, we propose to use archival XMM-Newton and Suzaku spectra to search for Ultra-Fast Outflows in a large number of radio sources. Over a period of two years, we will conduct a systematic, uniform analysis of the archival X-ray data, building on our extensive experience with a similar previous project for Seyferts, and using robust analysis and statistical methodologies. As an important side product, we will also obtain accurate, self- consistent measurements of the broad-band X-ray spectra of radio-loud AGN for comparison to radio-quiet, addressing the origin of the division between the two classes. In addition, the upcoming Astro-H mission will greatly benefit from the outcomes of this project, which will provide templates for realistic simulations to define the scientific requirements of the calorimeter, and a list of targets to design a sample for the core AGN projects of the team.
When fast is better: protein folding fundamentals and mechanisms from ultrafast approaches
Muñoz, Victor; Cerminara, Michele
2016-01-01
Protein folding research stalled for decades because conventional experiments indicated that proteins fold slowly and in single strokes, whereas theory predicted a complex interplay between dynamics and energetics resulting in myriad microscopic pathways. Ultrafast kinetic methods turned the field upside down by providing the means to probe fundamental aspects of folding, test theoretical predictions and benchmark simulations. Accordingly, experimentalists could measure the timescales for all relevant folding motions, determine the folding speed limit and confirm that folding barriers are entropic bottlenecks. Moreover, a catalogue of proteins that fold extremely fast (microseconds) could be identified. Such fast-folding proteins cross shallow free energy barriers or fold downhill, and thus unfold with minimal co-operativity (gradually). A new generation of thermodynamic methods has exploited this property to map folding landscapes, interaction networks and mechanisms at nearly atomic resolution. In parallel, modern molecular dynamics simulations have finally reached the timescales required to watch fast-folding proteins fold and unfold in silico. All of these findings have buttressed the fundamentals of protein folding predicted by theory, and are now offering the first glimpses at the underlying mechanisms. Fast folding appears to also have functional implications as recent results connect downhill folding with intrinsically disordered proteins, their complex binding modes and ability to moonlight. These connections suggest that the coupling between downhill (un)folding and binding enables such protein domains to operate analogically as conformational rheostats. PMID:27574021
U.S. EPA, Pesticide Product Label, SANTIMINE - 150, 01/31/1989
2011-04-21
... It •• ; u.1 ., l •• n •• f (h. I'",,, C •••• , 1 '" .fI' ,,, . UfO not .t' If! .,., Oil III" ., cl.'llIn~ 'h,af,1 " .... It~ .. ,of V •• , ,.t .. Of II(' ." • 14 ~n" ,"1111" Jl.", .. ...
A Skeptic's Bookshelf: Scientific Responses to Pseudoscience. An Annotated Bibliography.
ERIC Educational Resources Information Center
Fraknoi, Andrew
1984-01-01
Lists nontechnical books and articles on the various claims of "paranormal" events. Includes general references and materials on: astrology; unidentified flying objects (UFO's); ancient astronauts; lunacy and the moon; Velikovsky and "Worlds in Collision"; the Bermuda triangle; Sirius B and the Dogon; the Tunguska event; creationism; and…
Internet Investigations: Mixing Talent with Teachers and Telecommunications.
ERIC Educational Resources Information Center
Brown, Mark E.; Riley, Tracy L.
1998-01-01
Describes how teams of grade 4-9 gifted students investigated unsolved mysteries like Bigfoot, aliens and UFOs, the Loch Ness Monster, and Stonehenge to develop Internet and research skills. Highlights student observations on difficulties encountered using the Internet for research, notes student evaluation of the workshop, and provides addresses…
Aliens Among Us : Are They Already Here ?
NASA Astrophysics Data System (ADS)
McGaha, J.
2008-03-01
Popular culture, science fiction and mainstream belief, says they are! What is the evidence? Astronomer, skeptic and retired USAF pilot James McGaha examines this "Space Age" Mythology. From years of investigation of the physical evidence of aliens and there spacecraft (UFO's) here on earth, McGaha presents the scientific facts.
Close Encounters with the Fourth Dimension.
ERIC Educational Resources Information Center
Alexander, Mary, Ed.
1984-01-01
Most of the 11,108 sightings of unidentified flying objects (UFOs) between 1947 and 1966 were explained by the Air Force as astronomical phenomena, aircraft, or balloons. The document from the National Archives produced here for use in secondary classes is typical of those sighting reports. Classroom activities are suggested. (RM)
Creative Ventures: Mysteries and UFO's.
ERIC Educational Resources Information Center
Stark, Rebecca
This book published in 1987 provides open-ended activities to extend the imagination and creativity of students and encourage them to examine their feelings and values. Williams' model of cognitive-intellective and affective-feeling domains are addressed. Nearly 60 pages of exercises focus on the historical, the scientific, the mysterious, the…
Scientific Responses to Pseudoscience Related to Astronomy. An Annotated Bibliography.
ERIC Educational Resources Information Center
Fraknoi, Andrew
1990-01-01
Provided is a list of 92 references. Categories include general references, debunking astrology, identifying U.F.O.s, ancient astronauts, Velikovsky and worlds in collision, lunacy and the moon, Sirius B and the Dogon tribe, the face and pyramids on mars, the Tunguska Event, and the Bermuda Triangle. (CW)
Great Mysteries of the Earth: A New Geology Course
ERIC Educational Resources Information Center
Cazeau, Charles J.; Stoiber, George
1976-01-01
Describes an introductory undergraduate geology course which investigates geology-related, current topics of wide interest, such as the Bermuda Triangle, UFO's, etc. Purpose of the course is to show students how to sift fact from fiction, exercise basic logic, and critically analyze current writings of popular sensationalists. (SL)
A Mind/Brain/Matter Model Consistent with Quantum Physics and UFO phenomena
1979-01-01
precognitive nightmares indicating the horror of the Armageddon to come, and these nightmarish paranormal mutilations reveal the true nature of our times...strange, precognitive dreams that were foisted upon a king, nor was it foolish to interpret strange aerial phenomena in terms oi serious threats looming
Building Program Verifiers from Compilers and Theorem Provers
2015-05-14
Checking with SMT UFO • LLVM-based front-end (partially reused in SeaHorn) • Combines Abstract Interpretation with Interpolation-Based Model Checking • (no...assertions Counter-examples are long Hard to determine (from main) what is relevant Assertion Main 35 Building Verifiers from Comp and SMT Gurfinkel, 2015
Cooperative unfolding of apolipoprotein A-1 induced by chemical denaturation.
Eckhardt, D; Li-Blatter, X; Schönfeld, H-J; Heerklotz, H; Seelig, J
2018-05-25
Apolipoprotein A-1 (Apo A-1) plays an important role in lipid transfer and obesity. Chemical unfolding of α-helical Apo A-1 is induced with guanidineHCl and monitored with differential scanning calorimetry (DSC) and CD spectroscopy. The unfolding enthalpy and the midpoint temperature of unfolding decrease linearly with increasing guanidineHCl concentration, caused by the weak binding of denaturant. At room temperature, binding of 50-60 molecules guanidineHCl leads to a complete Apo A-1 unfolding. The entropy of unfolding decreases to a lesser extent than the unfolding enthalpy. Apo A-1 chemical unfolding is a dynamic multi-state equilibrium that is analysed with the Zimm-Bragg theory modified for chemical unfolding. The chemical Zimm-Bragg theory predicts the denaturant binding constant K D and the protein cooperativity σ. Chemical unfolding of Apo A-1 is two orders of magnitude less cooperative than thermal unfolding. The free energy of thermal unfolding is ~0.2 kcal/mol per amino acid residue and ~1.0 kcal/mol for chemical unfolding at room temperature. The Zimm-Bragg theory calculates conformational probabilities and the chemical Zimm-Bragg theory predicts stretches of α-helical segments in dynamic equilibrium, unfolding and refolding independently and fast. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
1989-11-01
the high risk of fuel cells damaging as a consequence of the unfolding and refolding operations. - Difficulties to perform acceptance inspection tests...corners sometimes present in the structures. (See FIG. 6, 7, 8). - Additional installation costs and risk of damaging due to fuel cells anchoring...performed manually by very complex tying operations. (See. FIG. 9). - Risk of damaging of the thicker reinforced zones of the flexible fuel cells where
Limiter heat loads during the first operation of the W7-X stellarator
NASA Astrophysics Data System (ADS)
Wurden, Glen; Niemann, Holger; Jakubowski, Marcin; Bozhenkov, Sergey; Biedermann, Christoph; Marsen, Stefan; Effenberg, Florian; Stephey, Laurie; Schmitz, Oliver; W7-X Team
2016-10-01
During the first operational phase (OP1.1) of the new W7-X stellarator, five poloidal graphite limiters served as the main boundary for the plasma. There was a dedicated set of diagnostics to observe the performance of the temporary poloidal limiters and infer basic transport behavior of the 3-D helical SOL plasma. We describe IR imaging of the limiters, which resulted in observations of 1) heat flux determination as a function of time and space, 2) total energy into the limiters, 3) high-frequency helical patterns of energy bursts onto the limiters, 4) changes in surface emissivity, and 5) detection of UFO's (small-to-large dusts). These measurements were made in 2 magnetic configuration discharges (differing iota), and in ones where the power loads to the limiters were systematically modified by the use of trim coils. Observed power fractions on the limiters ranged from 40% to 20% of the 0.6 to 4 MW ECRH input powers. Acknowledgement: Funded under DOE LANS Contract DE-AC5026NA25396 and DE-SC0014210, and within the EUROfusion Consortium under Euratom Grant 633053.
Integrating supply and demand aspects of transportation for mass evacuation under disasters.
DOT National Transportation Integrated Search
2009-10-15
This study seeks to address real-time operational needs in the context of the evacuation response problem by providing a capability to dynamically route vehicles under evacuation, thereby being responsive to the actual conditions unfolding in real-ti...
Unfolding and unfoldability of digital pulses in the z-domain
NASA Astrophysics Data System (ADS)
Regadío, Alberto; Sánchez-Prieto, Sebastián
2018-04-01
The unfolding (or deconvolution) technique is used in the development of digital pulse processing systems applied to particle detection. This technique is applied to digital signals obtained by digitization of analog signals that represent the combined response of the particle detectors and the associated signal conditioning electronics. This work describes a technique to determine if the signal is unfoldable. For unfoldable signals the characteristics of the unfolding system (unfolder) are presented. Finally, examples of the method applied to real experimental setup are discussed.
The Influence of Education Major: How Diverse Preservice Teachers View Pseudoscience Topics
ERIC Educational Resources Information Center
Losh, Susan Carol; Nzekwe, Brandon
2011-01-01
Pseudoscience beliefs (e.g., astrology, ghosts or UFOs) are rife in American society. Most research examines creation/evolution among liberal arts majors, general public adults, or, infrequently, middle or high school science teachers. Thus, research truncates the "range" of ersatz science thinking and the samples it studies. We examined diverse…
NASA Astrophysics Data System (ADS)
Storms, E.
This report attempts to update the status of the phenomenon of cold fusion. The new field is continuing to grow as a variety of nuclear reactions are discovered to occur in a variety of chemical environments at modest temperatures. However, it must be cautioned that most scientists consider cold fusion as something akin to UFO's, ESP, and numerology.
American Actions in the Dominican Republic and Grenada.
1985-06-01
conspiracy . Rivera Cuesta then confronted the conspirators and was arrested. 34 32Lowenthal, p. 39. 433 33Lowenthal, p. 50. 34Lowenthal, p. 61. 29 N er...Britain in 1974. Gairy, a former nightclub owner and spiritualist, was in New York to speak at the United Nations about UFOs when he was overthrown in
The Influence of Education Major: How Diverse Preservice Teachers View Pseudoscience Topics
NASA Astrophysics Data System (ADS)
Losh, Susan Carol; Nzekwe, Brandon
2011-10-01
Pseudoscience beliefs (e.g., astrology, ghosts or UFOs) are rife in American society. Most research examines creation/evolution among liberal arts majors, general public adults, or, infrequently, middle or high school science teachers. Thus, research truncates the range of ersatz science thinking and the samples it studies. We examined diverse beliefs, e.g., extraterrestrials, magic, Biblical creation, and evolution, among 540 female and 123 male future teachers, including 325 elementary education majors. We study how these cognitions related to education major and, because popular media often present pseudoscience "information", student media use. Future elementary educators most often rejected evolution and endorsed "creationism" or Intelligent Design. Education majors held similar beliefs about astrology, UFO landings, or magic. Compared with other education students, elementary education majors watched less news or science television and read fewer popular science magazines. However, religious and media variables explained more variation in creation/evolution beliefs than education major. We discuss implications of our findings for elementary school science education and how teacher educators may be able to affect pseudoscience beliefs among their elementary education students.
Fung, Erik; Hui, Elsie; Yang, Xiaobo; Lui, Leong T.; Cheng, King F.; Li, Qi; Fan, Yiting; Sahota, Daljit S.; Ma, Bosco H. M.; Lee, Jenny S. W.; Lee, Alex P. W.; Woo, Jean
2018-01-01
Heart failure and frailty are clinical syndromes that present with overlapping phenotypic characteristics. Importantly, their co-presence is associated with increased mortality and morbidity. While mechanical and electrical device therapies for heart failure are vital for select patients with advanced stage disease, the majority of patients and especially those with undiagnosed heart failure would benefit from early disease detection and prompt initiation of guideline-directed medical therapies. In this article, we review the problematic interactions between heart failure and frailty, introduce a focused cardiac screening program for community-living elderly initiated by a mobile communication device app leading to the Undiagnosed heart Failure in frail Older individuals (UFO) study, and discuss how the knowledge of pre-frailty and frailty status could be exploited for the detection of previously undiagnosed heart failure or advanced cardiac disease. The widespread use of mobile devices coupled with increasing availability of novel, effective medical and minimally invasive therapies have incentivized new approaches to heart failure case finding and disease management. PMID:29740330
Direct Observation of Markovian Behavior of the Mechanical Unfolding of Individual Proteins
Cao, Yi; Kuske, Rachel; Li, Hongbin
2008-01-01
Single-molecule force-clamp spectroscopy is a valuable tool to analyze unfolding kinetics of proteins. Previous force-clamp spectroscopy experiments have demonstrated that the mechanical unfolding of ubiquitin deviates from the generally assumed Markovian behavior and involves the features of glassy dynamics. Here we use single molecule force-clamp spectroscopy to study the unfolding kinetics of a computationally designed fast-folding mutant of the small protein GB1, which shares a similar β-grasp fold as ubiquitin. By treating the mechanical unfolding of polyproteins as the superposition of multiple identical Poisson processes, we developed a simple stochastic analysis approach to analyze the dwell time distribution of individual unfolding events in polyprotein unfolding trajectories. Our results unambiguously demonstrate that the mechanical unfolding of NuG2 fulfills all criteria of a memoryless Markovian process. This result, in contrast with the complex mechanical unfolding behaviors observed for ubiquitin, serves as a direct experimental demonstration of the Markovian behavior for the mechanical unfolding of a protein and reveals the complexity of the unfolding dynamics among structurally similar proteins. Furthermore, we extended our method into a robust and efficient pseudo-dwell-time analysis method, which allows one to make full use of all the unfolding events obtained in force-clamp experiments without categorizing the unfolding events. This method enabled us to measure the key parameters characterizing the mechanical unfolding energy landscape of NuG2 with improved precision. We anticipate that the methods demonstrated here will find broad applications in single-molecule force-clamp spectroscopy studies for a wide range of proteins. PMID:18375518
Protein unfolding in detergents: effect of micelle structure, ionic strength, pH, and temperature.
Otzen, Daniel E
2002-01-01
The 101-residue monomeric protein S6 unfolds in the anionic detergent sodium dodecyl sulfate (SDS) above the critical micelle concentration, with unfolding rates varying according to two different modes. Our group has proposed that spherical micelles lead to saturation kinetics in unfolding (mode 1), while cylindrical micelles prevalent at higher SDS concentrations induce a power-law dependent increase in the unfolding rate (mode 2). Here I investigate in more detail how micellar properties affect protein unfolding. High NaCl concentrations, which induce cylindrical micelles, favor mode 2. This is consistent with our model, though other effects such as electrostatic screening cannot be discounted. Furthermore, unfolding does not occur in mode 2 in the cationic detergent LTAB, which is unable to form cylindrical micelles. A strong retardation of unfolding occurs at higher LTAB concentrations, possibly due to the formation of dead-end protein-detergent complexes. A similar, albeit much weaker, effect is seen in SDS in the absence of salt. Chymotrypsin inhibitor 2 exhibits the same modes of unfolding in SDS as S6, indicating that this type of protein unfolding is not specific for S6. The unfolding process in mode 1 has an activation barrier similar in magnitude to that in water, while the activation barrier in mode 2 is strongly concentration-dependent. The strong pH-dependence of unfolding in SDS and LTAB suggests that the rate of unfolding in anionic detergent is modulated by repulsion between detergent headgroups and anionic side chains, while cationic side chains modulate unfolding rates in cationic detergents. PMID:12324439
Electrostatic effects in unfolded staphylococcal nuclease
Fitzkee, Nicholas C.; García-Moreno E, Bertrand
2008-01-01
Structure-based calculations of pK a values and electrostatic free energies of proteins assume that electrostatic effects in the unfolded state are negligible. In light of experimental evidence showing that this assumption is invalid for many proteins, and with increasing awareness that the unfolded state is more structured and compact than previously thought, a detailed examination of electrostatic effects in unfolded proteins is warranted. Here we address this issue with structure-based calculations of electrostatic interactions in unfolded staphylococcal nuclease. The approach involves the generation of ensembles of structures representing the unfolded state, and calculation of Coulomb energies to Boltzmann weight the unfolded state ensembles. Four different structural models of the unfolded state were tested. Experimental proton binding data measured with a variant of nuclease that is unfolded under native conditions were used to establish the validity of the calculations. These calculations suggest that weak Coulomb interactions are an unavoidable property of unfolded proteins. At neutral pH, the interactions are too weak to organize the unfolded state; however, at extreme pH values, where the protein has a significant net charge, the combined action of a large number of weak repulsive interactions can lead to the expansion of the unfolded state. The calculated pK a values of ionizable groups in the unfolded state are similar but not identical to the values in small peptides in water. These studies suggest that the accuracy of structure-based calculations of electrostatic contributions to stability cannot be improved unless electrostatic effects in the unfolded state are calculated explicitly. PMID:18227429
When fast is better: protein folding fundamentals and mechanisms from ultrafast approaches.
Muñoz, Victor; Cerminara, Michele
2016-09-01
Protein folding research stalled for decades because conventional experiments indicated that proteins fold slowly and in single strokes, whereas theory predicted a complex interplay between dynamics and energetics resulting in myriad microscopic pathways. Ultrafast kinetic methods turned the field upside down by providing the means to probe fundamental aspects of folding, test theoretical predictions and benchmark simulations. Accordingly, experimentalists could measure the timescales for all relevant folding motions, determine the folding speed limit and confirm that folding barriers are entropic bottlenecks. Moreover, a catalogue of proteins that fold extremely fast (microseconds) could be identified. Such fast-folding proteins cross shallow free energy barriers or fold downhill, and thus unfold with minimal co-operativity (gradually). A new generation of thermodynamic methods has exploited this property to map folding landscapes, interaction networks and mechanisms at nearly atomic resolution. In parallel, modern molecular dynamics simulations have finally reached the timescales required to watch fast-folding proteins fold and unfold in silico All of these findings have buttressed the fundamentals of protein folding predicted by theory, and are now offering the first glimpses at the underlying mechanisms. Fast folding appears to also have functional implications as recent results connect downhill folding with intrinsically disordered proteins, their complex binding modes and ability to moonlight. These connections suggest that the coupling between downhill (un)folding and binding enables such protein domains to operate analogically as conformational rheostats. © 2016 The Author(s).
Ultrafast outflows in radio-loud active galactic nuclei
NASA Astrophysics Data System (ADS)
Tombesi, F.; Tazaki, F.; Mushotzky, R. F.; Ueda, Y.; Cappi, M.; Gofford, J.; Reeves, J. N.; Guainazzi, M.
2014-09-01
Recent X-ray observations show absorbing winds with velocities up to mildly relativistic values of the order of ˜0.1c in a limited sample of six broad-line radio galaxies. They are observed as blueshifted Fe XXV-XXVI K-shell absorption lines, similarly to the ultrafast outflows (UFOs) reported in Seyferts and quasars. In this work we extend the search for such Fe K absorption lines to a larger sample of 26 radio-loud active galactic nuclei (AGN) observed with XMM-Newton and Suzaku. The sample is drawn from the Swift Burst Alert Telescope 58-month catalogue and blazars are excluded. X-ray bright Fanaroff-Riley Class II radio galaxies constitute the majority of the sources. Combining the results of this analysis with those in the literature we find that UFOs are detected in >27 per cent of the sources. However, correcting for the number of spectra with insufficient signal-to-noise ratio, we can estimate that the incidence of UFOs is this sample of radio-loud AGN is likely in the range f ≃ (50 ± 20) per cent. A photoionization modelling of the absorption lines with XSTAR allows us to estimate the distribution of their main parameters. The observed outflow velocities are broadly distributed between vout ≲ 1000 km s-1 and vout ≃ 0.4c, with mean and median values of vout ≃ 0.133c and vout ≃ 0.117c, respectively. The material is highly ionized, with an average ionization parameter of logξ ≃ 4.5 erg s-1 cm, and the column densities are larger than NH > 1022 cm-2. Overall, these characteristics are consistent with the presence of complex accretion disc winds in a significant fraction of radio-loud AGN and demonstrate that the presence of relativistic jets does not preclude the existence of winds, in accordance with several theoretical models.
Studying the unfolding process of protein G and protein L under physical property space
Zhao, Liling; Wang, Jihua; Dou, Xianghua; Cao, Zanxia
2009-01-01
Background The studies on protein folding/unfolding indicate that the native state topology is an important determinant of protein folding mechanism. The folding/unfolding behaviors of proteins which have similar topologies have been studied under Cartesian space and the results indicate that some proteins share the similar folding/unfolding characters. Results We construct physical property space with twelve different physical properties. By studying the unfolding process of the protein G and protein L under the property space, we find that the two proteins have the similar unfolding pathways that can be divided into three types and the one which with the umbrella-shape represents the preferred pathway. Moreover, the unfolding simulation time of the two proteins is different and protein L unfolding faster than protein G. Additionally, the distributing area of unfolded state ensemble of protein L is larger than that of protein G. Conclusion Under the physical property space, the protein G and protein L have the similar folding/unfolding behaviors, which agree with the previous results obtained from the studies under Cartesian coordinate space. At the same time, some different unfolding properties can be detected easily, which can not be analyzed under Cartesian coordinate space. PMID:19208146
Exploring Early Stages of the Chemical Unfolding of Proteins at the Proteome Scale
Candotti, Michela; Pérez, Alberto; Ferrer-Costa, Carles; Rueda, Manuel; Meyer, Tim; Gelpí, Josep Lluís; Orozco, Modesto
2013-01-01
After decades of using urea as denaturant, the kinetic role of this molecule in the unfolding process is still undefined: does urea actively induce protein unfolding or passively stabilize the unfolded state? By analyzing a set of 30 proteins (representative of all native folds) through extensive molecular dynamics simulations in denaturant (using a range of force-fields), we derived robust rules for urea unfolding that are valid at the proteome level. Irrespective of the protein fold, presence or absence of disulphide bridges, and secondary structure composition, urea concentrates in the first solvation shell of quasi-native proteins, but with a density lower than that of the fully unfolded state. The presence of urea does not alter the spontaneous vibration pattern of proteins. In fact, it reduces the magnitude of such vibrations, leading to a counterintuitive slow down of the atomic-motions that opposes unfolding. Urea stickiness and slow diffusion is, however, crucial for unfolding. Long residence urea molecules placed around the hydrophobic core are crucial to stabilize partially open structures generated by thermal fluctuations. Our simulations indicate that although urea does not favor the formation of partially open microstates, it is not a mere spectator of unfolding that simply displaces to the right of the folded←→unfolded equilibrium. On the contrary, urea actively favors unfolding: it selects and stabilizes partially unfolded microstates, slowly driving the protein conformational ensemble far from the native one and also from the conformations sampled during thermal unfolding. PMID:24348236
Ben-Naim, Arieh
2012-12-21
A new approach to the problem of pressure-denaturation (PD) and solute-denaturation (SD) of proteins is presented. The problem is formulated in terms of Le Chatelier principle, and a solution is sought in terms of the Kirkwood-Buff theory of solutions. It is found that both problems have one factor in common; the excluded volumes of the folded and the unfolded forms with respect to the solvent molecules. It is shown that solvent-induced effects operating on hydrophilic groups along the protein are probably the main reason for PD. On the other hand, the SD depends on the preferential solvation of the folded and the unfolded forms with respect to solvent and co-solvent molecules.
Theoretical aspects of pressure and solute denaturation of proteins: A Kirkwood-buff-theory approach
NASA Astrophysics Data System (ADS)
Ben-Naim, Arieh
2012-12-01
A new approach to the problem of pressure-denaturation (PD) and solute-denaturation (SD) of proteins is presented. The problem is formulated in terms of Le Chatelier principle, and a solution is sought in terms of the Kirkwood-Buff theory of solutions. It is found that both problems have one factor in common; the excluded volumes of the folded and the unfolded forms with respect to the solvent molecules. It is shown that solvent-induced effects operating on hydrophilic groups along the protein are probably the main reason for PD. On the other hand, the SD depends on the preferential solvation of the folded and the unfolded forms with respect to solvent and co-solvent molecules.
Bian, Liujiao; Ji, Xu
2014-01-01
Extensive and intensive studies on the unfolding of proteins require appropriate theoretical model and parameter to clearly illustrate the feature and characteristic of the unfolding system. Over the past several decades, four approaches have been proposed to describe the interaction between proteins and denaturants, but some ambiguity and deviations usually occur in the explanation of the experimental data. In this work, a theoretical model was presented to show the dependency of the residual activity ratio of the proteins on the molar denaturant concentration. Through the characteristic unfolding parameters ki and Δmi in this model, the distribution, transition and thermodynamic stability of protein conformations during the unfolding process can be quantitatively described. This model was tested with the two-state unfolding of bovine heart cytochrome c and the three-state unfolding of hen egg white lysozyme induced by both guanidine hydrochloride and urea, the four-state unfolding of bovine carbonic anhydrase b induced by guanidine hydrochloride and the unfolding of some other proteins induced by denaturants. The results illustrated that this model could be used accurately to reveal the distribution and transition of protein conformations in the presence of different concentrations of denaturants and to evaluate the unfolding tendency and thermodynamic stability of different conformations. In most denaturant-induced unfolding of proteins, the unfolding became increasingly hard in next transition step and the proteins became more unstable as they attained next successive stable conformation. This work presents a useful method for people to study the unfolding of proteins and may be used to describe the unfolding and refolding of other biopolymers induced by denaturants, inducers, etc.
2008-07-01
operators in Hilbert spaces. The homogenization procedure through successive multi- resolution projections is presented, followed by a numerical example of...is intended to be essentially self-contained. The mathematical ( Greenberg 1978; Gilbert 2006) and signal processing (Strang and Nguyen 1995...literature listed in the references. The ideas behind multi-resolution analysis unfold from the theory of linear operators in Hilbert spaces (Davis 1975
History of Canaveral District: 1950 - 1971
1971-07-01
world, the Canaveral sites had from the beginning required special precautions to alienate corrosion of exposed items. Special finishes were required...SHA’d rtr,. 111 E.xt 240 PAGE 5 UlI!IIIISTRATIVE Sl/PP(I!T NASA r-- __ .... J___ -. OfF I CZ Ufo ’ ,W,.:m. ’:;ERVI C:.s J. H. DAVl.:l Rrn 109
U.S. EPA, Pesticide Product Label, B-145 WEED KILLER, 10/04/1991
2011-04-19
... 1 I ," ,. 1 l , .' I I .. " ~ " t ."\\ I ~ i' t I_ ~" I Vft Ii"q I~I rllll!)11 /,,:. 11t.
UFOs as an Exercise in Discretionary Thinking in the Secondary School Classroom.
ERIC Educational Resources Information Center
Davis, Robert S., Jr.
1984-01-01
From the late 1940s through the 1970s the belief that we were being visited by intelligent guests from other worlds swept the United States and the world. Discusses how materials generated by the unidentified flying objects controversy can be used to encourage secondary students to examine a popular topic. (RM)
Binary Populations and Stellar Dynamics in Young Clusters
NASA Astrophysics Data System (ADS)
Vanbeveren, D.; Belkus, H.; Van Bever, J.; Mennekens, N.
2008-06-01
We first summarize work that has been done on the effects of binaries on theoretical population synthesis of stars and stellar phenomena. Next, we highlight the influence of stellar dynamics in young clusters by discussing a few candidate UFOs (unconventionally formed objects) like intermediate mass black holes, η Car, ζ Pup, γ2 Velorum and WR 140.
An Analysis of Marine Corps Beyond Line of Sight Wideband Satellite Communications Requirements
2010-09-01
Tactical SHF Satellite Terminal UFO ... what made it bearable. Stephen Musick: Thanks are due to my family and friends for their support and encouragement. I want to especially thank... what beyond LOS WB SATCOM capabilities the USMC requires in order to prepare for the future. A clear understanding of desired capabilities allows for
NASA Astrophysics Data System (ADS)
Popp, Alexander; Scheerer, David; Heck, Benjamin; Hauser, Karin
2017-06-01
Early events of protein folding can be studied with fast perturbation techniques triggering non-equilibrium relaxation dynamics. A nanosecond laser-excited pH-jump or temperature-jump (T-jump) was applied to initiate helix folding or unfolding of poly-L-glutamic acid (PGA). PGA is a homopolypeptide with titratable carboxyl side-chains whose protonation degree determines the PGA conformation. A pH-jump was realized by the photochemical release of protons and induces PGA folding due to protonation of the side-chains. Otherwise, the helical conformation can be unfolded by a T-jump. We operated under conditions where PGA does not aggregate and temperature and pH are the regulatory properties of its conformation. The experiments were performed in such a manner that the folding/unfolding jump proceeded to the same PGA conformation. We quantified the increase/decrease in helicity induced by the pH-/T-jump and demonstrated that the T-jump results in a relatively small change in helical content in contrast to the pH-jump. This is caused by the strong pH-dependence of the PGA conformation. The conformational changes were detected by time-resolved single wavelength IR-spectroscopy using quantum cascade lasers (QCL). We could independently observe the kinetics for α-helix folding and unfolding in PGA by using different perturbation techniques and demonstrate the high sensitivity of time-resolved IR-spectroscopy to study protein folding mechanisms.
Popp, Alexander; Scheerer, David; Heck, Benjamin; Hauser, Karin
2017-06-15
Early events of protein folding can be studied with fast perturbation techniques triggering non-equilibrium relaxation dynamics. A nanosecond laser-excited pH-jump or temperature-jump (T-jump) was applied to initiate helix folding or unfolding of poly-l-glutamic acid (PGA). PGA is a homopolypeptide with titratable carboxyl side-chains whose protonation degree determines the PGA conformation. A pH-jump was realized by the photochemical release of protons and induces PGA folding due to protonation of the side-chains. Otherwise, the helical conformation can be unfolded by a T-jump. We operated under conditions where PGA does not aggregate and temperature and pH are the regulatory properties of its conformation. The experiments were performed in such a manner that the folding/unfolding jump proceeded to the same PGA conformation. We quantified the increase/decrease in helicity induced by the pH-/T-jump and demonstrated that the T-jump results in a relatively small change in helical content in contrast to the pH-jump. This is caused by the strong pH-dependence of the PGA conformation. The conformational changes were detected by time-resolved single wavelength IR-spectroscopy using quantum cascade lasers (QCL). We could independently observe the kinetics for α-helix folding and unfolding in PGA by using different perturbation techniques and demonstrate the high sensitivity of time-resolved IR-spectroscopy to study protein folding mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.
Amyloidogenesis of Natively Unfolded Proteins
Uversky, Vladimir N.
2009-01-01
Aggregation and subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins. The accumulated data support the model where protein fibrillogenesis proceeds via the formation of a relatively unfolded amyloidogenic conformation, which shares many structural properties with the pre-molten globule state, a partially folded intermediate first found during the equilibrium and kinetic (un)folding studies of several globular proteins and later described as one of the structural forms of natively unfolded proteins. The flexibility of this structural form is essential for the conformational rearrangements driving the formation of the core cross-beta structure of the amyloid fibril. Obviously, molecular mechanisms describing amyloidogenesis of ordered and natively unfolded proteins are different. For ordered protein to fibrillate, its unique and rigid structure has to be destabilized and partially unfolded. On the other hand, fibrillogenesis of a natively unfolded protein involves the formation of partially folded conformation; i.e., partial folding rather than unfolding. In this review recent findings are surveyed to illustrate some unique features of the natively unfolded proteins amyloidogenesis. PMID:18537543
Time Projection Compton Spectrometer (TPCS). User`s guide
DOE Office of Scientific and Technical Information (OSTI.GOV)
Landron, C.O.; Baldwin, G.T.
1994-04-01
The Time Projection Compton Spectrometer (TPCS) is a radiation diagnostic designed to determine the time-integrated energy spectrum between 100 keV -- 2 MeV of flash x-ray sources. This guide is intended as a reference for the routine operator of the TPCS. Contents include a brief overview of the principle of operation, detailed component descriptions, detailed assembly and disassembly procedures, guide to routine operations, and troubleshooting flowcharts. Detailed principle of operation, signal analysis and spectrum unfold algorithms are beyond the scope of this guide; however, the guide makes reference to sources containing this information.
Del Galdo, Sara; Amadei, Andrea
2016-10-12
In this paper we apply the computational analysis recently proposed by our group to characterize the solvation properties of a native protein in aqueous solution, and to four model aqueous solutions of globular proteins in their unfolded states thus characterizing the protein unfolded state hydration shell and quantitatively evaluating the protein unfolded state partial molar volumes. Moreover, by using both the native and unfolded protein partial molar volumes, we obtain the corresponding variations (unfolding partial molar volumes) to be compared with the available experimental estimates. We also reconstruct the temperature and pressure dependence of the unfolding partial molar volume of Myoglobin dissecting the structural and hydration effects involved in the process.
Lethal factor unfolding is the most force-dependent step of anthrax toxin translocation
Thoren, Katie L.; Worden, Evan J.; Yassif, Jaime M.; Krantz, Bryan A.
2009-01-01
Cellular compartmentalization requires machinery capable of translocating polypeptides across membranes. In many cases, transported proteins must first be unfolded by means of the proton motive force and/or ATP hydrolysis. Anthrax toxin, which is composed of a channel-forming protein and two substrate proteins, is an attractive model system to study translocation-coupled unfolding, because the applied driving force can be externally controlled and translocation can be monitored directly by using electrophysiology. By controlling the driving force and introducing destabilizing point mutations in the substrate, we identified the barriers in the transport pathway, determined which barrier corresponds to protein unfolding, and mapped how the substrate protein unfolds during translocation. In contrast to previous studies, we find that the protein's structure next to the signal tag is not rate-limiting to unfolding. Instead, a more extensive part of the structure, the amino-terminal β-sheet subdomain, must disassemble to cross the unfolding barrier. We also find that unfolding is catalyzed by the channel's phenylalanine-clamp active site. We propose a broad molecular mechanism for translocation-coupled unfolding, which is applicable to both soluble and membrane-embedded unfolding machines. PMID:19926859
Ghosh, Rikhia; Roy, Susmita; Bagchi, Biman
2013-12-12
We carry out a series of long atomistic molecular dynamics simulations to study the unfolding of a small protein, chicken villin headpiece (HP-36), in water-ethanol (EtOH) binary mixture. The prime objective of this work is to explore the sensitivity of protein unfolding dynamics toward increasing concentration of the cosolvent and unravel essential features of intermediates formed in search of a dynamical pathway toward unfolding. In water-ethanol binary mixtures, HP-36 is found to unfold partially, under ambient conditions, that otherwise requires temperature as high as ∼600 K to denature in pure aqueous solvent. However, an interesting course of pathway is observed to be followed in the process, guided by the formation of unique intermediates. The first step of unfolding is essentially the separation of the cluster formed by three hydrophobic (phenylalanine) residues, namely, Phe-7, Phe-11, and Phe-18, which constitute the hydrophobic core, thereby initiating melting of helix-2 of the protein. The initial steps are similar to temperature-induced unfolding as well as chemical unfolding using DMSO as cosolvent. Subsequent unfolding steps follow a unique path. As water-ethanol shows composition-dependent anomalies, so do the details of unfolding dynamics. With an increase in cosolvent concentration, different partially unfolded intermediates are found to be formed. This is reflected in a remarkable nonmonotonic composition dependence of several order parameters, including fraction of native contacts and protein-solvent interaction energy. The emergence of such partially unfolded states can be attributed to the preferential solvation of the hydrophobic residues by the ethyl groups of ethanol. We further quantify the local dynamics of unfolding by using a Marcus-type theory.
Data Unfolding with Wiener-SVD Method
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tang, W.; Li, X.; Qian, X.
Here, data unfolding is a common analysis technique used in HEP data analysis. Inspired by the deconvolution technique in the digital signal processing, a new unfolding technique based on the SVD technique and the well-known Wiener filter is introduced. The Wiener-SVD unfolding approach achieves the unfolding by maximizing the signal to noise ratios in the effective frequency domain given expectations of signal and noise and is free from regularization parameter. Through a couple examples, the pros and cons of the Wiener-SVD approach as well as the nature of the unfolded results are discussed.
Data Unfolding with Wiener-SVD Method
Tang, W.; Li, X.; Qian, X.; ...
2017-10-04
Here, data unfolding is a common analysis technique used in HEP data analysis. Inspired by the deconvolution technique in the digital signal processing, a new unfolding technique based on the SVD technique and the well-known Wiener filter is introduced. The Wiener-SVD unfolding approach achieves the unfolding by maximizing the signal to noise ratios in the effective frequency domain given expectations of signal and noise and is free from regularization parameter. Through a couple examples, the pros and cons of the Wiener-SVD approach as well as the nature of the unfolded results are discussed.
Nanomechanics of Protein Unfolding outside Protease Nanopores
NASA Astrophysics Data System (ADS)
Luan, Binquan; Zhou, Ruhong
Protein folding and unfolding have been the subject of active research for decades. Most of previous studies in protein unfolding were focused on temperature, chemical and/or force (such as in AFM) induced denaturations. Recent studies on the functional roles of proteasomes (such as ClpXP) revealed a novel unfolding process in cell, during which a target protein is mechanically unfolded and pulled into a confined, pore-like geometry for degradation. While the proteasome nanomachine has been extensively studied, the mechanism for unfolding proteins with the proteasome pore is still poorly understood. Here, we investigate the mechanical unfolding process of ubiquitin with (or really outside) an idealized proteasome pore, and compare such process with that in the AFM pulling experiment. Unexpectedly, the required force by a proteosome can be much smaller than that by the AFM. Simulation results also unveiled different nanomechanics, tearing fracture vs. shearing friction, in these two distinct types of mechanical unfoldings.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Leder, A.; Anderson, A. J.; Billard, J.
Here, the Ricochet experiment seeks to measure Coherent (neutral-current) Elastic Neutrino-Nucleus Scattering (CEνNS) using dark-matter-style detectors with sub-keV thresholds placed near a neutrino source, such as the MIT (research) Reactor (MITR), which operates at 5.5 MW generating approximately 2.2 × 10 18 ν/second in its core. Currently, Ricochet is characterizing the backgrounds at MITR, the main component of which comes in the form of neutrons emitted from the core simultaneous with the neutrino signal. To characterize this background, we wrapped Bonner cylinders around a 3 2He thermal neutron detector, whose data was then unfolded via a Markov Chain Monte Carlo (MCMC) to producemore » a neutron energy spectrum across several orders of magnitude. We discuss the resulting spectrum and its implications for deploying Ricochet at the MITR site as well as the feasibility of reducing this background level via the addition of polyethylene shielding around the detector setup.« less
Leder, A.; Anderson, A. J.; Billard, J.; ...
2018-02-02
Here, the Ricochet experiment seeks to measure Coherent (neutral-current) Elastic Neutrino-Nucleus Scattering (CEνNS) using dark-matter-style detectors with sub-keV thresholds placed near a neutrino source, such as the MIT (research) Reactor (MITR), which operates at 5.5 MW generating approximately 2.2 × 10 18 ν/second in its core. Currently, Ricochet is characterizing the backgrounds at MITR, the main component of which comes in the form of neutrons emitted from the core simultaneous with the neutrino signal. To characterize this background, we wrapped Bonner cylinders around a 3 2He thermal neutron detector, whose data was then unfolded via a Markov Chain Monte Carlo (MCMC) to producemore » a neutron energy spectrum across several orders of magnitude. We discuss the resulting spectrum and its implications for deploying Ricochet at the MITR site as well as the feasibility of reducing this background level via the addition of polyethylene shielding around the detector setup.« less
Lin, Zong; Puchalla, Jason; Shoup, Daniel; Rye, Hays S.
2013-01-01
A key constraint on the growth of most organisms is the slow and inefficient folding of many essential proteins. To deal with this problem, several diverse families of protein folding machines, known collectively as molecular chaperones, developed early in evolutionary history. The functional role and operational steps of these remarkably complex nanomachines remain subjects of active debate. Here we present evidence that, for the GroEL-GroES chaperonin system, the non-native substrate protein enters the folding cycle on the trans ring of the double-ring GroEL-ATP-GroES complex rather than the ADP-bound complex. The properties of this ATP complex are designed to ensure that non-native substrate protein binds first, followed by ATP and finally GroES. This binding order ensures efficient occupancy of the open GroEL ring and allows for disruption of misfolded structures through two phases of multiaxis unfolding. In this model, repeated cycles of partial unfolding, followed by confinement within the GroEL-GroES chamber, provide the most effective overall mechanism for facilitating the folding of the most stringently dependent GroEL substrate proteins. PMID:24022487
NASA Astrophysics Data System (ADS)
Kawashima, Ryunosuke; Kanemoto, Toshiaki; Sakamoto, Kengo; Uno, Mitsuo
2010-06-01
The authors have proposed the unique centrifugal pump, in which the impeller dose not have the driving shaft but is driven by the magnetic induction, namely Lorentz force, without the stay. Then, the rotating posture of the impeller is not stable, just like UFO. To make the rotating posture of the impeller stable irrespective of the operating condition, the pressure in the impeller casing was investigated experimentally while the impeller rotates at the steady state, as the preliminarily stage. The pressure, as well known, fluctuates periodically in response to the blade number. Besides, the pressure on the impeller shrouds decreases with the increase of the gap between the front shroud and the suction cover where the water leaks to the suction pipe, and is distorted in the peripheral direction. Such pressure conditions contribute directly to the hydraulic force acting on the impeller. The unstable behaviors of the impeller are induced from the above hydraulic forces, which change unsteadily in the radial and the peripheral directions in the impeller casing. The forces are affected by not only the operating condition but also the rotating posture of the impeller.
Online Lexical Competition during Spoken Word Recognition and Word Learning in Children and Adults
ERIC Educational Resources Information Center
Henderson, Lisa; Weighall, Anna; Brown, Helen; Gaskell, Gareth
2013-01-01
Lexical competition that occurs as speech unfolds is a hallmark of adult oral language comprehension crucial to rapid incremental speech processing. This study used pause detection to examine whether lexical competition operates similarly at 7-8 years and tested variables that influence "online" lexical activity in adults. Children…
NASA Astrophysics Data System (ADS)
Shao, Dandan; Gao, Kaifu
2018-01-01
Not Available Project supported by the National Natural Science Foundation of China (Grant Nos. 11175068 and 11474117) and the Self-determined Research Funds of CCNU from the Colleges Basic Research and Operation of MOE, China (Grant No. 230-20205170054).
Ends Versus Means: A Critical Analysis of the Persian Gulf Crisis (1987- 1988)
1990-08-01
readily apparent that a 12 gjunX ýjM 1Q§ (Washington: National Archives and Records Service, uFo , 1981), p. 197. 13 Snyder, p. 81. 18 whole host of...the consequences of an Iranian victory in the Gulf War. . . . However, the Soviets also seek to avoid alienating Iran and, if possible, hope to improve
U.S. EPA, Pesticide Product Label, CHEMMATE - 20S, 03/10/1983
2011-04-21
... h .... ;l u· .t,jlj t, J 1, .·,I'r ~" ,!I'ill '. ~" , 1" ~ll:HI~ i 11\\" I • .J hi It ,', ., I Ufo/,·th. n\\\\'d~ u"'J""!" · III:I(.:I,.I(I,il":II'. lL_nl.:II.I,J!lir~;li.d!.' .• J
OBR-1-1/Fizika-LT(Letaushaya Tarelka/Flying Disk) experiment
2009-04-24
ISS019-E-010226 (24 April 2009) --- Cosmonaut Gennady Padalka, Expedition 19/20 commander, holds the OBR-1-1/?Fizika-LT? (Letaushaya Tarelka/Flying Disk) educational experiment, also called ?UFO?, in the Zvezda Service Module of the International Space Station. The OBR-1-1 is part of the OBRAZOVANIE (Education) suite of three educational demonstrations of physics in microgravity.
U.S. EPA, Pesticide Product Label, ABCO WKS-65 BRUSH KILLER, 11/11/1911
2011-04-14
... pl'h~ "I.nto. I" t'", ',I> IJv •• ,lur.· ,nh •• ""if '," p ..... Ufo ' 1 uJot ur ,I"rr hr •• h •• 1 ,., .'fIt'" I nm I'IR.:{"TII I~'i FOR I,:,J: J:A.!lo' 1" KII.I "'fllJS A~I) ... 1 ... " ...
Beyond the Textbook: Studying Roswell in the Social Studies Classroom
ERIC Educational Resources Information Center
Joseph, Brad
2008-01-01
Roswell has long been synonymous with aliens and UFOs, and people have been arguing over what happened that night in 1947 for many years. It is a topic left out of most textbooks and neglected in many social studies classrooms. However, Roswell has found a permanent place in American culture, and teaching about Roswell can be valuable to social…
Copernicus Architecture, Phase I: Requirements Definition
1991-08-01
control primarily over maritime patrol aircraft (MPA) and Integrated Undersea Surveillance System (IUSS) units; however, surface ships and other units...Intermediate System Integrated Services Digital Network Integrated Tactical-Stategic Data Network Integrated Undersea Surveillance System Joint Army Navy... TTE Technical Training Equipment TTY Teletype UFO UHF Follow On UHF Ultra High Frequency USA/USAF U. S. Army/U.S. Air Force USCINC U. S
NASA Astrophysics Data System (ADS)
Ailleris, P.
2011-10-01
This presentation will focus on providing an overview of the project and its current status, highlighting the latest results, infrastructure, outreach activities (e.g. partnerships with "Astronomers Without Borders", "The World At Night"), while exploring ideas for the future and requesting feedback from the community of planetary scientists.
NuSTAR REVEALS RELATIVISTIC REFLECTION BUT NO ULTRA-FAST OUTFLOW IN THE QUASAR PG 1211+143
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zoghbi, A.; Miller, J. M.; Walton, D. J.
We report on four epochs of observations of the quasar PG 1211+143 using NuSTAR. The net exposure time is 300 ks. Prior work on this source found suggestive evidence of an ultra-fast outflow (UFO) in the Fe K band with a velocity of approximately 0.1c. The putative flow would carry away a high-mass flux and kinetic power, with broad implications for feedback and black hole--galaxy co-evolution. NuSTAR detects PG 1211+143 out to 30 keV, meaning that the continuum is well-defined both through and above the Fe K band. A characteristic relativistic disk reflection spectrum is clearly revealed via a broadmore » Fe K emission line and Compton back-scattering curvature. The data offer only weak constraints on the spin of the black hole. A careful search for UFOs shows no significant absorption feature above 90% confidence. The limits are particularly tight when relativistic reflection is included. We discuss the statistics and the implications of these results in terms of connections between accretion onto quasars, Seyferts, and stellar-mass black holes, and feedback into their host environments.« less
Optimization of biodiesel production in a hydrodynamic cavitation reactor using used frying oil.
Ghayal, Dyneshwar; Pandit, Aniruddha B; Rathod, Virendra K
2013-01-01
The present work demonstrates the application of a hydrodynamic cavitation reactor for the synthesis of biodiesel with used frying oil as a feedstock. The synthesis involved the transesterification of used frying oil (UFO) with methanol in the presence of potassium hydroxide as a catalyst. The effect of geometry and upstream pressure of a cavitating orifice plate on the rate of transesterification reaction has been studied. It is observed that the micro level turbulence created by hydrodynamic cavitation somewhat overcomes the mass transfer limitations for triphasic transesterification reaction. The significant effects of upstream pressure on the rate of formation of methyl esters have been seen. It has been observed that flow geometry of orifice plate plays a crucial role in process intensification. With an optimized plate geometry of 2mm hole diameter and 25 holes, more than 95% of triglycerides have been converted to methyl esters in 10 min of reaction time with cavitational yield of 1.28 × 10(-3) (Grams of methyl esters produced per Joule of energy supplied). The potential of UFO to produce good quality methyl esters has been demonstrated. Copyright © 2012 Elsevier B.V. All rights reserved.
NuSTAR Reveals Relativistic Reflection But No Ultra-Fast Outflow in the Quasar Pg∼1211+143
NASA Astrophysics Data System (ADS)
Zoghbi, A.; Miller, J. M.; Walton, D. J.; Harrison, F. A.; Fabian, A. C.; Reynolds, C. S.; Boggs, S. E.; Christensen, F. E.; Craig, W.; Hailey, C. J.; Stern, D.; Zhang, W. W.
2015-01-01
We report on four epochs of observations of the quasar PG 1211+143 using NuSTAR. The net exposure time is 300 ks. Prior work on this source found suggestive evidence of an ultra-fast outflow (UFO) in the Fe K band with a velocity of approximately 0.1c. The putative flow would carry away a high-mass flux and kinetic power, with broad implications for feedback and black hole--galaxy co-evolution. NuSTAR detects PG 1211+143 out to 30 keV, meaning that the continuum is well-defined both through and above the Fe K band. A characteristic relativistic disk reflection spectrum is clearly revealed via a broad Fe K emission line and Compton back-scattering curvature. The data offer only weak constraints on the spin of the black hole. A careful search for UFOs shows no significant absorption feature above 90% confidence. The limits are particularly tight when relativistic reflection is included. We discuss the statistics and the implications of these results in terms of connections between accretion onto quasars, Seyferts, and stellar-mass black holes, and feedback into their host environments.
A Unified View of X-ray Absorbers in AGNs and XRBs with MHD Winds
NASA Astrophysics Data System (ADS)
Fukumura, Keigo; Kazanas, Demosthenes; Shrader, Chris R.; Tombesi, Francesco; Behar, Ehud; Contopoulos, John
2016-01-01
The presence of UV and X-ray absorbers (aka. warm absorbers or WAs) has been long known for decades from extensive spectroscopic studies across diverse AGN populations such as nearby Seyfert galaxies and distant quasars. Furthermore, another class of seemingly distinct type of absorbers, ultra-fast outflows or UFOs, is becoming increasingly known today. Nonetheless, a physical identification of such absorbers, such as geometrical property and physical conditions, is very elusive to date despite the recent state-of-the-art observations. We develop a coherent scenario in which the detected absorbers are driven primarily (if not exclusively) by the action of global magnetic fields originating from a black hole accretion disk. In the context of MHD disk-wind of density profile of n~1/r, it is found that the properties of the observed WAs/UFOs are successfully described assuming a characteristic SED. As a case study, we analyze PG1211+143 and GRO J1655-40 to demonstrate that our wind model can systematically unify apparently diverse absorbers in both AGNs and XRBs in terms of explaining their global behavior as well as individual spectral lines.
NASA Astrophysics Data System (ADS)
Nickell, Joe
2000-03-01
Since the beginning of the modern UFO craze in 1947, an elaborate mythology has developed concerning alleged extraterrestrial visitations. ``Flying saucer" sightings (typically involving misperceptions of such mundane phenomena as meteors and research balloons) began to be accompanied in the 1950s by reports from ``contactees," persons who claimed to have had close encounters with, even to have been transported to distant planets by, UFO occupants. By the 1960s came reports of sporadic ``abductions" which have proliferated in correlation with media interest. (Indeed, by interaction between claimants and media the portrayal of aliens has evolved from a multiplicity of types into the rather standardized big-eyed humanoid model.) While evidence of alien contact has often been faked--as by spurious photos, ``crop circles," and the notorious ``Alien Autopsy" film--few alien abduction reports appear to be hoaxes. Most seem instead to come from sincere, sane individuals. Nevertheless, not one has been authenticated, and serious investigation shows that such claims can be explained as sleep-related phenomena (notably ``waking dreams"), hypnotic confabulation, and other psychological factors. As is typical of other mythologies, the alien myth involves supernormal beings that may interact with humans, and it purports to explain the workings of the universe and humanity's place within it.
Folding in and out: passive morphing in flapping wings.
Stowers, Amanda K; Lentink, David
2015-03-25
We present a new mechanism for passive wing morphing of flapping wings inspired by bat and bird wing morphology. The mechanism consists of an unactuated hand wing connected to the arm wing with a wrist joint. Flapping motion generates centrifugal accelerations in the hand wing, forcing it to unfold passively. Using a robotic model in hover, we made kinematic measurements of unfolding kinematics as functions of the non-dimensional wingspan fold ratio (2-2.5) and flapping frequency (5-17 Hz) using stereo high-speed cameras. We find that the wings unfold passively within one to two flaps and remain unfolded with only small amplitude oscillations. To better understand the passive dynamics, we constructed a computer model of the unfolding process based on rigid body dynamics, contact models, and aerodynamic correlations. This model predicts the measured passive unfolding within about one flap and shows that unfolding is driven by centrifugal acceleration induced by flapping. The simulations also predict that relative unfolding time only weakly depends on flapping frequency and can be reduced to less than half a wingbeat by increasing flapping amplitude. Subsequent dimensional analysis shows that the time required to unfold passively is of the same order of magnitude as the flapping period. This suggests that centrifugal acceleration can drive passive unfolding within approximately one wingbeat in small and large wings. Finally, we show experimentally that passive unfolding wings can withstand impact with a branch, by first folding and then unfolding passively. This mechanism enables flapping robots to squeeze through clutter without sophisticated control. Passive unfolding also provides a new avenue in morphing wing design that makes future flapping morphing wings possibly more energy efficient and light-weight. Simultaneously these results point to possible inertia driven, and therefore metabolically efficient, control strategies in bats and birds to morph or recover within a beat.
Greenfield, Norma J.
2009-01-01
Circular dichroism (CD) is an excellent spectroscopic technique for following the unfolding and folding of proteins as a function of temperature. One of its principal applications is to determine the effects of mutations and ligands on protein and polypeptide stability If the change in CD as a function of temperature is reversible, analysis of the data may be used to determined the van't Hoff enthalpy (ΔH) and entropy (ΔS) of unfolding, the midpoint of the unfolding transition (TM) and the free energy (ΔG) of unfolding. Binding constants of protein-protein and protein-ligand interactions may also be estimated from the unfolding curves. Analysis of CD spectra obtained as a function of temperature is also useful to determine whether a protein has unfolding intermediates. Measurement of the spectra of five folded proteins and their unfolding curves at a single wavelength takes approximately eight hours. PMID:17406506
Erickson, Harold P
2017-02-01
Extracellular matrix fibrils of fibronectin (FN) are highly elastic, and are typically stretched three to four times their relaxed length. The mechanism of stretching has been controversial, in particular whether it involves tension-induced unfolding of FNIII domains. Recent studies have found that ∼5pN is the threshold isometric force for unfolding various protein domains. FNIII domains should therefore not be unfolded until the tension approaches 5pN. Integrins have been reported to generate forces ranging from 1 to >50pN, but I argue that studies reporting 1-2pN are the most convincing. This is not enough to unfold FNIII domains. Even if domains were unfolded, 2pN would only extend the worm-like-chain to about twice the length of the folded domain. Overall I conclude that stretching FN matrix fibrils involves primarily the compact to extended conformational change of FN dimers, with minimal contribution from unfolding FNIII domains. Copyright © 2016 Elsevier Ltd. All rights reserved.
Sapra, K. Tanuj; Balasubramanian, G. Prakash; Labudde, Dirk; Bowie, James U.; Muller, Daniel J.
2009-01-01
Using single-molecule force spectroscopy, we investigated the effect of single point mutations on the energy landscape and unfolding pathways of the transmembrane protein bacteriorhodopsin. We show that the unfolding energy barriers in the energy landscape of the membrane protein followed a simple two-state behavior and represent a manifestation of many converging unfolding pathways. Although the unfolding pathways of wild-type and mutant bacteriorhodopsin did not change, indicating the presence of same ensemble of structural unfolding intermediates, the free energies of the rate-limiting transition states of the bacteriorhodopsin mutants decreased as the distance of those transition states to the folded intermediate states decreased. Thus, all mutants exhibited Hammond behavior and a change in the free energies of the intermediates along the unfolding reaction coordinate and, consequently, their relative occupancies. This is the first experimental proof showing that point mutations can reshape the free energy landscape of a membrane protein and force single proteins to populate certain unfolding pathways over others. PMID:18191146
Prediction of change in protein unfolding rates upon point mutations in two state proteins.
Chaudhary, Priyashree; Naganathan, Athi N; Gromiha, M Michael
2016-09-01
Studies on protein unfolding rates are limited and challenging due to the complexity of unfolding mechanism and the larger dynamic range of the experimental data. Though attempts have been made to predict unfolding rates using protein sequence-structure information there is no available method for predicting the unfolding rates of proteins upon specific point mutations. In this work, we have systematically analyzed a set of 790 single mutants and developed a robust method for predicting protein unfolding rates upon mutations (Δlnku) in two-state proteins by combining amino acid properties and knowledge-based classification of mutants with multiple linear regression technique. We obtain a mean absolute error (MAE) of 0.79/s and a Pearson correlation coefficient (PCC) of 0.71 between predicted unfolding rates and experimental observations using jack-knife test. We have developed a web server for predicting protein unfolding rates upon mutation and it is freely available at https://www.iitm.ac.in/bioinfo/proteinunfolding/unfoldingrace.html. Prominent features that determine unfolding kinetics as well as plausible reasons for the observed outliers are also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.
Mihailidou, Chrysovalantou; Papavassiliou, Athanasios G; Kiaris, Hippokratis
2014-04-01
Type 2 diabetes (T2D) is a disease that is characterized by raised levels of glucose in the blood combined with insulin resistance and relative insulin deficiency. The pathogenesis of type 2 diabetes is associated with the induction of the unfolded protein response (UPR). While UPR aims to restore tissue homeostasis following stress of the endoplasmic reticulum (ER), prolonged ER stress triggers apoptosis at least in part through the unfolded protein response (UPR)-activated transcription factor C/EBP (CCAAT/enhancer binding protein) homologous protein (CHOP). CHOP has elevated as a critical mediator connecting accumulation and aggregation of unfolded proteins in the ER and oxidative stress and also contributes to the induction of apoptosis in β-cell (beta-cell) - cells under conditions of increased insulin demand. p21 is a cell cycle regulator that is implicated in the regulation of the UPR by various mechanisms involving inhibition of apoptosis and facilitation of the regeneration capacity of the β cells. In this review we summarize the role of ER stress in the pathogenesis of type 2 diabetes which is associated with the induction of the unfolded protein response (UPR). We also review recent evidence associating p21 activity with β cell health and regenerative capacity by mechanisms that may interfere with the effects of p21 in the UPR or operate independently of ER stress. Most likely understanding the molecular details of the pathogenesis of type 2 diabetes will be beneficial for the management of the disease. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fernandes, Andre T.; Lopes, Carlos; Martins, Ligia O.
2012-06-08
Highlights: Black-Right-Pointing-Pointer CotA-laccase unfolds with an intermediate state. Black-Right-Pointing-Pointer Copper stabilizes the native and the intermediate state. Black-Right-Pointing-Pointer Copper binding to the unfolded state prevents refolding through protein aggregation. Black-Right-Pointing-Pointer Copper incorporation in CotA-laccase occurs as a later step during folding. -- Abstract: Copper is a redox-active metal and the main player in electron transfer reactions occurring in multicopper oxidases. The role of copper in the unfolding pathway and refolding of the multicopper oxidase CotA laccase in vitro was solved using double-jump stopped-flow experiments. Unfolding of apo- and holo-CotA was described as a three-state process with accumulation of an intermediatemore » in between the native and unfolded state. Copper stabilizes the native holo-CotA but also the intermediate state showing that copper is still bound to this state. Also, copper binds to unfolded holo-CotA in a non-native coordination promoting CotA aggregation and preventing refolding to the native structure. These results gather information on unfolding/folding pathways of multicopper oxidases and show that copper incorporation in vivo should be a tight controlled process as copper binding to the unfolded state under native conditions promotes protein aggregation.« less
Frye, K. J.; Royer, C. A.
1998-01-01
The structural origin of the decrease in system volume upon protein denaturation by pressure has remained a puzzle for decades. This negative volume change upon unfolding is assumed to arise globally from more intimate interactions between the polypeptide chain and water, including electrostriction of buried charges that become exposed upon unfolding, hydration of the polypeptide backbone and amino acid side chains and elimination of packing defects and internal void volumes upon unfolding of the chain. However, the relative signs and magnitudes of each of these contributing factors have not been experimentally determined. Our laboratory has probed the fundamental basis for the volume change upon unfolding of staphylococcal nuclease (Snase) using variable solution conditions and point mutants of Snase (Royer CA et al., 1993, Biochemistry 32:5222-5232; Frye KJ et al., 1996, Biochemistry 35:10234-10239). Our prior results indicate that for Snase, neither electrostriction nor polar or nonpolar hydration contributes significantly to the value of the volume change of unfolding. In the present work, we investigate the pressure induced unfolding of three point mutants of Snase in which internal cavity size is altered. The experimentally determined volume changes of unfolding for the mutants suggest that loss of internal void volume upon unfolding represents the major contributing factor to the value of the volume change of Snase unfolding. PMID:9792110
Beetle wings are inflatable origami
NASA Astrophysics Data System (ADS)
Chen, Rui; Ren, Jing; Ge, Siqin; Hu, David
2015-11-01
Beetles keep their wings folded and protected under a hard shell. In times of danger, they must unfold them rapidly in order for them to fly to escape. Moreover, they must do so across a range of body mass, from 1 mg to 10 grams. How can they unfold their wings so quickly? We use high-speed videography to record wing unfolding times, which we relate to the geometry of the network of blood vessels in the wing. Larger beetles have longer unfolding times. Modeling of the flow of blood through the veins successfully accounts for the wing unfolding speed of large beetles. However, smaller beetles have anomalously short unfolding times, suggesting they have lower blood viscosity or higher driving pressure. The use of hydraulics to unfold complex objects may have implications in the design of micro-flying air vehicles.
History, rare, and multiple events of mechanical unfolding of repeat proteins
NASA Astrophysics Data System (ADS)
Sumbul, Fidan; Marchesi, Arin; Rico, Felix
2018-03-01
Mechanical unfolding of proteins consisting of repeat domains is an excellent tool to obtain large statistics. Force spectroscopy experiments using atomic force microscopy on proteins presenting multiple domains have revealed that unfolding forces depend on the number of folded domains (history) and have reported intermediate states and rare events. However, the common use of unspecific attachment approaches to pull the protein of interest holds important limitations to study unfolding history and may lead to discarding rare and multiple probing events due to the presence of unspecific adhesion and uncertainty on the pulling site. Site-specific methods that have recently emerged minimize this uncertainty and would be excellent tools to probe unfolding history and rare events. However, detailed characterization of these approaches is required to identify their advantages and limitations. Here, we characterize a site-specific binding approach based on the ultrastable complex dockerin/cohesin III revealing its advantages and limitations to assess the unfolding history and to investigate rare and multiple events during the unfolding of repeated domains. We show that this approach is more robust, reproducible, and provides larger statistics than conventional unspecific methods. We show that the method is optimal to reveal the history of unfolding from the very first domain and to detect rare events, while being more limited to assess intermediate states. Finally, we quantify the forces required to unfold two molecules pulled in parallel, difficult when using unspecific approaches. The proposed method represents a step forward toward more reproducible measurements to probe protein unfolding history and opens the door to systematic probing of rare and multiple molecule unfolding mechanisms.
Puri, Sarita; Chaudhuri, Tapan K
2017-03-01
The conformation and thermodynamic stability of monomeric GroEL were studied by CD and fluorescence spectroscopy. GroEL denaturation with urea and dilution in buffer leads to formation of a folded GroEL monomer. The monomeric nature of this protein was verified by size-exclusion chromatography and native PAGE. It has a well-defined secondary and tertiary structure, folding activity (prevention of aggregation) for substrate protein and is resistant to proteolysis. Being a properly folded and reversibly refoldable, monomeric GroEL is amenable for the study of thermodynamic stability by unfolding transition methods. We present the equilibrium unfolding of monomeric GroEL as studied by urea and heat mediated unfolding processes. The urea mediated unfolding shows two transitions and a single transition in the heat mediated unfolding process. In the case of thermal unfolding, some residual structure unfolds at a higher temperature (70-75°C). The process of folding/unfolding is reversible in both cases. Analysis of folding/unfolding data provides a measure of ΔG NU H 2 O , T m , ΔH van and ΔS van of monomeric GroEL. The thermodynamic stability parameter ΔG NU H 2 O is similar with both CD and intrinsic fluorescence i.e. 7.10±1.0kcal/mol. The calculated T m , ΔH van and ΔS van from the thermal unfolding transition is 46±0.5°C, 43.3±0.1kcal/mol and 143.9±0.1cal/mol/k respectively. Copyright © 2016 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Beedle, Amy E. M.; Lezamiz, Ainhoa; Stirnemann, Guillaume; Garcia-Manyes, Sergi
2015-08-01
Understanding the directionality and sequence of protein unfolding is crucial to elucidate the underlying folding free energy landscape. An extra layer of complexity is added in metalloproteins, where a metal cofactor participates in the correct, functional fold of the protein. However, the precise mechanisms by which organometallic interactions are dynamically broken and reformed on (un)folding are largely unknown. Here we use single molecule force spectroscopy AFM combined with protein engineering and MD simulations to study the individual unfolding pathways of the blue-copper proteins azurin and plastocyanin. Using the nanomechanical properties of the native copper centre as a structurally embedded molecular reporter, we demonstrate that both proteins unfold via two independent, competing pathways. Our results provide experimental evidence of a novel kinetic partitioning scenario whereby the protein can stochastically unfold through two distinct main transition states placed at the N and C termini that dictate the direction in which unfolding occurs.
Complex Stability of Single Proteins Explored by Forced Unfolding Experiments
Janovjak, Harald; Sapra, K. Tanuj; Müller, Daniel J.
2005-01-01
In the last decade atomic force microscopy has been used to measure the mechanical stability of single proteins. These force spectroscopy experiments have shown that many water-soluble and membrane proteins unfold via one or more intermediates. Recently, Li and co-workers found a linear correlation between the unfolding force of the native state and the intermediate in fibronectin, which they suggested indicated the presence of a molecular memory or multiple unfolding pathways (1). Here, we apply two independent methods in combination with Monte Carlo simulations to analyze the unfolding of α-helices E and D of bacteriorhodopsin (BR). We show that correlation analysis of unfolding forces is very sensitive to errors in force calibration of the instrument. In contrast, a comparison of relative forces provides a robust measure for the stability of unfolding intermediates. The proposed approach detects three energetically different states of α-helices E and D in trimeric BR. These states are not observed for monomeric BR and indicate that substantial information is hidden in forced unfolding experiments of single proteins. PMID:15792967
Complex stability of single proteins explored by forced unfolding experiments.
Janovjak, Harald; Sapra, K Tanuj; Müller, Daniel J
2005-05-01
In the last decade atomic force microscopy has been used to measure the mechanical stability of single proteins. These force spectroscopy experiments have shown that many water-soluble and membrane proteins unfold via one or more intermediates. Recently, Li and co-workers found a linear correlation between the unfolding force of the native state and the intermediate in fibronectin, which they suggested indicated the presence of a molecular memory or multiple unfolding pathways (1). Here, we apply two independent methods in combination with Monte Carlo simulations to analyze the unfolding of alpha-helices E and D of bacteriorhodopsin (BR). We show that correlation analysis of unfolding forces is very sensitive to errors in force calibration of the instrument. In contrast, a comparison of relative forces provides a robust measure for the stability of unfolding intermediates. The proposed approach detects three energetically different states of alpha-helices E and D in trimeric BR. These states are not observed for monomeric BR and indicate that substantial information is hidden in forced unfolding experiments of single proteins.
Writing the Observer back into the Equation
1976-03-05
death, a biological system, psi, consciousness, inception, telepathy , psychokinesis, UFO’s, God, and the collective unconscious can be taken...is postulated. From the model, constructs that model life, death, a biological system, psi, consciousness, inception, telepathy , psychokinesis...if you are doing it, because a thought comes through, and it fades immediately, almost as soon as it goes through. How fast do you forget a dream
CIA’s Role in the Study of UFOs, 1947-90
1997-01-01
Roswell incident, in which a flying saucer supposedly crashed in New ... flying saucer crash in New Mexico in 1947, the government not only recovered debris from the crashed saucer but also four or five alien bodies...ever since.9� In September 1994, the US Air Force released a new report on the Roswell incident that concluded that the debris found in New Mexico
A.B.C. Prunes, U.F.O. News, and Politicks: Parody in Media Literacy Education
ERIC Educational Resources Information Center
Ohta, Ralph
2005-01-01
Parody is a form of imitation with the added elements of comedic twists, turns, and exaggerations. To create a parody of something, one has to understand it before beginning to alter it for humorous effect. Parodies are used by teachers of writing, music, and art as a method of educating and evaluating students' understanding of the styles of the…
OBR-1-1/Fizika-LT(Letaushaya Tarelka/Flying Disk) experiment
2009-04-24
ISS019-E-010230 (24 April 2009) --- Cosmonaut Gennady Padalka, Expedition 19/20 commander, is pictured near the OBR-1-1/?Fizika-LT? (Letaushaya Tarelka/Flying Disk) educational experiment, also called ?UFO?, floating freely in the Zvezda Service Module of the International Space Station. The OBR-1-1 is part of the OBRAZOVANIE (Education) suite of three educational demonstrations of physics in microgravity.
OBR-1-1/Fizika-LT(Letaushaya Tarelka/Flying Disk) experiment
2009-04-24
ISS019-E-010081 (24 April 2009) --- Cosmonaut Gennady Padalka, Expedition 19/20 commander, is pictured near the OBR-1-1/?Fizika-LT? (Letaushaya Tarelka/Flying Disk) educational experiment, also called ?UFO?, floating freely in the Zvezda Service Module of the International Space Station. The OBR-1-1 is part of the OBRAZOVANIE (Education) suite of three educational demonstrations of physics in microgravity.
SWANEA (Southwest Asia-Northeast Africa): A Climatological Study. Volume 1. The Horn of Africa
1990-06-01
Trough axes (interior Africa and Indian axes. West of the Ethiopian Highlands, the. convergent Ocean) can temporarily link tip along the Horn or Af~rica...FeqecisofVsibties in B pedo M kis, YemndHglns and p~~revailing di rectionfo Yemen u Haig (hlands. n piadwa ylni ufo rmteRba Musai), ana, ndT iz.Eatery ompnetsfor
Enclosure Then and Now: Rural Schools and Communities in the Wake of Market-Driven Agriculture
ERIC Educational Resources Information Center
Theobald, Paul; Rochon, Ronald S.
2006-01-01
The following is an historically-based analysis of a new phenomenon affecting rural schools and communities: animal confinement operations. A contrast is made between "enclosure" as it unfolded in England a few centuries ago and the way animal concentration units constitute a second, "modern" form of enclosure today. In both…
Zhang, Cui; Gao, Chaohui; Qiu, Zhanglei
2013-01-01
Neuroglobin (Ngb), a recently discovered globin, is predominantly expressed in the brain, retina, and other nerve tissues of vertebrates. The unfolding processes of apo-neuroglobin (apoNgb) induced by guanidine hydrochloride (GdnHCl) and urea were investigated by spectroscopic methods. In the unfolding processes, apoNgb's tertiary structural transition was monitored by the changes of intrinsic fluorescence emission spectra, and its secondary structural transition was measured by the changes of far-ultraviolet circular dichroism (CD) spectra. In addition, 8-anilino-1-naphthalenesulfonic acid (ANS), a hydrophobic cluster binding dye, was also used to monitor the unfolding process of apoNgb and to explore its intermediates. Results showed that GdnHCl-induced unfolding of apoNgb was via a three-state pathway, that is, Native state (N) → Intermediate state (I) → Unfolded state (U), during which the intermediate was inferred by an increase in fluorescence intensity and the change of CD value. Gibbs free energy changes are 10.2 kJ·mol−1 for the first unfolding transition and 14.0 kJ·mol−1 for the second transition. However, urea-induced unfolding of apoNgb only underwent a two-state transition: Native state (N) → Partially unfolded state (P). The result showed that GdnHCl can efficiently affect the conformational states of apoNgb compared with those of urea. The work will benefit to have an understanding of the unfolding mechanism of apoNgb induced by GdnHCl and urea. PMID:23984347
Chemically crosslinked protein dimers: stability and denaturation effects.
Byrne, M. P.; Stites, W. E.
1995-01-01
Nine single substitution cysteine mutants of staphylococcal nuclease (nuclease) were preferentially crosslinked at the introduced cysteine residues using three different bifunctional crosslinking reagents; 1,6-bismaleimidohexane (BMH), 1,3-dibromo-2-propanol (DBP), and the chemical warfare agent, mustard gas (bis(2-chloroethyl)sulfide; mustard). BMH and mustard gas are highly specific reagents for cysteine residues, whereas DBP is not as specific. Guanidine hydrochloride (GuHCl) denaturations of the resulting dimeric proteins exhibited biphasic unfolding behavior that did not fit the two-state model of unfolding. The monofunctional reagent, epsilon-maleimidocaproic acid (MCA), was used as a control for the effects of alkylation. Proteins modified with MCA unfolded normally, showing that this unusual unfolding behavior is due to crosslinking. The data obtained from these crosslinked dimers was fitted to a three-state thermodynamic model of two successive transitions in which the individual subunits cooperatively unfold. These two unfolding transitions were very different from the unfolding of the monomeric protein. These differences in unfolding behavior can be attributed in large part to changes in the denatured state. In addition to GuHCl titrations, the crosslinked dimers were also thermally unfolded. In contrast to the GuHCl denaturations, analysis of this data fit a two-state model well, but with greatly elevated van't Hoff enthalpies in many cases. However, clear correlations between the thermal and GuHCl denaturations exist, and the differences in thermal unfolding can be rationalized by postulating interactions of the denatured crosslinked proteins. PMID:8580845
An outburst scenario for the X-ray spectral variability in 3C 111
NASA Astrophysics Data System (ADS)
Tombesi, F.; Reeves, J. N.; Reynolds, C. S.; García, J.; Lohfink, A.
2013-09-01
We present a combined Suzaku and Swift BAT broad-band E = 0.6-200 keV spectral analysis of three 3C 111 observations obtained in 2010. The data are well described with an absorbed power-law continuum and a weak (R ≃ 0.2) cold reflection component from distant material. We constrain the continuum cutoff at EC ≃ 150-200 keV, which is in accordance with X-ray Comptonization corona models and supports claims that the jet emission is only dominant at much higher energies. Fe XXVI Lyα emission and absorption lines are also present in the first and second observations, respectively. The modelling and interpretation of the emission line is complex and we explore three possibilities. If originating from ionized-disc reflection, this should be emitted at rin ≥ 50 rg or, in the lamp-post configuration, the illuminating source should be at a height of h ≥ 30 rg above the black hole. Alternatively, the line could be modelled with a hot collisionally ionized plasma with temperature kT = 22.0^{+6.1}_{-3.2} keV or a photoionized plasma with log ξ = 4.52^{+0.10}_{-0.16} erg s-1 cm and column density NH > 3 × 1023 cm-2. However, the first and second scenarios are less favoured on statistical and physical grounds, respectively. The blueshifted absorption line in the second observation can be modelled as an ultrafast outflow (UFO) with ionization parameter log ξ = 4.47^{+0.76}_{-0.04} erg s-1 cm, column density N_H = (5.3^{+1.8}_{-1.3})× 10^{22} cm-2 and outflow velocity vout = 0.104 ± 0.006c. Interestingly, the parameters of the photoionized emission model remarkably match those of the absorbing UFO, supporting the possibility that the same material could be responsible for both emission and absorption. We suggest an outburst scenario in which an accretion disc wind, initially lying out of the line of sight and observed in emission, then crosses our view to the source and it is observed in absorption as a mildly relativistic UFO.
The unfolding mechanism of monomeric mutant SOD1 by simulated force spectroscopy.
Habibi, Mona; Rottler, Jörg; Plotkin, Steven S
2017-11-01
Mechanical unfolding of mutated apo, disulfide-reduced, monomeric superoxide dismutase 1 protein (SOD1) has been simulated via force spectroscopy techniques, using both an all-atom (AA), explicit solvent model and a coarse-grained heavy-atom Gō (HA-Gō) model. The HA-Gō model was implemented at two different pulling speeds for comparison. The most-common sequence of unfolding in the AA model agrees well with the most-common unfolding sequence of the HA-Gō model, when the same normalized pulling rate was used. Clustering of partially-native structures as the protein unfolds shows that the AA and HA-Gō models both exhibit a dominant pathway for early unfolding, which eventually bifurcates repeatedly to multiple branches after the protein is about half-unfolded. The force-extension curve exhibits multiple force drops, which are concomitant with jumps in the local interaction potential energy between specific β-strands in the protein. These sudden jumps in the potential energy coincide with the dissociation of specific pairs of β-strands, and thus intermediate unfolding events. The most common sequence of β-strand dissociation in the unfolding pathway of the AA model is β-strands 5, 4, 8, 7, 1, 2, then finally β-strands 3 and 6. The observation that β-strand 5 is among the first to unfold here, but the last to unfold in simulations of loop-truncated SOD1, could imply the existence of an evolutionary compensation mechanism, which would stabilize β-strands flanking long loops against their entropic penalty by strengthening intramolecular interactions. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 Elsevier B.V. All rights reserved.
Roy, Susmita; Bagchi, Biman
2013-04-25
Unfolding of a protein often proceeds through partial unfolded intermediate states (PUIS). PUIS have been detected in several experimental and simulation studies. However, complete analyses of transitions between different PUIS and the unfolding trajectory are sparse. To understand such dynamical processes, we study chemical unfolding of a small protein, chicken villin head piece (HP-36), in aqueous dimethyl sulfoxide (DMSO) solution. We carry out molecular dynamics simulations at various solution compositions under ambient conditions. In each concentration, the initial step of unfolding involves separation of two adjacent native contacts, between phenyl alanine residues (11-18 and 7-18). This first step induces, under appropriate conditions, subsequent separation among other hydrophobic contacts, signifying a high degree of cooperativity in the unfolding process. The observed sequence of structural changes in HP-36 on increasing DMSO concentration and the observed sequence of PUIS, are in approximate agreement with earlier simulation results (in pure water) and experimental observations on unfolding of HP-36. Peculiar to water-DMSO mixture, an intervening structural transformation (around 15% of DMSO) in the binary mixture solvent retards the progression of unfolding as composition is increased. This is reflected in a remarkable nonmonotonic composition dependence of RMSD, radius of gyration and the fraction of native contacts. At 30% mole fraction of DMSO, we find the extended randomly coiled structure of the unfolded protein. The molecular mechanism of DMSO induced unfolding process is attributed to the initial preferential solvation of the hydrophobic side chain atoms through the methyl groups of DMSO, followed by the hydrogen bonding of the oxygen atom of DMSO to the exposed backbone NH groups of HP-36.
Unfolding study of a trimeric membrane protein AcrB.
Ye, Cui; Wang, Zhaoshuai; Lu, Wei; Wei, Yinan
2014-07-01
The folding of a multi-domain trimeric α-helical membrane protein, Escherichia coli inner membrane protein AcrB, was investigated. AcrB contains both a transmembrane domain and a large periplasmic domain. Protein unfolding in sodium dodecyl sulfate (SDS) and urea was monitored using the intrinsic fluorescence and circular dichroism spectroscopy. The SDS denaturation curve displayed a sigmoidal profile, which could be fitted with a two-state unfolding model. To investigate the unfolding of separate domains, a triple mutant was created, in which all three Trp residues in the transmembrane domain were replaced with Phe. The SDS unfolding profile of the mutant was comparable to that of the wild type AcrB, suggesting that the observed signal change was largely originated from the unfolding of the soluble domain. Strengthening of trimer association through the introduction of an inter-subunit disulfide bond had little effect on the unfolding profile, suggesting that trimer dissociation was not the rate-limiting step in unfolding monitored by fluorescence emission. Under our experimental condition, AcrB unfolding was not reversible. Furthermore, we experimented with the refolding of a monomeric mutant, AcrBΔloop , from the SDS unfolded state. The CD spectrum of the refolded AcrBΔloop superimposed well onto the spectra of the original folded protein, while the fluorescence spectrum was not fully recovered. In summary, our results suggested that the unfolding of the trimeric AcrB started with a local structural rearrangement. While the refolding of secondary structure in individual monomers could be achieved, the re-association of the trimer might be the limiting factor to obtain folded wild-type AcrB. © 2014 The Protein Society.
Studying pressure denaturation of a protein by molecular dynamics simulations.
Sarupria, Sapna; Ghosh, Tuhin; García, Angel E; Garde, Shekhar
2010-05-15
Many globular proteins unfold when subjected to several kilobars of hydrostatic pressure. This "unfolding-up-on-squeezing" is counter-intuitive in that one expects mechanical compression of proteins with increasing pressure. Molecular simulations have the potential to provide fundamental understanding of pressure effects on proteins. However, the slow kinetics of unfolding, especially at high pressures, eliminates the possibility of its direct observation by molecular dynamics (MD) simulations. Motivated by experimental results-that pressure denatured states are water-swollen, and theoretical results-that water transfer into hydrophobic contacts becomes favorable with increasing pressure, we employ a water insertion method to generate unfolded states of the protein Staphylococcal Nuclease (Snase). Structural characteristics of these unfolded states-their water-swollen nature, retention of secondary structure, and overall compactness-mimic those observed in experiments. Using conformations of folded and unfolded states, we calculate their partial molar volumes in MD simulations and estimate the pressure-dependent free energy of unfolding. The volume of unfolding of Snase is negative (approximately -60 mL/mol at 1 bar) and is relatively insensitive to pressure, leading to its unfolding in the pressure range of 1500-2000 bars. Interestingly, once the protein is sufficiently water swollen, the partial molar volume of the protein appears to be insensitive to further conformational expansion or unfolding. Specifically, water-swollen structures with relatively low radii of gyration have partial molar volume that are similar to that of significantly more unfolded states. We find that the compressibility change on unfolding is negligible, consistent with experiments. We also analyze hydration shell fluctuations to comment on the hydration contributions to protein compressibility. Our study demonstrates the utility of molecular simulations in estimating volumetric properties and pressure stability of proteins, and can be potentially extended for applications to protein complexes and assemblies. Proteins 2010. (c) 2009 Wiley-Liss, Inc.
FRUIT: An operational tool for multisphere neutron spectrometry in workplaces
NASA Astrophysics Data System (ADS)
Bedogni, Roberto; Domingo, Carles; Esposito, Adolfo; Fernández, Francisco
2007-10-01
FRUIT (Frascati Unfolding Interactive Tool) is an unfolding code for Bonner sphere spectrometers (BSS) developed, under the Labview environment, at the INFN-Frascati National Laboratory. It models a generic neutron spectrum as the superposition of up to four components (thermal, epithermal, fast and high energy), fully defined by up to seven positive parameters. Different physical models are available to unfold the sphere counts, covering the majority of the neutron spectra encountered in workplaces. The iterative algorithm uses Monte Carlo methods to vary the parameters and derive the final spectrum as limit of a succession of spectra fulfilling the established convergence criteria. Uncertainties on the final results are evaluated taking into consideration the different sources of uncertainty affecting the input data. Relevant features of FRUIT are (1) a high level of interactivity, allowing the user to follow the convergence process, (2) the possibility to modify the convergence tolerances during the run, allowing a rapid achievement of meaningful solutions and (3) the reduced dependence of the results from the initial hypothesis. This provides a useful instrument for spectrometric measurements in workplaces, where detailed a priori information is usually unavailable. This paper describes the characteristics of the code and presents the results of performance tests over a significant variety of reference and workplace neutron spectra ranging from thermal up to hundreds MeV neutrons.
Hackl, Ellen V
2015-02-01
Natively unfolded (intrinsically disordered) proteins have attracted growing attention due to their high abundance in nature, involvement in various signalling and regulatory pathways and direct association with many diseases. In the present work the combined effect of temperature and alcohols, trifluoroethanol (TFE) and hexafluoroisopropanol (HFIP), on the natively unfolded 4E-BP1 protein was studied to elucidate the balance between temperature-induced folding and unfolding in intrinsically disordered proteins. It was shown that elevated temperatures induce reversible partial folding of 4E-BP1 both in buffer and in the mixed solutions containing denaturants. In the mixed solutions containing TFE (HFIP) 4E-BP1 adopts a partially folded helical conformation. As the temperature increases, the initial temperature-induced protein folding is replaced by irreversible unfolding/melting only after a certain level of the protein helicity has been reached. Onset unfolding temperature decreases with TFE (HFIP) concentration in solution. It was shown that an increase in the temperature induces two divergent processes in a natively unfolded protein--hydrophobicity-driven folding and unfolding. Balance between these two processes determines thermal behaviour of a protein. The correlation between heat-induced protein unfolding and the amount of helical content in a protein is revealed. Heat-induced secondary structure formation can be a valuable test to characterise minor changes in the conformations of natively unfolded proteins as a result of site-directed mutagenesis. Mutants with an increased propensity to fold into a structured form reveal different temperature behaviour.
Unfolding of the cold shock protein studied with biased molecular dynamics.
Morra, Giulia; Hodoscek, Milan; Knapp, Ernst-Walter
2003-11-15
The cold shock protein from Bacillus caldolyticus is a small beta-barrel protein that folds in a two-state mechanism. For the native protein and for several mutants, a wealth of experimental data are available on stability and folding, so that it is an optimal system to study this process. We compare data from unfolding simulations (trajectories of 5 and up to 12 ns) obtained with a bias potential at room temperature and from unbiased thermal unfolding simulations with experimental data. The unfolding patterns derived from the trajectories starting from different native-like conformations and subject to different unfolding conditions agree. The transition state found in the simulations of unfolding is close to the native structure in agreement with experiment. Moreover, a lower value of the free energy barrier of unfolding was found for the mutant R3E than for the mutant E46A and the native protein, as indicated by experimental data. The first unfolding event involves the three-stranded beta-sheet whose decomposition corresponds to the transition state. In contrast to conclusions drawn from experiments, we found that the two-stranded beta-strand forms the most stable substructure, which decomposes very late in the unfolding process. However, assuming that this structure forms very early in the folding process, our findings would not contradict the experiments but require a different interpretation of them. Copyright 2003 Wiley-Liss, Inc.
Application of long-range order to predict unfolding rates of two-state proteins.
Harihar, B; Selvaraj, S
2011-03-01
Predicting the experimental unfolding rates of two-state proteins and models describing the unfolding rates of these proteins is quite limited because of the complexity present in the unfolding mechanism and the lack of experimental unfolding data compared with folding data. In this work, 25 two-state proteins characterized by Maxwell et al. (Protein Sci 2005;14:602–616) using a consensus set of experimental conditions were taken, and the parameter long-range order (LRO) derived from their three-dimensional structures were related with their experimental unfolding rates ln(k(u)). From the total data set of 30 proteins used by Maxwell et al. (Protein Sci 2005;14:602–616), five slow-unfolding proteins with very low unfolding rates were considered to be outliers and were not included in our data set. Except all beta structural class, LRO of both the all-alpha and mixed-class proteins showed a strong inverse correlation of r = -0.99 and -0.88, respectively, with experimental ln(k(u)). LRO shows a correlation of -0.62 with experimental ln(k(u)) for all-beta proteins. For predicting the unfolding rates, a simple statistical method has been used and linear regression equations were developed for individual structural classes of proteins using LRO, and the results obtained showed a better agreement with experimental results. Copyright © 2010 Wiley-Liss, Inc.
Nasedkin, Alexandr; Marcellini, Moreno; Religa, Tomasz L.; Freund, Stefan M.; Menzel, Andreas; Fersht, Alan R.; Jemth, Per; van der Spoel, David; Davidsson, Jan
2015-01-01
The folding and unfolding of protein domains is an apparently cooperative process, but transient intermediates have been detected in some cases. Such (un)folding intermediates are challenging to investigate structurally as they are typically not long-lived and their role in the (un)folding reaction has often been questioned. One of the most well studied (un)folding pathways is that of Drosophila melanogaster Engrailed homeodomain (EnHD): this 61-residue protein forms a three helix bundle in the native state and folds via a helical intermediate. Here we used molecular dynamics simulations to derive sample conformations of EnHD in the native, intermediate, and unfolded states and selected the relevant structural clusters by comparing to small/wide angle X-ray scattering data at four different temperatures. The results are corroborated using residual dipolar couplings determined by NMR spectroscopy. Our results agree well with the previously proposed (un)folding pathway. However, they also suggest that the fully unfolded state is present at a low fraction throughout the investigated temperature interval, and that the (un)folding intermediate is highly populated at the thermal midpoint in line with the view that this intermediate can be regarded to be the denatured state under physiological conditions. Further, the combination of ensemble structural techniques with MD allows for determination of structures and populations of multiple interconverting structures in solution. PMID:25946337
Nasedkin, Alexandr; Marcellini, Moreno; Religa, Tomasz L; Freund, Stefan M; Menzel, Andreas; Fersht, Alan R; Jemth, Per; van der Spoel, David; Davidsson, Jan
2015-01-01
The folding and unfolding of protein domains is an apparently cooperative process, but transient intermediates have been detected in some cases. Such (un)folding intermediates are challenging to investigate structurally as they are typically not long-lived and their role in the (un)folding reaction has often been questioned. One of the most well studied (un)folding pathways is that of Drosophila melanogaster Engrailed homeodomain (EnHD): this 61-residue protein forms a three helix bundle in the native state and folds via a helical intermediate. Here we used molecular dynamics simulations to derive sample conformations of EnHD in the native, intermediate, and unfolded states and selected the relevant structural clusters by comparing to small/wide angle X-ray scattering data at four different temperatures. The results are corroborated using residual dipolar couplings determined by NMR spectroscopy. Our results agree well with the previously proposed (un)folding pathway. However, they also suggest that the fully unfolded state is present at a low fraction throughout the investigated temperature interval, and that the (un)folding intermediate is highly populated at the thermal midpoint in line with the view that this intermediate can be regarded to be the denatured state under physiological conditions. Further, the combination of ensemble structural techniques with MD allows for determination of structures and populations of multiple interconverting structures in solution.
Folding thermodynamics of pseudoknotted chain conformations
Kopeikin, Zoia; Chen, Shi-Jie
2008-01-01
We develop a statistical mechanical framework for the folding thermodynamics of pseudoknotted structures. As applications of the theory, we investigate the folding stability and the free energy landscapes for both the thermal and the mechanical unfolding of pseudoknotted chains. For the mechanical unfolding process, we predict the force-extension curves, from which we can obtain the information about structural transitions in the unfolding process. In general, a pseudoknotted structure unfolds through multiple structural transitions. The interplay between the helix stems and the loops plays an important role in the folding stability of pseudoknots. For instance, variations in loop sizes can lead to the destabilization of some intermediate states and change the (equilibrium) folding pathways (e.g., two helix stems unfold either cooperatively or sequentially). In both thermal and mechanical unfolding, depending on the nucleotide sequence, misfolded intermediate states can emerge in the folding process. In addition, thermal and mechanical unfoldings often have different (equilibrium) pathways. For example, for certain sequences, the misfolded intermediates, which generally have longer tails, can fold, unfold, and refold again in the pulling process, which means that these intermediates can switch between two different average end-end extensions. PMID:16674261
Eschweiler, Joseph D.; Martini, Rachel M.; Ruotolo, Brandon T.
2017-01-01
Despite the growing application of gas-phase measurements in structural biology and drug discovery, the factors that govern protein stabilities and structures in a solvent-free environment are still poorly understood. Here, we examine the solvent-free unfolding pathway for a group of homologous serum albumins. Utilizing a combination of chemical probes and non-covalent reconstructions, we draw new specific conclusions regarding the unfolding of albumins in the gas-phase, as well as more-general inferences regarding the sensitivity of collision induced unfolding to changes in protein primary and tertiary structure. Our findings suggest that the general unfolding pathway of low charge state albumin ions is largely unaffected by changes in primary structure; however, the stabilities of intermediates along these pathways vary widely as sequences diverge. Additionally, we find that human albumin follows a domain associated unfolding pathway, and are able to assign each unfolded form observed in our gas-phase dataset to the disruption of specific domains within the protein. The totality of our data informs the first detailed mechanism for multi-domain protein unfolding in the gas phase, and highlights key similarities and differences from the known the solution-phase pathway. PMID:27959526
Roy, Susmita; Bagchi, Biman
2014-05-29
Elucidation of possible pathways between folded (native) and unfolded states of a protein is a challenging task, as the intermediates are often hard to detect. Here, we alter the solvent environment in a controlled manner by choosing two different cosolvents of water, urea, and dimethyl sulfoxide (DMSO) and study unfolding of four different proteins to understand the respective sequence of melting by computer simulation methods. We indeed find interesting differences in the sequence of melting of α helices and β sheets in these two solvents. For example, in 8 M urea solution, β-sheet parts of a protein are found to unfold preferentially, followed by the unfolding of α helices. In contrast, 8 M DMSO solution unfolds α helices first, followed by the separation of β sheets for the majority of proteins. Sequence of unfolding events in four different α/β proteins and also in chicken villin head piece (HP-36) both in urea and DMSO solutions demonstrate that the unfolding pathways are determined jointly by relative exposure of polar and nonpolar residues of a protein and the mode of molecular action of a solvent on that protein.
Impact of ion binding on poly-L-lysine (un)folding energy landscape and kinetics.
Xiong, Kan; Asher, Sanford A
2012-06-21
We utilize T-jump UV resonance Raman spectroscopy (UVRR) to study the impact of ion binding on the equilibrium energy landscape and on (un)folding kinetics of poly-L-lysine (PLL). We observe that the relaxation rates of the folded conformations (including π-helix (bulge), pure α-helix, and turns) of PLL are slower than those of short alanine-based peptides. The PLL pure α-helix folding time is similar to that of short alanine-based peptides. We for the first time have directly observed that turn conformations are α-helix and π-helix (bulge) unfolding intermediates. ClO(4)(-) binding to the Lys side chain -NH(3)(+) groups and the peptide backbone slows the α-helix unfolding rate compared to that in pure water, but little impacts the folding rate, resulting in an increased α-helix stability. ClO(4)(-) binding significantly increases the PLL unfolding activation barrier but little impacts the folding barrier. Thus, the PLL folding coordinate(s) differs from the unfolding coordinate(s). The-π helix (bulge) unfolding and folding coordinates do not directly go through the α-helix energy well. Our results clearly demonstrate that PLL (un)folding is not a two-state process.
Miyazaki, Yusuke; Chen, Ling-chun; Chu, Bernard W; Swigut, Tomek; Wandless, Thomas J
2015-01-01
Eukaryotic cells possess a variety of signaling pathways that prevent accumulation of unfolded and misfolded proteins. Chief among these is the heat shock response (HSR), which is assumed to respond to unfolded proteins in the cytosol and nucleus alike. In this study, we probe this axiom further using engineered proteins called ‘destabilizing domains’, whose folding state we control with a small molecule. The sudden appearance of unfolded protein in mammalian cells elicits a robust transcriptional response, which is distinct from the HSR and other known pathways that respond to unfolded proteins. The cellular response to unfolded protein is strikingly different in the nucleus and the cytosol, although unfolded protein in either compartment engages the p53 network. This response provides cross-protection during subsequent proteotoxic stress, suggesting that it is a central component of protein quality control networks, and like the HSR, is likely to influence the initiation and progression of human pathologies. DOI: http://dx.doi.org/10.7554/eLife.07687.001 PMID:26314864
Shen, Jana K
2010-06-02
It is now widely recognized that the unfolded state of a protein in equilibrium with the native state under folding conditions may contain significant residual structures. However, due to technical difficulties residue-specific interactions in the unfolded state remain elusive. Here we introduce a method derived from the Wyman-Tanford theory to determine residue-specific pK(a)'s in the unfolded state. This method requires equilibrium stability measurements of the wild type and single-point mutants in which titrable residues are replaced with charge-neutral ones under two pH conditions. Application of the proposed approach reveals a highly depressed pK(a) for Asp8 in the unfolded state of the NTL9 protein. Knowledge of unfolded-state pK(a)'s enables quantitative estimation of the unfolded-state electrostatic effects on protein stability. It also provides valuable benchmarks for the improvement of force fields and validation of microscopic information from molecular dynamics simulations.
High temperature unfolding of a truncated hemoglobin by molecular dynamics simulation.
Sharma, Ravi Datta; Kanwal, Rajnee; Lynn, Andrew M; Singh, Prerna; Pasha, Syed Tazeen; Fatma, Tasneem; Jawaid, Safdar
2013-09-01
Heme containing proteins are associated with peroxidase activity. The proteins like hemoglobin, myoglobins, cytochrome c and micro-peroxidase other than peroxidases have been shown to exhibit weak peroxidase-like activity. This weak peroxidase-like activity in hemoglobin-like molecules is due to heme moiety. We conducted molecular dynamics (MD) studies to decipher the unfolding path of Ba-Glb (a truncated hemoglobin from Bacillus anthracis) and the role of heme moiety to its unfolding path. The similar unfolding path is also observed in vitro by UV/VIS spectroscopy. The data confirmed that the unfolding of Ba-Glb follows a three state process with a meta-stable (intermediate) state between the native and unfolded conformations. The present study is supported by several unfolding parameters like root-mean-square-deviation (RMSD), dictionary of protein secondary structure (DSSP), and free energy landscape. Understanding the structure of hemoglobin like proteins in unicellular dreaded pathogens like B. anthracis will pave way for newer drug discovery targets and in the disease management of anthrax.
Ding, Yun; Fleming, Aaron M; He, Lidong; Burrows, Cynthia J
2015-07-22
Cytosine (C)-rich DNA can adopt i-motif folds under acidic conditions, with the human telomere i-motif providing a well-studied example. The dimensions of this i-motif are appropriate for capture in the nanocavity of the α-hemolysin (α-HL) protein pore under an electrophoretic force. Interrogation of the current vs time (i-t) traces when the i-motif interacts with α-HL identified characteristic signals that were pH dependent. These features were evaluated from pH 5.0 to 7.2, a region surrounding the transition pH of the i-motif (6.1). When the i-motif without polynucleotide tails was studied at pH 5.0, the folded structure entered the nanocavity of α-HL from either the top or bottom face to yield characteristic current patterns. Addition of a 5' 25-mer poly-2'-deoxyadensosine tail allowed capture of the i-motif from the unfolded terminus, and this was used to analyze the pH dependency of unfolding. At pH values below the transition point, only folded strands were observed, and when the pH was increased above the transition pH, the number of folded events decreased, while the unfolded events increased. At pH 6.8 and 7.2 4% and 2% of the strands were still folded, respectively. The lifetimes for the folded states at pH 6.8 and 7.2 were 21 and 9 ms, respectively, at 160 mV electrophoretic force. These lifetimes are sufficiently long to affect enzymes operating on DNA. Furthermore, these transient lifetimes are readily obtained using the α-HL nanopore, a feature that is not easily achievable by other methods.
Deng, Nan-jie; Dai, Wei
2013-01-01
Understanding how kinetics in the unfolded state affects protein folding is a fundamentally important yet less well-understood issue. Here we employ three different models to analyze the unfolded landscape and folding kinetics of the miniprotein Trp-cage. The first is a 208 μs explicit solvent molecular dynamics (MD) simulation from D. E. Shaw Research containing tens of folding events. The second is a Markov state model (MSM-MD) constructed from the same ultra-long MD simulation; MSM-MD can be used to generate thousands of folding events. The third is a Markov state model built from temperature replica exchange MD simulations in implicit solvent (MSM-REMD). All the models exhibit multiple folding pathways, and there is a good correspondence between the folding pathways from direct MD and those computed from the MSMs. The unfolded populations interconvert rapidly between extended and collapsed conformations on time scales ≤ 40 ns, compared with the folding time of ≈ 5 μs. The folding rates are independent of where the folding is initiated from within the unfolded ensemble. About 90 % of the unfolded states are sampled within the first 40 μs of the ultra-long MD trajectory, which on average explores ~27 % of the unfolded state ensemble between consecutive folding events. We clustered the folding pathways according to structural similarity into “tubes”, and kinetically partitioned the unfolded state into populations that fold along different tubes. From our analysis of the simulations and a simple kinetic model, we find that when the mixing within the unfolded state is comparable to or faster than folding, the folding waiting times for all the folding tubes are similar and the folding kinetics is essentially single exponential despite the presence of heterogeneous folding paths with non-uniform barriers. When the mixing is much slower than folding, different unfolded populations fold independently leading to non-exponential kinetics. A kinetic partition of the Trp-cage unfolded state is constructed which reveals that different unfolded populations have almost the same probability to fold along any of the multiple folding paths. We are investigating whether the results for the kinetics in the unfolded state of the twenty-residue Trp-cage is representative of larger single domain proteins. PMID:23705683
ERIC Educational Resources Information Center
ERIC Clearinghouse on Reading and Communication Skills, Urbana, IL.
This collection of abstracts is part of a continuing series providing information on recent doctoral dissertations. The 29 titles deal with a variety of topics, including the following: (1) science fiction in elementary school science education; (2) the portrayal of black characters in children's literature; (3) UFOs and their correlates as a…
Hellenic Amateur Astronomy Association's activities: Preliminary results on Perseids 2010
NASA Astrophysics Data System (ADS)
Maravelias, G.
2011-01-01
Preliminary results on the Perseids 2010 are presented. Visual and video observations were obtained by the author and a first reduction of the visual data shows that a maximum of ZHR ~120 was reached during the night 12-13 of August 2010. Moreover, a video setup was tested (DMK camera and UFO Capture v2) and the results show that, under some limitations, valuable data can be obtained.
Yip, L W; Goh, F S; Sim, R S
1998-03-01
This is a case report of an elderly lady with odynophagia because she accidentally swallowed a tablet which was still wrapped in its blister pack. A discussion of foreign body ingestion, particularly in the elderly, is included. To the authors' knowledge, this is the first paper that includes a lateral cervical radiograph of an ingested blister pack.
Some Axioms and Issues in the UFO Dynamic Analysis Framework
2003-05-01
6. AUTHOR( S ) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Naval Postgraduate School...Department of Computer Science,Monterey,CA,93943 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME( S ) AND ADDRESS(ES...10. SPONSOR/MONITOR’S ACRONYM( S ) 11. SPONSOR/MONITOR’S REPORT NUMBER( S ) 12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release
ERIC Educational Resources Information Center
Sgammato, Adrienne N.
2009-01-01
This study examined the applicability of a relatively new unidimensional, unfolding item response theory (IRT) model called the generalized graded unfolding model (GGUM; Roberts, Donoghue, & Laughlin, 2000). A total of four scaling methods were applied. Two commonly used cumulative IRT models for polytomous data, the Partial Credit Model and…
The fastest disk wind in APM 08279+5255 and its acceleration mechanism
NASA Astrophysics Data System (ADS)
Hagino, K.; Done, C.; Odaka, H.; Watanabe, S.; Takahashi, T.
2017-10-01
The luminous high-z quasar APM 08279+5255 has the most powerful ultra-fast outflow (UFO), which is claimed as the fastest disk wind with velocity of 0.7c. This extreme velocity is very important for constraining the physical mechanism to launch the UFOs because only magnetic driving mechanism can accelerate the winds up to velocities above 0.3c, at which radiation drag effects prevent radiation driving. We reanalyze all the observed data of this source with our spectral model of highly ionized disk winds constructed by 3D Monte Carlo radiation transfer simulation. This was applied to an archetypal disk wind in PDS 456, and successfully reproduced all the spectra observed with Suzaku in spite of their strong spectral variability. By applying our spectral model to APM 08279+5255, all the spectra observed with XMM-Newton, Chandra and Suzaku are explained with less extreme outflow velocities of 0.1-0.2c. In our analysis, the high energy absorption features, which were previously interpreted as absorption lines with extremely fast velocities, are produced by iron-K absorption edges from moderately ionized clumps embedded in the highly ionized wind. We also investigate the broadband SED, and find that it is X-ray weak and UV bright, which prefers the radiation driving.
Dust dynamics and diagnostic applications in quasi-neutral plasmas and magnetic fusion
NASA Astrophysics Data System (ADS)
Wang, Zhehui; Ticos, Catalin M.; Si, Jiahe; Delzanno, Gian Luca; Lapenta, Gianni; Wurden, Glen
2007-11-01
Little is known about dust dynamics in highly ionized quasi-neutral plasmas with ca. 1.0 e+20 per cubic meter density and ion temperature at a few eV and above, including in magnetic fusion. For example, dust motion in fusion, better known as UFO's, has been observed since 1980's but not explained. Solid understanding of dust dynamics is also important to International Thermonuclear Experimental Reactor (ITER) because of concerns about safety and dust contamination of fusion core. Compared with well studied strongly-coupled dusty plasma regime, new physics may arise in the higher density quasi-neutral plasma regime because of at least four orders of magnitude higher density and two orders of magnitude hotter ion temperature. Our recent laboratory experiments showed that plasma-flow drag force dominates over other forces in a quasi-neutral flowing plasma. In contrast, delicate balance among different forces in dusty plasma has led to many unique phenomena, in particular, the formation of dust crystal. Based on our experiments, we argue that 1) dust crystal will not form in the highly ionized plasmas with flows; 2) the UFO's are moving dust dragged by plasma flows; 3) dust can be used to measure plasma flow. Two diagnostic applications using dust for laboratory quasi-neutral plasmas and magnetic fusion will also be presented.
Evidence for ultrafast outflows in radio-quiet AGNs - III. Location and energetics
NASA Astrophysics Data System (ADS)
Tombesi, F.; Cappi, M.; Reeves, J. N.; Braito, V.
2012-05-01
Using the results of a previous X-ray photoionization modelling of blueshifted Fe K absorption lines on a sample of 42 local radio-quiet AGNs observed with XMM-Newton, in this Letter we estimate the location and energetics of the associated ultrafast outflows (UFOs). Due to significant uncertainties, we are essentially able to place only lower/upper limits. On average, their location is in the interval ˜0.0003-0.03 pc (˜ 102-104rs) from the central black hole, consistent with what is expected for accretion disc winds/outflows. The mass outflow rates are constrained between ˜0.01 and 1 M⊙ yr-1, corresponding to >rsim5-10 per cent of the accretion rates. The average lower/upper limits on the mechanical power are log? 42.6-44.6 erg s-1. However, the minimum possible value of the ratio between the mechanical power and bolometric luminosity is constrained to be comparable or higher than the minimum required by simulations of feedback induced by winds/outflows. Therefore, this work demonstrates that UFOs are indeed capable to provide a significant contribution to the AGN cosmological feedback, in agreement with theoretical expectations and the recent observation of interactions between AGN outflows and the interstellar medium in several Seyfert galaxies.
Titin domains progressively unfolded by force are homogenously distributed along the molecule.
Bianco, Pasquale; Mártonfalvi, Zsolt; Naftz, Katalin; Kőszegi, Dorina; Kellermayer, Miklós
2015-07-21
Titin is a giant filamentous protein of the muscle sarcomere in which stretch induces the unfolding of its globular domains. However, the mechanisms of how domains are progressively selected for unfolding and which domains eventually unfold have for long been elusive. Based on force-clamp optical tweezers experiments we report here that, in a paradoxical violation of mechanically driven activation kinetics, neither the global domain unfolding rate, nor the folded-state lifetime distributions of full-length titin are sensitive to force. This paradox is reconciled by a gradient of mechanical stability so that domains are gradually selected for unfolding as the magnitude of the force field increases. Atomic force microscopic screening of extended titin molecules revealed that the unfolded domains are distributed homogenously along the entire length of titin, and this homogeneity is maintained with increasing overstretch. Although the unfolding of domains with progressively increasing mechanical stability makes titin a variable viscosity damper, the spatially randomized variation of domain stability ensures that the induced structural changes are not localized but are distributed along the molecule's length. Titin may thereby provide complex safety mechanims for protecting the sarcomere against structural disintegration under excessive mechanical conditions. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Protein unfolding with a steric trap.
Blois, Tracy M; Hong, Heedeok; Kim, Tae H; Bowie, James U
2009-10-07
The study of protein folding requires a method to drive unfolding, which is typically accomplished by altering solution conditions to favor the denatured state. This has the undesirable consequence that the molecular forces responsible for configuring the polypeptide chain are also changed. It would therefore be useful to develop methods that can drive unfolding without the need for destabilizing solvent conditions. Here we introduce a new method to accomplish this goal, which we call steric trapping. In the steric trap method, the target protein is labeled with two biotin tags placed close in space so that both biotin tags can only be bound by streptavidin when the protein unfolds. Thus, binding of the second streptavidin is energetically coupled to unfolding of the target protein. Testing the method on a model protein, dihydrofolate reductase (DHFR), we find that streptavidin binding can drive unfolding and that the apparent binding affinity reports on changes in DHFR stability. Finally, by employing the slow off-rate of wild-type streptavidin, we find that DHFR can be locked in the unfolded state. The steric trap method provides a simple method for studying aspects of protein folding and stability in native solvent conditions, could be used to specifically unfold selected domains, and could be applicable to membrane proteins.
The Proteasomal ATPases Use a Slow but Highly Processive Strategy to Unfold Proteins
Snoberger, Aaron; Anderson, Raymond T.; Smith, David M.
2017-01-01
All domains of life have ATP-dependent compartmentalized proteases that sequester their peptidase sites on their interior. ATPase complexes will often associate with these compartmentalized proteases in order to unfold and inject substrates into the protease for degradation. Significant effort has been put into understanding how ATP hydrolysis is used to apply force to proteins and cause them to unfold. The unfolding kinetics of the bacterial ATPase, ClpX, have been shown to resemble a fast motor that traps unfolded intermediates as a strategy to unfold proteins. In the present study, we sought to determine if the proteasomal ATPases from eukaryotes and archaea exhibit similar unfolding kinetics. We found that the proteasomal ATPases appear to use a different kinetic strategy for protein unfolding, behaving as a slower but more processive and efficient translocation motor, particularly when encountering a folded domain. We expect that these dissimilarities are due to differences in the ATP binding/exchange cycle, the presence of a trans-arginine finger, or the presence of a threading ring (i.e., the OB domain), which may be used as a rigid platform to pull folded domains against. We speculate that these differences may have evolved due to the differing client pools these machines are expected to encounter. PMID:28421184
Socher, Eileen; Sticht, Heinrich
2016-11-23
HdeA and YmgD are structurally homologous proteins in the periplasm of Escherichia coli. HdeA has been shown to represent an acid-activated chaperone, whereas the function of YmgD has not yet been characterized. We performed pH-titrating molecular dynamics simulations (pHtMD) to investigate the structural changes of both proteins and to assess whether YmgD may also exhibit an unfolding behavior similar to that of HdeA. The unfolding pathway of HdeA includes partially unfolded dimer structures, which represent a prerequisite for subsequent dissociation. In contrast to the coupled unfolding and dissociation of HdeA, YmgD displays dissociation of the folded subunits, and the subunits do not undergo significant unfolding even at low pH values. The differences in subunit stability between HdeA and YmgD may be explained by the structural features of helix D, which represents the starting point of unfolding in HdeA. In summary, the present study suggests that YmgD either is not an acid-activated chaperone or, at least, does not require unfolding for activation.
Unfolding of Proteins: Thermal and Mechanical Unfolding
NASA Technical Reports Server (NTRS)
Hur, Joe S.; Darve, Eric
2004-01-01
We have employed a Hamiltonian model based on a self-consistent Gaussian appoximation to examine the unfolding process of proteins in external - both mechanical and thermal - force elds. The motivation was to investigate the unfolding pathways of proteins by including only the essence of the important interactions of the native-state topology. Furthermore, if such a model can indeed correctly predict the physics of protein unfolding, it can complement more computationally expensive simulations and theoretical work. The self-consistent Gaussian approximation by Micheletti et al. has been incorporated in our model to make the model mathematically tractable by signi cantly reducing the computational cost. All thermodynamic properties and pair contact probabilities are calculated by simply evaluating the values of a series of Incomplete Gamma functions in an iterative manner. We have compared our results to previous molecular dynamics simulation and experimental data for the mechanical unfolding of the giant muscle protein Titin (1TIT). Our model, especially in light of its simplicity and excellent agreement with experiment and simulation, demonstrates the basic physical elements necessary to capture the mechanism of protein unfolding in an external force field.
Unfolding of the bacterial nucleoid both in vivo and in vitro as a result of exposure to camphor.
Harrington, E W; Trun, N J
1997-01-01
Both prokaryotic and eukaryotic cells are sensitive to killing by camphor; however, the mechanism by which camphor kills has not been elucidated. We report here that camphor unfolds the nucleoid of Escherichia coli and that unfolding does not require DNA replication, translation, or cell division. We show that exposure of isolated nucleoids to camphor results in unfolding of the chromosome. PMID:9079934
Machinery of protein folding and unfolding.
Zhang, Xiaodong; Beuron, Fabienne; Freemont, Paul S
2002-04-01
During the past two years, a large amount of biochemical, biophysical and low- to high-resolution structural data have provided mechanistic insights into the machinery of protein folding and unfolding. It has emerged that dual functionality in terms of folding and unfolding might exist for some systems. The majority of folding/unfolding machines adopt oligomeric ring structures in a cooperative fashion and utilise the conformational changes induced by ATP binding/hydrolysis for their specific functions.
Freedman, Kevin J; Haq, S Raza; Edel, Joshua B; Jemth, Per; Kim, Min Jun
2013-01-01
Single molecule methods have provided a significantly new look at the behavior of biomolecules in both equilibrium and non-equilibrium conditions. Most notable are the stretching experiments performed by atomic force microscopes and laser tweezers. Here we present an alternative single molecule method that can unfold a protein domain, observed at electric fields greater than 10(6) V/m, and is fully controllable by the application of increasing voltages across the membrane of the pore. Furthermore this unfolding mechanism is characterized by measuring both the residence time of the protein within the nanopore and the current blockade. The unfolding data supports a gradual unfolding mechanism rather than the cooperative transition observed by classical urea denaturation experiments. Lastly it is shown that the voltage-mediated unfolding is a function of the stability of the protein by comparing two mutationally destabilized variants of the protein.
UNFOLD-SENSE: a parallel MRI method with self-calibration and artifact suppression.
Madore, Bruno
2004-08-01
This work aims at improving the performance of parallel imaging by using it with our "unaliasing by Fourier-encoding the overlaps in the temporal dimension" (UNFOLD) temporal strategy. A self-calibration method called "self, hybrid referencing with UNFOLD and GRAPPA" (SHRUG) is presented. SHRUG combines the UNFOLD-based sensitivity mapping strategy introduced in the TSENSE method by Kellman et al. (5), with the strategy introduced in the GRAPPA method by Griswold et al. (10). SHRUG merges the two approaches to alleviate their respective limitations, and provides fast self-calibration at any given acceleration factor. UNFOLD-SENSE further includes an UNFOLD artifact suppression scheme to significantly suppress artifacts and amplified noise produced by parallel imaging. This suppression scheme, which was published previously (4), is related to another method that was presented independently as part of TSENSE. While the two are equivalent at accelerations < or = 2.0, the present approach is shown here to be significantly superior at accelerations > 2.0, with up to double the artifact suppression at high accelerations. Furthermore, a slight modification of Cartesian SENSE is introduced, which allows departures from purely Cartesian sampling grids. This technique, termed variable-density SENSE (vdSENSE), allows the variable-density data required by SHRUG to be reconstructed with the simplicity and fast processing of Cartesian SENSE. UNFOLD-SENSE is given by the combination of SHRUG for sensitivity mapping, vdSENSE for reconstruction, and UNFOLD for artifact/amplified noise suppression. The method was implemented, with online reconstruction, on both an SSFP and a myocardium-perfusion sequence. The results from six patients scanned with UNFOLD-SENSE are presented.
Salt bridge as a gatekeeper against partial unfolding.
Hinzman, Mark W; Essex, Morgan E; Park, Chiwook
2016-05-01
Salt bridges are frequently observed in protein structures. Because the energetic contribution of salt bridges is strongly dependent on the environmental context, salt bridges are believed to contribute to the structural specificity rather than the stability. To test the role of salt bridges in enhancing structural specificity, we investigated the contribution of a salt bridge to the energetics of native-state partial unfolding in a cysteine-free version of Escherichia coli ribonuclease H (RNase H*). Thermolysin cleaves a protruding loop of RNase H(*) through transient partial unfolding under native conditions. Lys86 and Asp108 in RNase H(*) form a partially buried salt bridge that tethers the protruding loop. Investigation of the global stability of K86Q/D108N RNase H(*) showed that the salt bridge does not significantly contribute to the global stability. However, K86Q/D108N RNase H(*) is greatly more susceptible to proteolysis by thermolysin than wild-type RNase H(*) is. The free energy for partial unfolding determined by native-state proteolysis indicates that the salt bridge significantly increases the energy for partial unfolding by destabilizing the partially unfolded form. Double mutant cycles with single and double mutations of the salt bridge suggest that the partially unfolded form is destabilized due to a significant decrease in the interaction energy between Lys86 and Asp108 upon partial unfolding. This study demonstrates that, even in the case that a salt bridge does not contribute to the global stability, the salt bridge may function as a gatekeeper against partial unfolding that disturbs the optimal geometry of the salt bridge. © 2016 The Protein Society.
1968-11-01
of the existence of other highly developed life forms. To begin with, the observable universe -- that is, the distance to which we can observe luminous...been around long enough that life forms as developed as our own could exist. Implicit in further dis- cussion are the assumptions that: 1. Planets... life will exist; 3. Our own history of past evolution and development is neither slow nor fast, but average and tyoical for life forms. (Ours is the
Protein unfolding versus β-sheet separation in spider silk nanocrystals
NASA Astrophysics Data System (ADS)
Alam, Parvez
2014-03-01
In this communication a mechanism for spider silk strain hardening is proposed. Shear failure of β-sheet nanocrystals is the first failure mode that gives rise to the creation of smaller nanocrystals, which are of higher strength and stiffness. β-sheet unfolding requires more energy than nanocrystal separation in a shear mode of failure. As a result, unfolding occurs after the nanocrystals separate in shear. β-sheet unfolding yields a secondary strain hardening effect once the β-sheet conformation is geometrically stable and acts like a unidirectional fibre in a fibre reinforced composite. The mechanism suggested herein is based on molecular dynamics calculations of residual inter-β-sheet separation strengths against residual intra-β-sheet unfolding strengths.
Comparative Study of the Mechanical Unfolding Pathways of α- and β-Peptides.
Uribe, Lalita; Gauss, Jürgen; Diezemann, Gregor
2015-07-02
Using molecular simulations, we analyze the unfolding pathways of various peptides. We compare the mechanical unfolding of a β-alanine's octamer (β-HAla8) and an α-alanine's decamer (α-Ala10). Using force-probe molecular-dynamics simulations, to induce unfolding, we show that the 3(14)-helix formed by β-HAla8 is mechanically more stable than the α-helix formed by α-Ala10, although both structures are stabilized by six hydrogen bonds. Additionally, computations of the potential of mean force validate this result and show that also the thermal stability of the 3(14)-helix is higher. It is demonstrated that β-HAla8 unfolds in a two-step fashion with a stable intermediate. This is contrasted with the known single-step scenario of the unfolding of α-Ala10. Furthermore, we present a study of the chain-length dependence of the mechanical unfolding pathway of the 3(14)-helix. The calculation of the dynamic strength for oligomers with chain lengths ranging from 6 to 18 monomers shows that the unfolding pathway of helices with an integer and noninteger number of turns has m + 1 and m energy barriers, respectively, with m being the number of complete turns. The additional barrier for helices with an integer number of turns is shown to be related to the breaking of the N-terminus' hydrogen bond.
Resolution of the unfolded state.
NASA Astrophysics Data System (ADS)
Beaucage, Gregory
2008-03-01
The unfolded states in proteins and nucleic acids remain weakly understood despite their importance to protein folding; misfolding diseases (Parkinson's & Alzheimer's); natively unfolded proteins (˜ 30% of eukaryotic proteins); and to understanding ribozymes. Research has been hindered by the inability to quantify the residual (native) structure present in an unfolded protein or nucleic acid. Here, a scaling model is proposed to quantify the degree of folding and the unfolded state (Beaucage, 2004, 2007). The model takes a global view of protein structure and can be applied to a number of analytic methods and to simulations. Three examples are given of application to small-angle scattering from pressure induced unfolding of SNase (Panick, 1998), from acid unfolded Cyt c (Kataoka, 1993) and from folding of Azoarcus ribozyme (Perez-Salas, 2004). These examples quantitatively show 3 characteristic unfolded states for proteins, the statistical nature of a folding pathway and the relationship between extent of folding and chain size during folding for charge driven folding in RNA. Beaucage, G., Biophys. J., in press (2007). Beaucage, G., Phys. Rev. E. 70, 031401 (2004). Kataoka, M., Y. Hagihara, K. Mihara, Y. Goto J. Mol. Biol. 229, 591 (1993). Panick, G., R. Malessa, R. Winter, G. Rapp, K. J. Frye, C. A. Royer J. Mol. Biol. 275, 389 (1998). Perez-Salas U. A., P. Rangan, S. Krueger, R. M. Briber, D. Thirumalai, S. A. Woodson, Biochemistry 43 1746 (2004).
Kumar, Vijay; Prakash, Amresh; Pandey, Preeti; Lynn, Andrew M; Hassan, Md Imtaiyaz
2018-05-18
Misfolding and aggregation of Cu, Zn Superoxide dismutase (SOD1) is involved in the neurodegenerative disease, amyotrophic lateral sclerosis. Many studies have shown that metal-depleted, monomeric form of SOD1 displays substantial local unfolding dynamics and is the precursor for aggregation. Here, we have studied the structure and dynamics of different apo monomeric SOD1 variants associated with unfolding and aggregation in aqueous trifluoroethanol (TFE) through experiments and simulation. TFE induces partially unfolded β-sheet-rich extended conformations in these SOD1 variants, which subsequently develops aggregates with fibril-like characteristics. Fibrillation was achieved more easily in disulfide-reduced monomeric SOD1 when compared with wild-type and mutant monomeric SOD1. At higher concentrations of TFE, a native-like structure with the increase in α-helical content was observed. The molecular dynamics simulation results illustrate distinct structural dynamics for different regions of SOD1 variants and show uniform local unfolding of β-strands. The strands protected by the zinc-binding and electrostatic loops were found to unfold first in 20% (v/v) TFE, leading to a partial unfolding of β-strands 4, 5, and 6 which are prone to aggregation. Our results thus shed light on the role of local unfolding and conformational dynamics in SOD1 misfolding and aggregation. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zheng, Wenjun, E-mail: wjzheng@buffalo.edu; Glenn, Paul
2015-01-21
The Bacteriophage T4 Lysozyme (T4L) is a prototype modular protein comprised of an N-terminal and a C-domain domain, which was extensively studied to understand the folding/unfolding mechanism of modular proteins. To offer detailed structural and dynamic insights to the folded-state stability and the mechanical unfolding behaviors of T4L, we have performed extensive equilibrium and steered molecular dynamics simulations of both the wild-type (WT) and a circular permutation (CP) variant of T4L using all-atom and coarse-grained force fields. Our all-atom and coarse-grained simulations of the folded state have consistently found greater stability of the C-domain than the N-domain in isolation, whichmore » is in agreement with past thermostatic studies of T4L. While the all-atom simulation cannot fully explain the mechanical unfolding behaviors of the WT and the CP variant observed in an optical tweezers study, the coarse-grained simulations based on the Go model or a modified elastic network model (mENM) are in qualitative agreement with the experimental finding of greater unfolding cooperativity in the WT than the CP variant. Interestingly, the two coarse-grained models predict different structural mechanisms for the observed change in cooperativity between the WT and the CP variant—while the Go model predicts minor modification of the unfolding pathways by circular permutation (i.e., preserving the general order that the N-domain unfolds before the C-domain), the mENM predicts a dramatic change in unfolding pathways (e.g., different order of N/C-domain unfolding in the WT and the CP variant). Based on our simulations, we have analyzed the limitations of and the key differences between these models and offered testable predictions for future experiments to resolve the structural mechanism for cooperative folding/unfolding of T4L.« less
Kawakami, M; Smith, D A
2008-12-10
We have developed a new force ramp modification of the atomic force microscope (AFM) which can control multiple unfolding events of a multi-modular protein using software-based digital force feedback control. With this feedback the force loading rate can be kept constant regardless the length of soft elastic linkage or number of unfolded polypeptide domains. An unfolding event is detected as a sudden drop in force, immediately after which the feedback control reduces the applied force to a low value of a few pN by lowering the force set point. Hence the remaining folded domains can relax and the subsequent force ramp is applied to relaxed protein domains identically in each case. We have applied this technique to determine the kinetic parameters x(u), which is the distance between the native state and transition state, and α(0), which is the unfolding rate constant at zero force, for the mechanical unfolding of a pentamer of I27 domains of titin. In each force ramp the unfolding probability depends on the number of folded domains remaining in the system and we had to take account of this effect in the analysis of unfolding force data. We obtained values of x(u) and α(0) to be 0.28 nm and 1.02 × 10(-3) s(-1), which are in good agreement with those obtained from conventional constant velocity experiments. This method reveals unfolding data at low forces that are not seen in constant velocity experiments and corrects for the change in stiffness that occurs with most mechanical systems throughout the unfolding process to allow constant force ramp experiments to be carried out. In addition, a mechanically weak structure was detected, which formed from the fully extended polypeptide chain during a force quench. This indicates that the new technique will allow studies of the folding kinetics of previously hidden, mechanically weak species.
NASA Astrophysics Data System (ADS)
Agosteo, S.; Bedogni, R.; Caresana, M.; Charitonidis, N.; Chiti, M.; Esposito, A.; Ferrarini, M.; Severino, C.; Silari, M.
2012-12-01
The accurate determination of the ambient dose equivalent in the mixed neutron-photon fields encountered around high-energy particle accelerators still represents a challenging task. The main complexity arises from the extreme variability of the neutron energy, which spans over 10 orders of magnitude or more. Operational survey instruments, which response function attempts to mimic the fluence-to-ambient dose equivalent conversion coefficient up to GeV neutrons, are available on the market, but their response is not fully reliable over the entire energy range. Extended range rem counters (ERRC) do not require the exact knowledge of the energy distribution of the neutron field and the calibration can be done with a source spectrum. If the actual neutron field has an energy distribution different from the calibration spectrum, the measurement is affected by an added uncertainty related to the partial overlap of the fluence-to-ambient dose equivalent conversion curve and the response function. For this reason their operational use should always be preceded by an "in-field" calibration, i.e. a calibration made against a reference instrument exposed in the same field where the survey-meter will be employed. In practice the extended-range Bonner Sphere Spectrometer (ERBSS) is the only device which can serve as reference instrument in these fields, because of its wide energy range and the possibility to assess the neutron fluence and the ambient dose equivalent (H*(10)) values with the appropriate accuracy. Nevertheless, the experience gained by a number of experimental groups suggests that mandatory conditions for obtaining accurate results in workplaces are: (1) the use of a well-established response matrix, thus implying validation campaigns in reference monochromatic neutrons fields, (2) the expert and critical use of suitable unfolding codes, and (3) the performance test of the whole system (experimental set-up, elaboration and unfolding procedures) in a well controlled workplace field. The CERF (CERN-EU high-energy reference field) facility is a unique example of such a field, where a number of experimental campaigns and Monte Carlo simulations have been performed over the past years. With the aim of performing this kind of workplace performance test, four different ERBSS with different degrees of validation, operated by three groups (CERN, INFN-LNF and Politecnico of Milano), were exposed in two fixed positions at CERF. Using different unfolding codes (MAXED, GRAVEL, FRUIT and FRUIT SGM), the experimental data were analyzed to provide the neutron spectra and the related dosimetric quantities. The results allow assessing the overall performance of each ERBSS and of the unfolding codes, as well as comparing the performance of three ERRCs when used in a neutron field with energy distribution different from the calibration spectrum.
Juraszek, Jarek; Bolhuis, Peter G.
2010-01-01
Abstract We report a numerical study of the (un)folding routes of the truncated FBP28 WW domain at ambient conditions using a combination of four advanced rare event molecular simulation techniques. We explore the free energy landscape of the native state, the unfolded state, and possible intermediates, with replica exchange molecular dynamics. Subsequent application of bias-exchange metadynamics yields three tentative unfolding pathways at room temperature. Using these paths to initiate a transition path sampling simulation reveals the existence of two major folding routes, differing in the formation order of the two main hairpins, and in hydrophobic side-chain interactions. Having established that the hairpin strand separation distances can act as reasonable reaction coordinates, we employ metadynamics to compute the unfolding barriers and find that the barrier with the lowest free energy corresponds with the most likely pathway found by transition path sampling. The unfolding barrier at 300 K is ∼17 kBT ≈ 42 kJ/mol, in agreement with the experimental unfolding rate constant. This work shows that combining several powerful simulation techniques provides a more complete understanding of the kinetic mechanism of protein folding. PMID:20159161
Cooperative unfolding of distinctive mechanoreceptor domains transduces force into signals
Ju, Lining; Chen, Yunfeng; Xue, Lingzhou; Du, Xiaoping; Zhu, Cheng
2016-01-01
How cells sense their mechanical environment and transduce forces into biochemical signals is a crucial yet unresolved question in mechanobiology. Platelets use receptor glycoprotein Ib (GPIb), specifically its α subunit (GPIbα), to signal as they tether and translocate on von Willebrand factor (VWF) of injured arterial surfaces against blood flow. Force elicits catch bonds to slow VWF–GPIbα dissociation and unfolds the GPIbα leucine-rich repeat domain (LRRD) and juxtamembrane mechanosensitive domain (MSD). How these mechanical processes trigger biochemical signals remains unknown. Here we analyze these extracellular events and the resulting intracellular Ca2+ on a single platelet in real time, revealing that LRRD unfolding intensifies Ca2+ signal whereas MSD unfolding affects the type of Ca2+ signal. Therefore, LRRD and MSD are analog and digital force transducers, respectively. The >30 nm macroglycopeptide separating the two domains transmits force on the VWF–GPIbα bond (whose lifetime is prolonged by LRRD unfolding) to the MSD to enhance its unfolding, resulting in unfolding cooperativity at an optimal force. These elements may provide design principles for a generic mechanosensory protein machine. DOI: http://dx.doi.org/10.7554/eLife.15447.001 PMID:27434669
Thermodynamics of the Trp-cage Miniprotein Unfolding in Urea
Wafer, Lucas N. R.; Streicher, Werner W.; Makhatadze, George I.
2010-01-01
The thermodynamic properties of unfolding of the Trp-cage mini protein in the presence of various concentrations of urea have been characterized using temperature-induced unfolding monitored by far-UV circular dichroism spectroscopy. Analysis of the data using a two-state model allowed the calculation of the Gibbs energy of unfolding at 25°C as a function of urea concentration. This in turn was analyzed by the linear extrapolation model that yielded the dependence of Gibbs energy on urea concentration, i.e. the m-value for Trp-cage unfolding. The m-value obtained from the experimental data, as well as the experimental heat capacity change upon unfolding, were correlated with the structural parameters derived from the three dimensional structure of Trp-cage. It is shown that the m-value can be predicted well using a transfer model, while the heat capacity changes are in very good agreement with the empirical models based on model compounds studies. These results provide direct evidence that Trp-cage, despite its small size, is an excellent model for studies of protein unfolding and provide thermodynamic data that can be used to compare with atomistic computer simulations. PMID:20112418
Barackov, Ivana; Mause, Anika; Kapoor, Shobhna; Winter, Roland; Schembecker, Gerhard; Burghoff, Bernhard
2012-10-15
Purification and separation of proteins play a major role in biotechnology. Nowadays, alternatives to multistep operations suffering from low product yields and high costs are investigated closely amidst which one of the promising options is foam fractionation. The molecular behavior at the gas-liquid interface plays an important role in the formation and stabilization of enriched foam. This study for the first time correlates the physico-chemical parameters to the molecular structure in view of protein enrichment during foam fractionation of the two relatively different proteins lysozyme and β-casein employing biophysical techniques such as circular dichroism (CD) spectroscopy and infrared reflection absorption spectroscopy (IRRAS). In case of lysozyme, high enrichment was achieved at pH
Srivastava, Kinshuk Raj; Kumar, Anil; Goyal, Bhupesh; Durani, Susheel
2011-05-26
The competing interactions folding and unfolding protein structure remain obscure. Using homopolypeptides, we ask if poly-L structure may have a role. We mutate the structure to alternating-L,D stereochemistry and substitute water as the fold-promoting solvent with methanol and dimethyl sulfoxide (DMSO) as the fold-denaturing solvents. Circular dichroism and molecular dynamics established previously that, while both isomers were folded in water, the poly-L isomer was unfolded and alternating-L,D isomer folded in methanol. Nuclear magnetic resonance and molecular dynamics establish now that both isomers are unfolded in DMSO. We calculated energetics of folding-unfolding equilibrium with water and methanol as solvents. We have now calculated interactions of unfolded polypeptide structures with DMSO as solvent. Methanol was found to unfold and water fold poly-L structure as a dielectric. DMSO has now been found to unfold both poly-L and alternating-L,D structures by strong solvation of peptides to disrupt their hydrogen bonds. Accordingly, we propose that while linked peptides fold protein structure with hydrogen bonds they unfold the structure electrostatically due to the stereochemical effect of the poly-L structure. Protein folding to ordering of peptide hydrogen bonds with water as canonical solvent may thus involve two specific and independent solvent effects-one, strong screening of electrostatics of poly-L linked peptides, and two, weak dipolar solvation of peptides. Correspondingly, protein denaturation may involve two independent solvent effects-one, weak dielectric to unfold poly-L structure electrostatically, and two, strong polarity to disrupt peptide hydrogen bonds by solvation of peptides.
Rottler, Jörg; Plotkin, Steven S.
2016-01-01
Mechanical unfolding of a single domain of loop-truncated superoxide dismutase protein has been simulated via force spectroscopy techniques with both all-atom (AA) models and several coarse-grained models having different levels of resolution: A Gō model containing all heavy atoms in the protein (HA-Gō), the associative memory, water mediated, structure and energy model (AWSEM) which has 3 interaction sites per amino acid, and a Gō model containing only one interaction site per amino acid at the Cα position (Cα-Gō). To systematically compare results across models, the scales of time, energy, and force had to be suitably renormalized in each model. Surprisingly, the HA-Gō model gives the softest protein, exhibiting much smaller force peaks than all other models after the above renormalization. Clustering to render a structural taxonomy as the protein unfolds showed that the AA, HA-Gō, and Cα-Gō models exhibit a single pathway for early unfolding, which eventually bifurcates repeatedly to multiple branches only after the protein is about half-unfolded. The AWSEM model shows a single dominant unfolding pathway over the whole range of unfolding, in contrast to all other models. TM alignment, clustering analysis, and native contact maps show that the AWSEM pathway has however the most structural similarity to the AA model at high nativeness, but the least structural similarity to the AA model at low nativeness. In comparison to the AA model, the sequence of native contact breakage is best predicted by the HA-Gō model. All models consistently predict a similar unfolding mechanism for early force-induced unfolding events, but diverge in their predictions for late stage unfolding events when the protein is more significantly disordered. PMID:27898663
Unfolding of Ubiquitin Studied by Picosecond Time-Resolved Fluorescence of the Tyrosine Residue
Noronha, Melinda; Lima, João C.; Bastos, Margarida; Santos, Helena; Maçanita, António L.
2004-01-01
The photophysics of the single tyrosine in bovine ubiquitin (UBQ) was studied by picosecond time-resolved fluorescence spectroscopy, as a function of pH and along thermal and chemical unfolding, with the following results: First, at room temperature (25°C) and below pH 1.5, native UBQ shows single-exponential decays. From pH 2 to 7, triple-exponential decays were observed and the three decay times were attributed to the presence of tyrosine, a tyrosine-carboxylate hydrogen-bonded complex, and excited-state tyrosinate. Second, at pH 1.5, the water-exposed tyrosine of either thermally or chemically unfolded UBQ decays as a sum of two exponentials. The double-exponential decays were interpreted and analyzed in terms of excited-state intramolecular electron transfer from the phenol to the amide moiety, occurring in one of the three rotamers of tyrosine in UBQ. The values of the rate constants indicate the presence of different unfolded states and an increase in the mobility of the tyrosine residue during unfolding. Finally, from the pre-exponential coefficients of the fluorescence decays, the unfolding equilibrium constants (KU) were calculated, as a function of temperature or denaturant concentration. Despite the presence of different unfolded states, both thermal and chemical unfolding data of UBQ could be fitted to a two-state model. The thermodynamic parameters Tm = 54.6°C, ΔHTm = 56.5 kcal/mol, and ΔCp = 890 cal/mol//K, were determined from the unfolding equilibrium constants calculated accordingly, and compared to values obtained by differential scanning calorimetry also under the assumption of a two-state transition, Tm = 57.0°C, ΔHm= 51.4 kcal/mol, and ΔCp = 730 cal/mol//K. PMID:15454455
Habibi, Mona; Rottler, Jörg; Plotkin, Steven S
2016-11-01
Mechanical unfolding of a single domain of loop-truncated superoxide dismutase protein has been simulated via force spectroscopy techniques with both all-atom (AA) models and several coarse-grained models having different levels of resolution: A Gō model containing all heavy atoms in the protein (HA-Gō), the associative memory, water mediated, structure and energy model (AWSEM) which has 3 interaction sites per amino acid, and a Gō model containing only one interaction site per amino acid at the Cα position (Cα-Gō). To systematically compare results across models, the scales of time, energy, and force had to be suitably renormalized in each model. Surprisingly, the HA-Gō model gives the softest protein, exhibiting much smaller force peaks than all other models after the above renormalization. Clustering to render a structural taxonomy as the protein unfolds showed that the AA, HA-Gō, and Cα-Gō models exhibit a single pathway for early unfolding, which eventually bifurcates repeatedly to multiple branches only after the protein is about half-unfolded. The AWSEM model shows a single dominant unfolding pathway over the whole range of unfolding, in contrast to all other models. TM alignment, clustering analysis, and native contact maps show that the AWSEM pathway has however the most structural similarity to the AA model at high nativeness, but the least structural similarity to the AA model at low nativeness. In comparison to the AA model, the sequence of native contact breakage is best predicted by the HA-Gō model. All models consistently predict a similar unfolding mechanism for early force-induced unfolding events, but diverge in their predictions for late stage unfolding events when the protein is more significantly disordered.
Structure of a AAA+ unfoldase in the process of unfolding substrate
Ripstein, Zev A; Huang, Rui; Augustyniak, Rafal; Kay, Lewis E; Rubinstein, John L
2017-01-01
AAA+ unfoldases are thought to unfold substrate through the central pore of their hexameric structures, but how this process occurs is not known. VAT, the Thermoplasma acidophilum homologue of eukaryotic CDC48/p97, works in conjunction with the proteasome to degrade misfolded or damaged proteins. We show that in the presence of ATP, VAT with its regulatory N-terminal domains removed unfolds other VAT complexes as substrate. We captured images of this transient process by electron cryomicroscopy (cryo-EM) to reveal the structure of the substrate-bound intermediate. Substrate binding breaks the six-fold symmetry of the complex, allowing five of the six VAT subunits to constrict into a tight helix that grips an ~80 Å stretch of unfolded protein. The structure suggests a processive hand-over-hand unfolding mechanism, where each VAT subunit releases the substrate in turn before re-engaging further along the target protein, thereby unfolding it. DOI: http://dx.doi.org/10.7554/eLife.25754.001 PMID:28390173
Conformational dynamics of a protein in the folded and the unfolded state
NASA Astrophysics Data System (ADS)
Fitter, Jörg
2003-08-01
In a quasielastic neutron scattering experiment, the picosecond dynamics of α-amylase was investigated for the folded and the unfolded state of the protein. In order to ensure a reasonable interpretation of the internal protein dynamics, the protein was measured in D 2O-buffer solution. The much higher structural flexibility of the pH induced unfolded state as compared to the native folded state was quantified using a simple analytical model, describing a local diffusion inside a sphere. In terms of this model the conformational volume, which is explored mainly by confined protein side-chain movements, is parameterized by the radius of a sphere (folded state, r=1.2 Å; unfolded state, 1.8 Å). Differences in conformational dynamics between the folded and the unfolded state of a protein are of fundamental interest in the field of protein science, because they are assumed to play an important role for the thermodynamics of folding/unfolding transition and for protein stability.
Murciano-Calles, Javier; Güell-Bosch, Jofre; Villegas, Sandra; Martinez, Jose C
2016-01-12
PDZ domains are protein-protein interaction modules sharing the same structural arrangement. To discern whether they display common features in their unfolding/misfolding behaviour we have analyzed in this work the unfolding thermodynamics, together with the misfolding kinetics, of the PDZ fold using three archetypical examples: the second and third PDZ domains of the PSD95 protein and the Erbin PDZ domain. Results showed that all domains passed through a common intermediate, which populated upon unfolding, and that this in turn drove the misfolding towards worm-like fibrillar structures. Thus, the unfolding/misfolding behaviour appears to be shared within these domains. We have also analyzed how this landscape can be modified upon the inclusion of extra-elements, as it is in the nNOS PDZ domain, or the organization of swapped species, as happens in the second PDZ domain of the ZO2 protein. Although the intermediates still formed upon thermal unfolding, the misfolding was prevented to varying degrees.
Malchus, Nina; Weiss, Matthias
2010-01-01
A multitude of transmembrane proteins enters the endoplasmic reticulum (ER) as unfolded polypeptide chains. During their folding process, they interact repetitively with the ER's quality control machinery. Here, we have used fluorescence correlation spectroscopy to probe these interactions for a prototypical transmembrane protein, VSVG ts045, in vivo. While both folded and unfolded VSVG ts045 showed anomalous diffusion, the unfolded protein had a significantly stronger anomaly. This difference subsided when unfolded VSVG ts045 was in a complex with its chaperone calnexin, or when a mutant form of VSVG ts045 with only one glycan was used. Our experimental data and accompanying simulations suggest that the folding sensor of the quality control (UGT1) oligomerizes unfolded VSVG ts045, leading to a more anomalous/obstructed diffusion. In contrast, calnexin dissolves the oligomers, rendering unfolded VSVG ts045 more mobile, and hence prevents poisoning of the ER. PMID:20713018
Protein unfolding as a switch from self-recognition to high-affinity client binding
Groitl, Bastian; Horowitz, Scott; Makepeace, Karl A. T.; Petrotchenko, Evgeniy V.; Borchers, Christoph H.; Reichmann, Dana; Bardwell, James C. A.; Jakob, Ursula
2016-01-01
Stress-specific activation of the chaperone Hsp33 requires the unfolding of a central linker region. This activation mechanism suggests an intriguing functional relationship between the chaperone's own partial unfolding and its ability to bind other partially folded client proteins. However, identifying where Hsp33 binds its clients has remained a major gap in our understanding of Hsp33's working mechanism. By using site-specific Fluorine-19 nuclear magnetic resonance experiments guided by in vivo crosslinking studies, we now reveal that the partial unfolding of Hsp33's linker region facilitates client binding to an amphipathic docking surface on Hsp33. Furthermore, our results provide experimental evidence for the direct involvement of conditionally disordered regions in unfolded protein binding. The observed structural similarities between Hsp33's own metastable linker region and client proteins present a possible model for how Hsp33 uses protein unfolding as a switch from self-recognition to high-affinity client binding. PMID:26787517
An Outburst Scenario for the X-ray Spectral Variability in 3C 111
NASA Technical Reports Server (NTRS)
Tombesi, Francesco; Reeves, J. N.; Reynolds, Christopher S.; Garcia, J.; Lohfink, A.
2013-01-01
We present a combined Suzaku and Swift BAT broad-band E=0.6-200 keV spectral analysis of three 3C 111 observations obtained in 2010. The data are well described with an absorbed power-law continuum and a weak (R approximately equal to 0.2) cold reflection component from distant material. We constrain the continuum cutoff at E(sub C) approximately equal to 150- 200 keV, which is in accordance with X-ray Comptonization corona models and supports claims that the jet emission is only dominant at much higher energies. Fe XXVI Ly alpha emission and absorption lines are also present in the first and second observations, respectively. The modelling and interpretation of the emission line is complex and we explore three possibilities. If originating from ionized disc reflection, this should be emitted at r(sub in) greater than or equal to 50 r(sub g) or, in the lamp-post configuration, the illuminating source should be at a height of h greater than or equal to 30 r(sub g) over the black hole. Alternatively, the line could be modeled with a hot collisionally ionized plasma with temperature kT = 22.0(sup +6.1)(sub -3.2) keV or a photo-ionized plasma with logXi=4.52(sup +0.10)(sub -0.16) erg per second cm, and column density N(sub H) greater than 3×10(sup 23) per square centimeter. However, the first and second scenarios are less favored on statistical and physical grounds, respectively. The blue-shifted absorption line in the second observation can be modelled as an ultra-fast outflow (UFO) with ionization parameter logXi=4.47(sup +0.76) (sub -0.04) erg per second cm, column density NH=(5.3(sup +1.8)(sub -1.3))×10(sup 22) per square centimeter and outflow velocity v(sub out) = 0.104+/-0.006c. Interestingly, the parameters of the photoionized emission model remarkably match those of the absorbing UFO, supporting the possibility that the same material could be responsible for both emission and absorption. We suggest an outburst scenario in which an accretion disc wind, initially lying out of the line of sight and observed in emission, then crosses our view to the source and it is observed in absorption as a mildly-relativistic UFO.
2017-12-08
The Hubble Space Telescope has spotted a UFO — well, the UFO Galaxy, to be precise. NGC 2683 is a spiral galaxy seen almost edge-on, giving it the shape of a classic science fiction spaceship. This is why the astronomers at the Astronaut Memorial Planetarium and Observatory gave it this attention-grabbing nickname. While a bird’s eye view lets us see the detailed structure of a galaxy (such as this Hubble image of a barred spiral), a side-on view has its own perks. In particular, it gives astronomers a great opportunity to see the delicate dusty lanes of the spiral arms silhouetted against the golden haze of the galaxy’s core. In addition, brilliant clusters of young blue stars shine scattered throughout the disc, mapping the galaxy’s star-forming regions. Perhaps surprisingly, side-on views of galaxies like this one do not prevent astronomers from deducing their structures. Studies of the properties of the light coming from NGC 2683 suggest that this is a barred spiral galaxy, even though the angle we see it at does not let us see this directly. NGC 2683, discovered on 5 February 1788 by the famous astronomer William Herschel, lies in the Northern constellation of Lynx. A constellation named not because of its resemblance to the feline animal, but because it is fairly faint, requiring the “sensitive eyes of a cat” to discern it. And when you manage to get a look at it, you’ll find treasures like this, making it well worth the effort. This image is produced from two adjacent fields observed in visible and infrared light by Hubble’s Advanced Camera for Surveys. A narrow strip which appears slightly blurred and crosses most the image horizontally is a result of a gap between Hubble’s detectors. This strip has been patched using images from observations of the galaxy made by ground-based telescopes, which show significantly less detail. The field of view is approximately 6.5 by 3.3 arcminutes. Credit: ESA/Hubble & NASA NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram
Determination of thermodynamics and kinetics of RNA reactions by force
Tinoco, Ignacio; Li, Pan T. X.; Bustamante, Carlos
2008-01-01
Single-molecule methods have made it possible to apply force to an individual RNA molecule. Two beads are attached to the RNA; one is on a micropipette, the other is in a laser trap. The force on the RNA and the distance between the beads are measured. Force can change the equilibrium and the rate of any reaction in which the product has a different extension from the reactant. This review describes use of laser tweezers to measure thermodynamics and kinetics of unfolding/refolding RNA. For a reversible reaction the work directly provides the free energy; for irreversible reactions the free energy is obtained from the distribution of work values. The rate constants for the folding and unfolding reactions can be measured by several methods. The effect of pulling rate on the distribution of force-unfolding values leads to rate constants for unfolding. Hopping of the RNA between folded and unfolded states at constant force provides both unfolding and folding rates. Force-jumps and force-drops, similar to the temperature jump method, provide direct measurement of reaction rates over a wide range of forces. The advantages of applying force and using single-molecule methods are discussed. These methods, for example, allow reactions to be studied in non-denaturing solvents at physiological temperatures; they also simplify analysis of kinetic mechanisms because only one intermediate at a time is present. Unfolding of RNA in biological cells by helicases, or ribosomes, has similarities to unfolding by force. PMID:17040613
Force-Induced Unfolding of Fibronectin in the Extracellular Matrix of Living Cells
Smith, Michael L; Gourdon, Delphine; Little, William C; Kubow, Kristopher E; Eguiluz, R. Andresen; Luna-Morris, Sheila; Vogel, Viola
2007-01-01
Whether mechanically unfolded fibronectin (Fn) is present within native extracellular matrix fibrils is controversial. Fn extensibility under the influence of cell traction forces has been proposed to originate either from the force-induced lengthening of an initially compact, folded quaternary structure as is found in solution (quaternary structure model, where the dimeric arms of Fn cross each other), or from the force-induced unfolding of type III modules (unfolding model). Clarification of this issue is central to our understanding of the structural arrangement of Fn within fibrils, the mechanism of fibrillogenesis, and whether cryptic sites, which are exposed by partial protein unfolding, can be exposed by cell-derived force. In order to differentiate between these two models, two fluorescence resonance energy transfer schemes to label plasma Fn were applied, with sensitivity to either compact-to-extended conformation (arm separation) without loss of secondary structure or compact-to-unfolded conformation. Fluorescence resonance energy transfer studies revealed that a significant fraction of fibrillar Fn within a three-dimensional human fibroblast matrix is partially unfolded. Complete relaxation of Fn fibrils led to a refolding of Fn. The compactly folded quaternary structure with crossed Fn arms, however, was never detected within extracellular matrix fibrils. We conclude that the resting state of Fn fibrils does not contain Fn molecules with crossed-over arms, and that the several-fold extensibility of Fn fibrils involves the unfolding of type III modules. This could imply that Fn might play a significant role in mechanotransduction processes. PMID:17914904
How long does it take to equilibrate the unfolded state of a protein?
Levy, Ronald M; Dai, Wei; Deng, Nan-Jie; Makarov, Dmitrii E
2013-01-01
How long does it take to equilibrate the unfolded state of a protein? The answer to this question has important implications for our understanding of why many small proteins fold with two state kinetics. When the equilibration within the unfolded state U is much faster than the folding, the folding kinetics will be two state even if there are many folding pathways with different barriers. Yet the mean first passage times (MFPTs) between different regions of the unfolded state can be much longer than the folding time. This seems to imply that the equilibration within U is much slower than the folding. In this communication we resolve this paradox. We present a formula for estimating the time to equilibrate the unfolded state of a protein. We also present a formula for the MFPT to any state within U, which is proportional to the average lifetime of that state divided by the state population. This relation is valid when the equilibration within U is very fast as compared with folding as it often is for small proteins. To illustrate the concepts, we apply the formulas to estimate the time to equilibrate the unfolded state of Trp-cage and MFPTs within the unfolded state based on a Markov State Model using an ultra-long 208 microsecond trajectory of the miniprotein to parameterize the model. The time to equilibrate the unfolded state of Trp-cage is ∼100 ns while the typical MFPTs within U are tens of microseconds or longer. PMID:23963761
Phenomenology of the Higgs effective Lagrangian via F eynR ules
NASA Astrophysics Data System (ADS)
Alloul, Adam; Fuks, Benjamin; Sanz, Verónica
2014-04-01
The Higgs discovery and the lack of any other hint for new physics favor a description of non-standard Higgs physics in terms of an effective field theory. We present an implementation of a general Higgs effective Lagrangian containing operators up to dimension six in the framework of F eynR ules and provide details on the translation between the mass and interaction bases, in particular for three- and four-point interaction vertices involving Higgs and gauge bosons. We illustrate the strengths of this implementation by using the UFO interface of F eynR ules capable to generate model files that can be understood by the M adG raph 5 event generator and that have the specificity to contain all interaction vertices, without any restriction on the number of external legs or on the complexity of the Lorentz structures. We then investigate several new physics effects in total rates and differential distributions for different Higgs production modes, including gluon fusion, associated production with a gauge boson and di-Higgs production. We finally study contact interactions of gauge and Higgs bosons to fermions.
The vTAS suite: A simulator for classical and multiplexed three-axis neutron spectrometers
NASA Astrophysics Data System (ADS)
Boehm, M.; Filhol, A.; Raoul, Y.; Kulda, J.; Schmidt, W.; Schmalzl, K.; Farhi, E.
2013-01-01
The vTAS suite provides graphical assistance to prepare and perform inelastic neutron scattering experiments on a TAS instrument, including latest multiplexed instrumental configurations, such as FlatCone, IMPS and UFO. The interactive display allows for flexible translation between instrument positions in real space and neutron scattering conditions represented in reciprocal space. It is a platform independent public domain software tool, available for download from the website of the Institut Laue Langevin (ILL).
The Evolution of Massive Stars: a Selection of Facts and Questions
NASA Astrophysics Data System (ADS)
Vanbeveren, D.
In the present paper we discuss a selection of facts and questions related to observations and evolutionary calculations of massive single stars and massive stars in interacting binaries. We focus on the surface chemical abundances, the role of stellar winds, the early Be-stars, the high mass X-ray binaries and the effects of rotation on stellar evolution. Finally, we present an unconventionally formed object scenario (UFO-scenario) of WR binaries in dense stellar environments.
Evidence for Ultra-Fast Outflows in Radio-Quiet AGNs: III - Location and Energetics
NASA Technical Reports Server (NTRS)
Tombesi, F.; Cappi, M.; Reeves, J. N.; Braito, V.
2012-01-01
Using the results of a previous X-ray photo-ionization modelling of blue-shifted Fe K absorption lines on a sample of 42 local radio-quiet AGNs observed with XMM-Newton, in this letter we estimate the location and energetics of the associated ultrafast outflows (UFOs). Due to significant uncertainties, we are essentially able to place only lower/upper limits. On average, their location is in the interval approx.0.0003-0.03pc (approx.10(exp 2)-10(exp 4)tau(sub s) from the central black hole, consistent with what is expected for accretion disk winds/outflows. The mass outflow rates are constrained between approx.0.01- 1 Stellar Mass/y, corresponding to approx. or >5-10% of the accretion rates. The average lower-upper limits on the mechanical power are logE(sub K) approx. or = 42.6-44.6 erg/s. However, the minimum possible value of the ratio between the mechanical power and bolometric luminosity is constrained to be comparable or higher than the minimum required by simulations of feedback induced by winds/outflows. Therefore, this work demonstrates that UFOs are indeed capable to provide a significant contribution to the AGN r.osmological feedback, in agreement with theoretical expectations and the recent observation of interactions between AGN outflows and the interstellar medium in several Seyferts galaxies .
Deafferentation in thalamic and pontine areas in severe traumatic brain injury.
Laouchedi, M; Galanaud, D; Delmaire, C; Fernandez-Vidal, S; Messé, A; Mesmoudi, S; Oulebsir Boumghar, F; Pélégrini-Issac, M; Puybasset, L; Benali, H; Perlbarg, V
2015-07-01
Severe traumatic brain injury (TBI) is characterized mainly by diffuse axonal injuries (DAI). The cortico-subcortical disconnections induced by such fiber disruption play a central role in consciousness recovery. We hypothesized that these cortico-subcortical deafferentations inferred from diffusion MRI data could differentiate between TBI patients with favorable or unfavorable (death, vegetative state, or minimally conscious state) outcome one year after injury. Cortico-subcortical fiber density maps were derived by using probabilistic tractography from diffusion tensor imaging data acquired in 24 severe TBI patients and 9 healthy controls. These maps were compared between patients and controls as well as between patients with favorable (FO) and unfavorable (UFO) 1-year outcome to identify the thalamo-cortical and ponto-thalamo-cortical pathways involved in the maintenance of consciousness. Thalamo-cortical and ponto-thalamo-cortical fiber density was significantly lower in TBI patients than in healthy controls. Comparing FO and UFO TBI patients showed thalamo-cortical deafferentation associated with unfavorable outcome for projections from ventral posterior and intermediate thalamic nuclei to the associative frontal, sensorimotor and associative temporal cortices. Specific ponto-thalamic deafferentation in projections from the upper dorsal pons (including the reticular formation) was also associated with unfavorable outcome. Fiber density of cortico-subcortical pathways as measured from diffusion MRI tractography is a relevant candidate biomarker for early prediction of one-year favorable outcome in severe TBI. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Mortality among young injection drug users in San Francisco: a 10-year follow-up of the UFO study.
Evans, Jennifer L; Tsui, Judith I; Hahn, Judith A; Davidson, Peter J; Lum, Paula J; Page, Kimberly
2012-02-15
This study examined associations between mortality and demographic and risk characteristics among young injection drug users in San Francisco, California, and compared the mortality rate with that of the population. A total of 644 young (<30 years) injection drug users completed a baseline interview and were enrolled in a prospective cohort study, known as the UFO ("U Find Out") Study, from November 1997 to December 2007. Using the National Death Index, the authors identified 38 deaths over 4,167 person-years of follow-up, yielding a mortality rate of 9.1 (95% confidence interval: 6.6, 12.5) per 1,000 person-years. This mortality rate was 10 times that of the general population. The leading causes of death were overdose (57.9%), self-inflicted injury (13.2%), trauma/accidents (10.5%), and injection drug user-related medical conditions (13.1%). Mortality incidence was significantly higher among those who reported injecting heroin most days in the past month (adjusted hazard ratio = 5.8, 95% confidence interval: 1.4, 24.3). The leading cause of death in this group was overdose, and primary use of heroin was the only significant risk factor for death observed in the study. These findings highlight the continued need for public health interventions that address the risk of overdose in this population in order to reduce premature deaths.
Mortality Among Young Injection Drug Users in San Francisco: A 10-Year Follow-up of the UFO Study
Evans, Jennifer L.; Tsui, Judith I.; Hahn, Judith A.; Davidson, Peter J.; Lum, Paula J.; Page, Kimberly
2012-01-01
This study examined associations between mortality and demographic and risk characteristics among young injection drug users in San Francisco, California, and compared the mortality rate with that of the population. A total of 644 young (<30 years) injection drug users completed a baseline interview and were enrolled in a prospective cohort study, known as the UFO (“U Find Out”) Study, from November 1997 to December 2007. Using the National Death Index, the authors identified 38 deaths over 4,167 person-years of follow-up, yielding a mortality rate of 9.1 (95% confidence interval: 6.6, 12.5) per 1,000 person-years. This mortality rate was 10 times that of the general population. The leading causes of death were overdose (57.9%), self-inflicted injury (13.2%), trauma/accidents (10.5%), and injection drug user-related medical conditions (13.1%). Mortality incidence was significantly higher among those who reported injecting heroin most days in the past month (adjusted hazard ratio = 5.8, 95% confidence interval: 1.4, 24.3). The leading cause of death in this group was overdose, and primary use of heroin was the only significant risk factor for death observed in the study. These findings highlight the continued need for public health interventions that address the risk of overdose in this population in order to reduce premature deaths. PMID:22227793
Fast Ionized X-ray Absorbers in AGNs
NASA Astrophysics Data System (ADS)
Fukumura, K.; Tombesi, F.; Kazanas, D.; Shrader, C.; Behar, E.; Contopoulos, I.
2015-07-01
We present a study of X-ray ionization of MHD accretion-disk wind models in an effort to explain the highly-ionized ultra-fast outflows (UFOs) identified as X-ray absorbers recently detected in various sub-classes of Seyfert AGNs. Our primary focus is to show that magnetically-driven outflows are physically plausible candidates to account for the AGN X-ray spectroscopic observations. We calculate its X-ray ionization and the ensuing X-ray absorption line spectra in comparison with an XXM-Newton/EPIC spectrum of the narrow-line Seyfert AGN, PG 1211+143. We find, through identifying the detected features with Fe Kα transitions, that the absorber has a characteristic ionization parameter of log(xi[erg cm/s]) = 5-6 and a hydrogen-equivalent column density on the order of 1e23 cm-2, outflowing at a sub-relativistic velocity of v/c = 0.1-0.2. The best-fit model favors its radial location at R = 200 Rs (Rs is the Schwarzschild radius), with a disk inner truncation radius at Rt = 30Rs. The overall K-shell feature in data is suggested to be dominated by Fe XXV with very little contribution from Fe XXVI and weakly-ionized iron, which is in a good agreement with a series of earlier analysis of the UFOs in various AGNs including PG 1211+143.
1987-03-23
the decisive bridge heads across the )¶erderet Rive.-, by which the American forces would move westward to cut off the Cotentin Peninsula and seal the...these forces marched away from the bridgehead to seek some lesser objective, leaving the bridge uncovered. In consequence, the progress of the Corps was...the entire operation. They did not understand how their superior visioned the battle unfolding. They did not see the need of that particular bridge to
A Latent Class Unfolding Model for Analyzing Single Stimulus Preference Ratings.
ERIC Educational Resources Information Center
De Soete, Geert; Heiser, Willem J.
1993-01-01
A latent class unfolding model is developed for single stimulus preference ratings. One advantage is the possibility of testing the spatial unfolding model against the unconstrained latent class model for rating data. The model is applied to data about party preferences of members of the Dutch parliament. (SLD)
XBP1, Unfolded Protein Response, and Endocrine Responsiveness
2011-05-01
initially modeled in yeast cells (21, 22). Components of the unfolded protein response (UPR) are also conserved across species and these include...response in tumors. Mol Cancer Res 2005;3:597–605. 38. Sriburi R, Jackowski S, Mori K, Brewer JW. XBP1: a link between the unfolded protein response
Unfolding Case-Based Practicum Curriculum Infusing Crisis, Trauma, and Disaster Preparation
ERIC Educational Resources Information Center
Greene, Catie A.; Williams, Amy E.; Harris, Pamela N.; Travis, Sterling P.; Kim, Sharon Y.
2016-01-01
The authors evaluated an unfolding case-based approach to a practicum in counseling course infusing crisis, trauma, and disaster preparation for changes in students' crisis self-efficacy across a semester. The course, informed by constructivist-developmental pedagogy and centered on the unfolding case, resulted in significant increases in…
Unfolding the prompt gamma ray spectra measured in a Lanthanum Bromide detector using GRAVEL method
NASA Astrophysics Data System (ADS)
De, S.; Thomas, R. G.; Rout, P. C.; Suryanarayana, S. V.; Nayak, B. K.; Saxena, A.
2018-02-01
Prompt fission Upsilon -ray energy spectra in spontaneous fission of 252Cf has been measured using a 6'' LaBr3(Ce) detector. Unfolding of the measured Upsilon -ray energy spectra has been carried out using GRAVEL method. The response matrix of the detector has been simulated using GEANT4 and the unfolding of Upsilon -ray energy spectra for 60Co and 137Cs sources have been validated. This unfolding technique has then been applied to the prompt gamma spectra obtained from the spontaneous fission of 252Cf.
Dalby, Andrew; Shamsir, Mohd Shahir
2015-01-01
Molecular dynamics simulations have been used extensively to model the folding and unfolding of proteins. The rates of folding and unfolding should follow the Arrhenius equation over a limited range of temperatures. This study shows that molecular dynamic simulations of the unfolding of crambin between 500K and 560K do follow the Arrhenius equation. They also show that while there is a large amount of variation between the simulations the average values for the rate show a very high degree of correlation.
Dalby, Andrew; Shamsir, Mohd Shahir
2015-01-01
Molecular dynamics simulations have been used extensively to model the folding and unfolding of proteins. The rates of folding and unfolding should follow the Arrhenius equation over a limited range of temperatures. This study shows that molecular dynamic simulations of the unfolding of crambin between 500K and 560K do follow the Arrhenius equation. They also show that while there is a large amount of variation between the simulations the average values for the rate show a very high degree of correlation. PMID:26539292
Proof-of-principle to unfold an angle-energy dependent source from forward and adjoint calculations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pace, J.V. III
For many years there has existed a discrepancy between the measured and calculated responses from the Little Boy weapon in Hiroshima. A myriad of solutions have been proposed, but to no avail. If one can rationalize to himself that it does not really matter exactly what happened with the weapon when it exploded, and if sufficient information exist about the measurements, one should be able to unfold the source. Moreover, if a source can be unfolded in a controlled environment, then it should be possible to unfold a more complicated source, for example, the Little Boy source. This report recordsmore » the findings of a proof-of-principle test to unfold a source in the controlled environment.« less
Unfolding mechanism of lysozyme in various urea solutions: Insights from fluorescence spectroscopy
NASA Astrophysics Data System (ADS)
Chen, Bang; Zhang, Hongjia; Xi, Wenying; Zhao, Liqing; Liang, Li; Chen, Yantao
2014-11-01
Fluorescence spectroscopic technique is very popular in exploring the folding/unfolding process of proteins. In this paper, unfolding process of hen egg-white lysozyme was investigated in various denaturing solutions. Firstly, polymer solution theory was employed to comprehend the dependence of fluorescence quenching effect on protein concentration, and dynamic contact concentration was suggested as a critical value for related fluorescence experiment. Secondly, it was found that urea alone could not completely unfold lysozyme but did when together with DTT or HCl. Lysozyme was destabilized in concentrated urea solution, but still could maintain its spatial structure. Phase diagram of fluorescence intensities revealed that HCl could enhance the denaturing capacity of urea, resulting in the emergence of intermediate state in the thermodynamic unfolding process of lysozyme.
NASA Astrophysics Data System (ADS)
Matsushita, Yu-ichiro; Nishi, Hirofumi; Iwata, Jun-ichi; Kosugi, Taichi; Oshiyama, Atsushi
2018-01-01
We propose an unfolding scheme to analyze energy spectra of complex large-scale systems which are inherently of double periodicity on the basis of the density-functional theory. Applying our method to a twisted bilayer graphene (tBLG) and a stack of monolayer MoS2 on graphene (MoS2/graphene) as examples, we first show that the conventional unfolding scheme in the past using a single primitive-cell representation causes serious problems in analyses of the energy spectra. We then introduce our multispace representation scheme in the unfolding method and clarify its validity. Velocity renormalization of Dirac electrons in tBLG and mini gaps of Dirac cones in MoS2/graphene are elucidated in the present unfolding scheme.
NASA Astrophysics Data System (ADS)
Bura, E.; Zhmurov, A.; Barsegov, V.
2009-01-01
Dynamic force spectroscopy and steered molecular simulations have become powerful tools for analyzing the mechanical properties of proteins, and the strength of protein-protein complexes and aggregates. Probability density functions of the unfolding forces and unfolding times for proteins, and rupture forces and bond lifetimes for protein-protein complexes allow quantification of the forced unfolding and unbinding transitions, and mapping the biomolecular free energy landscape. The inference of the unknown probability distribution functions from the experimental and simulated forced unfolding and unbinding data, as well as the assessment of analytically tractable models of the protein unfolding and unbinding requires the use of a bandwidth. The choice of this quantity is typically subjective as it draws heavily on the investigator's intuition and past experience. We describe several approaches for selecting the "optimal bandwidth" for nonparametric density estimators, such as the traditionally used histogram and the more advanced kernel density estimators. The performance of these methods is tested on unimodal and multimodal skewed, long-tailed distributed data, as typically observed in force spectroscopy experiments and in molecular pulling simulations. The results of these studies can serve as a guideline for selecting the optimal bandwidth to resolve the underlying distributions from the forced unfolding and unbinding data for proteins.
Dasgupta, Amrita; Udgaonkar, Jayant B; Das, Payel
2014-06-19
The unfolding of the SH3 domain of the PI3 kinase in aqueous urea has been studied using a synergistic experiment-simulation approach. The experimental observation of a transient wet molten globule intermediate, IU, with an unusual non-native burial of the sole Trp residue, W53, provides the benchmark for the unfolding simulations performed (eight in total, each at least 0.5 μs long). The simulations reveal that the partially unfolded IU ensemble is preceded by an early native-like molten globule intermediate ensemble I*. In the very initial stage of unfolding, dry globule conformations with the protein core filled with urea instead of water are transiently observed within the I* ensemble. Water penetration into the urea-filled core of dry globule conformations is frequently accompanied by very transient burial of W53. Later during gradual unfolding, W53 is seen to again become transiently buried in the IU ensemble for a much longer time. In the structurally heterogeneous IU ensemble, conformational flexibility of the C-terminal β-strands enables W53 burial by the formation of non-native, tertiary contacts with hydrophobic residues, which could serve to protect the protein from aggregation during unfolding.
Armen, Roger S; Daggett, Valerie
2005-12-13
The self-assembly of beta(2)-microglobulin into fibrils leads to dialysis-related amyloidosis. pH-mediated partial unfolding is required for the formation of the amyloidogenic intermediate that then self-assembles into amyloid fibrils. Two partially folded intermediates of beta(2)-microglobulin have been identified experimentally and linked to the formation of fibrils of distinct morphology, yet it remains difficult to characterize these partially unfolded states at high resolution using experimental approaches. Consequently, we have performed molecular dynamics simulations at neutral and low pH to determine the structures of these partially unfolded amyloidogenic intermediates. In the low-pH simulations, we observed the formation of alpha-sheet structure, which was first proposed by Pauling and Corey. Multiple simulations were performed, and two distinct intermediate state ensembles were identified that may account for the different fibril morphologies. The predominant early unfolding intermediate was nativelike in structure, in agreement with previous NMR studies. The late unfolding intermediate was significantly disordered, but it maintained an extended elongated structure, with hydrophobic clusters and residual alpha-extended chain strands in specific regions of the sequence that map to amyloidogenic peptides. We propose that the formation of alpha-sheet facilitates self-assembly into partially unfolded prefibrillar amyloidogenic intermediates.
Branches of Triangulated Origami Near the Unfolded State
NASA Astrophysics Data System (ADS)
Chen, Bryan Gin-ge; Santangelo, Christian D.
2018-01-01
Origami structures are characterized by a network of folds and vertices joining unbendable plates. For applications to mechanical design and self-folding structures, it is essential to understand the interplay between the set of folds in the unfolded origami and the possible 3D folded configurations. When deforming a structure that has been folded, one can often linearize the geometric constraints, but the degeneracy of the unfolded state makes a linear approach impossible there. We derive a theory for the second-order infinitesimal rigidity of an initially unfolded triangulated origami structure and use it to study the set of nearly unfolded configurations of origami with four boundary vertices. We find that locally, this set consists of a number of distinct "branches" which intersect at the unfolded state, and that the number of these branches is exponential in the number of vertices. We find numerical and analytical evidence that suggests that the branches are characterized by choosing each internal vertex to either "pop up" or "pop down." The large number of pathways along which one can fold an initially unfolded origami structure strongly indicates that a generic structure is likely to become trapped in a "misfolded" state. Thus, new techniques for creating self-folding origami are likely necessary; controlling the popping state of the vertices may be one possibility.
Montecinos-Franjola, Felipe; Ross, Justin A.; Sánchez, Susana A.; Brunet, Juan E.; Lagos, Rosalba; Jameson, David M.; Monasterio, Octavio
2012-01-01
FtsZ is a major protein in bacterial cytokinesis that polymerizes into single filaments. A dimer has been proposed to be the nucleating species in FtsZ polymerization. To investigate the influence of the self-assembly of FtsZ on its unfolding pathway, we characterized its oligomerization and unfolding thermodynamics. We studied the assembly using size-exclusion chromatography and fluorescence spectroscopy, and the unfolding using circular dichroism and two-photon fluorescence correlation spectroscopy. The chromatographic analysis demonstrated the presence of monomers, dimers, and tetramers with populations dependent on protein concentration. Dilution experiments using fluorescent conjugates revealed dimer-to-monomer and tetramer-to-dimer dissociation constants in the micromolar range. Measurements of fluorescence lifetimes and rotational correlation times of the conjugates supported the presence of tetramers at high protein concentrations and monomers at low protein concentrations. The unfolding study demonstrated that the three-state unfolding of FtsZ was due to the mainly dimeric state of the protein, and that the monomer unfolds through a two-state mechanism. The monomer-to-dimer equilibrium characterized here (Kd = 9 μM) indicates a significant fraction (∼10%) of stable dimers at the critical concentration for polymerization, supporting a role of the dimeric species in the first steps of FtsZ polymerization. PMID:22824282
Kishore, Devesh; Kundu, Suman; Kayastha, Arvind M.
2012-01-01
Background In this case study, we analysed the properties of unfolded states and pathways leading to complete denaturation of a multimeric chick pea β-galactosidase (CpGAL), as obtained from treatment with guanidium hydrochloride, urea, elevated temperature and extreme pH. Methodology/Principal Findings CpGAL, a heterodimeric protein with native molecular mass of 85 kDa, belongs to α+β class of protein. The conformational stability and thermodynamic parameters of CpGAL unfolding in different states were estimated and interpreted using circular dichroism and fluorescence spectroscopic measurements. The enzyme was found to be structurally and functionally stable in the entire pH range and upto 50°C temperature. Further increase in temperature induces unfolding followed by aggregation. Chemical induced denaturation was found to be cooperative and transitions were irreversible, non-coincidental and sigmoidal. Free energy of protein unfolding (ΔG0) and unfolding constant (Kobs) were also calculated for chemically denatured CpGAL. Significance The protein seems to use different pathways for unfolding in different environments and is a classical example of how the environment dictates the path a protein might take to fold while its amino acid sequence only defines its final three-dimensional conformation. The knowledge accumulated could be of immense biotechnological significance as well. PMID:23185611
First Passage Times, Lifetimes, and Relaxation Times of Unfolded Proteins
NASA Astrophysics Data System (ADS)
Dai, Wei; Sengupta, Anirvan M.; Levy, Ronald M.
2015-07-01
The dynamics of proteins in the unfolded state can be quantified in computer simulations by calculating a spectrum of relaxation times which describes the time scales over which the population fluctuations decay to equilibrium. If the unfolded state space is discretized, we can evaluate the relaxation time of each state. We derive a simple relation that shows the mean first passage time to any state is equal to the relaxation time of that state divided by the equilibrium population. This explains why mean first passage times from state to state within the unfolded ensemble can be very long but the energy landscape can still be smooth (minimally frustrated). In fact, when the folding kinetics is two-state, all of the unfolded state relaxation times within the unfolded free energy basin are faster than the folding time. This result supports the well-established funnel energy landscape picture and resolves an apparent contradiction between this model and the recently proposed kinetic hub model of protein folding. We validate these concepts by analyzing a Markov state model of the kinetics in the unfolded state and folding of the miniprotein NTL9 (where NTL9 is the N -terminal domain of the ribosomal protein L9), constructed from a 2.9 ms simulation provided by D. E. Shaw Research.
First Passage Times, Lifetimes, and Relaxation Times of Unfolded Proteins.
Dai, Wei; Sengupta, Anirvan M; Levy, Ronald M
2015-07-24
The dynamics of proteins in the unfolded state can be quantified in computer simulations by calculating a spectrum of relaxation times which describes the time scales over which the population fluctuations decay to equilibrium. If the unfolded state space is discretized, we can evaluate the relaxation time of each state. We derive a simple relation that shows the mean first passage time to any state is equal to the relaxation time of that state divided by the equilibrium population. This explains why mean first passage times from state to state within the unfolded ensemble can be very long but the energy landscape can still be smooth (minimally frustrated). In fact, when the folding kinetics is two-state, all of the unfolded state relaxation times within the unfolded free energy basin are faster than the folding time. This result supports the well-established funnel energy landscape picture and resolves an apparent contradiction between this model and the recently proposed kinetic hub model of protein folding. We validate these concepts by analyzing a Markov state model of the kinetics in the unfolded state and folding of the miniprotein NTL9 (where NTL9 is the N-terminal domain of the ribosomal protein L9), constructed from a 2.9 ms simulation provided by D. E. Shaw Research.
Isothermal chemical denaturation of large proteins: Path-dependence and irreversibility.
Wafer, Lucas; Kloczewiak, Marek; Polleck, Sharon M; Luo, Yin
2017-12-15
State functions (e.g., ΔG) are path independent and quantitatively describe the equilibrium states of a thermodynamic system. Isothermal chemical denaturation (ICD) is often used to extrapolate state function parameters for protein unfolding in native buffer conditions. The approach is prudent when the unfolding/refolding processes are path independent and reversible, but may lead to erroneous results if the processes are not reversible. The reversibility was demonstrated in several early studies for smaller proteins, but was assumed in some reports for large proteins with complex structures. In this work, the unfolding/refolding of several proteins were systematically studied using an automated ICD instrument. It is shown that: (i) the apparent unfolding mechanism and conformational stability of large proteins can be denaturant-dependent, (ii) equilibration times for large proteins are non-trivial and may introduce significant error into calculations of ΔG, (iii) fluorescence emission spectroscopy may not correspond to other methods, such as circular dichroism, when used to measure protein unfolding, and (iv) irreversible unfolding and hysteresis can occur in the absence of aggregation. These results suggest that thorough confirmation of the state functions by, for example, performing refolding experiments or using additional denaturants, is needed when quantitatively studying the thermodynamics of protein unfolding using ICD. Copyright © 2017 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Malau, N. D.; Sumaryada, T.
2016-01-01
The mechanism that explains the unfolding/refolding process of the protein is still a major problem that has not been fully understood. In this paper we present our study on the unfolding and refolding pathway of Chymotrypsin Inhibitor 2 (CI2) protein through a molecular dynamics simulation technique. The high temperature unfolding simulation were performed at 500 K for 35 ns. While the low temperature refolding simulation performed at 200 K for 35 ns. The unfolding and refolding pathway of protein were analysed by looking at the dynamics of root mean squared deviation (RMSD) and secondary structure profiles. The signatures of unfolding were observed from significant increase of RMSD within the time span of 10 ns to 35 ns. For the refolding process, the initial structure was prepared from the structure of unfolding protein at t=15 ns and T=500 K. Analysis have shown that some of the secondary structures of CI2 protein that have been damaged at high temperature can be refolded back to its initial structure at low temperature simulation. Our results suggest that most of α-helix structure of CI2 protein can be refolded back to its initial state, while only half beta-sheet structure can be reformed.
Shen, Tao; Cao, Yi; Zhuang, Shulin; Li, Hongbin
2012-01-01
Determining the structure of the transition state is critical for elucidating the mechanism behind how proteins fold and unfold. Due to its high free energy, however, the transition state generally cannot be trapped and studied directly using traditional structural biology methods. Thus, characterizing the structure of the transition state that occurs as proteins fold and unfold remains a major challenge. Here, we report a novel (to our knowledge) method that uses engineered bi-histidine (bi-His) metal-binding sites to directly map the structure of the mechanical unfolding transition state of proteins. This method is adapted from the traditional ψ-value analysis, which uses engineered bi-His metal chelation sites to probe chemical (un)folding transition-state structure. The ϕM2+U-value is defined as ΔΔG‡-N/ΔΔGU-N, which is the energetic effects of metal chelation by the bi-His site on the unfolding energy barrier (ΔG‡-N) relative to its thermodynamic stability (ΔGU-N) and can be used to obtain information about the transition state in the mutational site. As a proof of principle, we used the small protein GB1 as a model system and set out to map its mechanical unfolding transition-state structure. Using single-molecule atomic force microscopy and spectrofluorimetry, we directly quantified the effect of divalent metal ion binding on the mechanical unfolding free energy and thermodynamic stability of GB1, which allowed us to quantify ϕM2+U-values for different sites in GB1. Our results enabled us to map the structure of the mechanical unfolding transition state of GB1. Within GB1’s mechanical unfolding transition state, the interface between force-bearing β-strands 1 and 4 is largely disrupted, and the first β-hairpin is partially disordered while the second β-hairpin and the α-helix remain structured. Our results demonstrate the unique application of ψ-value analysis in elucidating the structure of the transition state that occurs during the mechanical unfolding process, offering a potentially powerful new method for investigating the design of novel elastomeric proteins. PMID:22947942
Shen, Tao; Cao, Yi; Zhuang, Shulin; Li, Hongbin
2012-08-22
Determining the structure of the transition state is critical for elucidating the mechanism behind how proteins fold and unfold. Due to its high free energy, however, the transition state generally cannot be trapped and studied directly using traditional structural biology methods. Thus, characterizing the structure of the transition state that occurs as proteins fold and unfold remains a major challenge. Here, we report a novel (to our knowledge) method that uses engineered bi-histidine (bi-His) metal-binding sites to directly map the structure of the mechanical unfolding transition state of proteins. This method is adapted from the traditional ψ-value analysis, which uses engineered bi-His metal chelation sites to probe chemical (un)folding transition-state structure. The φ(M2+)(U)-value is defined as ΔΔG(‡-N)/ΔΔG(U-N), which is the energetic effects of metal chelation by the bi-His site on the unfolding energy barrier (ΔG(‡-N)) relative to its thermodynamic stability (ΔG(U-N)) and can be used to obtain information about the transition state in the mutational site. As a proof of principle, we used the small protein GB1 as a model system and set out to map its mechanical unfolding transition-state structure. Using single-molecule atomic force microscopy and spectrofluorimetry, we directly quantified the effect of divalent metal ion binding on the mechanical unfolding free energy and thermodynamic stability of GB1, which allowed us to quantify φ(M2+)(U)-values for different sites in GB1. Our results enabled us to map the structure of the mechanical unfolding transition state of GB1. Within GB1's mechanical unfolding transition state, the interface between force-bearing β-strands 1 and 4 is largely disrupted, and the first β-hairpin is partially disordered while the second β-hairpin and the α-helix remain structured. Our results demonstrate the unique application of ψ-value analysis in elucidating the structure of the transition state that occurs during the mechanical unfolding process, offering a potentially powerful new method for investigating the design of novel elastomeric proteins. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Sequential protein unfolding through a carbon nanotube pore
NASA Astrophysics Data System (ADS)
Xu, Zhonghe; Zhang, Shuang; Weber, Jeffrey K.; Luan, Binquan; Zhou, Ruhong; Li, Jingyuan
2016-06-01
An assortment of biological processes, like protein degradation and the transport of proteins across membranes, depend on protein unfolding events mediated by nanopore interfaces. In this work, we exploit fully atomistic simulations of an artificial, CNT-based nanopore to investigate the nature of ubiquitin unfolding. With one end of the protein subjected to an external force, we observe non-canonical unfolding behaviour as ubiquitin is pulled through the pore opening. Secondary structural elements are sequentially detached from the protein and threaded into the nanotube, interestingly, the remaining part maintains native-like characteristics. The constraints of the nanopore interface thus facilitate the formation of stable ``unfoldon'' motifs above the nanotube aperture that can exist in the absence of specific native contacts with the other secondary structure. Destruction of these unfoldons gives rise to distinct force peaks in our simulations, providing us with a sensitive probe for studying the kinetics of serial unfolding events. Our detailed analysis of nanopore-mediated protein unfolding events not only provides insight into how related processes might proceed in the cell, but also serves to deepen our understanding of structural arrangements which form the basis for protein conformational stability.An assortment of biological processes, like protein degradation and the transport of proteins across membranes, depend on protein unfolding events mediated by nanopore interfaces. In this work, we exploit fully atomistic simulations of an artificial, CNT-based nanopore to investigate the nature of ubiquitin unfolding. With one end of the protein subjected to an external force, we observe non-canonical unfolding behaviour as ubiquitin is pulled through the pore opening. Secondary structural elements are sequentially detached from the protein and threaded into the nanotube, interestingly, the remaining part maintains native-like characteristics. The constraints of the nanopore interface thus facilitate the formation of stable ``unfoldon'' motifs above the nanotube aperture that can exist in the absence of specific native contacts with the other secondary structure. Destruction of these unfoldons gives rise to distinct force peaks in our simulations, providing us with a sensitive probe for studying the kinetics of serial unfolding events. Our detailed analysis of nanopore-mediated protein unfolding events not only provides insight into how related processes might proceed in the cell, but also serves to deepen our understanding of structural arrangements which form the basis for protein conformational stability. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00410e
pH dependent unfolding characteristics of DLC8 dimer: Residue level details from NMR.
Mohan, P M Krishna; Hosur, Ramakrishna V
2008-11-01
Environment dependence of folding and unfolding of a protein is central to its function. In the same vein, knowledge of pH dependence of stability and folding/unfolding is crucial for many biophysical equilibrium and kinetic studies designed to understand protein folding mechanisms. In the present study we investigated the guanidine induced unfolding transition of dynein light chain protein (DLC8), a cargo adaptor of the dynein complex in the pH range 7-10. It is observed that while the protein remains a dimer in the entire pH range, its stability is somewhat reduced at alkaline pH. Global unfolding features monitored using fluorescence spectroscopy revealed that the unfolding transition of DLC8 at pH 7 is best described by a three-state model, whereas, that at pH 10 is best described by a two-state model. Chemical shift perturbations due to pH change provided insights into the corresponding residue level structural perturbations in the DLC8 dimer. Likewise, backbone (15)N relaxation measurements threw light on the corresponding motional changes in the dimeric protein. These observations have been rationalized on the basis of expected changes with increasing pH in the protonation states of the titratable residues on the structure of the protein. These, in turn provide an explanation for the change from three-state to two-state guanidine induced unfolding transition as the pH is increased from 7 to 10. All these results exemplify and highlight the role of environment vis-à-vis the sequence and structure of a given protein in dictating its folding/unfolding characteristics.
Gupta, Asmita; Bansal, Manju
2016-10-19
Mechanical unfolding studies on Ribonucleic Acid (RNA) structures are a subject of tremendous interest as they shed light on the principles of higher order assembly of these structures. Pseudoknotting is one of the most elementary ways in which this higher order assembly is achieved as discrete secondary structural units in RNA are brought in close proximity to form a tertiary structure. Using steered molecular dynamics (SMD) simulations, we have studied the unfolding of five RNA pseudoknot structures that differ from each other either by base substitutions in helices or loops. Our SMD simulations reveal the manner in which a biologically functional RNA pseudoknot unfolds and the effect of changes in the primary structure on this unfolding pathway, providing necessary insights into the driving forces behind the functioning of these structures. We observed that an A → C mutation in the loop sequence makes the pseudoknot far more resistant against force induced disruption relative to its wild type structure. In contrast to this, a base-pair substitution GC → AU near the pseudoknot junction region renders it more vulnerable to this disruption. The quantitative estimation of differences in the unfolding paths was carried out using force extension curves, potential of mean force profiles, and the opening of different Watson-Crick and non-Watson-Crick interactions. The results provide a quantified view in which the unfolding paths of the small RNA structures can be used for investigating the programmability of RNA chains for designing RNA switches and aptamers as their biological folding and unfolding could be assessed and manipulated.
Equilibrium unfolding of A. niger RNase: pH dependence of chemical and thermal denaturation.
Kumar, Gundampati Ravi; Sharma, Anurag; Kumari, Moni; Jagannadham, Medicherla V; Debnath, Mira
2011-08-01
Equilibrium unfolding of A. niger RNase with chemical denaturants, for example GuHCl and urea, and thermal unfolding have been studied as a function of pH using fluorescence, far-UV, near-UV, and absorbance spectroscopy. Because of their ability to affect electrostatic interactions, pH and chemical denaturants have a marked effect on the stability, structure, and function of many globular proteins. ANS binding studies have been conducted to enable understanding of the folding mechanism of the protein in the presence of the denaturants. Spectroscopic studies by absorbance, fluorescence, and circular dichroism and use of K2D software revealed that the enzyme has α + β type secondary structure with approximately 29% α-helix, 24% β-sheet, and 47% random coil. Under neutral conditions the enzyme is stable in urea whereas GuHCl-induced equilibrium unfolding was cooperative. A. niger RNase has little ANS binding even under neutral conditions. Multiple intermediates were populated during the pH-induced unfolding of A. niger RNase. Urea and temperature-induced unfolding of A. niger RNase into the molten globule-like state is non-cooperative, in contrast to the cooperativity seen with the native protein, suggesting the presence of two parts/domains, in the molecular structure of A. niger RNase, with different stability that unfolds in steps. Interestingly, the GuHCl-induced unfolding of the A state (molten globule state) of A. niger RNase is unique, because a low concentration of denaturant not only induces structural change but also facilitates transition from one molten globule like state (A(MG1)) into another (I(MG2)).
NASA Astrophysics Data System (ADS)
Tombesi, F.; Cappi, M.; Reeves, J. N.; Palumbo, G. G. C.; Yaqoob, T.; Braito, V.; Dadina, M.
2010-10-01
Context. Blue-shifted Fe K absorption lines have been detected in recent years between 7 and 10 keV in the X-ray spectra of several radio-quiet AGNs. The derived blue-shifted velocities of the lines can often reach mildly relativistic values, up to 0.2-0.4c. These findings are important because they suggest the presence of a previously unknown massive and highly ionized absorbing material outflowing from their nuclei, possibly connected with accretion disk winds/outflows. Aims: The scope of the present work is to statistically quantify the parameters and incidence of the blue-shifted Fe K absorption lines through a uniform analysis on a large sample of radio-quiet AGNs. This allows us to assess their global detection significance and to overcome any possible publication bias. Methods: We performed a blind search for narrow absorption features at energies greater than 6.4 keV in a sample of 42 radio-quiet AGNs observed with XMM-Newton. A simple uniform model composed by an absorbed power-law plus Gaussian emission and absorption lines provided a good fit for all the data sets. We derived the absorption lines parameters and calculated their detailed detection significance making use of the classical F-test and extensive Monte Carlo simulations. Results: We detect 36 narrow absorption lines on a total of 101 XMM-Newton EPIC pn observations. The number of absorption lines at rest-frame energies higher than 7 keV is 22. Their global probability to be generated by random fluctuations is very low, less than 3 × 10-8, and their detection have been independently confirmed by a spectral analysis of the MOS data, with associated random probability <10-7. We identify the lines as Fe XXV and Fe XXVI K-shell resonant absorption. They are systematically blue-shifted, with a velocity distribution ranging from zero up to ~0.3c, with a peak and mean value at ~0.1c. We detect variability of the lines on both EWs and blue-shifted velocities among different XMM-Newton observations even on time-scales as short as a few days, possibly suggesting somewhat compact absorbers. Moreover, we find no significant correlation between the cosmological red-shifts of the sources and the lines blue-shifted velocities, ruling out any systematic contamination by local absorption. If we define ultra-fast outflows (UFOs) those highly ionized absorbers with outflow velocities higher than 104 km s-1, then the majority of the lines are consistent with being associated to UFOs and the fraction of objects with detected UFOs in the whole sample is at least ~35%. This fraction is similar for type 1 and type 2 sources. The global covering fraction of the absorbers is consequently estimated to be in the range C ˜ 0.4-0.6, thereby implying large opening angles. Conclusions: From our systematic X-ray spectral analysis on a large sample of radio-quiet AGNs we have been able to clearly assess the global veracity of the blue-shifted Fe K absorption lines at E > 7 keV and to overcome their publication bias. These lines indicate that UFOs are a rather common phenomenon observable in the central regions of these sources and they are probably the direct signature of AGN accretion disk winds/ejecta. The detailed photo-ionization modeling of these absorbers is presented in a companion paper. Appendices are only available in electronic form at http://www.aanda.org
NASA Astrophysics Data System (ADS)
Arteca, Gustavo A.; Tapia, O.
Using computer-simulated molecular dynamics, we study the effect of sequence mutation on the unfolding mechanism of a native fold. The system considered is the native fold of hen egg-white lysozyme, exposed to centrifugal unfolding in vacuo. This unfolding bias elicits configurational transitions that imitate the behaviour of anhydrous proteins diffusing after electrospraying from neutral-pH solutions. By changing the sequences threaded onto the native fold of lysozyme, we probe the role of disulfide bridges and the effect of a global mutation. We find that the initial denaturing steps share common characteristics for the tested sequences. Recurrent features are: (i) the presence of dumbbell conformers with significant residual secondary structure, (ii) the ubiquitous formation of hairpins and two-stranded β-sheets regardless of disulfide bridges, and (iii) an unfolding pattern where the reduction in folding complexity is highly correlated with the decrease in chain compactness. These findings appear to be intrinsic to the shape of the native fold, suggesting that similar unfolding pathways may be accessible to many protein sequences.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Leder, A.; Anderson, A. J.; Billard, J.
2018-02-02
The Ricochet experiment seeks to measure Coherent (neutral-current) Elastic Neutrino-Nucleus Scattering (CEνNS) using dark-matter-style detectors with sub-keV thresholds placed near a neutrino source, such as the MIT (research) Reactor (MITR), which operates at 5.5 MW generating approximately 2.2 × 1018 ν/second in its core. Currently, Ricochet is characterizing the backgrounds at MITR, the main component of which comes in the form of neutrons emitted from the core simultaneous with the neutrino signal. To characterize this background, we wrapped Bonner cylinders around a 32He thermal neutron detector, whose data was then unfolded via a Markov Chain Monte Carlo (MCMC) to produce a neutron energymore » spectrum across several orders of magnitude. We discuss the resulting spectrum and its implications for deploying Ricochet at the MITR site as well as the feasibility of reducing this background level via the addition of polyethylene shielding around the detector setup.« less
NASA Astrophysics Data System (ADS)
Leder, A.; Anderson, A. J.; Billard, J.; Figueroa-Feliciano, E.; Formaggio, J. A.; Hasselkus, C.; Newman, E.; Palladino, K.; Phuthi, M.; Winslow, L.; Zhang, L.
2018-02-01
The Ricochet experiment seeks to measure Coherent (neutral-current) Elastic Neutrino-Nucleus Scattering (CEνNS) using dark-matter-style detectors with sub-keV thresholds placed near a neutrino source, such as the MIT (research) Reactor (MITR), which operates at 5.5 MW generating approximately 2.2 × 1018 ν/second in its core. Currently, Ricochet is characterizing the backgrounds at MITR, the main component of which comes in the form of neutrons emitted from the core simultaneous with the neutrino signal. To characterize this background, we wrapped Bonner cylinders around a 32He thermal neutron detector, whose data was then unfolded via a Markov Chain Monte Carlo (MCMC) to produce a neutron energy spectrum across several orders of magnitude. We discuss the resulting spectrum and its implications for deploying Ricochet at the MITR site as well as the feasibility of reducing this background level via the addition of polyethylene shielding around the detector setup.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Leder, A.; Anderson, A. J.; Billard, J.
2017-10-02
The Ricochet experiment seeks to measure Coherent (neutral-current) Elastic Neutrino-Nucleus Scattering using dark-matter-style detectors with sub-keV thresholds placed near a neutrino source, such as the MIT (research) Reactor (MITR), which operates at 5.5 MW generating approximately 2.2e18 neutrinos/second at the core. Currently, Ricochet is characterizing the backgrounds at MITR, the main component of which comes in the form of neutrons emitted from the core simultaneous with the neutrino signal. To characterize this background, we wrapped a Bonner cylinder around a He-3 thermal neutron detector, whose data was then unfolded to produce a neutron energy spectrum across several orders of magnitude.more » We discuss the resulting spectrum and its implications for deploying Ricochet in the future at the MITR site as well as the feasibility of reducing this background level via the addition of polyethylene shielding around the detector setup.« less
Multidimensional free energy surface of unfolding of HP-36: Microscopic origin of ruggedness
NASA Astrophysics Data System (ADS)
Ghosh, Rikhia; Roy, Susmita; Bagchi, Biman
2014-10-01
The protein folding funnel paradigm suggests that folding and unfolding proceed as directed diffusion in a multidimensional free energy surface where a multitude of pathways can be traversed during the protein's sojourn from initial to final state. However, finding even a single pathway, with the detail chronicling of intermediates, is an arduous task. In this work we explore the free energy surface of unfolding pathway through umbrella sampling, for a small globular α-helical protein chicken-villin headpiece (HP-36) when the melting of secondary structures is induced by adding DMSO in aqueous solution. We find that the unfolding proceeds through the initial separation or melting of aggregated hydrophobic core that comprises of three phenylalanine residues (Phe7, Phe11, and Phe18). This separation is accompanied by simultaneous melting of the second helix. Unfolding is found to be a multistage process involving crossing of three consecutive minima and two barriers at the initial stage. At a molecular level, Phe18 is observed to reorient itself towards other hydrophobic grooves to stabilize the intermediate states. We identify the configuration of the intermediates and correlate the intermediates with those obtained in our previous works. We also give an estimate of the barriers for different transition states and observe the softening of the barriers with increasing DMSO concentration. We show that higher concentration of DMSO tunes the unfolding pathway by destabilizing the third minimum and stabilizing the second one, indicating the development of a solvent modified, less rugged pathway. The prime outcome of this work is the demonstration that mixed solvents can profoundly transform the nature of the energy landscape and induce unfolding via a modified route. A successful application of Kramer's rate equation correlating the free energy simulation results shows faster rate of unfolding with increasing DMSO concentration. This work perhaps presents the first systematic theoretical study of the effect of a chemical denaturant on the microscopic free energy surface and rates of unfolding of HP-36.
Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin
2018-01-01
Mechanical stability is a key feature in the regulation of structural scaffolding proteins and their functions. Despite the abundance of α-helical structures among the human proteome and their undisputed importance in health and disease, the fundamental principles of their behavior under mechanical load are poorly understood. Talin and α-catenin are two key molecules in focal adhesions and adherens junctions, respectively. In this study, we used a combination of atomistic steered molecular dynamics (SMD) simulations, polyprotein engineering, and single-molecule atomic force microscopy (smAFM) to investigate unfolding of these proteins. SMD simulations revealed that talin rod α-helix bundles as well as α-catenin α-helix domains unfold through stable 3-helix intermediates. While the 5-helix bundles were found to be mechanically stable, a second stable conformation corresponding to the 3-helix state was revealed. Mechanically weaker 4-helix bundles easily unfolded into a stable 3-helix conformation. The results of smAFM experiments were in agreement with the findings of the computational simulations. The disulfide clamp mutants, designed to protect the stable state, support the 3-helix intermediate model in both experimental and computational setups. As a result, multiple discrete unfolding intermediate states in the talin and α-catenin unfolding pathway were discovered. Better understanding of the mechanical unfolding mechanism of α-helix proteins is a key step towards comprehensive models describing the mechanoregulation of proteins. PMID:29698481
The Graded Unfolding Model: A Unidimensional Item Response Model for Unfolding Graded Responses.
ERIC Educational Resources Information Center
Roberts, James S.; Laughlin, James E.
Binary or graded disagree-agree responses to attitude items are often collected for the purpose of attitude measurement. Although such data are sometimes analyzed with cumulative measurement models, recent investigations suggest that unfolding models are more appropriate (J. S. Roberts, 1995; W. H. Van Schuur and H. A. L. Kiers, 1994). Advances in…
ERIC Educational Resources Information Center
Roberts, James S.; Laughlin, James E.
1996-01-01
A parametric item response theory model for unfolding binary or graded responses is developed. The graded unfolding model (GUM) is a generalization of the hyperbolic cosine model for binary data of D. Andrich and G. Luo (1993). Applicability of the GUM to attitude testing is illustrated with real data. (SLD)
Immobilized unfolded cytochrome c acts as a catalyst for dioxygen reduction.
Tavagnacco, Claudio; Monari, Stefano; Ranieri, Antonio; Bortolotti, Carlo Augusto; Peressini, Silvia; Borsari, Marco
2011-10-21
Unfolding turns immobilized cytochrome c into a His-His ligated form endowed with catalytic activity towards O(2), which is absent in the native protein. Dioxygen could be used by naturally occurring unfolded cytochrome c as a substrate for the production of partially reduced oxygen species (PROS) contributing to the cell oxidative stress.
Using Data Augmentation and Markov Chain Monte Carlo for the Estimation of Unfolding Response Models
ERIC Educational Resources Information Center
Johnson, Matthew S.; Junker, Brian W.
2003-01-01
Unfolding response models, a class of item response theory (IRT) models that assume a unimodal item response function (IRF), are often used for the measurement of attitudes. Verhelst and Verstralen (1993)and Andrich and Luo (1993) independently developed unfolding response models by relating the observed responses to a more common monotone IRT…
ERIC Educational Resources Information Center
Van Deun, Katrijn; Heiser, Willem J.; Delbeke, Luc
2007-01-01
A multidimensional unfolding technique that is not prone to degenerate solutions and is based on multidimensional scaling of a complete data matrix is proposed: distance information about the unfolding data and about the distances both among judges and among objects is included in the complete matrix. The latter information is derived from the…
Modified Likelihood-Based Item Fit Statistics for the Generalized Graded Unfolding Model
ERIC Educational Resources Information Center
Roberts, James S.
2008-01-01
Orlando and Thissen (2000) developed an item fit statistic for binary item response theory (IRT) models known as S-X[superscript 2]. This article generalizes their statistic to polytomous unfolding models. Four alternative formulations of S-X[superscript 2] are developed for the generalized graded unfolding model (GGUM). The GGUM is a…
ERIC Educational Resources Information Center
Wang, Wen-Chung; Liu, Chen-Wei; Wu, Shiu-Lien
2013-01-01
The random-threshold generalized unfolding model (RTGUM) was developed by treating the thresholds in the generalized unfolding model as random effects rather than fixed effects to account for the subjective nature of the selection of categories in Likert items. The parameters of the new model can be estimated with the JAGS (Just Another Gibbs…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ali, E. S. M.; McEwen, M. R.; Rogers, D. W. O.
2012-11-15
Purpose: In a recent computational study, an improved physics-based approach was proposed for unfolding linac photon spectra and incident electron energies from transmission data. In this approach, energy differentiation is improved by simultaneously using transmission data for multiple attenuators and detectors, and the unfolding robustness is improved by using a four-parameter functional form to describe the photon spectrum. The purpose of the current study is to validate this approach experimentally, and to demonstrate its application on a typical clinical linac. Methods: The validation makes use of the recent transmission measurements performed on the Vickers research linac of National Research Councilmore » Canada. For this linac, the photon spectra were previously measured using a NaI detector, and the incident electron parameters are independently known. The transmission data are for eight beams in the range 10-30 MV using thick Be, Al and Pb bremsstrahlung targets. To demonstrate the approach on a typical clinical linac, new measurements are performed on an Elekta Precise linac for 6, 10 and 25 MV beams. The different experimental setups are modeled using EGSnrc, with the newly added photonuclear attenuation included. Results: For the validation on the research linac, the 95% confidence bounds of the unfolded spectra fall within the noise of the NaI data. The unfolded spectra agree with the EGSnrc spectra (calculated using independently known electron parameters) with RMS energy fluence deviations of 4.5%. The accuracy of unfolding the incident electron energy is shown to be {approx}3%. A transmission cutoff of only 10% is suitable for accurate unfolding, provided that the other components of the proposed approach are implemented. For the demonstration on a clinical linac, the unfolded incident electron energies and their 68% confidence bounds for the 6, 10 and 25 MV beams are 6.1 {+-} 0.1, 9.3 {+-} 0.1, and 19.3 {+-} 0.2 MeV, respectively. The unfolded spectra for the clinical linac agree with the EGSnrc spectra (calculated using the unfolded electron energies) with RMS energy fluence deviations of 3.7%. The corresponding measured and EGSnrc-calculated transmission data agree within 1.5%, where the typical transmission measurement uncertainty on the clinical linac is 0.4% (not including the uncertainties on the incident electron parameters). Conclusions: The approach proposed in an earlier study for unfolding photon spectra and incident electron energies from transmission data is accurate and practical for clinical use.« less
Forced-Unfolding and Force-Quench Refolding of RNA Hairpins
Hyeon, Changbong; Thirumalai, D.
2006-01-01
Nanomanipulation of individual RNA molecules, using laser optical tweezers, has made it possible to infer the major features of their energy landscape. Time-dependent mechanical unfolding trajectories, measured at a constant stretching force (fS) of simple RNA structures (hairpins and three-helix junctions) sandwiched between RNA/DNA hybrid handles show that they unfold in a reversible all-or-none manner. To provide a molecular interpretation of the experiments we use a general coarse-grained off-lattice Gō-like model, in which each nucleotide is represented using three interaction sites. Using the coarse-grained model we have explored forced-unfolding of RNA hairpin as a function of fS and the loading rate (rf). The simulations and theoretical analysis have been done both with and without the handles that are explicitly modeled by semiflexible polymer chains. The mechanisms and timescales for denaturation by temperature jump and mechanical unfolding are vastly different. The directed perturbation of the native state by fS results in a sequential unfolding of the hairpin starting from their ends, whereas thermal denaturation occurs stochastically. From the dependence of the unfolding rates on rf and fS we show that the position of the unfolding transition state is not a constant but moves dramatically as either rf or fS is changed. The transition-state movements are interpreted by adopting the Hammond postulate for forced-unfolding. Forced-unfolding simulations of RNA, with handles attached to the two ends, show that the value of the unfolding force increases (especially at high pulling speeds) as the length of the handles increases. The pathways for refolding of RNA from stretched initial conformation, upon quenching fS to the quench force fQ, are highly heterogeneous. The refolding times, upon force-quench, are at least an order-of-magnitude greater than those obtained by temperature-quench. The long fQ-dependent refolding times starting from fully stretched states are analyzed using a model that accounts for the microscopic steps in the rate-limiting step, which involves the trans to gauche transitions of the dihedral angles in the GAAA tetraloop. The simulations with explicit molecular model for the handles show that the dynamics of force-quench refolding is strongly dependent on the interplay of their contour length and persistence length and the RNA persistence length. Using the generality of our results, we also make a number of precise experimentally testable predictions. PMID:16473903
Bustamante, Carlos
2005-11-01
During the last 15 years, scientists have developed methods that permit the direct mechanical manipulation of individual molecules. Using this approach, they have begun to investigate the effect of force and torque in chemical and biochemical reactions. These studies span from the study of the mechanical properties of macromolecules, to the characterization of molecular motors, to the mechanical unfolding of individual proteins and RNA. Here I present a review of some of our most recent results using mechanical force to unfold individual molecules of RNA. These studies make it possible to follow in real time the trajectory of each molecule as it unfolds and characterize the various intermediates of the reaction. Moreover, if the process takes place reversibly it is possible to extract both kinetic and thermodynamic information from these experiments at the same time that we characterize the forces that maintain the three-dimensional structure of the molecule in solution. These studies bring us closer to the biological unfolding processes in the cell as they simulate in vitro, the mechanical unfolding of RNAs carried out in the cell by helicases. If the unfolding process occurs irreversibly, I show here that single-molecule experiments can still provide equilibrium, thermodynamic information from non-equilibrium data by using recently discovered fluctuation theorems. Such theorems represent a bridge between equilibrium and non-equilibrium statistical mechanics. In fact, first derived in 1997, the first experimental demonstration of the validity of fluctuation theorems was obtained by unfolding mechanically a single molecule of RNA. It is perhaps a sign of the times that important physical results are these days used to extract information about biological systems and that biological systems are being used to test and confirm fundamental new laws in physics.
Investigating the structural transitions of proteins during dissolution by mass spectrometry.
Gong, Xiaoyun; Xiong, Xingchuang; Qi, Lin; Fang, Xiang
2017-03-01
An appropriate solvent environment is essential for the implementation of biological functions of proteins. Interactions between protein residues and solvent molecules are of great importance for proteins to maintain their active structure and catalyze biochemical reactions. In this study, we investigated such interactions and studied the structural transitions of proteins during their dissolution process. Our previously developed technique, namely solvent assisted electric field induced desorption/ionization, was used for the dissolution and immediate ionization of proteins. Different solvents and proteins were involved in the investigation. According to the results, cytochrome c underwent significant unfolding during dissolution in the most commonly used NH 4 Ac buffer. The unfolding got more serious when the concentration of NH 4 Ac was further increased. Extending the dissolution time resulted in the re-folding of cytochrome c. In comparison, no unfolding was observed if cytochrome c was pre-dissolved in NH 4 Ac buffer and detected by nano-ESI. Furthermore, no unfolding was observed during the dissolution process of cytochrome c in water. Interactions between the residues of cytochrome c and the solute of NH 4 Ac might be the reason for the unfolding phenomenon. Similar unfolding phenomenon was observed on holo-myoglobin. However, the observed dissolution feature of insulin was different. No unfolding was observed on insulin during dissolution in NH 4 Ac buffers. Insulin underwent observable unfolding when water was used for dissolution. This might be due to the structural difference between different proteins. The obtained results in the present study furthered our insights into the interactions between proteins and the solvents during the phase transition of dissolution. Copyright © 2016 Elsevier B.V. All rights reserved.
Moczygemba, Charmaine; Guidry, Jesse; Jones, Kathryn L.; Gomes, Cláudio M.; Teixeira, Miguel; Wittung-Stafshede, Pernilla
2001-01-01
The ferredoxin from the thermophilic archaeon Acidianus ambivalens is a small monomeric seven-iron protein with a thermal midpoint (Tm) of 122°C (pH 7). To gain insight into the basis of its thermostability, we have characterized unfolding reactions induced chemically and thermally at various pHs. Thermal unfolding of this ferredoxin, in the presence of various guanidine hydrochloride (GuHCl) concentrations, yields a linear correlation between unfolding enthalpies (ΔH[Tm]) and Tm from which an upper limit for the heat capacity of unfolding (ΔCP) was determined to be 3.15 ± 0.1 kJ/(mole • K). Only by the use of the stronger denaturant guanidine thiocyanate (GuSCN) is unfolding of A. ambivalens ferredoxin at pH 7 (20°C) observed ([GuSCN]1/2 = 3.1 M; ΔGU[H2O] = 79 ± 8 kJ/mole). The protein is, however, less stable at low pH: At pH 2.5, Tm is 64 ± 1°C, and GuHCl-induced unfolding shows a midpoint at 2.3 M (ΔGU[H2O] = 20 ± 1 kJ/mole). These results support that electrostatic interactions contribute significantly to the stability. Analysis of the three-dimensional molecular model of the protein shows that there are several possible ion pairs on the surface. In addition, ferredoxin incorporates two iron–sulfur clusters and a zinc ion that all coordinate deprotonated side chains. The zinc remains bound in the unfolded state whereas the iron–sulfur clusters transiently form linear three-iron species (in pH range 2.5 to 10), which are associated with the unfolded polypeptide, before their complete degradation. PMID:11468351
Microscopic dynamics of water around unfolded structures of barstar at room temperature
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pal, Somedatta; Chakraborty, Kaushik; Khatua, Prabir
2015-02-07
The breaking of the native structure of a protein and its influences on the dynamic response of the surrounding solvent is an important issue in protein folding. In this work, we have carried out atomistic molecular dynamics simulations to unfold the protein barstar at two different temperatures (400 K and 450 K). The two unfolded forms obtained at such high temperatures are further studied at room temperature to explore the effects of nonuniform unfolding of the protein secondary structures along two different pathways on the microscopic dynamical properties of the surface water molecules. It is demonstrated that though the structuralmore » transition of the protein in general results in less restricted water motions around its segments, but there are evidences of formation of new conformational motifs upon unfolding with increasingly confined environment around them, thereby resulting in further restricted water mobility in their hydration layers. Moreover, it is noticed that the effects of nonuniform unfolding of the protein segments on the relaxation times of the protein–water (PW) and the water–water (WW) hydrogen bonds are correlated with hindered hydration water motions. However, the kinetics of breaking and reformation of such hydrogen bonds are found to be influenced differently at the interface. It is observed that while the effects of unfolding on the PW hydrogen bond kinetics seem to be minimum, but the kinetics involving the WW hydrogen bonds around the protein segments exhibit noticeably heterogeneous characteristics. We believe that this is an important observation, which can provide valuable insights on the origin of heterogeneous influence of unfolding of a protein on the microscopic properties of its hydration water.« less
Unfolding single- and multilayers
NASA Astrophysics Data System (ADS)
Llorens, Maria-Gema; Bons, Paul D.; Griera, Albert; Gomez-Rivas, Enrique
2014-05-01
When planar structures (e.g. sedimentary layers, veins, dykes, cleavages, etc.) are subjected to deformation, they have about equal chances to be shortened or stretched. The most common shortening and stretching structures are folds and boudinage, respectively. However, boudinage requires additional deformation mechanisms apart from viscous flow, like formation of fractures or strain localization. When folded layers are subjected to extension, they could potentially unfold back to straight layers. Although probably not uncommon, this would be difficult to recognize. Open questions are whether folded layers can unfold, what determines their mechanical behaviour and how we can recognize them in the field. In order to approach these questions, we present a series of numerical experiments that simulate stretching of previously folded single- and multi-layers in simple shear, using the two dimensional numerical modelling platform ELLE, including the finite element module BASIL that calculates viscous deformation. We investigate the parameters that affect a fold train once it rotates into the extensional field. The results show that the unfolding process strongly depends on the viscosity contrast between the layer and matrix (Llorens et al., 2013). Layers do not completely unfold when they experience softening before or during the stretching process or when other neighbouring competent layers prevent them from unfolding. The foliation refraction patterns are the main indicators of unfolded folds. Additionally, intrafolial folds and cusp-like folds adjacent to straight layers, as well as variations in fold amplitudes and limb lengths of irregular folds can also be used as indicators of stretching of a layer after shortening and folding. References: Llorens, M-.G., Bons, P.D., Griera, A. and Gomez-Rivas, E. 2013. When do folds unfold during progressive shear?. Geology, 41, 563-566.
Žoldák, Gabriel; Jancura, Daniel; Sedlák, Erik
2017-06-01
Monitoring the fluorescence of proteins, particularly the fluorescence of intrinsic tryptophan residues, is a popular method often used in the analysis of unfolding transitions (induced by temperature, chemical denaturant, and pH) in proteins. The tryptophan fluorescence provides several suitable parameters, such as steady-state fluorescence intensity, apparent quantum yield, mean fluorescence lifetime, position of emission maximum that are often utilized for the observation of the conformational/unfolding transitions of proteins. In addition, the fluorescence intensities ratio at different wavelengths (usually at 330 nm and 350 nm) is becoming an increasingly popular parameter for the evaluation of thermal transitions. We show that, under certain conditions, the use of this parameter for the analysis of unfolding transitions leads to the incorrect determination of thermodynamic parameters characterizing unfolding transitions in proteins (e.g., melting temperature) and, hence, can compromise the hit identification during high-throughput drug screening campaigns. © 2017 The Protein Society.
NASA Astrophysics Data System (ADS)
Tripathy, S. P.; Bakshi, A. K.; Sathian, V.; Tripathi, S. M.; Vega-carrillo, H. R.; Nandy, M.; Sarkar, P. K.; Sharma, D. N.
2009-01-01
The neutron spectra from a Pb-covered and a bare (without Pb-cover) 241Am-Be (α,n) source were measured using thermoluminescent detector (TLD) pairs of 6LiF and 7LiF with high-density polyethylene (HDPE) multi-spheres of seven different diameters. A total of 8 distinct neutron response signals (including a bare mode exposure) were obtained from which the energy distribution for the entire energy range was generated with the help of different neutron spectrum unfolding methods, viz. BUNKI, BUNKIUT and Frascati unfolding interactive tool (FRUIT). Shape of these spectra are matching very well and is also comparable with the standard IAEA 241Am-Be spectrum, thus, validating the unfolding methods used in this work. The effect of Pb-cover on the spectrum and the unfolding details are reported in the paper.
GroEL stimulates protein folding through forced unfolding
Lin, Zong; Madan, Damian; Rye, Hays S
2013-01-01
Many proteins cannot fold without the assistance of chaperonin machines like GroEL and GroES. The nature of this assistance, however, remains poorly understood. Here we demonstrate that unfolding of a substrate protein by GroEL enhances protein folding. We first show that capture of a protein on the open ring of a GroEL–ADP–GroES complex, GroEL’s physiological acceptor state for non-native proteins in vivo, leaves the substrate protein in an unexpectedly compact state. Subsequent binding of ATP to the same GroEL ring causes rapid, forced unfolding of the substrate protein. Notably, the fraction of the substrate protein that commits to the native state following GroES binding and protein release into the GroEL–GroES cavity is proportional to the extent of substrate-protein unfolding. Forced protein unfolding is thus a central component of the multilayered stimulatory mechanism used by GroEL to drive protein folding. PMID:18311152
Toward an atomistic description of the urea-denatured state of proteins.
Candotti, Michela; Esteban-Martín, Santiago; Salvatella, Xavier; Orozco, Modesto
2013-04-09
We present here the characterization of the structural, dynamics, and energetics of properties of the urea-denatured state of ubiquitin, a small prototypical soluble protein. By combining state-of-the-art molecular dynamics simulations with NMR and small-angle X-ray scattering data, we were able to: (i) define the unfolded state ensemble, (ii) understand the energetics stabilizing unfolded structures in urea, (iii) describe the dedifferential nature of the interactions of the fully unfolded proteins with urea and water, and (iv) characterize the early stages of protein refolding when chemically denatured proteins are transferred to native conditions. The results presented herein are unique in providing a complete picture of the chemically unfolded state of proteins and contribute to deciphering the mechanisms that stabilize the native state of proteins, as well as those that maintain them unfolded in the presence of urea.
Toward an atomistic description of the urea-denatured state of proteins
Candotti, Michela; Esteban-Martín, Santiago; Salvatella, Xavier; Orozco, Modesto
2013-01-01
We present here the characterization of the structural, dynamics, and energetics of properties of the urea-denatured state of ubiquitin, a small prototypical soluble protein. By combining state-of-the-art molecular dynamics simulations with NMR and small-angle X-ray scattering data, we were able to: (i) define the unfolded state ensemble, (ii) understand the energetics stabilizing unfolded structures in urea, (iii) describe the dedifferential nature of the interactions of the fully unfolded proteins with urea and water, and (iv) characterize the early stages of protein refolding when chemically denatured proteins are transferred to native conditions. The results presented herein are unique in providing a complete picture of the chemically unfolded state of proteins and contribute to deciphering the mechanisms that stabilize the native state of proteins, as well as those that maintain them unfolded in the presence of urea. PMID:23536295
Structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers
Feld, Geoffrey K.; Thoren, Katie L.; Kintzer, Alexander F.; Sterling, Harry J.; Tang, Iok I.; Greenberg, Shoshana G.; Williams, Evan R.; Krantz, Bryan A.
2011-01-01
The protein transporter, anthrax lethal toxin, is comprised of protective antigen (PA), a transmembrane translocase, and lethal factor (LF), a cytotoxic enzyme. Following assembly into holotoxin complexes, PA forms an oligomeric channel that unfolds LF and translocates it into the host cell. We report the crystal structure of the core of a lethal toxin complex to 3.1-Å resolution; the structure contains a PA octamer bound to four LF PA-binding domains (LFN). The first α helix and β strand of each LFN unfold and dock into a deep amphipathic cleft on the surface of the PA octamer, which we call the α clamp. The α clamp possesses nonspecific polypeptide binding activity and is functionally relevant to efficient holotoxin assembly, PA octamer formation, and LF unfolding and translocation. This structure provides insight on the mechanism of translocation-coupled protein unfolding. PMID:21037566
Signatures of unfolding in the early stages of protein denaturation
NASA Astrophysics Data System (ADS)
Gray, Harry B.; Winkler, Jay R.; Kozak, John J.
2012-04-01
A comparative study of the early stages of unfolding of five proteins: cyt c, c-b 562, cyt c‧, azurin, and lysozyme is reported. From crystallographic data, helical regions and intervening non-helical (or 'turning') regions are identified in each. Exploiting a previously introduced geometrical model, the paper describes quantitatively the stepwise extension of a polypeptide chain subject to the geometrical constraint that the spatial relationship among the residues of each triplet is fixed by native-state crystallographic data. Despite differences among the above-cited proteins, remarkable universality of behavior is found in the early stages of unfolding. At the very earliest stages, internal residues in each helical region have a common unfolding history; the terminal residues, however, are extraordinarily sensitive to structural perturbations. Residues in non-helical sections of the polypeptide unfold after residues in the internal helical regions, but with increasing steric perturbation playing a dominant role in advancing denaturation.
Development and Application of a High Throughput Protein Unfolding Kinetic Assay
Wang, Qiang; Waterhouse, Nicklas; Feyijinmi, Olusegun; Dominguez, Matthew J.; Martinez, Lisa M.; Sharp, Zoey; Service, Rachel; Bothe, Jameson R.; Stollar, Elliott J.
2016-01-01
The kinetics of folding and unfolding underlie protein stability and quantification of these rates provides important insights into the folding process. Here, we present a simple high throughput protein unfolding kinetic assay using a plate reader that is applicable to the studies of the majority of 2-state folding proteins. We validate the assay by measuring kinetic unfolding data for the SH3 (Src Homology 3) domain from Actin Binding Protein 1 (AbpSH3) and its stabilized mutants. The results of our approach are in excellent agreement with published values. We further combine our kinetic assay with a plate reader equilibrium assay, to obtain indirect estimates of folding rates and use these approaches to characterize an AbpSH3-peptide hybrid. Our high throughput protein unfolding kinetic assays allow accurate screening of libraries of mutants by providing both kinetic and equilibrium measurements and provide a means for in-depth ϕ-value analyses. PMID:26745729
Expansion and internal friction in unfolded protein chain.
Yasin, U Mahammad; Sashi, Pulikallu; Bhuyan, Abani K
2013-10-10
Similarities in global properties of homopolymers and unfolded proteins provide approaches to mechanistic description of protein folding. Here, hydrodynamic properties and relaxation rates of the unfolded state of carbonmonoxide-liganded cytochrome c (cyt-CO) have been measured using nuclear magnetic resonance and laser photolysis methods. Hydrodynamic radius of the unfolded chain gradually increases as the solvent turns increasingly better, consistent with theory. Curiously, however, the rate of intrachain contact formation also increases with an increasing denaturant concentration, which, by Szabo, Schulten, and Schulten theory for the rate of intramolecular contact formation in a Gaussian polymer, indicates growing intramolecular diffusion. It is argued that diminishing nonbonded atom interactions with increasing denaturant reduces internal friction and, thus, increases the rate of polypeptide relaxation. Qualitative scaling of the extent of unfolding with nonbonded repulsions allows for description of internal friction by a phenomenological model. The degree of nonbonded atom interactions largely determines the extent of internal friction.
Soft Vibrational Modes Predict Breaking Events during Force-Induced Protein Unfolding.
Habibi, Mona; Plotkin, Steven S; Rottler, Jörg
2018-02-06
We investigate the correlation between soft vibrational modes and unfolding events in simulated force spectroscopy of proteins. Unfolding trajectories are obtained from molecular dynamics simulations of a Gō model of a monomer of a mutant of superoxide dismutase 1 protein containing all heavy atoms in the protein, and a normal mode analysis is performed based on the anisotropic network model. We show that a softness map constructed from the superposition of the amplitudes of localized soft modes correlates with unfolding events at different stages of the unfolding process. Soft residues are up to eight times more likely to undergo disruption of native structure than the average amino acid. The memory of the softness map is retained for extensions of up to several nanometers, but decorrelates more rapidly during force drops. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Zeng, Xiaojun; Zhang, Liyun; Xiao, Xiuchan; Jiang, Yuanyuan; Guo, Yanzhi; Yu, Xinyan; Pu, Xuemei; Li, Menglong
2016-04-01
Thrombin-binding aptamer (TBA) with the sequence 5‧GGTTGGTGTGGTTGG3‧ could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation.
Characterization of the Protein Unfolding Processes Induced by Urea and Temperature
Rocco, Alessandro Guerini; Mollica, Luca; Ricchiuto, Piero; Baptista, António M.; Gianazza, Elisabetta; Eberini, Ivano
2008-01-01
Correct folding is critical for the biological activities of proteins. As a contribution to a better understanding of the protein (un)folding problem, we studied the effect of temperature and of urea on peptostreptococcal Protein L destructuration. We performed standard molecular dynamics simulations at 300 K, 350 K, 400 K, and 480 K, both in 10 M urea and in water. Protein L followed at least two alternative unfolding pathways. Urea caused the loss of secondary structure acting preferentially on the β-sheets, while leaving the α-helices almost intact; on the contrary, high temperature preserved the β-sheets and led to a complete loss of the α-helices. These data suggest that urea and high temperature act through different unfolding mechanisms, and protein secondary motives reveal a differential sensitivity to various denaturant treatments. As further validation of our results, replica-exchange molecular dynamics simulations of the temperature-induced unfolding process in the presence of urea were performed. This set of simulations allowed us to compute the thermodynamical parameters of the process and confirmed that, in the configurational space of Protein L unfolding, both of the above pathways are accessible, although to a different relative extent. PMID:18065481
The Role of Binding Site on the Mechanical Unfolding Mechanism of Ubiquitin
NASA Astrophysics Data System (ADS)
Cao, Penghui; Yoon, Gwonchan; Tao, Weiwei; Eom, Kilho; Park, Harold S.
2015-03-01
We apply novel atomistic simulations based on potential energy surface exploration to investigate the constant force-induced unfolding of ubiquitin. At the experimentally-studied force clamping level of 100 pN, we find a new unfolding mechanism starting with the detachment between β5 and β3 involving the binding site of ubiquitin, the Ile44 residue. This new unfolding pathway leads to the discovery of new intermediate configurations, which correspond to the end-to-end extensions previously seen experimentally. More importantly, it demonstrates the novel finding that the binding site of ubiquitin can be responsible not only for its biological functions, but also its unfolding dynamics. We also report in contrast to previous single molecule constant force experiments that when the clamping force becomes smaller than about 300 pN, the number of intermediate configurations increases dramatically, where almost all unfolding events at 100 pN involve an intermediate configuration. By directly calculating the life times of the intermediate configurations from the height of the barriers that were crossed on the potential energy surface, we demonstrate that these intermediate states were likely not observed experimentally due to their lifetimes typically being about two orders of magnitude smaller than the experimental temporal resolution.
Kowalik, Grzegorz T; Knight, Daniel S; Steeden, Jennifer A; Tann, Oliver; Odille, Freddy; Atkinson, David; Taylor, Andrew; Muthurangu, Vivek
2015-02-01
To develop a real-time phase contrast MR sequence with high enough temporal resolution to assess cardiac time intervals. The sequence utilized spiral trajectories with an acquisition strategy that allowed a combination of temporal encoding (Unaliasing by fourier-encoding the overlaps using the temporal dimension; UNFOLD) and parallel imaging (Sensitivity encoding; SENSE) to be used (UNFOLDed-SENSE). An in silico experiment was performed to determine the optimum UNFOLD filter. In vitro experiments were carried out to validate the accuracy of time intervals calculation and peak mean velocity quantification. In addition, 15 healthy volunteers were imaged with the new sequence, and cardiac time intervals were compared to reference standard Doppler echocardiography measures. For comparison, in silico, in vitro, and in vivo experiments were also carried out using sliding window reconstructions. The in vitro experiments demonstrated good agreement between real-time spiral UNFOLDed-SENSE phase contrast MR and the reference standard measurements of velocity and time intervals. The protocol was successfully performed in all volunteers. Subsequent measurement of time intervals produced values in keeping with literature values and good agreement with the gold standard echocardiography. Importantly, the proposed UNFOLDed-SENSE sequence outperformed the sliding window reconstructions. Cardiac time intervals can be successfully assessed with UNFOLDed-SENSE real-time spiral phase contrast. Real-time MR assessment of cardiac time intervals may be beneficial in assessment of patients with cardiac conditions such as diastolic dysfunction. © 2014 Wiley Periodicals, Inc.
Declining global warming effects on the phenology of spring leaf unfolding.
Fu, Yongshuo H; Zhao, Hongfang; Piao, Shilong; Peaucelle, Marc; Peng, Shushi; Zhou, Guiyun; Ciais, Philippe; Huang, Mengtian; Menzel, Annette; Peñuelas, Josep; Song, Yang; Vitasse, Yann; Zeng, Zhenzhong; Janssens, Ivan A
2015-10-01
Earlier spring leaf unfolding is a frequently observed response of plants to climate warming. Many deciduous tree species require chilling for dormancy release, and warming-related reductions in chilling may counteract the advance of leaf unfolding in response to warming. Empirical evidence for this, however, is limited to saplings or twigs in climate-controlled chambers. Using long-term in situ observations of leaf unfolding for seven dominant European tree species at 1,245 sites, here we show that the apparent response of leaf unfolding to climate warming (ST, expressed in days advance of leaf unfolding per °C warming) has significantly decreased from 1980 to 2013 in all monitored tree species. Averaged across all species and sites, ST decreased by 40% from 4.0 ± 1.8 days °C(-1) during 1980-1994 to 2.3 ± 1.6 days °C(-1) during 1999-2013. The declining ST was also simulated by chilling-based phenology models, albeit with a weaker decline (24-30%) than observed in situ. The reduction in ST is likely to be partly attributable to reduced chilling. Nonetheless, other mechanisms may also have a role, such as 'photoperiod limitation' mechanisms that may become ultimately limiting when leaf unfolding dates occur too early in the season. Our results provide empirical evidence for a declining ST, but also suggest that the predicted strong winter warming in the future may further reduce ST and therefore result in a slowdown in the advance of tree spring phenology.
Mark, M R; Scadden, D T; Wang, Z; Gu, Q; Goddard, A; Godowski, P J
1994-04-08
We have isolated cDNA clones that encode the human and murine forms of a novel receptor-type tyrosine kinase termed Rse. Sequence analysis indicates that human Rse contains 890 amino acids, with an extracellular region composed of two immunoglobulin-like domains followed by two fibronectin type III domains. Murine Rse contains 880 amino acids and shares 90% amino acid identity with its human counterpart. Rse is structurally similar to the receptor-type tyrosine kinase Axl/Ufo, and the two proteins have 35 and 63% sequence identity in their extracellular and intracellular domains, respectively. To study the synthesis and activation of this putative receptor-type tyrosine kinase, we constructed a version of Rse (termed gD-Rse, where gD represents glycoprotein D) that contains an NH2-terminal epitope tag. NIH3T3 cells were engineered to express gD-Rse, which could be detected at the cell surface by fluorescence-activated cell sorting. Moreover, gD-Rse was rapidly phosphorylated on tyrosine residues upon incubation of the cells with an antibody directed against the epitope tag, suggesting that rse encodes an active tyrosine kinase. In the human tissues we examined, the highest level of expression of rse mRNA was observed in the brain; rse mRNA was also detected in the premegakaryocytopoietic cell lines CMK11-5 and Dami. The gene for rse was localized to human chromosome 15.
Yang, A S; Honig, B
1994-04-15
A recently developed approach to calculate the pH dependence of protein stability from three-dimensional structure information is applied to the analysis of acid denaturation of sperm whale apomyoglobin. The finite difference Poisson-Boltzmann method is used to calculate pKa values and these are used to obtain titration curves for the folded protein as well as for compact intermediates. The total electrostatic free energy change involved in apomyoglobin unfolding is then evaluated. Calculations are carried out of the unfolding free energy of the native (N) and the compact intermediate (I) of apomyoglobin relative to the unfolded state (U) over a range of pH at various ionic strengths. The contributions from key ionizable groups to the unfolding process are discussed. For the acid-induced partial unfolding of apomyoglobin near pH 5, the transition from N to I is found to be driven by three histidines that are exposed when the B, C, D and E helices unfold. Similarly, the unfolding of the compact intermediate I consisting of the A, G and H helices is driven primarily by a few carboxylic acids with low pKa values in the compact state. This picture is in contrast to the view which attributes acid denaturation to electrostatic repulsion resulting from the build up of positive charge. In fact, charge-charge interactions in myoglobin are found to be attractive at all pH values where the protein unfolds. pH-dependent changes in these interactions contribute to acid denaturation but other electrostatic effects, such as hydrogen bonding and solvation, are important as well. The effect of increasing ionic strength on unfolding is attributed to the decrease of attractive charge-charge interactions which destabilize the N state relative to I, but stabilize the I state relative to U by reducing the pKa shifts of a few critical carboxylic acids. The I state is found to be more stable than U at neutral pH thus accounting for its presence as an intermediate on the protein folding pathway. Our results have implications for the origins of compact intermediates or "molten globule" states.
Cerminara, Michele; Campos, Luis A.; Ramanathan, Ravishankar; Muñoz, Victor
2013-01-01
A battery of thermodynamic, kinetic, and structural approaches has indicated that the small α-helical protein BBL folds-unfolds via the one-state downhill scenario. Yet, single-molecule fluorescence spectroscopy offers a more conflicting view. Single-molecule experiments at pH 6 show a unique half-unfolded conformational ensemble at mid denaturation, whereas other experiments performed at higher pH show a bimodal distribution, as expected for two-state folding. Here we use thermodynamic and laser T-jump kinetic experiments combined with theoretical modeling to investigate the pH dependence of BBL stability, folding kinetics and mechanism within the pH 6–11 range. We find that BBL unfolding is tightly coupled to the protonation of one of its residues with an apparent pKa of ∼7. Therefore, in chemical denaturation experiments around neutral pH BBL unfolds gradually, and also converts in binary fashion to the protonated species. Moreover, under the single-molecule experimental conditions (denaturant midpoint and 279 K), we observe that proton transfer is much slower than the ∼15 microseconds folding-unfolding kinetics of BBL. The relaxation kinetics is distinctly biphasic, and the overall relaxation time (i.e. 0.2–0.5 ms) becomes controlled by the proton transfer step. We then show that a simple theoretical model of protein folding coupled to proton transfer explains quantitatively all these results as well as the two sets of single-molecule experiments, including their more puzzling features. Interestingly, this analysis suggests that BBL unfolds following a one-state downhill folding mechanism at all conditions. Accordingly, the source of the bimodal distributions observed during denaturation at pH 7–8 is the splitting of the unique conformational ensemble of BBL onto two slowly inter-converting protonation species. Both, the unprotonated and protonated species unfold gradually (one-state downhill), but they exhibit different degree of unfolding at any given condition because the native structure is less stable for the protonated form. PMID:24205082
Das, Atanu; Mukhopadhyay, Chaitali
2007-10-28
We have performed molecular dynamics (MD) simulation of the thermal denaturation of one protein and one peptide-ubiquitin and melittin. To identify the correlation in dynamics among various secondary structural fragments and also the individual contribution of different residues towards thermal unfolding, principal component analysis method was applied in order to give a new insight to protein dynamics by analyzing the contribution of coefficients of principal components. The cross-correlation matrix obtained from MD simulation trajectory provided important information regarding the anisotropy of backbone dynamics that leads to unfolding. Unfolding of ubiquitin was found to be a three-state process, while that of melittin, though smaller and mostly helical, is more complicated.
NASA Astrophysics Data System (ADS)
Das, Atanu; Mukhopadhyay, Chaitali
2007-10-01
We have performed molecular dynamics (MD) simulation of the thermal denaturation of one protein and one peptide—ubiquitin and melittin. To identify the correlation in dynamics among various secondary structural fragments and also the individual contribution of different residues towards thermal unfolding, principal component analysis method was applied in order to give a new insight to protein dynamics by analyzing the contribution of coefficients of principal components. The cross-correlation matrix obtained from MD simulation trajectory provided important information regarding the anisotropy of backbone dynamics that leads to unfolding. Unfolding of ubiquitin was found to be a three-state process, while that of melittin, though smaller and mostly helical, is more complicated.
Odijk excluded volume interactions during the unfolding of DNA confined in a nanochannel.
Reifenberger, Jeffrey G; Cao, Han; Dorfman, Kevin D
2018-02-13
We report experimental data on the unfolding of human and E. coli genomic DNA molecules shortly after injection into a 45 nm nanochannel. The unfolding dynamics are deterministic, consistent with previous experiments and modeling in larger channels, and do not depend on the biological origin of the DNA. The measured entropic unfolding force per friction per unit contour length agrees with that predicted by combining the Odijk excluded volume with numerical calculations of the Kirkwood diffusivity of confined DNA. The time scale emerging from our analysis has implications for genome mapping in nanochannels, especially as the technology moves towards longer DNA, by setting a lower bound for the delay time before making a measurement.
NASA Astrophysics Data System (ADS)
Vaattovaara, P.; Huttunen, P. E.; Yoon, Y. J.; Joutsensaari, J.; Lehtinen, K. E. J.; O'Dowd, C. D.; Laaksonen, A.
2006-04-01
Newly-formed nanometer-sized particles have been observed at coastal and marine environments worldwide. Interestingly, organic species have so far not been detected in those newly-formed nucleation mode particles. In this study, we applied the UFO-TDMA (ultrafine organic tandem differential mobility analyzer) method to study the possible existence of an organic fraction in recently formed coastal nucleation mode particles (d<20 nm) at the Mace Head research station. Furthermore, effects of those nucleation events to potential CCN (cloud condensation nuclei) were studied. The coastal events were typical for the Mace Head region and they occurred at low tide conditions during efficient solar radiation and high biological activity (HBA, i.e. a high mass concentration of chlorophyll a of the ocean) in spring 2002. Additionally, a PHA-UCPC (pulse height analyzer ultrafine condensation particle counter) technique was used to study the composition of newly-formed particles formed in low tide conditions during a lower biological activity (LBA, i.e. a lower mass concentration of chlorophyll a of the ocean) in October 2002. The overall results of the UFO-TDMA and the PHA-UCPC measurements indicate that those coastally/marinely formed nucleation mode particles include a remarkable fraction of secondary organic products, beside iodine oxides, which are likely to be responsible for the nucleation. During clean marine air mass conditions, the origin of those secondary organic oxidation compounds can be related to marine/coastal biota and thus a major fraction of the organics may originate from biosynthetic production of alkenes such as isoprene and their oxidation by iodine, hydroxyl radical, and ozone. During modified marine conditions, also anthropogenic secondary organic compounds may contribute to the nucleation mode organic mass, in addition to biogenic secondary organic compounds. Thus, the UFO-TDMA results suggest that the secondary organic compounds may, in addition to being significant contributors to the nucleation mode processes, accelerate the growth of freshly nucleated particles and increase their survival probability to CCN and even larger radiatively active particle sizes. The results give new insights to the coastal/marine particle formation, growth, and properties. The marine biota driven secondary organic contributions to coastal/marine particle formation and composition can be anticipated in other species specific biologically active oceans and fresh-waters areas around the world and thus, they may be significant also to the global radiative bugdet, atmosphere-biosphere feedbacks, and climate change.
Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine
Aubin-Tam, Marie-Eve; Olivares, Adrian O.; Sauer, Robert T.; Baker, Tania A.; Lang, Matthew J.
2011-01-01
All cells employ ATP-powered proteases for protein-quality control and regulation. In the ClpXP protease, ClpX is a AAA+ machine that recognizes specific protein substrates, unfolds these molecules, and then translocates the denatured polypeptide through a central pore and into ClpP for degradation. Here, we use optical-trapping nanometry to probe the mechanics of enzymatic unfolding and translocation of single molecules of a multidomain substrate. Our experiments demonstrate the capacity of ClpXP and ClpX to perform mechanical work under load, reveal very fast and highly cooperative unfolding of individual substrate domains, suggest a translocation step size of 5–8 amino acids, and support a power-stroke model of denaturation in which successful enzyme-mediated unfolding of stable domains requires coincidence between mechanical pulling by the enzyme and a transient stochastic reduction in protein stability. We anticipate that single-molecule studies of the mechanical properties of other AAA+ proteolytic machines will reveal many shared features with ClpXP. PMID:21496645
ERIC Educational Resources Information Center
Roberts, James S.; Donoghue, John R.; Laughlin, James E.
The generalized graded unfolding model (J. Roberts, J. Donoghue, and J. Laughlin, 1998, 1999) is an item response theory model designed to unfold polytomous responses. The model is based on a proximity relation that postulates higher levels of expected agreement with a given statement to the extent that a respondent is located close to the…
Mechanisms of m-cresol induced protein aggregation studied using a model protein cytochrome c†
Singh, Surinder M.; Hutchings, Regina L.; Mallela, Krishna M.G.
2014-01-01
Multi-dose protein formulations require an effective antimicrobial preservative (AP) to inhibit microbial growth during long-term storage of unused formulations. m-cresol is one such AP, but has been shown to cause protein aggregation. However, the fundamental physical mechanisms underlying such AP-induced protein aggregation are not understood. In this study, we used a model protein cytochrome c to identify the protein unfolding that triggers protein aggregation. m-cresol induced cytochrome c aggregation at preservative concentrations that are commonly used to inhibit microbial growth. Addition of m-cresol decreased the temperature at which the protein aggregated and increased the aggregation rate. However, m-cresol did not perturb the tertiary or secondary structure of cytochrome c. Instead, it populated an “invisible” partially unfolded intermediate where a local protein region around the methionine residue at position 80 was unfolded. Stabilizing the Met80 region drastically decreased the protein aggregation, which conclusively shows that this local protein region acts as an aggregation “hot-spot”. Based on these results, we propose that APs induce protein aggregation by partial rather than global unfolding. Because of the availability of site-specific probes to monitor different levels of protein unfolding, cytochrome c provided a unique advantage in characterizing the partial protein unfolding that triggers protein aggregation. PMID:21229618
Yan, Chunli; Pattani, Varun; Tunnell, James W.; Ren, Pengyu
2010-01-01
Thermal disruption of protein structure and function is a potentially powerful therapeutic vehicle. With the emerging nanoparticle-targeting and femtosecond laser technology, it is possible to deliver heating locally to specific molecules. It is therefore important to understand how fast a protein can unfold or lose its function at high temperatures, such as near the water boiling point. In this study, the thermal damage of EGF was investigated by combining the replica exchange (136 replicas) and conventional molecular dynamics simulations. The REMD simulation was employed to rigorously explore the free energy landscape of EGF unfolding. Interestingly, besides the native and unfolded states, we also observed a distinct molten globule (MG) state that retained substantial amount of native contacts. Based on the understanding that which the unfolding of EGF is a three-state process, we have examined the unfolding kinetics of EGF (N→ MG→h multiple 20-ns conventional MD simulations. The Arrhenius prefactors and activation energy barriers determined from the simulation are within the range of previously studied proteins. In contrast to the thermal damage of cells and tissues which take place on the time scale of seconds to hours at relatively low temperatures, the denaturation of proteins occur in nanoseconds when the temperature of heat bath approaches the boiling point. PMID:20466569
Chen, Kai-Chun; Xu, Ming; Wedemeyer, William J.; Roder, Heinrich
2011-01-01
The microsecond folding and unfolding kinetics of ovine prion proteins (ovPrP) were measured under various solution conditions. A fragment comprising residues 94–233 of the full-length ovPrP was studied for four variants with differing susceptibilities to classical scrapie in sheep. The observed biexponential unfolding kinetics of ovPrP provides evidence for an intermediate species. However, in contrast to previous results for human PrP, there is no evidence for an intermediate under refolding conditions. Global analysis of the kinetic data, based on a sequential three-state mechanism, quantitatively accounts for all folding and unfolding data as a function of denaturant concentration. The simulations predict that an intermediate accumulates under both folding and unfolding conditions, but is observable only in unfolding experiments because the intermediate is optically indistinguishable from the native state. The relative population of intermediates in two ovPrP variants, both transiently and under destabilizing equilibrium conditions, correlates with their propensities for classical scrapie. The variant susceptible to classical scrapie has a larger population of the intermediate state than the resistant variant. Thus, the susceptible variant should be favored to undergo the PrPC to PrPSc conversion and oligomerization. PMID:21889460
A hypothesis to reconcile the physical and chemical unfolding of proteins
de Oliveira, Guilherme A. P.; Silva, Jerson L.
2015-01-01
High pressure (HP) or urea is commonly used to disturb folding species. Pressure favors the reversible unfolding of proteins by causing changes in the volumetric properties of the protein–solvent system. However, no mechanistic model has fully elucidated the effects of urea on structure unfolding, even though protein–urea interactions are considered to be crucial. Here, we provide NMR spectroscopy and 3D reconstructions from X-ray scattering to develop the “push-and-pull” hypothesis, which helps to explain the initial mechanism of chemical unfolding in light of the physical events triggered by HP. In studying MpNep2 from Moniliophthora perniciosa, we tracked two cooperative units using HP-NMR as MpNep2 moved uphill in the energy landscape; this process contrasts with the overall structural unfolding that occurs upon reaching a threshold concentration of urea. At subdenaturing concentrations of urea, we were able to trap a state in which urea is preferentially bound to the protein (as determined by NMR intensities and chemical shifts); this state is still folded and not additionally exposed to solvent [fluorescence and small-angle X-ray scattering (SAXS)]. This state has a higher susceptibility to pressure denaturation (lower p1/2 and larger ΔVu); thus, urea and HP share concomitant effects of urea binding and pulling and water-inducing pushing, respectively. These observations explain the differences between the molecular mechanisms that control the physical and chemical unfolding of proteins, thus opening up new possibilities for the study of protein folding and providing an interpretation of the nature of cooperativity in the folding and unfolding processes. PMID:25964355
Thermal unfolding of tetrameric melittin: comparison with the molten globule state of cytochrome c.
Hagihara, Y.; Oobatake, M.; Goto, Y.
1994-01-01
Whereas melittin at micromolar concentrations is unfolded under conditions of low salt at neutral pH, it transforms to a tetrameric alpha-helical structure under several conditions, such as high peptide concentration, high anion concentration, or alkaline pH. The anion- and pH-dependent stabilization of the tetrameric structure is similar to that of the molten globule state of several acid-denatured proteins, suggesting that tetrameric melittin might be a state similar to the molten globule state. To test this possibility, we studied the thermal unfolding of tetrameric melittin using far-UV CD and differential scanning calorimetry. The latter technique revealed a broad but distinct heat absorption peak. The heat absorption curves were consistent with the unfolding transition observed by CD and were explainable by a 2-state transition mechanism between the tetrameric alpha-helical state and the monomeric unfolded state. From the peptide or salt-concentration dependence of unfolding, the heat capacity change upon unfolding was estimated to be 5 kJ (mol of tetramer)-1 K-1 at 30 degrees C and decreased with increasing temperature. The observed change in heat capacity was much smaller than that predicted from the crystallographic structure (9.2 kJ (mol of tetramer)-1 K-1), suggesting that the hydrophobic residues of tetrameric melittin in solution are exposed in comparison with the crystallographic structure. However, the results also indicate that the structure is more ordered than that of a typical molten globule state. We consider that the conformation is intermediate between the molten globule state and the native state of globular proteins. PMID:7833804
A neutron spectrum unfolding computer code based on artificial neural networks
NASA Astrophysics Data System (ADS)
Ortiz-Rodríguez, J. M.; Reyes Alfaro, A.; Reyes Haro, A.; Cervantes Viramontes, J. M.; Vega-Carrillo, H. R.
2014-02-01
The Bonner Spheres Spectrometer consists of a thermal neutron sensor placed at the center of a number of moderating polyethylene spheres of different diameters. From the measured readings, information can be derived about the spectrum of the neutron field where measurements were made. Disadvantages of the Bonner system are the weight associated with each sphere and the need to sequentially irradiate the spheres, requiring long exposure periods. Provided a well-established response matrix and adequate irradiation conditions, the most delicate part of neutron spectrometry, is the unfolding process. The derivation of the spectral information is not simple because the unknown is not given directly as a result of the measurements. The drawbacks associated with traditional unfolding procedures have motivated the need of complementary approaches. Novel methods based on Artificial Intelligence, mainly Artificial Neural Networks, have been widely investigated. In this work, a neutron spectrum unfolding code based on neural nets technology is presented. This code is called Neutron Spectrometry and Dosimetry with Artificial Neural networks unfolding code that was designed in a graphical interface. The core of the code is an embedded neural network architecture previously optimized using the robust design of artificial neural networks methodology. The main features of the code are: easy to use, friendly and intuitive to the user. This code was designed for a Bonner Sphere System based on a 6LiI(Eu) neutron detector and a response matrix expressed in 60 energy bins taken from an International Atomic Energy Agency compilation. The main feature of the code is that as entrance data, for unfolding the neutron spectrum, only seven rate counts measured with seven Bonner spheres are required; simultaneously the code calculates 15 dosimetric quantities as well as the total flux for radiation protection purposes. This code generates a full report with all information of the unfolding in the HTML format. NSDann unfolding code is freely available, upon request to the authors.
Exploration of oxide-based diluted magnetic semiconductors toward transparent spintronics
NASA Astrophysics Data System (ADS)
Fukumura, T.; Yamada, Y.; Toyosaki, H.; Hasegawa, T.; Koinuma, H.; Kawasaki, M.
2004-02-01
A review is given for the recent progress of research in the field of oxide-based diluted magnetic semiconductor (DMS), which was triggered by combinatorial discovery of transparent ferromagnet. The possible advantages of oxide semiconductor as a host of DMS are described in comparison with conventional compound semiconductors. Limits and problems for identifying novel ferromagnetic DMS are described in view of recent reports in this field. Several characterization techniques are proposed in order to eliminate unidentified ferromagnetism of oxide-based DMS unidentified ferromagnetic oxide (UFO). Perspectives and possible devices are also given.
Removing micron size particles from coal liquids
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rodgers, B.R.; Westmoreland, P.R.
This paper reports results of an investigation which was undertaken in order to improve purification of liquid fuels obtained by coal liquefaction processes. It is shown that settling and filtration rates increased substantially after agglomeration. And, ground coal was found to be an economical substitute for diatomaceous earth in filtration. The effects of certain solvents on the agglomerating tendencies of solids in the unfiltered oil (UFO) from the SRC and COED processes were determined by oil immersion microscopy. The significant results obtained by these experiments are listed. Economic advantages are presented. 13 references.
The Effects of Stellar Dynamics on the Evolution of Young, Dense Stellar Systems
NASA Astrophysics Data System (ADS)
Belkus, H.; van Bever, J.; Vanbeveren, D.
In this paper, we report on first results of a project in Brussels in which we study the effects of stellar dynamics on the evolution of young dense stellar systems using 3 decades of expertise in massive-star evolution and our population (number and spectral) synthesis code. We highlight an unconventionally formed object scenario (UFO-scenario) for Wolf Rayet binaries and study the effects of a luminous blue variable-type instability wind mass-loss formalism on the formation of intermediate-mass black holes.
Alarm!!! A UFO inside the heart.
Santoro, Giuseppe; Castaldi, Biagio; Iacono, Carola; Giugno, Luca; Gaio, Gianpiero; Russo, Maria G
2012-10-01
An 8-year-old asymptomatic child was referred for surgical repair of coronary sinus atrial septal defect resulting in significant left-to-right shunt and right chamber volume overload. The septal fenestration was located near to its drainage site into the right atrium. Due to this seemingly favourable anatomy, transcatheter closure of the septal defect was performed using an Amplatzer Septal Occluder device. The echocardiographic postprocedural evaluation imaged the occluding device almost perpendicular to the atrial septum, seemingly floating above the mitral valve orifice, like an alien spaceship inside the heart.
Rapidly variable relatvistic absorption
NASA Astrophysics Data System (ADS)
Parker, M.; Pinto, C.; Fabian, A.; Lohfink, A.; Buisson, D.; Alston, W.; Jiang, J.
2017-10-01
I will present results from the 1.5Ms XMM-Newton observing campaign on the most X-ray variable AGN, IRAS 13224-3809. We find a series of nine absorption lines with a velocity of 0.24c from an ultra-fast outflow. For the first time, we are able to see extremely rapid variability of the UFO features, and can link this to the X-ray variability from the inner accretion disk. We find a clear flux dependence of the outflow features, suggesting that the wind is ionized by increasing X-ray emission.
Ultra high frequency follow-on communications satellite system
NASA Astrophysics Data System (ADS)
Hassien, Michael J.
1992-03-01
The existing constellation of UHF communications satellites (LEASAT and FLTSAT) provide key command and control links for mobile forces of the DoD and other government agencies. The UHF Follow-On satellite program will provide for a new generation of communications satellites to replace the existing ones as they reach the end of their life cycle beginning in 1992. Continued coverage is required for both peacetime and crisis environments, and must be maintained indefinitely. An eight-satellite UFO constellation (two per coverage area) will replenish the existing FLTSATCOM constellation.
Unfolding sphere size distributions with a density estimator based on Tikhonov regularization
DOE Office of Scientific and Technical Information (OSTI.GOV)
Weese, J.; Korat, E.; Maier, D.
1997-12-01
This report proposes a method for unfolding sphere size distributions given a sample of radii that combines the advantages of a density estimator with those of Tikhonov regularization methods. The following topics are discusses in this report to achieve this method: the relation between the profile and the sphere size distribution; the method for unfolding sphere size distributions; the results based on simulations; and the experimental data comparison.
NASA Astrophysics Data System (ADS)
Yeh, Chun-Ping; Huang, Jiunn-Yuan
2018-04-01
Low-alloy steels used as structural materials in nuclear power plants are subjected to cyclic stresses during power plant operations. As a result, cracks may develop and propagate through the material. The alternating current potential drop technique is used to measure the lengths of cracks in metallic components. The depth of the penetration of the alternating current is assumed to be small compared to the crack length. This assumption allows the adoption of the unfolding technique to simplify the problem to a surface Laplacian field. The numerical modelling of the electric potential and current density distribution prediction model for a compact tension specimen and the unfolded crack model are presented in this paper. The goal of this work is to conduct numerical simulations to reduce deviations occurring in the crack length measurements. Numerical simulations were conducted on AISI 4340 low-alloy steel with different crack lengths to evaluate the electric potential distribution. From the simulated results, an optimised position for voltage measurements in the crack region was proposed.
Folding and unfolding phylogenetic trees and networks.
Huber, Katharina T; Moulton, Vincent; Steel, Mike; Wu, Taoyang
2016-12-01
Phylogenetic networks are rooted, labelled directed acyclic graphswhich are commonly used to represent reticulate evolution. There is a close relationship between phylogenetic networks and multi-labelled trees (MUL-trees). Indeed, any phylogenetic network N can be "unfolded" to obtain a MUL-tree U(N) and, conversely, a MUL-tree T can in certain circumstances be "folded" to obtain aphylogenetic network F(T) that exhibits T. In this paper, we study properties of the operations U and F in more detail. In particular, we introduce the class of stable networks, phylogenetic networks N for which F(U(N)) is isomorphic to N, characterise such networks, and show that they are related to the well-known class of tree-sibling networks. We also explore how the concept of displaying a tree in a network N can be related to displaying the tree in the MUL-tree U(N). To do this, we develop aphylogenetic analogue of graph fibrations. This allows us to view U(N) as the analogue of the universal cover of a digraph, and to establish a close connection between displaying trees in U(N) and reconciling phylogenetic trees with networks.
An interactive Doppler velocity dealiasing scheme
NASA Astrophysics Data System (ADS)
Pan, Jiawen; Chen, Qi; Wei, Ming; Gao, Li
2009-10-01
Doppler weather radars are capable of providing high quality wind data at a high spatial and temporal resolution. However, operational application of Doppler velocity data from weather radars is hampered by the infamous limitation of the velocity ambiguity. This paper reviews the cause of velocity folding and presents the unfolding method recently implemented for the CINRAD systems. A simple interactive method for velocity data, which corrects de-aliasing errors, has been developed and tested. It is concluded that the algorithm is very efficient and produces high quality velocity data.
Efficient dynamic optimization of logic programs
NASA Technical Reports Server (NTRS)
Laird, Phil
1992-01-01
A summary is given of the dynamic optimization approach to speed up learning for logic programs. The problem is to restructure a recursive program into an equivalent program whose expected performance is optimal for an unknown but fixed population of problem instances. We define the term 'optimal' relative to the source of input instances and sketch an algorithm that can come within a logarithmic factor of optimal with high probability. Finally, we show that finding high-utility unfolding operations (such as EBG) can be reduced to clause reordering.
NASA Astrophysics Data System (ADS)
Casoli, P.; Authier, N.; Jacquet, X.; Cartier, J.
2014-04-01
Caliban and Prospero are two highly enriched uranium metallic core reactors operated on the CEA Center of Valduc. These critical assemblies are suitable for integral experiments, such as fission yields measurements or perturbation measurements, which have been carried out recently on the Caliban reactor. Different unfolding methods, based on activation foils and fission chambers measurements, are used to characterize the reactor spectra and especially the Caliban spectrum, which is very close to a pure fission spectrum.
Meinhold, Derrick W.; Wright, Peter E.
2011-01-01
Detailed understanding of protein function and malfunction hinges on the ability to characterize transiently populated states and the transitions between them. Here, we use 15N, , and 13CO NMR R2 relaxation dispersion to investigate spontaneous unfolding and refolding events of native apomyoglobin. Above pH 5.0, dispersion is dominated by processes involving fluctuations of the F-helix region, which is invisible in NMR spectra. Measurements of R2 dispersion for residues contacted by the F-helix region in the native (N) structure reveal a transient state formed by local unfolding of helix F and undocking from the protein core. A similar state was detected at pH 4.75–4.95 and determined to be an on-pathway intermediate (I1) in a linear three-state unfolding scheme (N⇆I1⇆MG) leading to a transiently populated molten globule (MG) state. The slowest steps in unfolding and refolding are N → I1 (36 s-1) and MG → I1 (26 s-1), respectively. Differences in chemical shift between N and I1 are very small, except in regions adjacent to helix F, showing that their core structures are similar. Chemical shift changes between the N and MG states, obtained from R2 dispersion, reveal that the transient MG state is structurally similar to the equilibrium MG observed previously at high temperature and low pH. Analysis of MG state chemical shifts shows the location of residual helical structure in the transient intermediate and identifies regions that unfold or rearrange into nonnative structure during the N → MG transition. The experiments also identify regions of energetic frustration that “crack” during unfolding and impede the refolding process. PMID:21562212
Spontaneous Unfolding-Refolding of Fibronectin Type III Domains Assayed by Thiol Exchange
Shah, Riddhi; Ohashi, Tomoo; Erickson, Harold P.; Oas, Terrence G.
2017-01-01
Globular proteins are not permanently folded but spontaneously unfold and refold on time scales that can span orders of magnitude for different proteins. A longstanding debate in the protein-folding field is whether unfolding rates or folding rates correlate to the stability of a protein. In the present study, we have determined the unfolding and folding kinetics of 10 FNIII domains. FNIII domains are one of the most common protein folds and are present in 2% of animal proteins. FNIII domains are ideal for this study because they have an identical seven-strand β-sandwich structure, but they vary widely in sequence and thermodynamic stability. We assayed thermodynamic stability of each domain by equilibrium denaturation in urea. We then assayed the kinetics of domain opening and closing by a technique known as thiol exchange. For this we introduced a buried Cys at the identical location in each FNIII domain and measured the kinetics of labeling with DTNB over a range of urea concentrations. A global fit of the kinetics data gave the kinetics of spontaneous unfolding and refolding in zero urea. We found that the folding rates were relatively similar, ∼0.1–1 s−1, for the different domains. The unfolding rates varied widely and correlated with thermodynamic stability. Our study is the first to address this question using a set of domains that are structurally homologous but evolved with widely varying sequence identity and thermodynamic stability. These data add new evidence that thermodynamic stability correlates primarily with unfolding rate rather than folding rate. The study also has implications for the question of whether opening of FNIII domains contributes to the stretching of fibronectin matrix fibrils. PMID:27909052
Carr, Carolyn E; Khutsishvili, Irine; Marky, Luis A
2018-06-22
Triplex formation occurs via interaction of a third strand with the major groove of double stranded nucleic acid, through Hoogsteen hydrogen bonding. In this work, we use a combination of temperature-dependent UV spectroscopy and differential scanning calorimetry to determine complete thermodynamic profiles for the unfolding of poly(rA)•poly(rU) (Duplex) and poly(rA)•2poly(rU) (Triplex). Our thermodynamic results are in good agreement with the much earlier work of Krakauer and Sturtevant using only UV melting techniques. The folding of these two helices yielded an uptake of ions, ΔnNa+ = 0.15 mol Na+/mol base-pair (Duplex) and 0.30 mol Na+/mole base-triplet (Triplex), which are consistent with their polymer behavior and the higher charge density parameter of triple helices. The osmotic stress technique yielded a release of structural water, ΔnW = 2 mol H2O/mol base-pair (Duplex unfolding into single strands) and an uptake of structural water, ΔnW = 2 mol H2O/mole base-pair (Triplex unfolding into Duplex and a single strand). However, an overall release of electrostricted waters is obtained for the unfolding of both complexes from pressure perturbation calorimetric experiments. In total, the ΔV values obtained for the unfolding of Triplex into Duplex and a single strand correspond to an immobilization of two structural waters and a release of three electrostricted waters. The ΔV values obtained for the unfolding of Duplex into two single strands correspond to the release of two structural waters and the immobilization of four electrostricted water molecules.
Shirdel, S Akram; Khalifeh, Khosrow; Ranjbar, Bijan; Golestani, Abolfazl; Khajeh, Khosro
2016-11-01
We had previously investigated the role of a loop on the activity and conformational stability of chondroitinase ABC Ι (cABC Ι) by constructing some representative mutants in which a network interaction around Asp 689 was manipulated. Here we extended our study by measuring the proteolytic resistance, long term and thermal stability as well as unfolding kinetics of these variants. Long term stability data at 4 and 25°C for 3 weeks indicates that all mutants remain considerably active at 4°C. Thermoinactivation rates for all variants shows that the wild type (WT) enzyme retained 50% of its activity after 2min keeping at 40°C, while L701T, H700N and H700N/L701T as conformationally stabilized variants, have slower inactivation rate. It was also found that compact and thermodynamically stabilized variants are more resistant to tryptolytic digestion. Also, kinetic curves of chemical unfolding of the enzyme variants from stopped-flow fluorescence measurements were best fitted into a three-exponential function with three rate constants and corresponding amplitudes. We found that the energy barrier of the fast unfolding phase is lower in stabilized variants; while the amplitude of this phase to the whole amplitude of the unfolding reaction is lower than that of destabilized variants, indicating more population of stabilized mutants unfold via slower unfolding phase. We concluded that the rate of local conformational change alone is not the same that is expected from global thermodynamic stability; however the corresponding amplitude can compensate the rate constant toward thermodynamic stability. Copyright © 2016 Elsevier Inc. All rights reserved.
A thiol probe for measuring unfolded protein load and proteostasis in cells.
Chen, Moore Z; Moily, Nagaraj S; Bridgford, Jessica L; Wood, Rebecca J; Radwan, Mona; Smith, Trevor A; Song, Zhegang; Tang, Ben Zhong; Tilley, Leann; Xu, Xiaohong; Reid, Gavin E; Pouladi, Mahmoud A; Hong, Yuning; Hatters, Danny M
2017-09-07
When proteostasis becomes unbalanced, unfolded proteins can accumulate and aggregate. Here we report that the dye, tetraphenylethene maleimide (TPE-MI) can be used to measure cellular unfolded protein load. TPE-MI fluorescence is activated upon labelling free cysteine thiols, normally buried in the core of globular proteins that are exposed upon unfolding. Crucially TPE-MI does not become fluorescent when conjugated to soluble glutathione. We find that TPE-MI fluorescence is enhanced upon reaction with cellular proteomes under conditions promoting accumulation of unfolded proteins. TPE-MI reactivity can be used to track which proteins expose more cysteine residues under stress through proteomic analysis. We show that TPE-MI can report imbalances in proteostasis in induced pluripotent stem cell models of Huntington disease, as well as cells transfected with mutant Huntington exon 1 before the formation of visible aggregates. TPE-MI also detects protein damage following dihydroartemisinin treatment of the malaria parasites Plasmodium falciparum. TPE-MI therefore holds promise as a tool to probe proteostasis mechanisms in disease.Proteostasis is maintained through a number of molecular mechanisms, some of which function to protect the folded state of proteins. Here the authors demonstrate the use of TPE-MI in a fluorigenic dye assay for the quantitation of unfolded proteins that can be used to assess proteostasis on a cellular or proteome scale.
Prakash, Amresh; Kumar, Vijay; Meena, Naveen Kumar; Hassan, Md Imtaiyaz; Lynn, Andrew M
2018-01-10
TAR DNA-binding protein 43 (TDP-43) inclusions have been found in Amyotrophic lateral sclerosis (ALS) and several other neurodegenerative diseases. Many studies suggest the involvement of RNA recognition motifs (RRMs) in TDP-43 proteinopathy. To elucidate the structural stability and the unfolding dynamics of RRMs, we have carried out atomistic molecular dynamics simulations at two different temperatures (300 and 500 K). The simulations results indicate that there are distinct structural differences in the unfolding pathway between the two domains and RRM1 unfolds faster than RRM2 in accordance with the lower thermal stability found experimentally. The unfolding behaviors of secondary structures showed that the α-helix was more stable than β-sheet and structural rearrangements of β-sheets results in formation of additional α-helices. At higher temperature, RRM1 exhibit increased overall flexibility and unfolding than RRM2. The temperature-dependent free energy landscapes consist of multiple metastable states stabilized by non-native contacts and hydrogen bonds in RRM2, thus rendering the RRM2 more prone to misfolding. The structural rearrangements of RRM2 could lead to aberrant protein-protein interactions that may account for enhanced aggregation and toxicity of TDP-43. Our analysis, thus identify the structural and thermodynamic characteristics of the RRMs of TDP-43, which will serve to uncover molecular mechanisms and driving forces in TDP-43 misfolding and aggregation.
How cooperative are protein folding and unfolding transitions?
Malhotra, Pooja
2016-01-01
Abstract A thermodynamically and kinetically simple picture of protein folding envisages only two states, native (N) and unfolded (U), separated by a single activation free energy barrier, and interconverting by cooperative two‐state transitions. The folding/unfolding transitions of many proteins occur, however, in multiple discrete steps associated with the formation of intermediates, which is indicative of reduced cooperativity. Furthermore, much advancement in experimental and computational approaches has demonstrated entirely non‐cooperative (gradual) transitions via a continuum of states and a multitude of small energetic barriers between the N and U states of some proteins. These findings have been instrumental towards providing a structural rationale for cooperative versus noncooperative transitions, based on the coupling between interaction networks in proteins. The cooperativity inherent in a folding/unfolding reaction appears to be context dependent, and can be tuned via experimental conditions which change the stabilities of N and U. The evolution of cooperativity in protein folding transitions is linked closely to the evolution of function as well as the aggregation propensity of the protein. A large activation energy barrier in a fully cooperative transition can provide the kinetic control required to prevent the accumulation of partially unfolded forms, which may promote aggregation. Nevertheless, increasing evidence for barrier‐less “downhill” folding, as well as for continuous “uphill” unfolding transitions, indicate that gradual non‐cooperative processes may be ubiquitous features on the free energy landscape of protein folding. PMID:27522064
Unfolding the HIV-1 reverse transcriptase RNase H domain – how to lose a molecular tug-of-war
Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.; ...
2016-01-14
Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of themore » isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. As a result, this study demonstrates the feasibility of directly targeting RT maturation with therapeutics.« less
Unfolding the HIV-1 reverse transcriptase RNase H domain – how to lose a molecular tug-of-war
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.
Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of themore » isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. As a result, this study demonstrates the feasibility of directly targeting RT maturation with therapeutics.« less
Soranno, Andrea; Buchli, Brigitte; Nettels, Daniel; Cheng, Ryan R.; Müller-Späth, Sonja; Pfeil, Shawn H.; Hoffmann, Armin; Lipman, Everett A.; Makarov, Dmitrii E.; Schuler, Benjamin
2012-01-01
Internal friction, which reflects the “roughness” of the energy landscape, plays an important role for proteins by modulating the dynamics of their folding and other conformational changes. However, the experimental quantification of internal friction and its contribution to folding dynamics has remained challenging. Here we use the combination of single-molecule Förster resonance energy transfer, nanosecond fluorescence correlation spectroscopy, and microfluidic mixing to determine the reconfiguration times of unfolded proteins and investigate the mechanisms of internal friction contributing to their dynamics. Using concepts from polymer dynamics, we determine internal friction with three complementary, largely independent, and consistent approaches as an additive contribution to the reconfiguration time of the unfolded state. We find that the magnitude of internal friction correlates with the compactness of the unfolded protein: its contribution dominates the reconfiguration time of approximately 100 ns of the compact unfolded state of a small cold shock protein under native conditions, but decreases for more expanded chains, and approaches zero both at high denaturant concentrations and in intrinsically disordered proteins that are expanded due to intramolecular charge repulsion. Our results suggest that internal friction in the unfolded state will be particularly relevant for the kinetics of proteins that fold in the microsecond range or faster. The low internal friction in expanded intrinsically disordered proteins may have implications for the dynamics of their interactions with cellular binding partners. PMID:22492978
Soranno, Andrea; Buchli, Brigitte; Nettels, Daniel; Cheng, Ryan R; Müller-Späth, Sonja; Pfeil, Shawn H; Hoffmann, Armin; Lipman, Everett A; Makarov, Dmitrii E; Schuler, Benjamin
2012-10-30
Internal friction, which reflects the "roughness" of the energy landscape, plays an important role for proteins by modulating the dynamics of their folding and other conformational changes. However, the experimental quantification of internal friction and its contribution to folding dynamics has remained challenging. Here we use the combination of single-molecule Förster resonance energy transfer, nanosecond fluorescence correlation spectroscopy, and microfluidic mixing to determine the reconfiguration times of unfolded proteins and investigate the mechanisms of internal friction contributing to their dynamics. Using concepts from polymer dynamics, we determine internal friction with three complementary, largely independent, and consistent approaches as an additive contribution to the reconfiguration time of the unfolded state. We find that the magnitude of internal friction correlates with the compactness of the unfolded protein: its contribution dominates the reconfiguration time of approximately 100 ns of the compact unfolded state of a small cold shock protein under native conditions, but decreases for more expanded chains, and approaches zero both at high denaturant concentrations and in intrinsically disordered proteins that are expanded due to intramolecular charge repulsion. Our results suggest that internal friction in the unfolded state will be particularly relevant for the kinetics of proteins that fold in the microsecond range or faster. The low internal friction in expanded intrinsically disordered proteins may have implications for the dynamics of their interactions with cellular binding partners.
Viseu, Maria Isabel; Melo, Eduardo P.; Carvalho, Teresa Isabel; Correia, Raquel F.; Costa, Sílvia M. B.
2007-01-01
The β→α transition of β-lactoglobulin, a globular protein abundant in the milk of several mammals, is investigated in this work. This transition, induced by the cationic surfactant dodecyltrimethylammonium chloride (DTAC), is accompanied by partial unfolding of the protein. In this work, unfolding of bovine β-lactoglobulin in DTAC is compared with its unfolding induced by the chemical denaturant guanidine hydrochloride (GnHCl). The final protein states attained in the two media have quite different secondary structure: in DTAC the α-helical content increases, leading to the so-called α-state; in GnHCl the amount of ordered secondary-structure decreases, resulting in a random coil-rich final state (denatured, or D, state). To obtain information on both mechanistic routes, in DTAC and GnHCl, and to characterize intermediates, the kinetics of unfolding were investigated in the two media. Equilibrium and kinetic data show the partial accumulation of an on-pathway intermediate in each unfolding route: in DTAC, an intermediate (I1) with mostly native secondary structure but loose tertiary structure appears between the native (β) and α-states; in GnHCl, another intermediate (I2) appears between states β and D. Kinetic rate constants follow a linear Chevron-plot representation in GnHCl, but show a more complex mechanism in DTAC, which acts like a stronger binding species. PMID:17693475
Effect of antimicrobial preservatives on partial protein unfolding and aggregation†
Hutchings, Regina L.; Singh, Surinder M.; Cabello-Villegas, Javier; Mallela, Krishna M. G.
2014-01-01
One-third of protein formulations are multi-dose. These require antimicrobial preservatives (APs); however, some APs have been shown to cause protein aggregation. Our previous work on a model protein cytochrome c indicated that partial protein unfolding, rather than complete unfolding, triggers aggregation. Here, we examined the relative strength of five commonly used APs on such unfolding and aggregation, and explored whether stabilizing the aggregation “hot-spot” reduces such aggregation. All APs induced protein aggregation in the order m-cresol > phenol > benzyl alcohol > phenoxyethanol > chlorobutanol. All these enhanced the partial protein unfolding that includes a local region which was predicted to be the aggregation “hot-spot”. The extent of destabilization correlated with the extent of aggregation. Further, we show that stabilizing the “hot-spot” reduces aggregation induced by all five APs. These results indicate that m-cresol causes the most protein aggregation, whereas chlorobutanol causes the least protein aggregation. The same protein region acts as the “hot-spot” for aggregation induced by different APs, implying that developing strategies to prevent protein aggregation induced by one AP will also work for others. PMID:23169345
Gribenko, Alexey V; Keiffer, Timothy R; Makhatadze, George I
2006-08-01
The heat capacity change upon unfolding (deltaC(p)) is a thermodynamic parameter that defines the temperature dependence of the thermodynamic stability of proteins; however, physical basis of the heat capacity change is not completely understood. Although empirical surface area-based calculations can predict heat capacity changes reasonably well, accumulating evidence suggests that changes in hydration of those surfaces is not the only parameter contributing to the observed heat capacity changes upon unfolding. Because packing density in the protein interior is similar to that observed in organic crystals, we hypothesized that changes in protein dynamics resulting in increased rigidity of the protein structure might contribute to the observed heat capacity change upon unfolding. Using differential scanning calorimetry we characterized the thermodynamic behavior of a serine protease inhibitor eglin C and two eglin C variants with altered native state dynamics, as determined by NMR. We found no evidence of changes in deltaC(p) in either of the variants, suggesting that changes in rigidity do not contribute to the heat capacity change upon unfolding in this model system. Copyright 2006 Wiley-Liss, Inc.
Mechanical Unfolding Studies on Single-Domain SUMO and Multi-Domain Periplasmic Binding Proteins
NASA Astrophysics Data System (ADS)
Kotamarthi, Hema Chandra; Ainavarapu, Sri Rama Koti
Protein mechanics is a key component of many cellular and sub-cellular processes. The current review focuses on recent studies from our laboratory that probe the effect of sequence on the mechanical stability of structurally similar proteins and the unfolding mechanisms of multi-domain periplasmic binding proteins. Ubiquitin and small ubiquitin-related modifiers (SUMOs) are structurally similar and possess different mechanical stabilities, ubiquitin being stronger than SUMOs as revealed from their unfolding forces. These differences are plausibly due to the variation in number of inter-residue contacts. The unfolding potential widths determined from the pulling speed-dependent studies revealed that SUMOs are mechanically more flexible than ubiquitin. This flexibility of SUMOs plays a role in ligand binding and our single-molecule studies on SUMO interaction with SUMO binding motifs (SBMs) have shown that ligand binding decreases the SUMO flexibility and increases its mechanical stability. Studies on multi-domain periplasmic binding proteins have revealed that the unfolding energy landscape of these proteins is complex and they follow kinetic partitioning between two-state and multiple three-state pathways.
Unfolding energetics and stability of banana lectin.
Gupta, Garima; Sinha, Sharmistha; Surolia, Avadhesha
2008-08-01
The unfolding pathway of banana lectin from Musa paradisiaca was determined by isothermal denaturation induced by the chaotrope GdnCl. The unfolding was found to be a reversible process. The data obtained by isothermal denaturation provided information on conformational stability of banana lectin. The high values of DeltaG of unfolding at various temperatures indicated the strength of intersubunit interactions. It was found that banana lectin is a very stable and denatures at high chaotrope concentrations only. The basis of the stability may be attributed to strong hydrogen bonds of the order 2.5-3.1 A at the dimeric interface along with the presence of water bridges. This is perhaps very unique example in proteins where subunit association is not a consequence of the predominance of hydrophobic interactions. (c) 2008 Wiley-Liss, Inc.
Two Years of Site Diversity Measurements in Guam, USA
NASA Technical Reports Server (NTRS)
Acosta, Roberto J.; Morse, J.; Zemba, M.; Nessel, J.
2012-01-01
As NASA communication networks upgrade to higher frequencies, such as Ka-Band, atmospherically induced attenuation can become significant. This attenuation is caused by rain, clouds and atmospheric gases (oxygen and water vapor), with rain having the most noticeable effects. One technique to circumvent the increase in attenuation is to operate two terminals separated by a distance that exceeds the average rain cell size. The fact that rain cells are of finite size can then be exploited by rerouting the signal to the terminal with the strongest link. This technique, known as site diversity, is best suited for climates that have compact (less than 2km) and intense rain cells such as in Guam. In order to study the potential diversity gain at the Tracking and Data Relay Satellite (TDRS) Remote Ground Terminal (GRGT) complex in Guam a site test interferometer (STI) was installed in May of 2010. The STI is composed of two terminals with a 900m baseline that observe the same unmodulated beacon signal broadcast from a geostationary satellite (e.g., UFO 8). The potential site diversity gain is calculated by measuring the difference in signal attenuation seen at each terminal. Over the two years of data collection the cumulative distribution function (CDF) of the site diversity gain shows a better than 3 dB improvement for 90% of the time over standard operation. These results show that the use of site diversity in Guam can be very effective in combating rain fades.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Friddle, R W
2008-01-14
Harris, Song and Kiang [1] (HSK) describe their results on reconstructing the free energy profiles for both the stretch of the titin polymer, and the unfolding of an individual I27 domain. The new finding reported in [1] is the measurement of the free energy barrier (or activation energy) to unfolding the I27 domain. Due to a misinterpretation of the mechanics involved, the free energy surface (and thus the energy barrier) to unfolding the I27 domain was not measured.
The origin of ultrafast outflows in AGN: Monte Carlo simulations of the wind in PDS 456
NASA Astrophysics Data System (ADS)
Hagino, Kouichi; Odaka, Hirokazu; Done, Chris; Gandhi, Poshak; Watanabe, Shin; Sako, Masao; Takahashi, Tadayuki
2015-01-01
Ultrafast outflows (UFOs) are seen in many AGN, giving a possible mode for AGN feedback on to the host galaxy. However, the mechanism(s) for the launch and acceleration of these outflows are currently unknown, with UV line driving apparently strongly disfavoured as the material along the line of sight is so highly ionized that it has no UV transitions. We revisit this issue using the Suzaku X-ray data from PDS 456, an AGN with the most powerful UFO seen in the local Universe. We explore conditions in the wind by developing a new 3D Monte Carlo code for radiation transport. The code only handles highly ionized ions, but the data show the ionization state of the wind is high enough that this is appropriate, and this restriction makes it fast enough to explore parameter space. We reproduce the results of earlier work, confirming that the mass-loss rate in the wind is around 30 per cent of the inferred inflow rate through the outer disc. We show for the first time that UV line driving is likely to be a major contribution to the wind acceleration. The mass-loss rate in the wind matches that predicted from a purely line driven system, and this UV absorption can take place out of the line of sight. Continuum driving should also play a role as the source is close to Eddington. This predicts that the most extreme outflows will be produced from the highest mass accretion rate flows on to high-mass black holes, as observed.
Ambiguity resolution in precise point positioning with hourly data for global single receiver
NASA Astrophysics Data System (ADS)
Zhang, Xiaohong; Li, Pan; Guo, Fei
2013-01-01
Integer ambiguity resolution (IAR) can improve precise point positioning (PPP) performance significantly. IAR for PPP became a highlight topic in global positioning system (GPS) community in recent years. More and more researchers focus on this issue. Progress has been made in the latest years. In this paper, we aim at investigating and demonstrating the performance of a global zero-differenced (ZD) PPP IAR service for GPS users by providing routine ZD uncalibrated fractional offsets (UFOs) for wide-lane and narrow-lane. Data sets from all IGS stations collected on DOY 1, 100, 200 and 300 of 2010 are used to validate and demonstrate this global service. Static experiment results show that an accuracy better than 1 cm in horizontal and 1-2 cm in vertical could be achieved in ambiguity-fixed PPP solution with only hourly data. Compared with PPP float solution, an average improvement reaches 58.2% in east, 28.3% in north and 23.8% in vertical for all tested stations. Results of kinematic experiments show that the RMS of kinematic PPP solutions can be improved from 21.6, 16.6 and 37.7 mm to 12.2, 13.3 and 34.3 mm for the fixed solutions in the east, north and vertical components, respectively. Both static and kinematic experiments show that wide-lane and narrow-lane UFO products of all satellites can be generated and provided in a routine way accompanying satellite orbit and clock products for the PPP user anywhere around the world, to obtain accurate and reliable ambiguity-fixed PPP solutions.
Active commuting reduces the risk of wrist fractures in middle-aged women-the UFO study.
Englund, U; Nordström, P; Nilsson, J; Hallmans, G; Svensson, O; Bergström, U; Pettersson-Kymmer, U
2013-02-01
Middle-aged women with active commuting had significantly lower risk for wrist fracture than women commuting by car/bus. Our purpose was to investigate whether a physically active lifestyle in middle-aged women was associated with a reduced risk of later sustaining a low-trauma wrist fracture. The Umeå Fracture and Osteoporosis (UFO) study is a population-based nested case-control study investigating associations between lifestyle and fragility fractures. From a cohort of ~35,000 subjects, we identified 376 female wrist fracture cases who had reported data regarding their commuting habits, occupational, and leisure physical activity, before they sustained their fracture. Each fracture case was compared with at least one control drawn from the same cohort and matched for age and week of reporting data, yielding a total of 778 subjects. Mean age at baseline was 54.3 ± 5.8 years, and mean age at fracture was 60.3 ± 5.8 years. Conditional logistic regression analysis with adjustments for height, body mass index, smoking, and menopausal status showed that subjects with active commuting (especially walking) were at significantly lower risk of sustaining a wrist fracture (OR 0.48; 95 % CI 0.27-0.88) compared with those who commuted by car or bus. Leisure time activities such as dancing and snow shoveling were also associated with a lower fracture risk, whereas occupational activity, training, and leisure walking or cycling were unrelated to fracture risk. This study suggests that active commuting is associated with a lower wrist fracture risk, in middle-aged women.
Bachhawat, K; Kapoor, M; Dam, T K; Surolia, A
2001-06-19
Allium sativum agglutinin (ASAI) is a heterodimeric mannose-specific bulb lectin possessing two polypeptide chains of molecular mass 11.5 and 12.5 kDa. The thermal unfolding of ASAI, characterized by differential scanning calorimetry and circular dichroism, shows it to be highly reversible and can be defined as a two-state process in which the folded dimer is converted directly to the unfolded monomers (A2 if 2U). Its conformational stability has been determined as a function of temperature, GdnCl concentration, and pH using a combination of thermal and isothermal GdnCl-induced unfolding monitored by DSC, far-UV CD, and fluorescence, respectively. Analyses of these data yielded the heat capacity change upon unfolding (DeltaC(p) and also the temperature dependence of the thermodynamic parameters, namely, DeltaG, DeltaH, and DeltaS. The fit of the stability curve to the modified Gibbs-Helmholtz equation provides an estimate of the thermodynamic parameters DeltaH(g), DeltaS(g), and DeltaC(p) as 174.1 kcal x mol(-1), 0.512 kcal x mol(-1) x K(-1), and 3.41 kcal x mol(-1) x K(-1), respectively, at T(g) = 339.4 K. Also, the free energy of unfolding, DeltaG(s), at its temperature of maximum stability (T(s) = 293 K) is 13.13 kcal x mol(-1). Unlike most oligomeric proteins studied so far, the lectin shows excellent agreement between the experimentally determined DeltaC(p) (3.2 +/- 0.28 kcal x mol(-1) x K(-1)) and those evaluated from a calculation of its accessible surface area. This in turn suggests that the protein attains a completely unfolded state irrespective of the method of denaturation. The absence of any folding intermediates suggests the quaternary interactions to be the major contributor to the conformational stability of the protein, which correlates well with its X-ray structure. The small DeltaC(p) for the unfolding of ASAI reflects a relatively small, buried hydrophobic core in the folded dimeric protein.
Trehalose delays the reversible but not the irreversible thermal denaturation of cutinase.
Baptista, R P; Cabral, J M; Melo, E P
2000-12-20
The effect of trehalose (0.5 M) on the thermal stability of cutinase in the alkaline pH range was studied. The thermal unfolding induced by increasing temperature was analyzed in the absence and in the presence of trehalose according to a two-state model (which assumes that only the folded and unfolded states of cutinase were present). Trehalose delays the reversible unfolding. The midpoint temperature of the unfolding transition (Tm) increases by 4.0 degrees C and 2. 6 degrees C at pH 9.2 and 10.5, respectively, in the presence of trehalose. At pH 9.2 the thermal unfolding occurs at higher temperatures (Tm is 52.6 degrees C compared to 42.0 degrees C at pH 10.5) and a refolding yield of around 80% was obtained upon cooling. This pH value was chosen to study the irreversible inactivation (long-term stability) of cutinase. Temperatures in the transition range from folded to unfolded state were selected and the rate constants of irreversible inactivation determined. Inactivation followed first-order kinetics and trehalose reduced the observed rate constants of inactivation, pointing to a stabilizing effect on the irreversible inactivation step of thermal denaturation. However, if the contribution of reversible unfolding on the irreversible inactivation of cutinase was taken into account, i.e., considering the fraction of cutinase molecules in the reversible unfolded conformation, the intrinsic rate constants can be calculated. Based on the intrinsic rate constants it was concluded that trehalose does not delay the irreversible inactivation. This conclusion was further supported by comparing the activation energy of the irreversible inactivation in the absence and in the presence of trehalose. The apparent activation energy in the absence and in the presence of trehalose were 67 and 99 Kcal/mol, respectively. The activation energy calculated from intrinsic rate constants was higher in the absence (30 Kcal/mol) than in the presence of trehalose (16 Kcal/mol), showing that kinetics of the irreversible inactivation step increased in the presence of trehalose. In fact, trehalose stabilized only the reversible step of thermal denaturation of cutinase.
Collision induced unfolding of isolated proteins in the gas phase: past, present, and future.
Dixit, Sugyan M; Polasky, Daniel A; Ruotolo, Brandon T
2018-02-01
Rapidly characterizing the three-dimensional structures of proteins and the multimeric machines they form remains one of the great challenges facing modern biological and medical sciences. Ion mobility-mass spectrometry based techniques are playing an expanding role in characterizing these functional complexes, especially in drug discovery and development workflows. Despite this expansion, ion mobility-mass spectrometry faces many challenges, especially in the context of detecting small differences in protein tertiary structure that bear functional consequences. Collision induced unfolding is an ion mobility-mass spectrometry method that enables the rapid differentiation of subtly-different protein isoforms based on their unfolding patterns and stabilities. In this review, we summarize the modern implementation of such gas-phase unfolding experiments and provide an overview of recent developments in both methods and applications. Copyright © 2017 Elsevier Ltd. All rights reserved.
Understanding disordered and unfolded proteins using single-molecule FRET and polymer theory.
Hofmann, Hagen
2016-11-17
Understanding protein folding and the functional properties of intrinsically disordered proteins (IDPs) requires detailed knowledge of the forces that act in polypeptide chains. These forces determine the dimensions and dynamics of unfolded and disordered proteins and have been suggested to impact processes such as the coupled binding and folding of IDPs, or the rate of protein folding reactions. Much of the progress in understanding the physical and chemical properties of unfolded and intrinsically disordered polypeptide chains has been made possible by the recent developments in single-molecule fluorescence techniques. However, the interpretation of the experimental results requires concepts from polymer physics in order to be understood. Here, I review some of the theories used to describe the dimensions of unfolded polypeptide chains under varying solvent conditions together with their more recent application to experimental data.
Molecular dynamics study of unfolding of lysozyme in water and its mixtures with dimethyl sulfoxide.
Sedov, Igor A; Magsumov, Timur I
2017-09-01
All-atom explicit solvent molecular dynamics was used to study the process of unfolding of hen egg white lysozyme in water and mixtures of water with dimethyl sulfoxide at different compositions. We have determined the kinetic parameters of unfolding at a constant temperature 450K. For each run, the time of disruption of the tertiary structure of lysozyme t u was defined as the moment when a certain structural criterion computed from the trajectory reaches its critical value. A good agreement is observed between the results obtained using several different criteria. The secondary structure according to DSSP calculations is found to be partially unfolded to the moment of disruption of tertiary structure, but some of its elements keep for a long time after that. The values of t u averaged over ten 30ns-long trajectories for each solvent composition are shown to decrease very rapidly with addition of dimethyl sulfoxide, and rather small amounts of dimethyl sulfoxide are found to change the pathway of unfolding. In pure water, despite the loss of tertiary contacts and disruption of secondary structure elements, the protein preserves its compact globular state at least over 130ns of simulation, while even at 5mol percents of dimethyl sulfoxide it loses its compactness within 30ns. The proposed methodology is a generally applicable tool to quantify the rate of protein unfolding in simulation studies. Copyright © 2017 Elsevier Inc. All rights reserved.
Interactions of urea with native and unfolded proteins: a volumetric study.
Son, Ikbae; Shek, Yuen Lai; Tikhomirova, Anna; Baltasar, Eduardo Hidalgo; Chalikian, Tigran V
2014-11-26
We describe a statistical thermodynamic approach to analyzing urea-dependent volumetric properties of proteins. We use this approach to analyze our urea-dependent data on the partial molar volume and adiabatic compressibility of lysozyme, apocytochrome c, ribonuclease A, and α-chymotrypsinogen A. The analysis produces the thermodynamic properties of elementary urea-protein association reactions while also yielding estimates of the effective solvent-accessible surface areas of the native and unfolded protein states. Lysozyme and apocytochrome c do not undergo urea-induced transitions. The former remains folded, while the latter is unfolded between 0 and 8 M urea. In contrast, ribonuclease A and α-chymotrypsinogen A exhibit urea-induced unfolding transitions. Thus, our data permit us to characterize urea-protein interactions in both the native and unfolded states. We interpreted the urea-dependent volumetric properties of the proteins in terms of the equilibrium constant, k, and changes in volume, ΔV0, and compressibility, ΔKT0, for a reaction in which urea binds to a protein with a concomitant release of two waters of hydration to the bulk. Comparison of the values of k, ΔV0, and ΔKT0 with the similar data obtained on small molecules mimicking protein groups reveals lack of cooperative effects involved in urea-protein interactions. In general, the volumetric approach, while providing a unique characterization of cosolvent-protein interactions, offers a practical way for evaluating the effective solvent accessible surface area of biologically significant fully or partially unfolded polypeptides.
Galzitskaya, Oxana; Deryusheva, Eugenia; Machulin, Andrey; Nemashkalova, Ekaterina; Glyakina, Anna
2018-06-21
High prediction accuracy of flexible loops in different protein families is a challenge because of the crucial functions associated with these regions. Results of the currently available programs for prediction of loops vary from protein to protein. For prediction of flexible regions in the G-domain for 23 representatives of G-proteins with the known 3D structure we have used eight programs. The results of predictions demonstrate that the FoldUnfold program predicts better loop positions than the PONDR, RОNN, DisEMBL, IUPred, GlobPlot 2, FoldIndex, and MobiDB programs. When classifying the predicted loops (rigid/flexible) according to the Debye-Waller fluctuation factors, our data reveal the existing weak correlation between the B-factors and the average number of closed residues according to the FoldUnfold program; the percentage of overlapping characteristics (residue fold/unfold status) of the protein residues from the two methods is about 60-70%. According to the FoldUnfold program, for G-proteins with the posttranslational modifications, the surrounding binding site residues by disordered-promoting glycine and alanine residues conduces to a more flexible position of the binding sites for fatty acid, while methionine, cysteine and isoleucine residues provide more rigid binding sites. Thus, our research demonstrates additional possibilities of the FoldUnfold program for prediction of flexible regions and characteristics of individual residues in a different protein family. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Takatori, Osamu; Usui, Soichiro; Okajima, Masaki; Kaneko, Shuichi; Ootsuji, Hiroshi; Takashima, Shin-Ichiro; Kobayashi, Daisuke; Murai, Hisayoshi; Furusho, Hiroshi; Takamura, Masayuki
2017-05-01
The unfolded protein response (UPR) plays a pivotal role in ischemia-reperfusion (I/R) injury in various organs such as heart, brain, and liver. Sodium 4-phenylbutyrate (PBA) reportedly acts as a chemical chaperone that reduces UPR. In the present study, we evaluated the effect of PBA on reducing the UPR and protecting against myocardial I/R injury in mice. Male C57BL/6 mice were subjected to 30-minute myocardial I/R, and were treated with phosphate-buffered saline (as a vehicle) or PBA. At 4 hours after reperfusion, mice treated with PBA had reduced serum cardiac troponin I levels and numbers of apoptotic cells in left ventricles (LVs) in myocardial I/R. Infarct size had also reduced in mice treated with PBA at 48 hours after reperfusion. At 2 hours after reperfusion, UPR markers, including eukaryotic initiation of the factor 2α-subunit, activating transcription factor-6, inositol-requiring enzyme-1, glucose-regulated protein 78, CCAAT/enhancer-binding protein (C/EBP) homologous protein, and caspase-12, were significantly increased in mice treated with vehicle compared to sham-operated mice. Administration of PBA significantly reduced the I/R-induced increases of these markers. Cardiac function and dimensions were assessed at 21 days after I/R. Sodium 4-phenylbutyrate dedicated to the improvement of cardiac parameters deterioration including LV end-diastolic diameter and LV fractional shortening. Consistently, PBA reduced messenger RNA expression levels of cardiac remodeling markers such as collagen type 1α1, brain natriuretic peptide, and α skeletal muscle actin in LV at 21 days after I/R. Unfolded protein response mediates myocardial I/R injury. Administration of PBA reduces the UPR, apoptosis, infarct size, and preserved cardiac function. Hence, PBA may be a therapeutic option to attenuate myocardial I/R injury in clinical practice.