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Bench-scale and pilot plant development of solvent refined coal (SRC) processes is reviewed. Large SRC demonstration plants are described. Commercialization of the process is envisioned for the 1980's.
Introduction: Numerous X-ray crystal structures of the c-Src SH3 domain have provideda large sampling of atomic-level information for this important signaling domain. Multiple crystalforms have been reported, with variable crystal lattice contacts and chemical crystallizationconditions. Materials and Methods: We crystallized the c-Src SH3 domain in a crystallization buffercontaining NiCl2. Results: A unique crystal structure of the Src SH3 domain in the trigonal space group H32 isdetermined to 1.45 Å resolution. Crystal packing and anomalous scattering reveal that this crystalform is mediated by two ordered nickel ions provided by the crystallization buffer. Nickelcoordination occurs in a 2:2 stoichiometry, which dimerizes two SH3 domain monomers across apseudo-twofold rotation axis and involves the native N-terminal c-Src SH3 amino acid sequence, asurface-exposed histidine residue, and ordered water molecules. Discussion: This study provides an example of metal-mediated crystallization and metal binding byN-terminal protein residues, contrasting with the Amino-Terminal Copper and Nickel Binding(ATCUN) motif. Conclusion: Alternative avenues help widen the potential for future crystallography-based studiesof the c-Src SH3 domain.
We report Swift Burst Alert Telescope (BAT) observations of the X-ray flash (XRF) XRF 050416A. The fluence ratio between the 15-25 and 25-50 keV energy bands of this event is 1.5, thus making it the softest gamma-ray burst (GRB) observed by BAT so far. The spectrum is well fitted by a Band function with E(sup obs)(sub peak) of 15.0(sup +2.3)(sub -2.7) keV. Assuming the redshift of the host galaxy (z = 0.6535), the isotropic equivalent radiated energy E(sub iso) and the peak energy at the GRB rest frame (E(sup src)(sub peak)) of XRF 050416A are not only consistent with the correlation found by Amati et al. and extended to XRFs by Sakamoto et al. but also fill in the gap of this relation around the 30-80 keV range of E(sup src)(sub peak). This result tightens the validity of the E(sup src)(sub Peak)-E(sup src)(sub peak) relation from XRFs to GRBs. We also find that the jet break time estimated using the empirical relation between E(sup src)(sub peak) and the collimation corrected energy E(sub gamma), is inconsistent with the afterglow observation by the Swift X-Ray Telescope. This could be due to the extra external shock emission overlaid around the jet break time or to the nonexistence of a jet break feature for XRFs, which might be a further challenge for GRB jet emission models and XRF/GRB unification scenarios.
Palmitic acid (PA)-induced hepatocyte apoptosis is critical for the progression of nonalcoholic fatty liver disease (NAFLD). Inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) is an intracellular Ca{sup 2+}-release channel and is involved in PA-induced hepatocyte apoptosis. While the expression of IP3R1 is elevated in patients with NAFLD and in hepatocytes treated with PA, it remains unclear how PA promotes the expression of IP3R1. In present study, our results showed that PA induced mitochondrial dysfunction and apoptosis, which is accompanied with the increase of the IP3R1 expression in hepatic cells. The inhibition of IP3R1 expression using siRNA ameliorated the PA-induced mitochondrial dysfunction. Furthermore, PA enhanced the stability of the IP3R1 protein instead of an increase in its mRNA levels. PA also promoted the phosphorylation of IP3R1 at the Tyr353 site and increased the phosphorylation of src in hepatic cells. Moreover, an inhibitor of src kinase (SU6656) significantly reduced the Tyr353 phosphorylation of IP3R1 and decreased its stability. In addition, SU6656 improved mitochondrial function and reduced apoptosis in hepatocytes. Conclusion: PA promotes the Tyr353 phosphorylation of IP3R1 by activating the src pathway and increasing the protein stability of IP3R1, which consequently results in mitochondrial Ca{sup 2+} overload and mitochondrial dysfunction in hepatic cells. Our results also suggested that inhibition of the src/IP3R1 pathway, such as by SU6656, may be a novel potential therapeutic approach for the treatment of NAFLD.
Highlights: • YAP1 enters the nucleus in response to heat shock. • YAP1 spontaneously returns to the cytoplasm after heat shock. • SRC is involved in the nuclear accumulation of YAP1. • HSP90 is involved in the return to the cytoplasm of YAP1. • YAP1 cross-talks with NF-κB signaling in response to heat shock. Yes-associated protein 1 (YAP1), a co-transcription activator, shuttles between the cytoplasm and the nucleus. Phosphorylation by large tumor suppressor kinases (LATS1/2) is the major determinant of YAP1 subcellular localization. Unphosphorylated YAP1 interacts with transcription factors in the nucleus and regulates gene transcription, while phosphorylated YAP1 is trapped in the cytoplasm and is degraded. We found that when U2OS and HeLa cells are exposed to 42 °C, YAP1 enters the nucleus within 30 min and returns to the cytoplasm at 4 h. SRC and HSP90 are involved in nuclear accumulation and return to the cytoplasm, respectively. Upon heat shock, LATS2 forms aggregates including protein phosphatase 1 and is dephosphorylated and inactivated. SRC activation is necessary for the formation of aggregates, while HSP90 is required for their dissociation. YAP1 is involved in heat shock-induced NF-κB signaling. Mechanistically, YAP1 is implicated in strengthening the interaction between RELA and DPF3, a component of SWI/SNF chromatin remodeling complex, in response to heat shock. Thus, YAP1 plays a role as a thermosensor.
Arrestins regulate a wide range of signaling events, most notably when bound to active G protein-coupled receptors (GPCRs). Among the known effectors recruited by GPCR-bound arrestins are Src family kinases, which regulate cellular growth and proliferation. Here, we focus on arrestin-3 interactions with Fgr kinase, a member of the Src family. Previous reports demonstrated that Fgr exhibits high constitutive activity, but can be further activated by both arrestin-dependent and arrestin-independent pathways. We report that arrestin-3 modulates Fgr activity with a hallmark bell-shaped concentration-dependence, consistent with a role as a signaling scaffold. Here, we further demonstrate using NMR spectroscopy that a polyproline motif within arrestin-3 interacts directly with the SH3 domain of Fgr. To provide a framework for this interaction, we determined the crystal structure of the Fgr SH3 domain at 1.9 Å resolution and developed a model for the GPCR-arrestin-3-Fgr complex that is supported by mutagenesis. This model suggests that Fgr interacts with arrestin-3 at multiple sites and is consistent with the locations of disease-associated Fgr mutations. Collectively, these studies provide a structural framework for arrestin-dependent activation of Fgr.
This is the AmeriFlux Management Project (AMP) created FLUXNET-1F version of the carbon flux data for the site US-SRC Santa Rita Creosote. This is the FLUXNET version of the carbon flux data for the site US-SRC Santa Rita Creosote produced by applying the standard ONEFlux (1F) software. Site Description - Part of the Santa Rita Experimental Range since 1901; Site vegetation has been dominated by Creosote bush since at least 1934
Collectors at 1173K (900 C) were exposed to the combustion products of a Mach 0.3 burner rig fueled with various industrial turbine liquid fuels from solvent refined coals. Four fuels were employed: a naphtha, a light oil, a wash solvent and a mid-heavy distillate blend. The response of four superalloys (IN-100, U 700, IN 792 and M-509) to exposure to the combustion gases from the SRC-2 naphtha and resultant deposits was also determined. The SRC-2 fuel analysis and insights obtained during the combustion experience are discussed. Particular problems encountered were fuel instability and reactions of the fuel with hardware components. The major metallic elements which contributed to the deposits were copper, iron, chromium, calcium, aluminum, nickel, silicon, titanium, zinc, and sodium. The deposits were found to be mainly metal oxides. An equilibrium thermodynamic analysis was employed to predict the chemical composition of the deposits. The agreement between the predicted and observed compounds was excellent. No hot corrosion was observed. This was expected because the deposits contained very little sodium or potassium and consisted mainly of the unreactive oxides. However, the amounts of deposits formed indicated that fouling is a potential problem with the use of these fuels.
SrC is Halite, Rock Salt structured and crystallizes in the cubic Fm-3m space group. The structure is three-dimensional. Sr2+ is bonded to six equivalent C2- atoms to form a mixture of edge and corner-sharing SrC6 octahedra. The corner-sharing octahedral tilt angles are 0°. All Sr–C bond lengths are 2.84 Å. C2- is bonded to six equivalent Sr2+ atoms to form a mixture of edge and corner-sharing CSr6 octahedra. The corner-sharing octahedral tilt angles are 0°.
Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK); however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK Y18-phosphorylation and spontaneous activation of CD 8+ and CD 4+ T cells, resulting in inhibited growth of transplanted ICB-resistant tumours. Furthermore, ICB treatment of castration-resistant prostate cancer (CRPC) patients results in re-activation of ACK1/pY18-CSK signalling, confirming the involvement of this pathway in ICB insensitivity. An ACK1 small-molecule inhibitor, (R)-9b, recapitulates inhibition of ICB-resistant tumours, which provides evidence for ACK1 enzymatic activity playing a pivotal role in generating ICB resistance. Overall, our study identifies an important mechanism of ICB resistance and holds potential for expanding the scope of ICB therapy to tumours that are currently unresponsive.
We study short-range correlations (SRC) using the generalized contact formalism (GCF) and quantum Monte Carlo (QMC) calculations of nuclei from deuteron to 40 Ca. We employ different realistic nuclear interactions and extract spin/isospin-dependent nuclear contacts in both coordinate and momentum space.
Overview of Jefferson Lab SRC results from inclusive electron scattering.
The Saskatchewan Research Council (SRC) collected surface meteorological and radiation data from December 1993 until December 1996. The data set comprises Suite A (meteorological and energy balance measurements) and Suite B (diffuse solar and longwave measurements) components. Suite A measurements were taken at each of ten sites, and Suite B measurements were made at five of the Suite A sites. The data cover an approximate area of 500 km (North-South) by 1000 km (East-West) (a large portion of northern Manitoba and northern Saskatchewan). The measurement network was designed to provide researchers with a sufficient record of near-surface meteorological and radiation measurements. The data are provided in tabular ASCII files, and were collected by Aircraft Flux and Meteorology (AFM)-7. The surface meteorological and radiation data are available from the Earth Observing System Data and Information System (EOSDIS) Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC). The data files are available on a CD-ROM (see document number 20010000884).
The primary mission of the NASA Mars Sample Return (MSR) Campaign is to return samples of the Martian surface to Earth for scientific study. As part of this campaign, NASA is developing a Mars Ascent Vehicle (MAV). This vehicle must survive an approximate two year journey to the Martian surface as a payload aboard a separate lander spacecraft. After residing on the surface for another year, the MAV will carry a payload of samples into orbit. From there, following ejection from the MAV, the samples will rendezvous with an Earth return spacecraft for capture, and ultimately, return to Earth.The design of the MAV represents a number of unique challenges, as no launch vehicle has ever left the surface of a planet other than Earth. Although conceptual designs for a MAV have been in various levels of development since the 1970s, none have achieved the level of fidelity and support that exists in the current MSR-MAV design. Early MSR-MAV concept studies examined multiple methods of propulsion, ultimately deciding that a Two Stage to Orbit (TSTO) solid propulsion vehicle would provide the most capable performance in a Martian environment. Following this key architecture decision, the vehicle design was further matured to a Solid-Solid Guided-Guided (SSGG) architecture for NASA Key Decision Point A (KDP-A). Although the SSGG design was able to meet all mission constraints, concerns were raised regarding limited mass margin on other elements of the MSR campaign at such an early phase. A design challenge was issued to reduce MAV total mass by as much as possible. It was ultimately determined that by moving a number of components of the vehicle second stage to the first stage, the overall vehicle mass could be reduced significantly. The new design featured a much smaller and completely unguided second stage. This paper describes the resultant Solid-Solid Guided-Unguided (SSGU) MAV design concept developed as part of the Systems Requirement Cycle (SRC). This design was developed primarily by NASA Marshall Space Flight Center (MSFC), in association with NASA Jet Propulsion Laboratory (JPL) and NASA Langley Research Center (LaRC). The TSTO vehicle includes one solid rocket motor per stage. As the vehicle second stage is unguided, it features spin-stabilization to maintain vehicle stability during flight. An electromechanically actuated Thrust Vector Control (TVC) and a monopropellant Reaction Control System (RCS) is employed for active guidance on the first stage. The vehicle is designed to deliver up to 0.47kg of Martian samples to a Mars circular orbit of 380km at 27° inclination. Due to the extremely unique design constraints of this mission, and a recent transition to a Risk Class A posture, the MAV team was compelled to devise unconventional solutions to the vehicle design. The detailed design and analysis of these subsystems and the vehicle as a whole are discussed in this paper relative to all of the engineering disciplines involved.
The primary mission of the NASA Mars Sample Return (MSR) Campaign is to return samples of the Martian surface to Earth for scientific study. As part of this campaign, NASA is developing a Mars Ascent Vehicle (MAV). This vehicle must survive an approximate two-year journey to the Martian surface as a payload aboard a separate lander spacecraft. After residing on the surface for another year, the MAV will carry a payload of samples into orbit. From there, following ejection from the MAV, the samples will rendezvous with an Earth return spacecraft for capture, and ultimately, return to Earth. The design of the MAV represents a number of unique challenges, as no launch vehicle has ever left the surface of a planet other than Earth. Although conceptual designs for a MAV have been in various levels of development since the 1970s, none have achieved the level of fidelity and support that exists in the current MSR-MAV design. Early MSR-MAV concept studies examined multiple methods of propulsion, ultimately deciding that a Two-Stage-to-Orbit (TSTO) solid propulsion vehicle would provide the most capable performance in a Martian environment. Following this key architecture decision, the vehicle design was further matured to a Solid-Solid Guided-Guided (SSGG) architecture for NASA Key Decision Point A (KDP-A). Although the SSGG design was able to meet all mission constraints, concerns were raised regarding limited mass margin on other elements of the MSR campaign at such an early phase. A design challenge was issued to reduce MAV total mass by as much as possible. It was ultimately determined that by moving a number of components of the vehicle second stage to the first stage, the overall vehicle mass could be reduced significantly. The new design features a much smaller and completely unguided second stage. This paper describes the resultant Solid-Solid Guided-Unguided (SSGU) MAV design concept developed as part of the Systems Requirement Cycle (SRC). This design was developed primarily by NASA Marshall Space Flight Center (MSFC), in association with NASA Jet Propulsion Laboratory (JPL) and NASA Langley Research Center (LaRC). The TSTO vehicle includes one solid rocket motor per stage. As the vehicle second stage is unguided, it features spin-stabilization to maintain vehicle stability during flight. An electromechanically actuated Thrust Vector Control (TVC) system and a monopropellant Reaction Control System (RCS) are employed for active guidance on the first stage. The vehicle is designed to deliver up to 0.47kg of Martian samples to a Mars circular orbit of 380km at 27° inclination. Due to the extremely unique design constraints of this mission, and a recent transition to a Risk Class A posture, the MAV team was compelled to devise unconventional solutions to the vehicle design. The detailed design and analysis of these subsystems and the vehicle as a whole are discussed in this paper relative to all of the engineering disciplines involved.
The objective of the NASA Mars Sample Return (MSR) Campaign is to collect samples from the surface of Mars and return them to Earth for scientific research. The Mars Ascent Vehicle (MAV) will be integrated into a larger Mars Sample Retrieval Lander (SRL) for transit to and storage on Mars. After all Martian samples have been collected and loaded into the MAV payload assembly, MAV will deliver the samples from the Martian surface to Mars orbit. A separate spacecraft, the Earth Return Orbiter (ERO) will retrieve the samples from Mars orbit and return them to Earth. To address common systems engineering challenges associated with using traditional systems engineering practices on complex projects, the MAV systems engineering team has explored implementation of Model-Based Systems Engineering (MBSE) tools and languages. This paper describes the current state of implementation and development of the MAV MBSE model with the Systems Modeling Language (SysML) within the scope of the MAV Systems Requirement Cycle (SRC) systems engineering workflow. The MAV MBSE model has been developed within Magic Draw – a SysML editor commonly used to implement MBSE. The MAV MBSE model has been used to develop mission phase functional flow diagrams for the Concept of Operations, decompose mission to vehicle subsystem functions, develop a functional decomposition, derive functional requirements, trace requirements up to customer-imposed requirements, trace requirements within MAV requirement space, identify requirements trace gaps, define and map the physical design space architecture, allocate requirements to subsystems, develop validation items, define assembly, integration, and test (AI&T) operations, and trace these items across driving goals to develop an integrated digital thread of systems engineering information used to drive design specifications, decision making, and ultimately design verification and validation. Findings and results associated with implementing MBSE in these ways, alongside traditional methods will be discussed.
The objective of the NASA Mars Sample Return (MSR) Campaign is to collect samples from the surface of Mars and return them to Earth for scientific research. The Mars Ascent Vehicle (MAV) will be integrated into a larger Mars Sample Retrieval Lander (SRL) for transit to and storage on Mars. After all Martian samples have been collected and loaded into the MAV payload assembly, MAV will deliver the samples from the Martian surface to Mars orbit. A separate spacecraft, the Earth Return Orbiter (ERO) will retrieve the samples from Mars orbit and return them to Earth. To address common systems engineering challenges associated with using traditional systems engineering practices on complex projects, the MAV systems engineering team has explored implementation of Model-Based Systems Engineering (MBSE) tools and languages. This paper describes the current state of implementation and development of the MAV MBSE model with the Systems Modeling Language (SysML) within the scope of the MAV Systems Requirement Cycle (SRC) systems engineering workflow. The MAV MBSE model has been developed within Magic Draw – a SysML editor commonly used to implement MBSE. The MAV MBSE model has been used to develop mission phase functional flow diagrams for the Concept of Operations, decompose mission to vehicle subsystem functions, develop a functional decomposition, derive functional requirements, trace requirements up to customer-imposed requirements, trace requirements within MAV requirement space, identify requirements trace gaps, define and map the physical design space architecture, allocate requirements to subsystems, develop validation items, define assembly, integration, and test (AI&T) operations, and trace these items across driving goals to develop an integrated digital thread of systems engineering information used to drive design specifications, decision making, and ultimately design verification and validation. Findings and results associated with implementing MBSE in these ways, alongside traditional methods will be discussed.