Mini-BRU/BIPS 1300 watt (sub)e dynamic power conversion system development: Executive summary
NASA Technical Reports Server (NTRS)
1978-01-01
The status of the Brayton Isotope Power System (BIPS) is summarized. A 1200 watt sub e ground development unit was built and tested in a 0.000010 torr vacuum environment. Peformance mapping and 1000 hours of proof of concept system testing were completed. Specific components, primarily turbocompressor/alternator and recuperator performed according to predictions, thus achieving the design goal of 25 percent net power conversion efficiency. The system was fabricated from superalloy (Hastelloy-X and Waspaloy) thus placing it entirely within current state-of-the-art technology. The system could be flyable in the early 1980's pending flight qualification.
NASA Astrophysics Data System (ADS)
Yang, Zhao; Han, Dan; Chen, Guohong; Chen, Shiyou
2018-03-01
The III-V binary compound semiconductors such as GaN, GaP, InN and InP have extensive applications in various optoelectronic, microwave and power-electronic devices. Using first-principles calculation, we systematically studied the structural and electronic properties of the V-V binary compounds (BiN, BiP, SbN and SbP) that are isoelectronic to GaN, GaP, InN and InP if Bi and Sb are in the +3 valence state. Interestingly, we found that the ground-state structures of BiP, SbN and SbP have the R-3m symmetry and are isostructural to the layered structure of gray arsenic, whereas BiN prefers a different ground-state structure with the C2 symmetry. Electronic structure calculations showed that the bulk BiN is a narrow bandgap semiconductor for its bandgap is about 0.2 eV. In contrast, BiP, SbN and SbP are metallic. The layered ground-state structure of the V-V binary compounds motivates us to study the electronic properties of their few-layer structures. As the structure becomes monolayer, their bandgaps increase significantly and are all in the range from about 1 eV to 1.7 eV, which are comparative to the bandgap of the monolayer gray arsenic. The monolayer BiP, SbN and SbP have indirect bandgaps, and they show a semiconductor-metal transition as the number of layers increase. Interestingly, the monolayer BiP has the largest splitting (350 meV) of the CBM valley, and thus may have potential application in novel spintronics and valleytronics devices.
The Computer as a Tutorial Laboratory: The Stanford BIP Project.
ERIC Educational Resources Information Center
Barr, Avron; And Others
The BASIC Instructional Program (BIP) is an interactive problem-solving laboratory that offers tutorial assistance to students solving introductory programing problems in the BASIC language. After a brief review of the rationale and origins of the BIP instructional system, the design and implementation of BIP's curriculum information network are…
Proceedings of the Air Force Forum for Intelligent Tutoring Systems
1989-04-01
interface help the students find facts? I recently developed an expert system that is used at the JFK Airport to help workers assign incoming planes to...of their errors and to make comparisons with optimal solution paths. Chapters 2, and 5 BIP, BIP II: Basic Instructional Program BIP applied knowledge...OFFICE SYMBOL 7a NAME OF MONITORING ORGANIZATION Center for Applied Artificial (If applicable) Training Systems Division Intelligence 1 6. ADDRESS (City
Nimbus 4/IRLS Balloon Interrogation Package (BIP)
NASA Technical Reports Server (NTRS)
1971-01-01
The balloon interrogation package (BIP), an integral part of the overall interrogation, recording, and location subsystems (IRLS) for the Nimbus 4 program, is described. The BIP is a self-contained, integrated transponder designed to be carried aloft by a constant altitude, superpressure balloon to an altitude of 67,000 or 78,000 feet. After launch the BIP senses high-altitude balloon overpressure and temperature, and upon receipt of an interrogated command from the IRLS aboard the Nimbus 4 satellite, the BIP enodes the data on a real-time basis into a pulse-code modulation (PCM) format and transmits this data to the satellite. A summary of the program activity to produce 30 BIP systems and to support balloon launches from Ascension Island is presented.
Siegenthaler, Kevin D; Pareja, Kristeen A; Wang, Jie; Sevier, Carolyn S
2017-01-01
Unfavorable redox conditions in the endoplasmic reticulum (ER) can decrease the capacity for protein secretion, altering vital cell functions. While systems to manage reductive stress are well-established, how cells cope with an overly oxidizing ER remains largely undefined. In previous work (Wang et al., 2014), we demonstrated that the chaperone BiP is a sensor of overly oxidizing ER conditions. We showed that modification of a conserved BiP cysteine during stress beneficially alters BiP chaperone activity to cope with suboptimal folding conditions. How this cysteine is reduced to reestablish 'normal' BiP activity post-oxidative stress has remained unknown. Here we demonstrate that BiP's nucleotide exchange factor – Sil1 – can reverse BiP cysteine oxidation. This previously unexpected reductant capacity for yeast Sil1 has potential implications for the human ataxia Marinesco-Sjögren syndrome, where it is interesting to speculate that a disruption in ER redox-signaling (due to genetic defects in SIL1) may influence disease pathology. DOI: http://dx.doi.org/10.7554/eLife.24141.001 PMID:28257000
BASIC Instructional Program: System Documentation.
ERIC Educational Resources Information Center
Dageforde, Mary L.
This report documents the BASIC Instructional Program (BIP), a "hands-on laboratory" that teaches elementary programming in the BASIC language, as implemented in the MAINSAIL language, a machine-independent revision of SAIL which should facilitate implementation of BIP on other computing systems. Eight instructional modules which make up…
Picoli, E A.T.; Otoni, W C.; Figueira, M L.; Carolino, S M.B.; Almeida, R S.; Silva, E A.M.; Carvalho, C R.; Fontes, E P.B.
2001-04-01
The hyperhydricity in eggplant (Solanum melongena L.) plants was monitored by the induction of the ER-luminal resident protein BiP. Although tissue culture conditions may induce BiP synthesis, the accumulation of BiP in hyperhydric shoots was consistently higher than in non-hyperhydric shoots. The leaf and stem anatomy in non-hyperhydric and hyperhydric eggplant was investigated aiming to identify structural changes associated with this phenomenon. In non-hyperhydric organs there were smaller and more organized cells, besides a more differentiated vascular system when compared with its hyperhydric counterpart. Scanning electron microscopy of leaves showed that leaf surface and stomata differentiation were also affected in hyperhydric plants.
Program Completion and Re-Arrest in a Batterer Intervention System
ERIC Educational Resources Information Center
Bennett, Larry W.; Stoops, Charles; Call, Christine; Flett, Heather
2007-01-01
Objective: The authors examine the effects of batterer intervention program (BIP) completion on domestic violence re-arrest in an urban system of 30 BIPs with a common set of state standards, common program completion criteria, and centralized criminal justice supervision. Method: 899 men arrested for domestic violence were assessed and completed…
The ball in play demands of international rugby union.
Pollard, Benjamin T; Turner, Anthony N; Eager, Robin; Cunningham, Daniel J; Cook, Christian J; Hogben, Patrick; Kilduff, Liam P
2018-03-03
Rugby union is a high intensity intermittent sport, typically analysed via set time periods or rolling average methods. This study reports the demands of international rugby union via global positioning system (GPS) metrics expressed as mean ball in play (BiP), maximum BiP (max BiP), and whole match outputs. Single cohort cross sectional study involving 22 international players, categorised as forwards and backs. A total of 88 GPS files from eight international test matches were collected during 2016. An Opta sportscode timeline was integrated into the GPS software to split the data into BiP periods. Metres per min (mmin -1 ), high metabolic load per min (HML), accelerations per min (Acc), high speed running per min (HSR), and collisions per min (Coll) were expressed relative to BiP periods and over the whole match (>60min). Whole match metrics were significantly lower than all BiP metrics (p<0.001). Mean and max BiP HML, (p<0.01) and HSR (p<0.05) were significantly higher for backs versus forwards, whereas Coll were significantly higher for forwards (p<0.001). In plays lasting 61s or greater, max BiP mmin -1 were higher for backs. Max BiP mmin -1 , HML, HSR and Coll were all time dependant (p<0.05) showing that both movement metrics and collision demands differ as length of play continues. This study uses a novel method of accurately assessing the BiP demands of rugby union. It also reports typical and maximal demands of international rugby union that can be used by practitioners and scientists to target training of worst-case scenario's equivalent to international intensity. Backs covered greater distances at higher speeds and demonstrated higher HML, in general play as well as 'worst case scenarios'; conversely forwards perform a higher number of collisions. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.
Trends in Ground-State Entropies for Transition Metal Based Hydrogen Atom Transfer Reactions
Mader, Elizabeth A.; Manner, Virginia W.; Markle, Todd F.; Wu, Adam; Franz, James A.; Mayer, James M.
2009-01-01
Reported herein are thermochemical studies of hydrogen atom transfer (HAT) reactions involving transition metal H-atom donors MIILH and oxyl radicals. [FeII(H2bip)3]2+, [FeII(H2bim)3]2+, [CoII(H2bim)3]2+ and RuII(acac)2(py-imH) [H2bip = 2,2’-bi-1,4,5,6-tetrahydropyrimidine, H2bim = 2,2’-bi-imidazoline, acac = 2,4-pentandionato, py-imH = 2-(2’-pyridyl)-imidazole)] each react with TEMPO (2,2,6,6-tetramethyl-1-piperidinoxyl) or tBu3PhO• (2,4,6-tri-tert-butylphenoxyl) to give the deprotonated, oxidized metal complex MIIIL, and TEMPOH or tBu3PhOH. Solution equilibrium measurements for the reaction of [CoII(H2bim)3]2+ with TEMPO show a large, negative ground-state entropy for hydrogen atom transfer, −41 ± 2 cal mol−1 K−1. This is even more negative than the ΔSoHAT = −30 ± 2 cal mol−1 K−1 for the two iron complexes and the ΔSoHAT for RuII(acac)2(py-imH) + TEMPO, 4.9 ± 1.1 cal mol−1 K−1, as reported earlier. Calorimetric measurements quantitatively confirm the enthalpy of reaction for [FeII(H2bip)3]2+ + TEMPO, thus also confirming ΔSoHAT. Calorimetry on TEMPOH + tBu3PhO• gives ΔHoHAT = −11.2 ± 0.5 kcal mol−1 which matches the enthalpy predicted from the difference in literature solution BDEs. A brief evaluation of the literature thermochemistry of TEMPOH and tBu3PhOH supports the common assumption that ΔSoHAT ≈ 0 for HAT reactions of organic and small gas-phase molecules. However, this assumption does not hold for transition metal based HAT reactions. The trend in magnitude of |ΔSoHAT| for reactions with TEMPO, RuII(acac)2(py-imH) << [FeII(H2bip)3]2+ = [FeII(H2bim)3]2+ < [CoII(H2bim)3]2+, is surprisingly well predicted by the trends for electron transfer half-reaction entropies, ΔSoET, in aprotic solvents. This is because both ΔSoET and ΔSoHAT have substantial contributions from vibrational entropy, which varies significantly with the metal center involved. The close connection between ΔSoHAT and ΔSoET provides an important link between these two fields and provides a starting point from which to predict which HAT systems will have important ground-state entropy effects. PMID:19275235
Using iKidTools™ Software Support Systems to Develop and Implement Self-Monitoring Interventions
ERIC Educational Resources Information Center
Patti, Angela L.; Miller, Kevin J.
2011-01-01
Educational teams often are faced with the task of developing and implementing Behavioral Intervention Plans (BIPs) for students who present challenging and/or disruptive behaviors. This article describes the steps used to develop and implement a self-monitoring BIP that incorporated an innovative software system, iKidTools™. An authentic case…
ERIC Educational Resources Information Center
Adams, Jerry; Kenny, Thomas J.
1973-01-01
In this study, BIP records previously reported by Kenny (1971) were reused to determine the accuracy of identification of children with cerebral dysfunction and to update the results of using the revised BIP scoring system. (Author)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yan, Ming; Li, Jingzhi; Sha, Bingdong
2013-01-16
Sil1 functions as a NEF (nucleotide-exchange factor) for the ER (endoplasmic reticulum) Hsp70 (heat-shock protein of 70 kDa) Bip in eukaryotic cells. Sil1 may catalyse the ADP release from Bip by interacting directly with the ATPase domain of Bip. In the present study we show the complex crystal structure of the yeast Bip and the NEF Sil1 at the resolution of 2.3 {angstrom} (1 {angstrom} = 0.1 nm). In the Sil1-Bip complex structure, the Sil1 molecule acts as a 'clamp' which binds lobe IIb of the Bip ATPase domain. The binding of Sil1 causes the rotation of lobe IIb {approx}more » 13.5{sup o} away from the ADP-binding pocket. The complex formation also induces lobe Ib to swing in the opposite direction by {approx} 3.7{sup o}. These conformational changes open up the nucleotide-binding pocket in the Bip ATPase domain and disrupt the hydrogen bonds between Bip and bound ADP, which may catalyse ADP release. Mutation of the Sil1 residues involved in binding the Bip ATPase domain compromise the binding affinity of Sil1 to Bip, and these Sil1 mutants also abolish the ability to stimulate the ATPase activity of Bip.« less
Patterson, Dianne K.; Van Petten, Cyma; Beeson, Pélagie M.; Rapcsak, Steven Z.; Plante, Elena
2014-01-01
This paper introduces a Bidirectional Iterative Parcellation (BIP) procedure designed to identify the location and size of connected cortical regions (parcellations) at both ends of a white matter tract in diffusion weighted images. The procedure applies the FSL option “probabilistic tracking with classification targets” in a bidirectional and iterative manner. To assess the utility of BIP, we applied the procedure to the problem of parcellating a limited set of well-established gray matter seed regions associated with the dorsal (arcuate fasciculus/superior longitudinal fasciculus) and ventral (extreme capsule fiber system) white matter tracts in the language networks of 97 participants. These left hemisphere seed regions and the two white matter tracts, along with their right hemisphere homologues, provided an excellent test case for BIP because the resulting parcellations overlap and their connectivity via the arcuate fasciculi and extreme capsule fiber systems are well studied. The procedure yielded both confirmatory and novel findings. Specifically, BIP confirmed that each tract connects within the seed regions in unique, but expected ways. Novel findings included increasingly left-lateralized parcellations associated with the arcuate fasciculus/superior longitudinal fasciculus as a function of age and education. These results demonstrate that BIP is an easily implemented technique that successfully confirmed cortical connectivity patterns predicted in the literature, and has the potential to provide new insights regarding the architecture of the brain. PMID:25173414
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fan, Haitian; Hahm, Joseph; Diggs, Stephen
The translational GTPase BipA regulates the expression of virulence and pathogenicity factors in several eubacteria. BipA-dependent expression of virulence factors occurs under starvation conditions, such as encountered during infection of a host. Under these conditions, BipA associates with the small ribosomal subunit. BipA also has a second function to promote the efficiency of late steps in biogenesis of large ribosomal subunits at low temperatures, presumably while bound to the ribosome. During starvation, the cellular concentration of stress alarmone guanosine-3', 5'-bis pyrophosphate (ppGpp) is increased. This increase allows ppGpp to bind to BipA and switch its binding specificity from ribosomes tomore » small ribosomal subunits. A conformational change of BipA upon ppGpp binding could explain the ppGpp regulation of the binding specificity of BipA. Here, we present the structures of the full-length BipA from Escherichia coli in apo, GDP-, and ppGpp-bound forms. The crystal structure and small-angle x-ray scattering data of the protein with bound nucleotides, together with a thermodynamic analysis of the binding of GDP and of ppGpp to BipA, indicate that the ppGpp-bound form of BipA adopts the structure of the GDP form. This suggests furthermore, that the switch in binding preference only occurs when both ppGpp and the small ribosomal subunit are present. Finally, this molecular mechanism would allow BipA to interact with both the ribosome and the small ribosomal subunit during stress response.« less
Fan, Haitian; Hahm, Joseph; Diggs, Stephen; ...
2015-07-10
The translational GTPase BipA regulates the expression of virulence and pathogenicity factors in several eubacteria. BipA-dependent expression of virulence factors occurs under starvation conditions, such as encountered during infection of a host. Under these conditions, BipA associates with the small ribosomal subunit. BipA also has a second function to promote the efficiency of late steps in biogenesis of large ribosomal subunits at low temperatures, presumably while bound to the ribosome. During starvation, the cellular concentration of stress alarmone guanosine-3', 5'-bis pyrophosphate (ppGpp) is increased. This increase allows ppGpp to bind to BipA and switch its binding specificity from ribosomes tomore » small ribosomal subunits. A conformational change of BipA upon ppGpp binding could explain the ppGpp regulation of the binding specificity of BipA. Here, we present the structures of the full-length BipA from Escherichia coli in apo, GDP-, and ppGpp-bound forms. The crystal structure and small-angle x-ray scattering data of the protein with bound nucleotides, together with a thermodynamic analysis of the binding of GDP and of ppGpp to BipA, indicate that the ppGpp-bound form of BipA adopts the structure of the GDP form. This suggests furthermore, that the switch in binding preference only occurs when both ppGpp and the small ribosomal subunit are present. Finally, this molecular mechanism would allow BipA to interact with both the ribosome and the small ribosomal subunit during stress response.« less
Zacchi, Lucía F.; Wu, Hui-Chuan; Bell, Samantha L.; Millen, Linda; Paton, Adrienne W.; Paton, James C.; Thomas, Philip J.; Zolkiewski, Michal; Brodsky, Jeffrey L.
2014-01-01
Early-onset torsion dystonia (EOTD) is a neurological disorder characterized by involuntary and sustained muscle contractions that can lead to paralysis and abnormal posture. EOTD is associated with the deletion of a glutamate (ΔE) in torsinA, an endoplasmic reticulum (ER) resident AAA+ ATPase. To date, the effect of ΔE on torsinA and the reason that this mutation results in EOTD are unclear. Moreover, there are no specific therapeutic options to treat EOTD. To define the underlying biochemical defects associated with torsinAΔE and to uncover factors that might be targeted to offset defects associated with torsinAΔE, we developed a yeast torsinA expression system and tested the roles of ER chaperones in mediating the folding and stability of torsinA and torsinAΔE. We discovered that the ER lumenal Hsp70, BiP, an associated Hsp40, Scj1, and a nucleotide exchange factor, Lhs1, stabilize torsinA and torsinAΔE. BiP also maintained torsinA and torsinAΔE solubility. Mutations predicted to compromise specific torsinA functional motifs showed a synthetic interaction with the ΔE mutation and destabilized torsinAΔE, suggesting that the ΔE mutation predisposes torsinA to defects in the presence of secondary insults. In this case, BiP was required for torsinAΔE degradation, consistent with data that specific chaperones exhibit either pro-degradative or pro-folding activities. Finally, using two independent approaches, we established that BiP stabilizes torsinA and torsinAΔE in mammalian cells. Together, these data define BiP as the first identified torsinA chaperone, and treatments that modulate BiP might improve symptoms associated with EOTD. PMID:24627482
Aβ mediates Sigma receptor degradation via CaN/NFAT pathway
Fang, Min; Zhang, Pei; Zhao, Yanxin; Jin, Aiping; Liu, Xueyuan
2016-01-01
Sigma receptor is an endoplasmic reticulum protein and belongs to non-opioid receptor. Increasing evidence shows that Sigma receptor activation can significantly attenuate AD induced neurological dysfunction and the functional deficiency of Sigma receptor plays an important role in the Aβ induced neuronal loss. This study aimed to investigate the influence of extracellular accumulation of Aβ on the Sigma receptor expression. Our results showed the increase in extracellular Aβ had little influence on the mRNA expression of Sigma receptor, but gradually reduced its protein expression. Co-immunoprecipitation was employed to evaluate the interaction of Sigma receptor with other proteins. Results showed BIP could bind to Sigma receptor to affect the ubiquitination of Sigma receptor. Further investigation showed there was a NFAT binding site at the promoter of BIP. Then, Western blot assay was performed to detect NFAT expression. Results showed extracellular Aβ affected the nuclear translocation of NFAT and the CaN activity of NFAT also increased with the accumulation of extracellular Aβ. In this study, NFAT-BIP luciferase reporter gene system was constructed. Results showed NFAT was able to regulate the transcription of BIP. Thus, we speculate that extracellular Aβ accumulation may activate CaN/NFAT signaling pathway to induce chaperone BIP expression, which results in Sigma receptor ubiquitination and its degradation. PMID:27648137
Salmonella Enterica Serovar Typhimurium BipA Exhibits Two Distinct Ribosome Binding Modes
DOE Office of Scientific and Technical Information (OSTI.GOV)
deLivron, M.; Robinson, V
BipA is a highly conserved prokaryotic GTPase that functions to influence numerous cellular processes in bacteria. In Escherichia coli and Salmonella enterica serovar Typhimurium, BipA has been implicated in controlling bacterial motility, modulating attachment and effacement processes, and upregulating the expression of virulence genes and is also responsible for avoidance of host defense mechanisms. In addition, BipA is thought to be involved in bacterial stress responses, such as those associated with virulence, temperature, and symbiosis. Thus, BipA is necessary for securing bacterial survival and successful invasion of the host. Steady-state kinetic analysis and pelleting assays were used to assess themore » GTPase and ribosome-binding properties of S. enterica BipA. Under normal bacterial growth, BipA associates with the ribosome in the GTP-bound state. However, using sucrose density gradients, we demonstrate that the association of BipA and the ribosome is altered under stress conditions in bacteria similar to those experienced during virulence. The data show that this differential binding is brought about by the presence of ppGpp, an alarmone that signals the onset of stress-related events in bacteria.« less
Yu, Mei; Gao, Qiong
2011-01-01
Background and Aims The ability to simulate plant competition accurately is essential for plant functional type (PFT)-based models used in climate-change studies, yet gaps and uncertainties remain in our understanding of the details of the competition mechanisms and in ecosystem responses at a landscape level. This study examines secondary succession in a temperate deciduous forest in eastern China with the aim of determining if competition between tree types can be explained by differences in leaf ecophysiological traits and growth allometry, and whether ecophysiological traits and habitat spatial configurations among PFTs differentiate their responses to climate change. Methods A temperate deciduous broadleaved forest in eastern China was studied, containing two major vegetation types dominated by Quercus liaotungensis (OAK) and by birch/poplar (Betula platyphylla and Populus davidiana; BIP), respectively. The Terrestrial Ecosystem Simulator (TESim) suite of models was used to examine carbon and water dynamics using parameters measured at the site, and the model was evaluated against long-term data collected at the site. Key Results Simulations indicated that a higher assimilation rate for the BIP vegetation than OAK led to the former's dominance during early successional stages with relatively low competition. In middle/late succession with intensive competition for below-ground resources, BIP, with its lower drought tolerance/resistance and smaller allocation to leaves/roots, gave way to OAK. At landscape scale, predictions with increased temperature extrapolated from existing weather records resulted in increased average net primary productivity (NPP; +19 %), heterotrophic respiration (+23 %) and net ecosystem carbon balance (+17 %). The BIP vegetation in higher and cooler habitats showed 14 % greater sensitivity to increased temperature than the OAK at lower and warmer locations. Conclusions Drought tolerance/resistance and morphology-related allocation strategy (i.e. more allocation to leaves/roots) played key roles in the competition between the vegetation types. The overall site-average impacts of increased temperature on NPP and carbon stored in plants were found to be positive, despite negative effects of increased respiration and soil water stress, with such impacts being more significant for BIP located in higher and cooler habitats. PMID:21835816
Gassab, L; Mechri, A; Bacha, M; Gaddour, N; Gaha, L
2008-10-01
Recent research postulated that temperaments represent the subclinical foundations of affective disorders, and an early clue for a recurrent, prebipolar disorder. Akiskal et al. operationalized five types of temperaments: depressive, hyperthymic, irritable, cyclothymic and anxious. The aims of this study were to compare the affective temperaments scores in patients with bipolar I, II and recurrent depression disorders and to explore the relation between temperaments scores and clinical features of those affective disorders. This was a comparative cross-sectional study, concerning three groups: patients with bipolar I disorder (BIP I) (n=31, 20 men and 11 women, mean age=42.0+/-10.1 years), patients with bipolar II disorder (BIP II) (n=18, 11 men and seven women, mean age=40.7+/-10.8 years) and patients with recurrent depressive disorder (RDD) (n=66, 28 men and 38 women, mean age=45.0+/-9.3 years). All patients were in remission of a major depressive episode. The affective temperaments were assessed by the Akiskal and Mallya Affective Temperament questionnaires. Hyperthymic temperament mean scores were higher in BIP I (10.8+/-5.4) and BIP II (10.3+/-5.5) groups compared to RDD group (5.5+/-4.0) (p<10(-3)). Depressive temperament mean score was significantly higher in RDD group (10.5+/-4.3), compared to BIP I (7.3+/-4.6) and BIP II (5.4+/-2.9) groups (p<10(-3)). Cyclothymic temperament mean score was higher in BIP II group (4.7+/-5.8) compared to BIP I (3.3+/-3.9) and RDD (2.5+/-3.9) groups, but this difference was not significant (p=0.08). No difference was found between the three groups concerning irritable temperament scores. Negative correlation was found between hyperthymic and depressive temperament scores in BIP I (r=-0.81, p<0.001) and RDD (r=-0.73, p<0.001) groups, but not in BIP II group. Concerning the clinical correlates with affective temperament scores, negative correlation was found between hyperthymic temperament score and number of depressive episodes in BIP II group (r=-0.53, p=0.02). Hyperthymic temperament score was associated with psychotic features in the last depressive episode in BIP I (p=0.01) and BIP II (p=0.008) groups and seasonal features in BIP II group (p=0.02). Moreover, cyclothymic temperament score was associated with psychotic (p=0.009) and seasonal features (p=0.03) in BIP II group. Despite the small sample sizes for our study groups, we can conclude that hyperthymic and cyclothymic temperaments characterized bipolar disorders and are correlated with other markers of bipolarity such as psychotic and seasonal features. Thus, temperament assessment might become a useful tool to predict bipolarity in association with those markers.
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Zhu, Jiantang; Hao, Pengchao; Chen, Guanxing; Han, Caixia; Li, Xiaohui; Zeller, Friedrich J; Hsam, Sai L K; Hu, Yingkao; Yan, Yueming
2014-10-01
The endoplasmic reticulum chaperone binding protein (BiP) is an important functional protein, which is involved in protein synthesis, folding assembly, and secretion. In order to study the role of BiP in the process of wheat seed development, we cloned three BiP homologous cDNA sequences in bread wheat (Triticum aestivum), completed by rapid amplification of cDNA ends (RACE), and examined the expression of wheat BiP in wheat tissues, particularly the relationship between BiP expression and the subunit types of HMW-GS using near-isogenic lines (NILs) of HMW-GS silencing, and under abiotic stress. Sequence analysis demonstrated that all BiPs contained three highly conserved domains present in plants, animals, and microorganisms, indicating their evolutionary conservation among different biological species. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed that TaBiP (Triticum aestivum BiP) expression was not organ-specific, but was predominantly localized to seed endosperm. Furthermore, immunolocalization confirmed that TaBiP was primarily located within the protein bodies (PBs) in wheat endosperm. Three TaBiP genes exhibited significantly down-regulated expression following high molecular weight-glutenin subunit (HMW-GS) silencing. Drought stress induced significantly up-regulated expression of TaBiPs in wheat roots, leaves, and developing grains. The high conservation of BiP sequences suggests that BiP plays the same role, or has common mechanisms, in the folding and assembly of nascent polypeptides and protein synthesis across species. The expression of TaBiPs in different wheat tissue and under abiotic stress indicated that TaBiP is most abundant in tissues with high secretory activity and with high proportions of cells undergoing division, and that the expression level of BiP is associated with the subunit types of HMW-GS and synthesis. The expression of TaBiPs is developmentally regulated during seed development and early seedling growth, and under various abiotic stresses.
78 FR 11136 - Submission for OMB Review; Comment Request
Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-15
... Broadband Initiatives Program (BIP). The Rural Utilities Service (RUS) established the BIP which may extend... establishes for BIP financing. Description of Respondents: Business or other for-profit. Number of Respondents...
Miura, Yosuke; Kaira, Kyoichi; Sakurai, Reiko; Imai, Hisao; Tomizawa, Yoshio; Sunaga, Noriaki; Minato, Koichi; Hisada, Takeshi; Oyama, Tetsunari; Yamada, Masanobu
2017-10-01
Glucose-regulated protein (GRP) 78/immunoglobulin heavy chain binding protein (BiP) is a member of the endoplasmic reticulum chaperone family, and its role in various types of human malignancies has recently been investigated. However, the clinicopathological characteristics of GRP78/BiP in advanced thymic carcinoma (ATC) remain unknown. We aimed to examine the relationship between GRP78/BiP expression and the clinical outcomes of ATC patients. Thirty-four patients with ATC receiving combination chemotherapy at three institutions between April 1998 and April 2014 were enrolled in this study. We retrospectively collected patient characteristics such as therapeutic efficacy, pathological findings, and survival data from their medical records. We performed immunohistochemical analysis to evaluate the expression of GRP78/BiP in tumor specimens obtained from surgical resection or biopsy. This study included 21 men (68%) and 13 women (32%) with a median age of 62 years (range 36-75 years). GRP78/BiP overexpression was observed in 65% of the patients (22 of 34 patients). There was no correlation between GRP78/BiP expression and any patient characteristic. Patients with a high level of GRP78/BiP expression had significantly longer overall survival (OS) compared to those with a low level (46.2 vs. 16.8 months, p = 0.04). Multivariate analysis demonstrated that a high level of GRP78/BiP expression was an independent prognostic factor for prolonged OS. Our findings indicate that the overexpression of GRP78/BiP is a novel predictor of favorable outcomes in patients with ATC who receive combination chemotherapy.
Reis, Pedro A A; Rosado, Gustavo L; Silva, Lucas A C; Oliveira, Luciana C; Oliveira, Lucas B; Costa, Maximiller D L; Alvim, Fátima C; Fontes, Elizabeth P B
2011-12-01
The molecular chaperone binding protein (BiP) participates in the constitutive function of the endoplasmic reticulum (ER) and protects the cell against stresses. In this study, we investigated the underlying mechanism by which BiP protects plant cells from stress-induced cell death. We found that enhanced expression of BiP in soybean (Glycine max) attenuated ER stress- and osmotic stress-mediated cell death. Ectopic expression of BiP in transgenic lines attenuated the leaf necrotic lesions that are caused by the ER stress inducer tunicamycin and also maintained shoot turgidity upon polyethylene glycol-induced dehydration. BiP-mediated attenuation of stress-induced cell death was confirmed by the decreased percentage of dead cell, the reduced induction of the senescence-associated marker gene GmCystP, and reduced DNA fragmentation in BiP-overexpressing lines. These phenotypes were accompanied by a delay in the induction of the cell death marker genes N-RICH PROTEIN-A (NRP-A), NRP-B, and GmNAC6, which are involved in transducing a cell death signal generated by ER stress and osmotic stress through the NRP-mediated signaling pathway. The prosurvival effect of BiP was associated with modulation of the ER stress- and osmotic stress-induced NRP-mediated cell death signaling, as determined in transgenic tobacco (Nicotiana tabacum) lines with enhanced (sense) and suppressed (antisense) BiP levels. Enhanced expression of BiP prevented NRP- and NAC6-mediated chlorosis and the appearance of senescence-associated markers, whereas silencing of endogenous BiP accelerated the onset of leaf senescence mediated by NRPs and GmNAC6. Collectively, these results implicate BiP as a negative regulator of the stress-induced NRP-mediated cell death response.
Reis, Pedro A.A.; Rosado, Gustavo L.; Silva, Lucas A.C.; Oliveira, Luciana C.; Oliveira, Lucas B.; Costa, Maximiller D.L.; Alvim, Fátima C.; Fontes, Elizabeth P.B.
2011-01-01
The molecular chaperone binding protein (BiP) participates in the constitutive function of the endoplasmic reticulum (ER) and protects the cell against stresses. In this study, we investigated the underlying mechanism by which BiP protects plant cells from stress-induced cell death. We found that enhanced expression of BiP in soybean (Glycine max) attenuated ER stress- and osmotic stress-mediated cell death. Ectopic expression of BiP in transgenic lines attenuated the leaf necrotic lesions that are caused by the ER stress inducer tunicamycin and also maintained shoot turgidity upon polyethylene glycol-induced dehydration. BiP-mediated attenuation of stress-induced cell death was confirmed by the decreased percentage of dead cell, the reduced induction of the senescence-associated marker gene GmCystP, and reduced DNA fragmentation in BiP-overexpressing lines. These phenotypes were accompanied by a delay in the induction of the cell death marker genes N-RICH PROTEIN-A (NRP-A), NRP-B, and GmNAC6, which are involved in transducing a cell death signal generated by ER stress and osmotic stress through the NRP-mediated signaling pathway. The prosurvival effect of BiP was associated with modulation of the ER stress- and osmotic stress-induced NRP-mediated cell death signaling, as determined in transgenic tobacco (Nicotiana tabacum) lines with enhanced (sense) and suppressed (antisense) BiP levels. Enhanced expression of BiP prevented NRP- and NAC6-mediated chlorosis and the appearance of senescence-associated markers, whereas silencing of endogenous BiP accelerated the onset of leaf senescence mediated by NRPs and GmNAC6. Collectively, these results implicate BiP as a negative regulator of the stress-induced NRP-mediated cell death response. PMID:22007022
Poucher, Stephanie M
In 1997, Congress amended the Individuals with Disabilities Education Act ("IDEA") to include provisions meant to assist school districts in educating students with behavioral needs. These amendments required schools to use functional behavioral assessments ("FBA") and behavior intervention plans ("BIP") under certain circumstances. Congress did not, however, include a definition of or substantive requirements for either system of behavior management. As a result, although BIPs and FBAs are now federally mandated requirements, and it is clear that disregarding behavioral issues is a denial of a free appropriate public education ("FAPE"), the IDEA’s adjudicative standard, there is no clear consensus as to whether a student with behavioral needs must have an FBA or a BIP or what either must include. The IDEA’s lack of guidance has resulted in inconsistent and often contradictory court rulings, and the lack of specific definitions and procedures has allowed schools to develop purportedly legal but substantively deficient behavior evaluations and intervention plans for special needs students. Despite this confusion, some courts have properly looked to the administrative record for guidance on the substantive elements of FBAs and BIPs. Deference to hearing officers, along with other provisions within the IDEA, such as Child Find and inclusion obligations, may assist courts in determining whether a school’s failure to use an FBA and a BIP for a student with behavioral needs falls short of Board of Education v. Rowley’s requirements for FAPE. FBAs and BIPs aim to prevent and correct student misconduct before it escalates and results in drastic disciplinary action. Given the impact punitive school discipline policies have had on students with special needs, the added procedural safeguards these proactive behavior management schemes could provide are imperative to dismantling the school-to-prison pipeline.
Bloch, Rebecca A; Cronin, Kimberly; Hoover, John P; Pechman, Robert D; Payton, Mark E
2010-03-01
Barium impregnated polyethylene spheres (BIPS) are used in small animal medicine as an alternative to barium sulfate for radiographic studies of the gastrointestinal tract. To determine the usefulness of BIPS as an alternative to barium suspension in measuring gastrointestinal (GI) transit time for avian species, ventrodorsal radiographs were used to follow the passage of BIPS and 30% barium sulfate suspension through the GI tracts of domestic pigeons (Columba livia). Gastrointestinal transit times of thirty 1.5-mm BIPS administered in moistened gelatin capsules and 30% barium sulfate suspension gavaged into the crop were compared in 6 pigeons. Although the barium suspension passed out of the GI tract of all pigeons within 24 hours, the 1.5-mm BIPS remained in the ventriculus for 368.0 +/- 176.8 hours and did not clear the GI tract for 424.0 +/- 204.6 hours. Although the times for passage of BIPS and 30% barium sulfate suspension from the crop into the ventriculus were not significantly different (P = .14), the times for passage of BIPS from the ventriculus into the large intestine-cloaca and for clearance from the GI tract of the pigeons were significantly longer (P < .001) than for the 30% barium sulfate suspension. From the results of this study, we conclude that BIPS are not useful for radiographically evaluating GI transit times in pigeons and are unlikely to be useful in other avian species that have a muscular ventriculus. BIPS may or may not be useful for evaluating GI transit times in species that lack a muscular ventriculus.
BIP induces mice CD19(hi) regulatory B cells producing IL-10 and highly expressing PD-L1, FasL.
Tang, Youfa; Jiang, Qing; Ou, Yanghui; Zhang, Fan; Qing, Kai; Sun, Yuanli; Lu, Wenjie; Zhu, Huifen; Gong, Feili; Lei, Ping; Shen, Guanxin
2016-01-01
Many studies have shown that B cells possess a regulatory function in mouse models of autoimmune diseases. Regulatory B cells can modulate immune response through many types of molecular mechanisms, including the production of IL-10 and the expression of PD-1 Ligand and Fas Ligand, but the microenvironmental factors and mechanisms that induce regulatory B cells have not been fully identified. BIP (binding immunoglobulin protein), a member of the heat shock protein 70 family, is a type of evolutionarily highly conserved protein. In this article, we have found that IL-10(+), PD-L1(hi) and FasL(hi) B cells are discrete cell populations, but enriched in CD19(hi) cells. BIP can induce IL-10-producing splenic B cells, IL-10 secretion and B cells highly expressing PD-L1 and FasL. CD40 signaling acts in synergy with BIP to induce regulatory B cells. BIP increased surface CD19 molecule expression intensity and IL-10(+), PD-L1(hi) and FasL(hi) B cells induced by BIP share the CD19(hi) phenotype. Furthermore, B cells treated with BIP and anti-CD40 can lead to suppression of T cell proliferation and the effect is partially IL-10-dependent and mainly BIP-induced. Taken together, our findings identify a novel function of BIP in the induction of regulatory B cells and add a new reason for the therapy of autoimmune disorders or other inflammatory conditions. Copyright © 2015. Published by Elsevier Ltd.
Molecular Chaperone BiP Interacts with Borna Disease Virus Glycoprotein at the Cell Surface▿ †
Honda, Tomoyuki; Horie, Masayuki; Daito, Takuji; Ikuta, Kazuyoshi; Tomonaga, Keizo
2009-01-01
Borna disease virus (BDV) is characterized by highly neurotropic infection. BDV enters its target cells using virus surface glycoprotein (G), but the cellular molecules mediating this process remain to be elucidated. We demonstrate here that the N-terminal product of G, GP1, interacts with the 78-kDa chaperone protein BiP. BiP was found at the surface of BDV-permissive cells, and anti-BiP antibody reduced BDV infection as well as GP1 binding to the cell surface. We also reveal that BiP localizes at the synapse of neurons. These results indicate that BiP may participate in the cell surface association of BDV. PMID:19776128
BiP clustering facilitates protein folding in the endoplasmic reticulum.
Griesemer, Marc; Young, Carissa; Robinson, Anne S; Petzold, Linda
2014-07-01
The chaperone BiP participates in several regulatory processes within the endoplasmic reticulum (ER): translocation, protein folding, and ER-associated degradation. To facilitate protein folding, a cooperative mechanism known as entropic pulling has been proposed to demonstrate the molecular-level understanding of how multiple BiP molecules bind to nascent and unfolded proteins. Recently, experimental evidence revealed the spatial heterogeneity of BiP within the nuclear and peripheral ER of S. cerevisiae (commonly referred to as 'clusters'). Here, we developed a model to evaluate the potential advantages of accounting for multiple BiP molecules binding to peptides, while proposing that BiP's spatial heterogeneity may enhance protein folding and maturation. Scenarios were simulated to gauge the effectiveness of binding multiple chaperone molecules to peptides. Using two metrics: folding efficiency and chaperone cost, we determined that the single binding site model achieves a higher efficiency than models characterized by multiple binding sites, in the absence of cooperativity. Due to entropic pulling, however, multiple chaperones perform in concert to facilitate the resolubilization and ultimate yield of folded proteins. As a result of cooperativity, multiple binding site models used fewer BiP molecules and maintained a higher folding efficiency than the single binding site model. These insilico investigations reveal that clusters of BiP molecules bound to unfolded proteins may enhance folding efficiency through cooperative action via entropic pulling.
Shah, Dinen D.; Singh, Surinder M.; Dzieciatkowska, Monika
2017-01-01
Binding immunoglobulin protein (BiP) is a molecular chaperone important for the folding of numerous proteins, which include millions of immunoglobulins in human body. It also plays a key role in the unfolded protein response (UPR) in the endoplasmic reticulum. Free radical generation is a common phenomenon that occurs in cells under healthy as well as under stress conditions such as ageing, inflammation, alcohol consumption, and smoking. These free radicals attack the cell membranes and generate highly reactive lipid peroxidation products such as 4-oxononenal (4-ONE). BiP is a key protein that is modified by 4-ONE. In this study, we probed how such chemical modification affects the biophysical properties of BiP. Upon modification, BiP shows significant tertiary structural changes with no changes in its secondary structure. The protein loses its thermodynamic stability, particularly, that of the nucleotide binding domain (NBD) where ATP binds. In terms of function, the modified BiP completely loses its ATPase activity with decreased ATP binding affinity. However, modified BiP retains its immunoglobulin binding function and its chaperone activity of suppressing non-specific protein aggregation. These results indicate that 4-ONE modification can significantly affect the structure-function of key proteins such as BiP involved in cellular pathways, and provide a molecular basis for how chemical modifications can result in the failure of quality control mechanisms inside the cell. PMID:28886061
1988-06-04
Life is full of bleeps these days. Apart from bleeping doctors and senior nurses, the ubiquitous aircall bleep seems to be as essential as the Filofax in certain quarters. Not to mention bleeping watches (which usually emit insistent bip-bip-bips during the quiet bits when you're at the cinema).
75 FR 4336 - Submission for OMB Review; Comment Request
Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-27
... billion of budget authority for establishing the Broadband Initiatives Program (BIP). The Rural Utilities Service (RUS) is establishing the BIP which may extend loans, grants, and loan/grant combinations to... establishes for BIP financing. Description of Respondents: Business or other for-profit. Number of Respondents...
Regulated release of ERdj3 from unfolded proteins by BiP
Jin, Yi; Awad, Walid; Petrova, Kseniya; Hendershot, Linda M
2008-01-01
DnaJ proteins often bind to unfolded substrates and recruit their Hsp70 partners. This induces a conformational change in the Hsp70 that stabilizes its binding to substrate. By some unknown mechanism, the DnaJ protein is released. We examined the requirements for the release of ERdj3, a mammalian ER DnaJ, from substrates and found that BiP promoted the release of ERdj3 only in the presence of ATP. Mutations in ERdj3 or BiP that disrupted their interaction interrupted the release of ERdj3. BiP mutants that were defective in any step of the ATPase cycle were also unable to release ERdj3. These results demonstrate that a functional interaction between ERdj3 and BiP, including both a direct interaction and the ability to stimulate BiP's ATPase activity are required to release ERdj3 from substrate and support a model where ERdj3 must recruit BiP and stimulate its high-affinity association with the substrate through activation of ATP hydrolysis to trigger its own release from substrates. On the basis of similarities among DnaJs and Hsp70s, this is likely to be applicable to other Hsp70–DnaJ pairs. PMID:18923428
Eckes, Annemarie H.; Gubała, Tomasz; Nowakowski, Piotr; Szymczyszyn, Tomasz; Wells, Rachel; Irwin, Judith A.; Horro, Carlos; Hancock, John M.; King, Graham; Dyer, Sarah C.; Jurkowski, Wiktor
2017-01-01
The Brassica Information Portal (BIP) is a centralised repository for brassica phenotypic data. The site hosts trait data associated with brassica research and breeding experiments conducted on brassica crops, that are used as oilseeds, vegetables, livestock forage and fodder and for biofuels. A key feature is the explicit management of meta-data describing the provenance and relationships between experimental plant materials, as well as trial design and trait descriptors. BIP is an open access and open source project, built on the schema of CropStoreDB, and as such can provide trait data management strategies for any crop data. A new user interface and programmatic submission/retrieval system helps to simplify data access for researchers, breeders and other end-users. BIP opens up the opportunity to apply integrative, cross-project analyses to data generated by the Brassica Research Community. Here, we present a short description of the current status of the repository. PMID:28529710
Tepe, Bektas; Sokmen, Atalay
2007-11-01
Methanolic extracts of three different Tanacetum subspecies [Tanacetum densum (Lab.) Schultz Bip. subsp. sivasicum Hub-Mor and Grierson, Tanacetum densum (Lab.) Schultz Bip. subsp. eginense Heywood and Tanacetum densum (Lab.) Schultz Bip. subsp. amani Heywood] which are endemic to Turkish flora were screened for their possible antioxidant activities by two complementary test systems namely DPPH free radical scavenging and beta-carotene/linoleic acid. In DPPH system, the most active plant was T. densum subsp. amani with an IC(50) value of 69.30+/-0.37 microg/ml. On the other hand, T. densum subsp. sivasicum exerted greater antioxidant activity than those of other subspecies in beta-carotene/linoleic acid system (79.10%+/-1.83). Antioxidant activities of BHT, curcumine and ascorbic acid were also determined as positive controls in parallel experiments. Total phenolic constituents of the extracts of Tanacetum subspecies were performed employing the literature methods involving Folin-Ciocalteu reagent and gallic acid as standard. The amount of total phenolics was highest in subsp. sivasicum (162.33+/-3.57 microg/mg), followed by subsp. amani (158.44+/-2.17 microg/mg). Especially, a positive correlation was observed between total phenolic content and antioxidant activity of the extracts.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-04-04
... Plan (BIP). This document is intended to describe the priority activities to occur during fiscal years.... The target audience for the BIP is the Nation (individuals, families, communities including all... the draft BIP document which address (1) Strategic Objective 4, Foster Integrated, Scalable Health...
False Negatives, Canter's Background Interference Procedure, the Trail Making Test, and Epileptics.
ERIC Educational Resources Information Center
McKinzey, Ronald K.; And Others
1985-01-01
Results of correlation studies of 141 adult epileptics' scores on the Background Interference Procedure (BIP) indicated that the BIP often does not agree with abnormal neurological diagnoses but often does agree with psychiatric diagnoses of Organic Brain Syndrome (OBS). Suggests that future BIP validity studies include a behavioral measure of OBS…
76 FR 24045 - Notice of HUD-Held Multifamily Loan Sale (MLS 2011-1)
Federal Register 2010, 2011, 2012, 2013, 2014
2011-04-29
... Package (BIP) was made available to qualified bidders on March 30, 2011. Submissions of bids for the loans... BIP, prospective bidders must have completed, executed, and submitted a Confidentiality Agreement and... comprised of non-performing mortgage loans. A final listing of the Mortgage Loans was included in the BIP...
Bio-inspired patterned networks (BIPS) for development of wearable/disposable biosensors
NASA Astrophysics Data System (ADS)
McLamore, E. S.; Convertino, M.; Hondred, John; Das, Suprem; Claussen, J. C.; Vanegas, D. C.; Gomes, C.
2016-05-01
Here we demonstrate a novel approach for fabricating point of care (POC) wearable electrochemical biosensors based on 3D patterning of bionanocomposite networks. To create Bio-Inspired Patterned network (BIPS) electrodes, we first generate fractal network in silico models that optimize transport of network fluxes according to an energy function. Network patterns are then inkjet printed onto flexible substrate using conductive graphene ink. We then deposit fractal nanometal structures onto the graphene to create a 3D nanocomposite network. Finally, we biofunctionalize the surface with biorecognition agents using covalent bonding. In this paper, BIPS are used to develop high efficiency, low cost biosensors for measuring glucose as a proof of concept. Our results on the fundamental performance of BIPS sensors show that the biomimetic nanostructures significantly enhance biosensor sensitivity, accuracy, response time, limit of detection, and hysteresis compared to conventional POC non fractal electrodes (serpentine, interdigitated, and screen printed electrodes). BIPs, in particular Apollonian patterned BIPS, represent a new generation of POC biosensors based on nanoscale and microscale fractal networks that significantly improve electrical connectivity, leading to enhanced sensor performance.
van Heugten, Caroline M; Geurtsen, Gert J; Derksen, R Elze; Martina, Juan D; Geurts, Alexander C H; Evers, Silvia M A A
2011-06-01
The objective of this study was to examine the intervention costs of a residential community reintegration programme for patients with acquired brain injury and to compare the societal costs before and after treatment. A cost-analysis was performed identifying costs of healthcare, informal care, and productivity losses. The costs in the year before the Brain Integration Programme (BIP) were compared with the costs in the year after the BIP using the following cost categories: care consumption, caregiver support, productivity losses. Dutch guidelines were used for cost valuation. Thirty-three cases participated (72% response). Mean age was 29.8 years, 59% traumatic brain injury. The BIP costs were €68,400. The informal care and productivity losses reduced significantly after BIP (p < 0.05), while healthcare consumption increased significantly (p < 0.05). The societal costs per patient were €48,449. After BIP these costs were €39,773; a significant reduction (p < 0.05). Assuming a stable situation the break-even point is after 8 years. The reduction in societal costs after the BIP advocates the allocation of resources and, from an economic perspective, favours reimbursement of the BIP costs by healthcare insurance companies. However, this cost-analysis is limited as it does not relate costs to clinical effectiveness. :
ERIC Educational Resources Information Center
Biomedical Interdisciplinary Curriculum Project, Berkeley, CA.
Described is the Biomedical Instrument Package (BIP) and its use. The BIP was developed for use in understanding colorimetry, sound, electricity, and bioelectric phenomena. It can also be used in a wide range of measurements such as current, voltage, resistance, temperature, and pH. Though it was developed primarily for use in biomedical science…
76 FR 47226 - Notice of HUD-Held Multifamily Loan Sale (MLS 2011-2)
Federal Register 2010, 2011, 2012, 2013, 2014
2011-08-04
... (BIP) was made available online to qualified bidders on June 29, 2011. Submission of bids for the loans...-performing mortgage loans. A final listing of the Mortgage Loans was included in the BIP. The Mortgage Loans... 2011-2. The Bidding Process The BIP described in detail the procedure for bidding in MLS 2011- 2. The...
Late-onset of spinal neurodegeneration in knock-in mice expressing a mutant BiP.
Jin, Hisayo; Mimura, Naoya; Kashio, Makiko; Koseki, Haruhiko; Aoe, Tomohiko
2014-01-01
Most human neurodegenerative diseases are sporadic, and appear later in life. While the underlying mechanisms of the progression of those diseases are still unclear, investigations into the familial forms of comparable diseases suggest that endoplasmic reticulum (ER) stress is involved in the pathogenesis. Binding immunoglobulin protein (BiP) is an ER chaperone that is central to ER function. We produced knock-in mice expressing a mutant BiP that lacked the retrieval sequence in order to evaluate the effect of a functional defect in an ER chaperone in multi-cellular organisms. Here we report that heterozygous mutant BiP mice revealed motor disabilities in aging. We found a degeneration of some motoneurons in the spinal cord accompanied by accumulations of ubiquitinated proteins. The defect in retrieval of BiP by the KDEL receptor leads to impaired activities in quality control and autophagy, suggesting that functional defects in the ER chaperones may contribute to the late onset of neurodegenerative diseases.
BiP negatively affects ricin transport.
Gregers, Tone F; Skånland, Sigrid S; Wälchli, Sébastien; Bakke, Oddmund; Sandvig, Kirsten
2013-05-10
The AB plant toxin ricin binds both glycoproteins and glycolipids at the cell surface via its B subunit. After binding, ricin is endocytosed and then transported retrogradely through the Golgi to the endoplasmic reticulum (ER). In the ER, the A subunit is retrotranslocated to the cytosol in a chaperone-dependent process, which is not fully explored. Recently two separate siRNA screens have demonstrated that ER chaperones have implications for ricin toxicity. ER associated degradation (ERAD) involves translocation of misfolded proteins from ER to cytosol and it is conceivable that protein toxins exploit this pathway. The ER chaperone BiP is an important ER regulator and has been implicated in toxicity mediated by cholera and Shiga toxin. In this study, we have investigated the role of BiP in ricin translocation to the cytosol. We first show that overexpression of BiP inhibited ricin translocation and protected cells against the toxin. Furthermore, shRNA-mediated depletion of BiP enhanced toxin translocation resulting in increased cytotoxicity. BiP-dependent inhibition of ricin toxicity was independent of ER stress. Our findings suggest that in contrast to what was shown with the Shiga toxin, the presence of BiP does not facilitate, but rather inhibits the entry of ricin into the cytosol.
BiP Negatively Affects Ricin Transport
Gregers, Tone F.; Skånland, Sigrid S.; Wälchli, Sébastien; Bakke, Oddmund; Sandvig, Kirsten
2013-01-01
The AB plant toxin ricin binds both glycoproteins and glycolipids at the cell surface via its B subunit. After binding, ricin is endocytosed and then transported retrogradely through the Golgi to the endoplasmic reticulum (ER). In the ER, the A subunit is retrotranslocated to the cytosol in a chaperone-dependent process, which is not fully explored. Recently two separate siRNA screens have demonstrated that ER chaperones have implications for ricin toxicity. ER associated degradation (ERAD) involves translocation of misfolded proteins from ER to cytosol and it is conceivable that protein toxins exploit this pathway. The ER chaperone BiP is an important ER regulator and has been implicated in toxicity mediated by cholera and Shiga toxin. In this study, we have investigated the role of BiP in ricin translocation to the cytosol. We first show that overexpression of BiP inhibited ricin translocation and protected cells against the toxin. Furthermore, shRNA-mediated depletion of BiP enhanced toxin translocation resulting in increased cytotoxicity. BiP-dependent inhibition of ricin toxicity was independent of ER stress. Our findings suggest that in contrast to what was shown with the Shiga toxin, the presence of BiP does not facilitate, but rather inhibits the entry of ricin into the cytosol. PMID:23666197
NASA Astrophysics Data System (ADS)
Pan, Jie; Zhang, Di; Xue, Zhen-Zhen; Wei, Li; Han, Song-De; Wang, Guo-Ming
2017-11-01
Three novel Zn(II)/Cd(II) coordination polymers, [Cd2(bip)2(m-bdc)2(H2O)2·3H2O]n (1), [Zn2(bip)2(p-bdc)2·2.5H2O]n (2) and [Zn(bip) (p-bdc)·3H2O]n (3), where bip = 3,5-bis(imidazole-1-yl)pyridine, m-H2bdc = 1,3-benzenedicarboxylic acid, p-H2bdc = 1,4-benzenedicarboxylic acid, have been successfully synthesized under solvothermal conditions. The linkage of different ligands with Cd(II) ions in compound 1 affords a (3,5)-connected layer. Furthermore, 2D→3D parallel polycatenation occurs wherein the layers are polycatenated with the adjacent two parallel layers to form a 3D framework. In 2 and 3, the polycarboxylates act as pillars to combine the metal-bip chains, yielding the layered structures. These 2D networks are extended to the final 3D supramolecular architectures by π-π stacking interactions. The results show that bip can act as a versatile building block for the construction of various coordination polymers. Moreover, the fluorescent properties of 1-3 in the solid state at room temperature have been investigated.
Espina, Marianela; Ausar, S. Fernando; Middaugh, C. Russell; Baxter, M. Aaron; Picking, William D.; Picking, Wendy L.
2007-01-01
Diverse Gram-negative bacteria use type III secretion systems (T3SS) to translocate effector proteins into the cytoplasm of eukaryotic cells. The type III secretion apparatus (T3SA) consists of a basal body spanning both bacterial membranes and an external needle. A sensor protein lies at the needle tip to detect environmental signals that trigger type III secretion. The Shigella flexneri T3SA needle tip protein, invasion plasmid antigen D (IpaD), possesses two independently folding domains in vitro. In this study, the solution behavior and thermal unfolding properties of IpaD's functional homologs SipD (Salmonella spp.), BipD (Burkholderia pseudomallei), LcrV (Yersinia spp.), and PcrV (Pseudomonas aeruginosa) were examined to identify common features within this protein family. CD and FTIR data indicate that all members within this group are α-helical with properties consistent with an intramolecular coiled-coil. SipD showed the most complex unfolding profile consisting of two thermal transitions, suggesting the presence of two independently folding domains. No evidence of multiple folding domains was seen, however, for BipD, LcrV, or PcrV. Thermal studies, including DSC, revealed significant destabilization of LcrV, PcrV, and BipD after N-terminal deletions. This contrasted with SipD and IpaD, which behaved like two-domain proteins. The results suggest that needle tip proteins share significant core structural similarity and thermal stability that may be the basis for their common function. Moreover, IpaD and SipD possess properties that distinguish them from the other tip proteins. PMID:17327391
Preconditioning with Endoplasmic Reticulum Stress Ameliorates Endothelial Cell Inflammation
Leonard, Antony; Paton, Adrienne W.; El-Quadi, Monaliza; Paton, James C.; Fazal, Fabeha
2014-01-01
Endoplasmic Reticulum (ER) stress, caused by disturbance in ER homeostasis, has been implicated in several pathological conditions such as ischemic injury, neurodegenerative disorders, metabolic diseases and more recently in inflammatory conditions. Our present study aims at understanding the role of ER stress in endothelial cell (EC) inflammation, a critical event in the pathogenesis of acute lung injury (ALI). We found that preconditioning human pulmonary artery endothelial cells (HPAEC) to ER stress either by depleting ER chaperone and signaling regulator BiP using siRNA, or specifically cleaving (inactivating) BiP using subtilase cytotoxin (SubAB), alleviates EC inflammation. The two approaches adopted to abrogate BiP function induced ATF4 protein expression and the phosphorylation of eIF2α, both markers of ER stress, which in turn resulted in blunting the activation of NF-κB, and restoring endothelial barrier integrity. Pretreatment of HPAEC with BiP siRNA inhibited thrombin-induced IκBα degradation and its resulting downstream signaling pathway involving NF-κB nuclear translocation, DNA binding, phosphorylation at serine536, transcriptional activation and subsequent expression of adhesion molecules. However, TNFα-mediated NF-κB signaling was unaffected upon BiP knockdown. In an alternative approach, SubAB-mediated inactivation of NF-κB was independent of IκBα degradation. Mechanistic analysis revealed that pretreatment of EC with SubAB interfered with the binding of the liberated NF-κB to the DNA, thereby resulting in reduced expression of adhesion molecules, cytokines and chemokines. In addition, both knockdown and inactivation of BiP stimulated actin cytoskeletal reorganization resulting in restoration of endothelial permeability. Together our studies indicate that BiP plays a central role in EC inflammation and injury via its action on NF-κB activation and regulation of vascular permeability. PMID:25356743
Preconditioning with endoplasmic reticulum stress ameliorates endothelial cell inflammation.
Leonard, Antony; Paton, Adrienne W; El-Quadi, Monaliza; Paton, James C; Fazal, Fabeha
2014-01-01
Endoplasmic Reticulum (ER) stress, caused by disturbance in ER homeostasis, has been implicated in several pathological conditions such as ischemic injury, neurodegenerative disorders, metabolic diseases and more recently in inflammatory conditions. Our present study aims at understanding the role of ER stress in endothelial cell (EC) inflammation, a critical event in the pathogenesis of acute lung injury (ALI). We found that preconditioning human pulmonary artery endothelial cells (HPAEC) to ER stress either by depleting ER chaperone and signaling regulator BiP using siRNA, or specifically cleaving (inactivating) BiP using subtilase cytotoxin (SubAB), alleviates EC inflammation. The two approaches adopted to abrogate BiP function induced ATF4 protein expression and the phosphorylation of eIF2α, both markers of ER stress, which in turn resulted in blunting the activation of NF-κB, and restoring endothelial barrier integrity. Pretreatment of HPAEC with BiP siRNA inhibited thrombin-induced IκBα degradation and its resulting downstream signaling pathway involving NF-κB nuclear translocation, DNA binding, phosphorylation at serine536, transcriptional activation and subsequent expression of adhesion molecules. However, TNFα-mediated NF-κB signaling was unaffected upon BiP knockdown. In an alternative approach, SubAB-mediated inactivation of NF-κB was independent of IκBα degradation. Mechanistic analysis revealed that pretreatment of EC with SubAB interfered with the binding of the liberated NF-κB to the DNA, thereby resulting in reduced expression of adhesion molecules, cytokines and chemokines. In addition, both knockdown and inactivation of BiP stimulated actin cytoskeletal reorganization resulting in restoration of endothelial permeability. Together our studies indicate that BiP plays a central role in EC inflammation and injury via its action on NF-κB activation and regulation of vascular permeability.
Iriyama, Takayuki; Kamei, Yoshimasa; Kozuma, Shiro; Taketani, Yuji
2009-02-13
Glutamate-induced excitotoxicity has been implicated in the pathogenesis of various neurological damages and disorders. In the brain damage of immature animals such as neonatal hypoxic-ischemic brain injury, the excitotoxicity appears to be more intimately involved through apoptosis. Bax, a member of the Bcl-2 family proteins, plays a key role in the promotion of apoptosis by translocation from the cytosol to the mitochondria and the release of apoptogenic factors such as cytochrome c. Recently, Bax-inhibiting peptide (BIP), a novel membrane-permeable peptide which can bind Bax in the cytosol and inhibit its translocation to the mitochondria, was developed. To investigate the possibility of a new neuroprotection strategy targeting Bax translocation in glutamate-induced neuronal cell death, cerebellar granule neurons (CGNs) were exposed to glutamate with or without BIP. Pretreatment of CGNs with BIP elicited a dose-dependent reduction of glutamate-induced neuronal cell death as measured by MTT assay. BIP significantly suppressed both the number of TUNEL-positive cells and the increase in caspases 3 and 9 activities induced by glutamate. In addition, immunoblotting after subcellular fractionation revealed that BIP prevented the glutamate-induced Bax translocation to the mitochondria and the release of cytochrome c from the mitochondria. These results suggest that agents capable of inhibiting Bax activity such as BIP might lead to new drugs for glutamate-related diseases in the future.
Preliminary design study of an alternate heat source assembly for a Brayton isotope power system
NASA Technical Reports Server (NTRS)
Strumpf, H. J.
1978-01-01
Results are presented for a study of the preliminary design of an alternate heat source assembly (HSA) intended for use in the Brayton isotope power system (BIPS). The BIPS converts thermal energy emitted by a radioactive heat source into electrical energy by means of a closed Brayton cycle. A heat source heat exchanger configuration was selected and optimized. The design consists of a 10 turn helically wound Hastelloy X tube. Thermal analyses were performed for various operating conditions to ensure that post impact containment shell (PICS) temperatures remain within specified limits. These limits are essentially satisfied for all modes of operation except for the emergency cooling system for which the PICS temperatures are too high. Neon was found to be the best choice for a fill gas for auxiliary cooling system operation. Low cycle fatigue life, natural frequency, and dynamic loading requirements can be met with minor modifications to the existing HSA.
BIPS: BIANA Interolog Prediction Server. A tool for protein-protein interaction inference.
Garcia-Garcia, Javier; Schleker, Sylvia; Klein-Seetharaman, Judith; Oliva, Baldo
2012-07-01
Protein-protein interactions (PPIs) play a crucial role in biology, and high-throughput experiments have greatly increased the coverage of known interactions. Still, identification of complete inter- and intraspecies interactomes is far from being complete. Experimental data can be complemented by the prediction of PPIs within an organism or between two organisms based on the known interactions of the orthologous genes of other organisms (interologs). Here, we present the BIANA (Biologic Interactions and Network Analysis) Interolog Prediction Server (BIPS), which offers a web-based interface to facilitate PPI predictions based on interolog information. BIPS benefits from the capabilities of the framework BIANA to integrate the several PPI-related databases. Additional metadata can be used to improve the reliability of the predicted interactions. Sensitivity and specificity of the server have been calculated using known PPIs from different interactomes using a leave-one-out approach. The specificity is between 72 and 98%, whereas sensitivity varies between 1 and 59%, depending on the sequence identity cut-off used to calculate similarities between sequences. BIPS is freely accessible at http://sbi.imim.es/BIPS.php.
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Fujimori, Tsutomu; Suno, Ryoji; Iemura, Shun-Ichiro; Natsume, Tohru; Wada, Ikuo; Hosokawa, Nobuko
2017-08-01
The folding of newly synthesized proteins in the endoplasmic reticulum (ER) is assisted by ER-resident chaperone proteins. BiP (immunoglobulin heavy-chain-binding protein), a member of the HSP70 family, plays a central role in protein quality control. The chaperone function of BiP is regulated by its intrinsic ATPase activity, which is stimulated by ER-resident proteins of the HSP40/DnaJ family, including ERdj3. Here, we report that two closely related proteins, SDF2 and SDF2L1, regulate the BiP chaperone cycle. Both are ER-resident, but SDF2 is constitutively expressed, whereas SDF2L1 expression is induced by ER stress. Both luminal proteins formed a stable complex with ERdj3 and potently inhibited the aggregation of different types of misfolded ER cargo. These proteins associated with non-native proteins, thus promoting the BiP-substrate interaction cycle. A dominant-negative ERdj3 mutant that inhibits the interaction between ERdj3 and BiP prevented the dissociation of misfolded cargo from the ERdj3-SDF2L1 complex. Our findings indicate that SDF2 and SDF2L1 associate with ERdj3 and act as components in the BiP chaperone cycle to prevent the aggregation of misfolded proteins, partly explaining the broad folding capabilities of the ER under various physiological conditions. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.
Miller, Camille; Cai, Yafei; Patton, Tadd; Graves, Sarai Hacker; Li, Honglin; Sabbatini, Maria Eugenia
2017-03-01
Alcoholism causes an imbalance of endoplasmic reticulum (ER) homeostasis in pancreatic acini. In those cells, the ER is involved in the synthesis and folding of pancreatic enzymes. Ubiquitin-fold modifier 1 (Ufm1) is part of a novel ubiquitin-like modification system involved in maintaining ER homeostasis. Among the components of the Ufm1 system, Regulator of C53 and DDRGK1 (RCAD) has recently been identified as a Ufm1-specific E3 ligase that promotes ufmylation of DDRGK1, an RCAD-interacting protein. We determined the importance of RCAD in the proper synthesis and secretion of pancreatic enzymes using mice with genetically deleted RCAD. The pancreas of RCAD-deficient mice was of normal size and histology. Using quantitative PCR and Western blotting, we found that amylase was upregulated in pancreas organs from RCAD-knockout (KO) mice. Constitutive amylase secretion was much higher in isolated pancreatic acini from RCAD KO mice, whereas CCK-stimulated amylase secretion was disturbed. RCAD deficiency caused a downregulation in expression of ER chaperone BiP, which affected ER homeostasis and activated both apoptosis and trypsin. We also found that both RCAD and DDRGK1 transcript levels were upregulated in pancreatic acini from alcohol-preferring rats. Elevated expression of RCAD and DDRGK1 was associated with increased ER stress and UPR activation. Because of the lack of BiP expression, caspase 3 and trypsin activation we enhanced in RCAD-deficient pancreatic acini upon treatment with ethanol and CCK. In conclusion, the RCAD/BiP pathway is required for proper synthesis and secretion of pancreatic enzymes. In alcoholism, increased levels of components of the Ufm1 system could prevent the deleterious effects of alcohol in the pancreas by regulating BiP levels. NEW & NOTEWORTHY RCAD/BiP pathway is required for the proper synthesis and secretion of amylase from pancreatic acini, as well as for the maintenance of the ER homeostasis. In alcoholism, the exocrine pancreas could increase the levels of components of the Ufm1 system to protect itself from alcohol's deleterious effects by regulating the expression of ER chaperone BiP. Copyright © 2017 the American Physiological Society.
Witt, S H; Streit, F; Jungkunz, M; Frank, J; Awasthi, S; Reinbold, C S; Treutlein, J; Degenhardt, F; Forstner, A J; Heilmann-Heimbach, S; Dietl, L; Schwarze, C E; Schendel, D; Strohmaier, J; Abdellaoui, A; Adolfsson, R; Air, T M; Akil, H; Alda, M; Alliey-Rodriguez, N; Andreassen, O A; Babadjanova, G; Bass, N J; Bauer, M; Baune, B T; Bellivier, F; Bergen, S; Bethell, A; Biernacka, J M; Blackwood, D H R; Boks, M P; Boomsma, D I; Børglum, A D; Borrmann-Hassenbach, M; Brennan, P; Budde, M; Buttenschøn, H N; Byrne, E M; Cervantes, P; Clarke, T-K; Craddock, N; Cruceanu, C; Curtis, D; Czerski, P M; Dannlowski, U; Davis, T; de Geus, E J C; Di Florio, A; Djurovic, S; Domenici, E; Edenberg, H J; Etain, B; Fischer, S B; Forty, L; Fraser, C; Frye, M A; Fullerton, J M; Gade, K; Gershon, E S; Giegling, I; Gordon, S D; Gordon-Smith, K; Grabe, H J; Green, E K; Greenwood, T A; Grigoroiu-Serbanescu, M; Guzman-Parra, J; Hall, L S; Hamshere, M; Hauser, J; Hautzinger, M; Heilbronner, U; Herms, S; Hitturlingappa, S; Hoffmann, P; Holmans, P; Hottenga, J-J; Jamain, S; Jones, I; Jones, L A; Juréus, A; Kahn, R S; Kammerer-Ciernioch, J; Kirov, G; Kittel-Schneider, S; Kloiber, S; Knott, S V; Kogevinas, M; Landén, M; Leber, M; Leboyer, M; Li, Q S; Lissowska, J; Lucae, S; Martin, N G; Mayoral-Cleries, F; McElroy, S L; McIntosh, A M; McKay, J D; McQuillin, A; Medland, S E; Middeldorp, C M; Milaneschi, Y; Mitchell, P B; Montgomery, G W; Morken, G; Mors, O; Mühleisen, T W; Müller-Myhsok, B; Myers, R M; Nievergelt, C M; Nurnberger, J I; O'Donovan, M C; Loohuis, L M O; Ophoff, R; Oruc, L; Owen, M J; Paciga, S A; Penninx, B W J H; Perry, A; Pfennig, A; Potash, J B; Preisig, M; Reif, A; Rivas, F; Rouleau, G A; Schofield, P R; Schulze, T G; Schwarz, M; Scott, L; Sinnamon, G C B; Stahl, E A; Strauss, J; Turecki, G; Van der Auwera, S; Vedder, H; Vincent, J B; Willemsen, G; Witt, C C; Wray, N R; Xi, H S; Tadic, A; Dahmen, N; Schott, B H; Cichon, S; Nöthen, M M; Ripke, S; Mobascher, A; Rujescu, D; Lieb, K; Roepke, S; Schmahl, C; Bohus, M; Rietschel, M
2017-06-20
Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10 -7 ) and PKP4 (P=8.67 × 10 -7 ); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, P FDR =0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (r g =0.28 [P=2.99 × 10 -3 ]), SCZ (r g =0.34 [P=4.37 × 10 -5 ]) and MDD (r g =0.57 [P=1.04 × 10 -3 ]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
NASA Astrophysics Data System (ADS)
Yu, Jianbo
2015-12-01
Prognostics is much efficient to achieve zero-downtime performance, maximum productivity and proactive maintenance of machines. Prognostics intends to assess and predict the time evolution of machine health degradation so that machine failures can be predicted and prevented. A novel prognostics system is developed based on the data-model-fusion scheme using the Bayesian inference-based self-organizing map (SOM) and an integration of logistic regression (LR) and high-order particle filtering (HOPF). In this prognostics system, a baseline SOM is constructed to model the data distribution space of healthy machine under an assumption that predictable fault patterns are not available. Bayesian inference-based probability (BIP) derived from the baseline SOM is developed as a quantification indication of machine health degradation. BIP is capable of offering failure probability for the monitored machine, which has intuitionist explanation related to health degradation state. Based on those historic BIPs, the constructed LR and its modeling noise constitute a high-order Markov process (HOMP) to describe machine health propagation. HOPF is used to solve the HOMP estimation to predict the evolution of the machine health in the form of a probability density function (PDF). An on-line model update scheme is developed to adapt the Markov process changes to machine health dynamics quickly. The experimental results on a bearing test-bed illustrate the potential applications of the proposed system as an effective and simple tool for machine health prognostics.
Miyamoto, Koji; Noda, Takashi; Satomi, Kazuhiro; Wada, Mitsuru; Nakajima, Ikutaro; Ishibashi, Kohei; Okamura, Hideo; Noguchi, Teruo; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Shimizu, Wataru; Aiba, Takeshi; Kamakura, Shiro; Kusano, Kengo
2016-08-01
Patients with ischemic and non-ischemic cardiomyopathy often have substrate for ventricular tachycardia (VT) in the endocardium (ENDO), epicardium (EPI), and/or intramural. Although it has been reported that the ENDO unipolar (UNI) voltage map is useful in detecting EPI substrate, its feasibility to detect intramural scarring and its usefulness in radiofrequency catheter ablation (RFCA) remain unclear. To assess the relationship between the left ventricle (LV) ENDO UNI voltage map and the LV EPI bipolar (BIP) voltage map, and to determine the usefulness of the ENDO UNI voltage map to guide RFCA for VT in patients with cardiomyopathy undergoing combined ENDO- and EPI RFCA. Eleven patients with VT undergoing detailed ENDO and EPI electroanatomical mapping of the LV were included (mean age 59 ± 11 years, 9 men). We assessed the value of the LV ENDO UNI voltage map in identifying EPI and/or intramural substrate in these 11 patients with non-ischemic or ischemic cardiomyopathy. The underlying heart disease was dilated cardiomyopathy in 4 patients, cardiac sarcoidosis in 3, hypertrophic cardiomyopathy in 2, and ischemic heart disease in 2 patients. The mean LV ejection fraction was 24 ± 7 %. The low voltage zone (LVZ) was defined as <1.5 mV for LV ENDO BIP electrograms (EGMs), <8.3 mV for LV ENDO UNI EGMs, and <1.0 mV for LV EPI BIP EGMs. The surface area of each LVZ was measured. We also measured the LVZ of the spatial overlap between ENDO UNI and EPI BIP voltage maps using the transparency mode on CARTO software. We performed RFCA at the ENDO and EPI based on activation and/or substrate maps, targeting the LVZ and/or abnormal EGMs. The LVZ was present in the LV ENDO BIP voltage map in 10 of 11 patients (42 ± 33 cm(2)), and in the LV ENDO UNI voltage map in 10 of 11 patients (72 ± 45 cm(2)). The LVZ was present in the EPI BIP voltage map in 9 of 11 patients (70 ± 61 cm(2)), and the LVZ in the ENDO UNI voltage map was also seen in all 9 patients. The location of the LVZ in the EPI BIP map matched that in 45 ± 28 % of ENDO UNI voltage maps. The LVZ in the ENDO UNI voltage map was larger than that in the EPI BIP voltage map in 6 of 11 patients, and RFCA failed in 5 of these 6 patients. In the remaining 5 patients with a smaller LVZ in the ENDO UNI voltage map compared with the EPI BIP voltage map or no LVZ both at ENDO UNI and EPI BIP voltage map, VT was successfully eliminated in 4 of 5 patients. The LV ENDO UNI voltage map is useful in detecting EPI substrate in patients with cardiomyopathy. A larger LVZ in the ENDO UNI voltage map compared to that in the EPI BIP voltage map may indicate the presence of intramural substrate, which leads to difficulty in eliminating VT, even with combined ENDO- and EPI RFCA.
Maddalo, Danilo; Neeb, Antje; Jehle, Katja; Schmitz, Katja; Muhle-Goll, Claudia; Shatkina, Liubov; Walther, Tamara Vanessa; Bruchmann, Anja; Gopal, Srinivasa M.; Wenzel, Wolfgang; Ulrich, Anne S.; Cato, Andrew C. B.
2012-01-01
The molecular chaperone GRP78/BiP is a key regulator of protein folding in the endoplasmic reticulum, and it plays a pivotal role in cancer cell survival and chemoresistance. Inhibition of its function has therefore been an important strategy for inhibiting tumor cell growth in cancer therapy. Previous efforts to achieve this goal have used peptides that bind to GRP78/BiP conjugated to pro-drugs or cell-death-inducing sequences. Here, we describe a peptide that induces prostate tumor cell death without the need of any conjugating sequences. This peptide is a sequence derived from the cochaperone Bag-1. We have shown that this sequence interacts with and inhibits the refolding activity of GRP78/BiP. Furthermore, we have demonstrated that it modulates the unfolded protein response in ER stress resulting in PARP and caspase-4 cleavage. Prostate cancer cells stably expressing this peptide showed reduced growth and increased apoptosis in in vivo xenograft tumor models. Amino acid substitutions that destroyed binding of the Bag-1 peptide to GRP78/BiP or downregulation of the expression of GRP78 compromised the inhibitory effect of this peptide. This sequence therefore represents a candidate lead peptide for anti-tumor therapy. PMID:23049684
Guo, Yan; Sun, Juan; Ye, Juan; Ma, Wenyu; Yan, Hualing; Wang, Gang
2016-01-01
Objective To investigate whether Saussurea tridactyla Sch. Bip.-derived polysaccharides and flavones exert apoptosis-inhibiting effects in ultraviolet B (UVB)-irradiated HaCaT cells. Methods We divided HaCaT cells into low radiation UVB and high radiation UVB groups. Low radiation UVB and high radiation UVB groups were further divided into a control group, UVB radiation group (UVB group), S. tridactyla Sch. Bip.-derived polysaccharides and flavones low-dose group, and S. tridactyla Sch. Bip.-derived polysaccharides and flavones high-dose group. Cell viability and morphology were assayed by MTT and trypan blue staining. Superoxide dismutase activity, glutathione content, malondialdehyde content, and catalase activity test kits were used to detect superoxide dismutase activity, glutathione content, malondialdehyde content, and catalase activity, respectively. Cell apoptosis, intracellular Ca2+ levels, and mitochondrial membrane potential (Δψ) were detected by flow cytometry. Protein levels were analyzed by Western blotting and immunofluorescence. Results S. tridactyla Sch. Bip.-derived polysaccharides and flavones were found to increase the absorbance of MTT, decrease cell death, alleviate the degree of cell edema, restore the cell morphology, reduce cell death fragments and chip phenomenon, increase superoxide dismutase activity, glutathione content, and catalase activity while decreasing the content of malondialdehyde, lowering the population of apoptotic cells, reducing the intracellular Ca2+ fluorescence, increasing the mitochondrial membrane potential (Δψ), increasing the expressions of p-38, p-53, Bcl-2, and decreasing the expressions of Bax and active-caspase-3. Conclusion S. tridactyla Sch. Bip.-derived polysaccharides and flavones can reduce cell apoptosis to protect HaCaT cells from oxidative damage after UVB irradiation; however, this effect does not occur via the p38MAPK pathway. PMID:26855564
Self-Chaperoning of the Type III Secretion System needle tip proteins IpaD and BipD
Johnson, Steven; Roversi, Pietro; Espina, Marianela; Olive, Andrew; Deane, Janet E.; Birket, Susan; Field, Terry; Picking, William D.; Blocker, Ariel; Galyov, Edouard E.; Picking, Wendy L.; Lea, Susan M.
2007-01-01
Bacteria expressing type III secretion systems (T3SS) have been responsible for the deaths of millions worldwide, acting as key virulence elements in diseases ranging from plague to typhoid fever. The T3SS is composed of a basal body, which traverses both bacterial membranes, and an external needle through which effector proteins are secreted. We report multiple crystal structures of two proteins that sit at the tip of the needle and are essential for virulence; IpaD from Shigella flexneri and BipD from Burkholderia pseudomallei. The structures reveal that the N-terminal domains of the molecules are intra-molecular chaperones that prevent premature oligomerization, as well as sharing structural homology with proteins involved in eukaryotic actin rearrangement. Crystal packing has allowed us to construct a model for the tip complex that is supported by mutations designed using the structure. PMID:17077085
Self-chaperoning of the type III secretion system needle tip proteins IpaD and BipD.
Johnson, Steven; Roversi, Pietro; Espina, Marianela; Olive, Andrew; Deane, Janet E; Birket, Susan; Field, Terry; Picking, William D; Blocker, Ariel J; Galyov, Edouard E; Picking, Wendy L; Lea, Susan M
2007-02-09
Bacteria expressing type III secretion systems (T3SS) have been responsible for the deaths of millions worldwide, acting as key virulence elements in diseases ranging from plague to typhoid fever. The T3SS is composed of a basal body, which traverses both bacterial membranes, and an external needle through which effector proteins are secreted. We report multiple crystal structures of two proteins that sit at the tip of the needle and are essential for virulence: IpaD from Shigella flexneri and BipD from Burkholderia pseudomallei. The structures reveal that the N-terminal domains of the molecules are intramolecular chaperones that prevent premature oligomerization, as well as sharing structural homology with proteins involved in eukaryotic actin rearrangement. Crystal packing has allowed us to construct a model for the tip complex that is supported by mutations designed using the structure.
Ero, Rya; Kumar, Veerendra; Chen, Yun; Gao, Yong-Gui
2016-12-01
EF-G, EF4, and BipA are members of the translation factor family of GTPases with a common ribosome binding mode and GTPase activation mechanism. However, topological variations of shared as well as unique domains ensure different roles played by these proteins during translation. Recent X-ray crystallography and cryo-electron microscopy studies have revealed the structural basis for the involvement of EF-G domain IV in securing the movement of tRNAs and mRNA during translocation as well as revealing how the unique C-terminal domains of EF4 and BipA interact with the ribosome and tRNAs contributing to the regulation of translation under certain conditions. EF-G, EF-4, and BipA are intriguing examples of structural variations on a common theme that results in diverse behavior and function. Structural studies of translational GTPase factors have been greatly facilitated by the use of antibiotics, which have revealed their mechanism of action.
Wang, Jie; Pareja, Kristeen A; Kaiser, Chris A; Sevier, Carolyn S
2014-01-01
Oxidative protein folding in the endoplasmic reticulum (ER) has emerged as a potentially significant source of cellular reactive oxygen species (ROS). Recent studies suggest that levels of ROS generated as a byproduct of oxidative folding rival those produced by mitochondrial respiration. Mechanisms that protect cells against oxidant accumulation within the ER have begun to be elucidated yet many questions still remain regarding how cells prevent oxidant-induced damage from ER folding events. Here we report a new role for a central well-characterized player in ER homeostasis as a direct sensor of ER redox imbalance. Specifically we show that a conserved cysteine in the lumenal chaperone BiP is susceptible to oxidation by peroxide, and we demonstrate that oxidation of this conserved cysteine disrupts BiP's ATPase cycle. We propose that alteration of BiP activity upon oxidation helps cells cope with disruption to oxidative folding within the ER during oxidative stress. DOI: http://dx.doi.org/10.7554/eLife.03496.001 PMID:25053742
[The Basel Interview for Psychosis (BIP): structure, reliability and validity].
Riecher-Rössler, A; Ackermann, T; Uttinger, M; Ittig, S; Koranyi, S; Rapp, C; Bugra, H; Studerus, E
2015-02-01
Although several instruments have been developed to identify patients with an at-risk mental state (ARMS) for psychosis and first episode of psychosis (FEP), up to now there were no instruments for a detailed assessment of risk factors and indicators of emerging psychosis and the temporal development of psychiatric symptoms over the whole life span in these patients. We therefore developed the Basle Interview for Psychosis (BIP). The aim of this study is to describe the development of the BIP and to report about its psychometric properties. The BIP is a comprehensive semi-structured interview that was developed for the Basel early detection of psychoses (FePsy) study. Its items were derived from the most important risk factors and indicators of psychosis described in the literature and from several existing instruments. It contains the following six sections: 1) social and physical development and family, 2) signs and symptoms, 3) vulnerability, 4) help-seeking behavior, 5) illness insight, 6) evaluation of the interview. To estimate the inter-rater reliabilities of the items of sections 2 and 3, 20 interviews were conducted and rated by 8 well-trained raters. The factorial structure of the BIP section "signs and symptoms" was explored in a sample of 120 ARMS and 77 FEP patients. On the basis of the discovered factorial structure, we created new subscales and assessed their reliabilities and validities. Of the 153 studied items of sections 2 and 3, 150 (98 %) were rated with sufficiently high agreement (inter-rater reliability > 0.4). The items of section "signs and symptoms" could be grouped into 5 subscales with predominantly good to very good internal consistencies, homogeneities, and discriminant and convergent validities. Predictive validities could be demonstrated for the subscales "Positive Psychotic Symptoms", "Disturbance of Thinking" and the total score. The BIP is the first interview for comprehensively assessing risk factors and indicators of emerging psychosis and the temporal development of psychiatric symptoms over the whole life span, which has been validated in ARMS and FEP patients. We could show that the BIP has excellent psychometric properties. © Georg Thieme Verlag KG Stuttgart · New York.
Imai, Saki; Kusakabe, Takahiro; Xu, Jian; Li, Zhiqing; Shirai, Shintaro; Mon, Hiroaki; Morokuma, Daisuke; Lee, Jae Man
2015-11-01
Baculovirus expression vector system (BEVS) is widely used for production of recombinant eukaryotic proteins in insect larvae or cultured cells. BEVS has advantages over bacterial expression system in producing post-translationally modified secreted proteins. However, for some unknown reason, it is very difficult for insects to secrete sufficiently for certain proteins of interest. To understand the reasons why insect cells fail to secrete some kinds of recombinant proteins, we here employed three mammalian proteins as targets, EPO, HGF, and Wnt3A, with different secretion levels in BEVS and investigated their mRNA transcriptions from the viral genome, subcellular localizations, and interactions with silkworm ER chaperones. Moreover, we observed that no significantly influence on the secretion amounts of all three proteins when depleting or overexpressing most endogenous ER chaperone genes in cultured silkworm cells. However, among all detected ER chaperones, the depletion of BiP severely decreased the recombinant protein secretion in BEVS, indicating the possible central role of Bip in silkworm secretion pathway.
Influence of Sport Education on Group Cohesion in University Physical Education
ERIC Educational Resources Information Center
Jenkins, Jayne M.; Alderman, Brandon L.
2011-01-01
The Sport Education ("SE") curricular model incorporated within university physical education Basic Instruction Program (BIP) may increase group cohesion. This study's purpose was to identify student perceptions of a BIP course taught within "SE," and investigate group cohesion in differing activity content. Participants…
PEER Business and Industry Partnership (BIP)
PEER logo Pacific Earthquake Engineering Research Center home about peer news events research Industry Partnership (BIP) Industry and government partners are an integral part of the research program at research and education programs and provides access to PEER researchers and products. Researchers share
Characterization of a bi-pistil mutant in Medicago truncatula Gaertn
USDA-ARS?s Scientific Manuscript database
We propose the name bi-pistil, bip, for a floral organ mutant observed in transgenic Medicago truncatula plants. The mutant has two separate stigmas borne on two separate styles that emerge from a single superior carpel primordium. The bip plant was crossed to a previously reported male sterile mtap...
Functional Behavioral Assessments and Intervention Plans in Early Intervention Settings.
ERIC Educational Resources Information Center
LaRocque, Michelle; Brown, Sharan E.; Johnson, Kurt L.
2001-01-01
This article advocates the use of functional behavioral assessments (FBAs) and behavior intervention plans (BIPs) in the development of Individualized Family Service Plans for children with or at risk of developing behavioral disorders. It describes the FBA and BIP processes and proposes a parent collaborative model for assessment and…
Photochromic molecular implementations of universal computation.
Chaplin, Jack C; Krasnogor, Natalio; Russell, Noah A
2014-12-01
Unconventional computing is an area of research in which novel materials and paradigms are utilised to implement computation. Previously we have demonstrated how registers, logic gates and logic circuits can be implemented, unconventionally, with a biocompatible molecular switch, NitroBIPS, embedded in a polymer matrix. NitroBIPS and related molecules have been shown elsewhere to be capable of modifying many biological processes in a manner that is dependent on its molecular form. Thus, one possible application of this type of unconventional computing is to embed computational processes into biological systems. Here we expand on our earlier proof-of-principle work and demonstrate that universal computation can be implemented using NitroBIPS. We have previously shown that spatially localised computational elements, including registers and logic gates, can be produced. We explain how parallel registers can be implemented, then demonstrate an application of parallel registers in the form of Turing machine tapes, and demonstrate both parallel registers and logic circuits in the form of elementary cellular automata. The Turing machines and elementary cellular automata utilise the same samples and same hardware to implement their registers, logic gates and logic circuits; and both represent examples of universal computing paradigms. This shows that homogenous photochromic computational devices can be dynamically repurposed without invasive reconfiguration. The result represents an important, necessary step towards demonstrating the general feasibility of interfacial computation embedded in biological systems or other unconventional materials and environments. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Robust ferroelectricity in two-dimensional SbN and BiP.
Liu, Chang; Wan, Wenhui; Ma, Jie; Guo, Wei; Yao, Yugui
2018-05-03
Based on first-principles calculations, we discover two new two-dimensional (2D) ferroelectric materials SbN and BiP. Both of them are stable in a phosphorene-like structure and maintain their ferroelectricity above room temperature. Till date, SbN has the largest in-plane spontaneous polarization of about 7.81 × 10-10 C m-1 ever found in 2D ferroelectric materials, and it can retain its ferroelectricity until melting at about 1700 K. The spontaneous polarizations and switching barriers can easily be tuned by strains. Additionally, the ferroelectricity can still be maintained in their multilayers. These advantages make SbN and BiP promising candidate materials for future integrated ferroelectric devices.
ERIC Educational Resources Information Center
Wood, Brenna K.; Drogan, Robin R.; Janney, Donna M.
2014-01-01
Reviewers analyzed studies published from 1990 to 2012 to determine early childhood practitioner involvement in functional behavioral assessment (FBA) and function-based behavioral intervention plans (BIP) for children with challenging behavior, age 6 and younger. Coding of 30 studies included practitioner involvement in FBA and BIP processes,…
Utilizing Qualitative Feedback to Investigate Student Perceptions of a Basic Instruction Program
ERIC Educational Resources Information Center
Russell, Jared A.
2008-01-01
This research represents the perceptions of two hundred (N = 200) students enrolled in a doctoral-research university's basic instruction program (BIP) regarding their instructional experiences. The purpose of this interpretive case-study conducted in a doctoral-research university's BIP was two-fold: (a) to examine the characteristics of…
FBA and BIP: Increasing the Behavior Adjustment of African American Boys in Schools
ERIC Educational Resources Information Center
Lo, Ya-yu; Cartledge, Gwendolyn
2006-01-01
Overrepresentation of African American boys in disciplinary and special education referrals has been a national concern. This study used functional behavioral assessments (FBAs) and behavioral intervention plans (BIPs) as a means to prevent disproportionality of African American boys. Based on FBA results, interventions were developed for four…
How Batterer Intervention Programs Work: Participant and Facilitator Accounts of Processes of Change
ERIC Educational Resources Information Center
Silvergleid, Courtenay S.; Mankowski, Eric S.
2006-01-01
Understanding what facilitates change in men who perpetrate domestic violence can aid the development of more effective batterer intervention programs (BIPs). To identify and describe key change processes, in-depth interviews were conducted with nine successful BIP completers and with 10 intervention group facilitators. The accounts described a…
Motivational Factors for Participating in Basic Instruction Programs
ERIC Educational Resources Information Center
Hardin, Robin; Andrew, Damon P. S.; Koo, Gi-Yong; Bemiller, Jim
2009-01-01
Enrollment trends in Basic Instruction Programs (BIPs) have shown a gradual decrease during the past four decades. This trend is significant because of the numerous studies that have declared Americans as unfit, inactive and leading unhealthy lifestyles. College and university BIPs are a means in which adults can be introduced to healthy…
ERIC Educational Resources Information Center
Collins, Lauren W.; Zirkel, Perry A.
2017-01-01
Functional behavior assessments (FBAs) and behavior intervention plans (BIPs) are critical components in the education of students with, or at risk for, emotional disturbance (ED). The purpose of this article is to compare the legal requirements with the professional requirements for FBAs and BIPs. The comparison is first according to the…
Optical Lock-In Detection of FRET Using Synthetic and Genetically Encoded Optical Switches
Mao, Shu; Benninger, Richard K. P.; Yan, Yuling; Petchprayoon, Chutima; Jackson, David; Easley, Christopher J.; Piston, David W.; Marriott, Gerard
2008-01-01
The Förster resonance energy transfer (FRET) technique is widely used for studying protein interactions within live cells. The effectiveness and sensitivity of determining FRET, however, can be reduced by photobleaching, cross talk, autofluorescence, and unlabeled, endogenous proteins. We present a FRET imaging method using an optical switch probe, Nitrobenzospiropyran (NitroBIPS), which substantially improves the sensitivity of detection to <1% FRET efficiency. Through orthogonal optical control of the colorful merocyanine and colorless spiro states of the NitroBIPS acceptor, donor fluorescence can be measured both in the absence and presence of FRET in the same FRET pair in the same cell. A SNAP-tag approach is used to generate a green fluorescent protein-alkylguaninetransferase fusion protein (GFP-AGT) that is labeled with benzylguanine-NitroBIPS. In vivo imaging studies on this green fluorescent protein-alkylguaninetransferase (GFP-AGT) (NitroBIPS) complex, employing optical lock-in detection of FRET, allow unambiguous resolution of FRET efficiencies below 1%, equivalent to a few percent of donor-tagged proteins in complexes with acceptor-tagged proteins. PMID:18281383
Gomez, Javier A; Rutkowski, D Thomas
2016-01-01
Endoplasmic reticulum (ER) stress is implicated in many chronic diseases, but very little is known about how the unfolded protein response (UPR) responds to persistent ER stress in vivo. Here, we experimentally reconstituted chronic ER stress in the mouse liver, using repeated injection of a low dose of the ER stressor tunicamycin. Paradoxically, this treatment led to feedback-mediated suppression of a select group of mRNAs, including those encoding the ER chaperones BiP and GRP94. This suppression was due to both silencing of the ATF6α pathway of UPR-dependent transcription and enhancement of mRNA degradation, possibly via regulated IRE1-dependent decay (RIDD). The suppression of mRNA encoding BiP was phenocopied by ectopic overexpression of BiP protein, and was also observed in obese mice. Our findings suggest that persistent cycles of UPR activation and deactivation create an altered, quasi-stable setpoint for UPR-dependent transcriptional regulation—an outcome that could be relevant to conditions such as metabolic syndrome. DOI: http://dx.doi.org/10.7554/eLife.20390.001 PMID:27938665
Goodwin, Edward C.; Lipovsky, Alex; Inoue, Takamasa; Magaldi, Thomas G.; Edwards, Anne P. B.; Van Goor, Kristin E. Y.; Paton, Adrienne W.; Paton, James C.; Atwood, Walter J.; Tsai, Billy; DiMaio, Daniel
2011-01-01
ABSTRACT Simian virus 40 (SV40) is a nonenveloped DNA virus that traffics through the endoplasmic reticulum (ER) en route to the nucleus, but the mechanisms of capsid disassembly and ER exit are poorly understood. We conducted an unbiased RNA interference screen to identify cellular genes required for SV40 infection. SV40 infection was specifically inhibited by up to 50-fold by knockdown of four different DNAJ molecular cochaperones or by inhibition of BiP, the Hsp70 partner of DNAJB11. These proteins were not required for the initiation of capsid disassembly, but knockdown markedly inhibited SV40 exit from the ER. In addition, BiP formed a complex with SV40 capsids in the ER in a DNAJB11-dependent fashion. These experiments identify five new cellular proteins required for SV40 infection and suggest that the binding of BiP to the capsid is required for ER exit. Further studies of these proteins will provide insight into the molecular mechanisms of polyomavirus infection and ER function. PMID:21673190
Square biphasic pulse deep brain stimulation for essential tremor: The BiP tremor study.
De Jesus, Sol; Almeida, Leonardo; Shahgholi, Leili; Martinez-Ramirez, Daniel; Roper, Jaimie; Hass, Chris J; Akbar, Umer; Wagle Shukla, Aparna; Raike, Robert S; Okun, Michael S
2018-01-01
Conventional deep brain stimulation (DBS) utilizes regular, high frequency pulses to treat medication-refractory symptoms in essential tremor (ET). Modifications of DBS pulse shape to achieve improved effectiveness is a promising approach. The current study assessed the safety, tolerability and effectiveness of square biphasic pulse shaping as an alternative to conventional ET DBS. This pilot study compared biphasic pulses (BiP) versus conventional DBS pulses (ClinDBS). Eleven ET subjects with clinically optimized ventralis intermedius nucleus DBS were enrolled. Objective measures were obtained over 3 h while ON BiP stimulation. There was observed benefit in the Fahn-Tolosa Tremor Rating Scale (TRS) for BiP conditions when compared to the DBS off condition and to ClinDBS setting. Total TRS scores during the DBS OFF condition (28.5 IQR = 24.5-35.25) were significantly higher than the other time points. Following active DBS, TRS improved to (20 IQR = 13.8-24.3) at ClinDBS setting and to (16.5 IQR = 12-20.75) at the 3 h period ON BiP stimulation (p = 0.001). Accelerometer recordings revealed improvement in tremor at rest (χ 2 = 16.1, p = 0.006), posture (χ 2 = 15.9, p = 0.007) and with action (χ 2 = 32.1, p=<0.001) when comparing median total scores at ClinDBS and OFF DBS conditions to 3 h ON BiP stimulation. There were no adverse effects and gait was not impacted. BiP was safe, tolerable and effective on the tremor symptoms when tested up to 3 h. This study demonstrated the feasibility of applying a novel DBS waveform in the clinic setting. Larger prospective studies with longer clinical follow-up will be required. Copyright © 2017. Published by Elsevier Ltd.
Moon, Ju Yeon; Lee, Jeong Hee; Oh, Chang-Sik; Kang, Hong-Gu; Park, Jeong Mee
2016-12-01
HRT is a plant coiled-coil, nucleotide-binding and leucine-rich repeat (CC-NB-LRR) disease resistance protein that triggers the hypersensitive response (HR) on recognition of Turnip crinkle virus (TCV) coat protein (CP). The molecular mechanism and significance of HR-mediated cell death for TCV resistance have not been fully elucidated. To identify the genes involved in HRT/TCV CP-mediated HR in Nicotiana benthamiana, we performed virus-induced gene silencing (VIGS) of 459 expressed sequence tags (ESTs) of pathogen-responsive Capsicum annuum genes. VIGS of CaBLP5, which encodes an endoplasmic reticulum (ER)-associated immunoglobulin-binding protein (BiP), silenced NbBiP4 and NbBiP5 and significantly reduced HRT-mediated HR. The induction of ER stress-responsive genes and the accumulation of ER-targeted BiPs in response to HRT-mediated HR suggest that ER is involved in HR in N. benthamiana. BiP4/5 silencing significantly down-regulated HRT at the mRNA and protein levels, and affected SGT1 and HSP90 expression. Co-expression of TCV CP in BiP4/5-silenced plants completely abolished HRT induction. Transient expression of TCV CP alone induced selected ER stress-responsive gene transcripts only in Tobacco rattle virus (TRV)-infected plants, and most of these genes were induced by HRT/TCV CP, except for bZIP60, which was induced specifically in response to HRT/TCV CP. TCV CP-mediated induction of ER stress-responsive genes still occurred in BiP4/5-silenced plants, but HRT/TCV CP-mediated induction of these genes was defective. Tunicamycin, a chemical that inhibits protein N-glycosylation, inhibited HRT-mediated HR, suggesting that ER has a role in HR regulation. These results indicate that BiP and ER, which modulate pattern recognition receptors in innate immunity, also regulate R protein-mediated resistance. © 2016 BSPP and John Wiley & Sons Ltd.
Lukschal, Anna; Wallmann, Julia; Bublin, Merima; Hofstetter, Gerlinde; Mothes-Luksch, Nadine; Breiteneder, Heimo; Pali-Schöll, Isabella; Jensen-Jarolim, Erika
2016-03-01
In the celery-mugwort-birch-spice syndrome, a significant proportion of IgE is directed against high molecular weight (HMW) glycoproteins, including the celery allergen Api g 5. BIP3, a monoclonal antibody originally raised against birch pollen, recognizes HMW allergens in birch and mugwort pollens, celery, and Apiaceae spices. Our aim was to generate mimotopes using BIP3 for immunization against the HMW allergens relevant in the celery-mugwort-birch-spice cross reactivity syndrome. Mimotopes were selected from a random-peptide display library by BIP3 and applied in IgE inhibition assays. The 3 phage clones with the highest inhibitory capacity were chosen for immunization of BALB/c mice. Mouse immune sera were tested for IgG binding to blotted birch pollen extract and used for inhibiting patients' IgE binding. Furthermore, sera were tested for binding to Api g 5, to horseradish peroxidase (HRP) as a second glycoprotein, or to non-glycosylated control allergen Phl p 5 in ELISA, and the specific Api g 5-specific IgG titers were determined. Three rounds of biopanning resulted in phage clones exhibiting 7 different sequences including 1 dominant, 1-6-cyclo-CHKLRCDKAIA. Three phage clones had the capacity to inhibit human IgE binding and induced IgG to the HMW antigen when used for immunizing BALB/c mice. The induced BIP3-mimotope IgG reached titers of 1:500 specifically to Api g 5, but hardly reacted to glycoprotein HRP, revealing a minor role of carbohydrates in their epitope. The mimotopes characterized in this study mimic the epitope of BIP3 relevant for Api g 5, one of the cross-reactive HMW allergens relevant in the celery-mugwort-birch-spice syndrome. BIP3 mimotopes may be used in the future for hyposensitization in this clinical syndrome by virtue of good and specific immunogenicity.
Gene regulatory network of unfolded protein response genes in endoplasmic reticulum stress.
Takayanagi, Sayuri; Fukuda, Riga; Takeuchi, Yuuki; Tsukada, Sakiko; Yoshida, Kenichi
2013-01-01
In the endoplasmic reticulum (ER), secretory and membrane proteins are properly folded and modified, and the failure of these processes leads to ER stress. At the same time, unfolded protein response (UPR) genes are activated to maintain homeostasis. Despite the thorough characterization of the individual gene regulation of UPR genes to date, further investigation of the mutual regulation among UPR genes is required to understand the complex mechanism underlying the ER stress response. In this study, we aimed to reveal a gene regulatory network formed by UPR genes, including immunoglobulin heavy chain-binding protein (BiP), X-box binding protein 1 (XBP1), C/EBP [CCAAT/enhancer-binding protein]-homologous protein (CHOP), PKR-like endoplasmic reticulum kinase (PERK), inositol-requiring 1 (IRE1), activating transcription factor 6 (ATF6), and ATF4. For this purpose, we focused on promoter-luciferase reporters for BiP, XBP1, and CHOP genes, which bear an ER stress response element (ERSE), and p5 × ATF6-GL3, which bears an unfolded protein response element (UPRE). We demonstrated that the luciferase activities of the BiP and CHOP promoters were upregulated by all the UPR genes, whereas those of the XBP1 promoter and p5 × ATF6-GL3 were upregulated by all the UPR genes except for BiP, CHOP, and ATF4 in HeLa cells. Therefore, an ERSE- and UPRE-centered gene regulatory network of UPR genes could be responsible for the robustness of the ER stress response. Finally, we revealed that BiP protein was degraded when cells were treated with DNA-damaging reagents, such as etoposide and doxorubicin; this finding suggests that the expression level of BiP is tightly regulated at the post-translational level, rather than at the transcriptional level, in the presence of DNA damage.
An Update of Judicial Rulings Specific to FBAs or BIPs under the IDEA and Corollary State Laws
ERIC Educational Resources Information Center
Zirkel, Perry A.
2017-01-01
Exemplifying the insufficient treatment of legal issues in refereed journals in special education and related fields, the limited legal coverage of functional behavioral assessments (FBAs) and behavior intervention plans (BIPs) tends to view the applicable case law through normative lenses. This skewed view characterizes the case law as requiring…
ERIC Educational Resources Information Center
Cook, Clayton R.; Mayer, G. Roy; Wright, Diana Browning; Kraemer, Bonnie; Wallace, Michele D.; Dart, Evan; Collins, Tai; Restori, Alberto
2012-01-01
Several researchers have argued that the functional behavior assessment (FBA) and behavior intervention plan (BIP) mandates in the Individuals With Disabilities Education Act of 2004 have gone beyond the current research base. For instance, although BIPs have been shown to improve student outcomes when implemented with strict control and oversight…
ERIC Educational Resources Information Center
Barfield, J. P.; Channell, Brian; Pugh, Chip; Tuck, Matt; Pendel, Dustin
2012-01-01
New resistance training programs such as CrossFit are gaining favor among college-aged students. CrossFit and related commercial resistance training programs may provide a valuable elective option within basic instruction program (BIP) curricula, but the fitness benefits of this course have not been compared with those of existing BIP resistance…
Are We on the Right Course? Lessons Learned about Current FBA/BIP Practices in Schools
ERIC Educational Resources Information Center
Van Acker, Richard; Boreson, Lynn; Gable, Robert A.; Potterton, Thomas
2005-01-01
Schools across the nation have been charged with the task of conducting functional behavioral assessments (FBAs) to aid in the development of behavior intervention plans (BIPs) to address the challenging behavior of students with special education needs. In response, schools have initiated efforts to provide the various members of their student…
ERIC Educational Resources Information Center
Ennis, Robin Parks; Jolivette, Kristine; Swoszowski, Nicole Cain
2017-01-01
Functional behavior assessment (FBA) is the process of collecting data to determine the function of an individual's behavior to develop a functionally-indicated behavioral intervention (BIP). Special adaptations may be needed to conduct FBA and implement BIPs in alternative educational settings. In this article, we highlight suggestions for…
FBAs and BIPs: Avoiding and Addressing Four Common Challenges Related to Fidelity
ERIC Educational Resources Information Center
Hirsch, Shanna E.; Bruhn, Allison L.; Lloyd, John Wills; Katsiyannis, Antonis
2017-01-01
There is substantial empirical evidence that the Functional Behavioral Assessment (FBA) process is an effective means to reduce student problem behavior and increase desirable behaviors (e.g., What Works Clearinghouse, 2016). The use of an FBA as the basis for a behavior intervention plan (BIP) has been a requirement for certain disciplinary…
ERIC Educational Resources Information Center
Maag, John W.; Katsiyannis, Antonis
2006-01-01
Reauthorization of the Individuals with Disabilities Education Act (IDEA) specifies that a behavioral intervention plan (BIP) must be developed for students with disabilities under certain disciplinary exclusions. IDEA, however, does not provide details as to what should be included in BIPs, and this lack of specific guidance often results in…
Radatz, Dana L; Wright, Emily M
2016-01-01
The majority of batterer intervention program (BIP) evaluations have indicated they are marginally effective in reducing domestic violence recidivism. Meanwhile, correctional programs used to treat a variety of offenders (e.g., substance users, violent offenders, and so forth) that adhere to the "principles of effective intervention" (PEI) have reported significant reductions in recidivism. This article introduces the PEI-the principles on which evidence-based practices in correctional rehabilitation are based-and identifies the degree to which they are currently integrated into BIPs. The case is made that batterer programs could be more effective if they incorporate the PEI. Recommendations for further integration of the principles into BIPs are also provided. © The Author(s) 2015.
Mini-Brayton heat source assembly development
NASA Technical Reports Server (NTRS)
Wein, D.; Zimmerman, W. F.
1978-01-01
The work accomplished on the Mini-Brayton Heat Source Assembly program is summarized. Required technologies to design, fabricate and assemble components for a high temperature Heat Source Assembly (HSA) which would generate and transfer the thermal energy for a spaceborne Brayton Isotope Power System (BIPS) were developed.
Kuhl, D; Kennedy, T E; Barzilai, A; Kandel, E R
1992-12-01
Long-term memory for sensitization of the gill- and siphon-withdrawal reflexes in Aplysia californica requires RNA and protein synthesis. These long-term behavioral changes are accompanied by long-term facilitation of the synaptic connections between the gill and siphon sensory and motor neurons, which are similarly dependent on transcription and translation. In addition to showing an increase in over-all protein synthesis, long-term facilitation is associated with changes in the expression of specific early, intermediate, and late proteins, and with the growth of new synaptic connections between the sensory and motor neurons of the reflex. We previously focused on early proteins and have identified four proteins as members of the immunoglobulin family of cell adhesion molecules related to NCAM and fasciclin II. We have now cloned the cDNA corresponding to one of the late proteins, and identified it as the Aplysia homolog of BiP, an ER resident protein involved in the folding and assembly of secretory and membrane proteins. Behavioral training increases the steady-state level of BiP mRNA in the sensory neurons. The increase in the synthesis of BiP protein is first detected 3 h after the onset of facilitation, when the increase in overall protein synthesis reaches its peak and the formation of new synaptic terminals becomes apparent. These findings suggest that the chaperon function of BiP might serve to fold proteins and assemble protein complexes necessary for the structural changes characteristic of long-term memory.
NAVAIR Portable Source Initiative (NPSI) Standard for Reusable Source Dataset Metadata (RSDM) V2.4
2012-09-26
defining a raster file format: <RasterFileFormat> <FormatName>TIFF</FormatName> <Order>BIP</Order> < DataType >8-BIT_UNSIGNED</ DataType ...interleaved by line (BIL); Band interleaved by pixel (BIP). element RasterFileFormatType/ DataType diagram type restriction of xsd:string facets
ERIC Educational Resources Information Center
Horner, Robert H.; Yell, Mitchell L.
2017-01-01
The authors discuss the journal article by Perry Zirkel on legal action in regard to functional behavioral assessment (FBA) and behavior intervention plans (BIPs). They contend that the Zirkel article opens larger questions that will be central to ongoing discussions at the national, state, district, school, and family levels. Such issues include…
Gentili, Pier Luigi; Rightler, Amanda L; Heron, B Mark; Gabbutt, Christopher D
2016-01-25
Photochromic fuzzy logic systems have been designed that extend human visual perception into the UV region. The systems are founded on a detailed knowledge of the activation wavelengths and quantum yields of a series of thermally reversible photochromic compounds. By appropriate matching of the photochromic behaviour unique colour signatures are generated in response differing UV activation frequencies.
ERIC Educational Resources Information Center
Chipley, Michael; Lyon, Wesley; Smilowitz, Robert; Williams, Pax; Arnold, Christopher; Blewett, William; Hazen, Lee; Krimgold, Fred
2012-01-01
This publication, part of the new Building and Infrastructure Protection Series (BIPS) published by the Department of Homeland Security (DHS) Science and Technology Directorate (S&T) Infrastructure Protection and Disaster Management Division (IDD), serves to advance high performance and integrated design for buildings and infrastructure. This…
The Biodiversity Informatics Potential Index
2011-01-01
Background Biodiversity informatics is a relatively new discipline extending computer science in the context of biodiversity data, and its development to date has not been uniform throughout the world. Digitizing effort and capacity building are costly, and ways should be found to prioritize them rationally. The proposed 'Biodiversity Informatics Potential (BIP) Index' seeks to fulfill such a prioritization role. We propose that the potential for biodiversity informatics be assessed through three concepts: (a) the intrinsic biodiversity potential (the biological richness or ecological diversity) of a country; (b) the capacity of the country to generate biodiversity data records; and (c) the availability of technical infrastructure in a country for managing and publishing such records. Methods Broadly, the techniques used to construct the BIP Index were rank correlation, multiple regression analysis, principal components analysis and optimization by linear programming. We built the BIP Index by finding a parsimonious set of country-level human, economic and environmental variables that best predicted the availability of primary biodiversity data accessible through the Global Biodiversity Information Facility (GBIF) network, and constructing an optimized model with these variables. The model was then applied to all countries for which sufficient data existed, to obtain a score for each country. Countries were ranked according to that score. Results Many of the current GBIF participants ranked highly in the BIP Index, although some of them seemed not to have realized their biodiversity informatics potential. The BIP Index attributed low ranking to most non-participant countries; however, a few of them scored highly, suggesting that these would be high-return new participants if encouraged to contribute towards the GBIF mission of free and open access to biodiversity data. Conclusions The BIP Index could potentially help in (a) identifying countries most likely to contribute to filling gaps in digitized biodiversity data; (b) assisting countries potentially in need (for example mega-diverse) to mobilize resources and collect data that could be used in decision-making; and (c) allowing identification of which biodiversity informatics-resourced countries could afford to assist countries lacking in biodiversity informatics capacity, and which data-rich countries should benefit most from such help. PMID:22373233
van der Schoot, Gabriela G F; Westerink, Nico-Derk L; Lubberts, Sjoukje; Nuver, Janine; Zwart, Nynke; Walenkamp, Annemiek M E; Wempe, Johan B; Meijer, Coby; Gietema, Jourik A
2016-05-01
Bleomycin and cisplatin are of key importance in testicular cancer treatment. Known potential serious adverse effects are bleomycin-induced pulmonary toxicity (BIP) and cisplatin-induced renal toxicity. Iron handling may play a role in development of this toxicity. Carriage of allelic variants of the HFE gene induces altered iron metabolism and may contribute to toxicity. We investigated the association between two common allelic variants of the HFE gene, H63D and C282Y, with development of pulmonary and renal toxicity during and after treatment with bleomycin- and cisplatin-containing chemotherapy. In 369 testicular cancer patients treated with bleomycin and cisplatin at the University Medical Center Groningen between 1978 and 2006, H63D and/or C282Y genotypes were determined with an allelic discrimination assay. Data were collected on development of BIP, pulmonary function parameters, renal function, and survival. BIP developed more frequently in patients who were heterozygote (16 in 75, 21%) and homozygote (2 in 4, 50%) for the H63D variant, compared with those who had the HFE wild-type gene (31 in 278, 11%) (p = 0.012). Overall survival, testicular cancer-related survival, and change in renal function were not associated with the H63D variant. We observed an association between presence of one or both H63D alleles and development of BIP in testicular cancer patients treated with bleomycin combination chemotherapy. In patients heterozygote and homozygote for the H63D variant, BIP occurred more frequently compared with wild-type patients. When validated and confirmed, HFE H63D genotyping may be used to identify patients with increased risk for pulmonary bleomycin toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.
Sigma receptor 1 modulates endoplasmic reticulum stress in retinal neurons.
Ha, Yonju; Dun, Ying; Thangaraju, Muthusamy; Duplantier, Jennifer; Dong, Zheng; Liu, Kebin; Ganapathy, Vadivel; Smith, Sylvia B
2011-01-01
To investigate the mechanism of σ receptor 1 (σR1) neuroprotection in retinal neurons. Oxidative stress, which is implicated in diabetic retinopathy, was induced in mouse primary ganglion cells (GCs) and RGC-5 cells, and the effect of the σR1 ligand (+)-pentazocine on pro- and anti-apoptotic and endoplasmic reticulum (ER) stress gene expression was examined. Binding of σR1 to BiP, an ER chaperone protein, and σR1 phosphorylation status were examined by immunoprecipitation. Retinas were harvested from Ins2Akita/+ diabetic mice treated with (+)-pentazocine, and the expression of ER stress genes and of the retinal transcriptome was evaluated. Oxidative stress induced the death of primary GCs and RGC-5 cells. The effect was decreased by the application of (+)-pentazocine. Stress increased σR1 binding to BiP and enhanced σR1 phosphorylation in RGC-5 cells. BiP binding was prevented, and σR1 phosphorylation decreased in the presence of (+)-pentazocine. The ER stress proteins PERK, ATF4, ATF6, IRE1α, and CHOP were upregulated in RGC-5 cells during oxidative stress, but decreased in the presence of (+)-pentazocine. A similar phenomenon was observed in retinas of Ins2Akita/+ diabetic mice. Retinal transcriptome analysis of Ins2Akita/+ mice compared with wild-type revealed differential expression of the genes critically involved in oxidative stress, differentiation, and cell death. The expression profile of those genes was reversed when the Ins2Akita/+ mice were treated with (+)-pentazocine. In retinal neurons, the molecular chaperone σR1 binds BiP under stressful conditions; (+)-pentazocine may exert its effects by dissociating σR1 from BiP. As stress in retinal cells increases, phosphorylation of σR1 is increased, which is attenuated when agonists bind to the receptor.
ERIC Educational Resources Information Center
Couvillon, Michael A.; Bullock, Lyndal M.; Gable, Robert A.
2009-01-01
Although functional behavioral assessments (FBAs) and behavior intervention plans (BIPs) have been utilized since the 1960s, their use has steadily increased since the passing of IDEA 1997 which mandated their use in specified circumstances. References to FBAs and BIPs in No Child Left Behind Act of 2001, the 2004 re-authorization of IDEA, and in…
Homochiral coordination polymers with helixes and metal clusters based on lactate derivatives
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Zhong-Xuan, E-mail: xuzhongxuan4201@163.com; Ma, Yu-Lu; Lv, Guo-ling
2017-05-15
Utilizing the lactic acid derivatives (R)-4-(1-carboxyethoxy)benzoic acid (denoted: (R)-H{sub 2}CBA) and (S)-4-(1-carboxyethoxy)benzoic acid (denoted: (S)-H{sub 2}CBA)as chiral linkers to self-assemble with 4, 4′-bipyridine (denoted: BIP) and Cd(II) ions, a couple of three-dimensional homochiral coordination polymers, namely [Cd{sub 3}((R)-CBA){sub 3} (BIP){sub 2}(H{sub 2}O)]·xGuest (1-D) and [Cd{sub 3}((S)-CBA){sub 3}(BIP){sub 2}(H{sub 2}O)]·xGuest (1-L), have been synthesized under solvothermal reaction condition. Single crystal X-ray diffraction analysis reveals the two complexes contain single helical chains based on enantiopure ligands and cadmium clusters. Moreover, some physical characteristics such as PXRD, thermal stability, solid-state circular dichroism (CD) and luminescent were also investigated. - Graphical abstract: Utilizing enantiomericmore » lactic acid derivatives (R)-H{sub 2}CBA and (S)-H{sub 2}CBA to assemble with Cd{sup 2+} ions and ancillary BIP ligands, a couple of 3D homochiral coordination polymers with metal clusters and helical chains have been prepared by hydrothermal reaction. - Highlights: • Chiral lactic acid derivative. • Enantiomeric coordination polymer. • Helical chain. • Trinuclear cadmium cluster.« less
NASA Technical Reports Server (NTRS)
Morgenthaler, George W.; Glover, Fred W.; Woodcock, Gordon R.; Laguna, Manuel
2005-01-01
The 1/14/04 USA Space Exploratiofltilization Initiative invites all Space-faring Nations, all Space User Groups in Science, Space Entrepreneuring, Advocates of Robotic and Human Space Exploration, Space Tourism and Colonization Promoters, etc., to join an International Space Partnership. With more Space-faring Nations and Space User Groups each year, such a Partnership would require Multi-year (35 yr.-45 yr.) Space Mission Planning. With each Nation and Space User Group demanding priority for its missions, one needs a methodology for obiectively selecting the best mission sequences to be added annually to this 45 yr. Moving Space Mission Plan. How can this be done? Planners have suggested building a Reusable, Sustainable, Space Transportation Infrastructure (RSSn) to increase Mission synergism, reduce cost, and increase scientific and societal returns from this Space Initiative. Morgenthaler and Woodcock presented a Paper at the 55th IAC, Vancouver B.C., Canada, entitled Constrained Optimization Models For Optimizing Multi - Year Space Programs. This Paper showed that a Binary Integer Programming (BIP) Constrained Optimization Model combined with the NASA ATLAS Cost and Space System Operational Parameter Estimating Model has the theoretical capability to solve such problems. IAA Commission III, Space Technology and Space System Development, in its ACADEMY DAY meeting at Vancouver, requested that the Authors and NASA experts find several Space Exploration Architectures (SEAS), apply the combined BIP/ATLAS Models, and report the results at the 56th Fukuoka IAC. While the mathematical Model is in Ref.[2] this Paper presents the Application saga of that effort.
BiP: Master Regulator of the Unfolded Protein Response and Crucial Factor in Flavivirus Biology
Lewy, Tyler G.; Grabowski, Jeffrey M.; Bloom, Marshall E.
2017-01-01
Flaviviruses have an intimate relationship with their host cells, utilizing host proteins during replication. Much of viral genome replication and virion assembly occurs on and within the endoplasmic reticulum (ER). As a cellular protein folding hub, the ER provides an ideal environment for flaviviruses to replicate. Flaviviruses can interact with several ER processes, including the unfolded protein response (UPR), a cellular stress mechanism responsible for managing unfolded protein accumulation and ER stress. The UPR can alter the ER environment in several ways, including increasing ER volume and quantity of available chaperones, both of which can favor viral replication. BiP, a chaperone and master regulator of the UPR, has been demonstrated to play a key role in several flavivirus infections. Here we describe what is known in regard to BiP, its implicated role with flavivirus infection, and what remains to be discovered. PMID:28656015
BiP: Master Regulator of the Unfolded Protein Response and Crucial Factor in Flavivirus Biology .
Lewy, Tyler G; Grabowski, Jeffrey M; Bloom, Marshall E
2017-06-01
Flaviviruses have an intimate relationship with their host cells, utilizing host proteins during replication. Much of viral genome replication and virion assembly occurs on and within the endoplasmic reticulum (ER). As a cellular protein folding hub, the ER provides an ideal environment for flaviviruses to replicate. Flaviviruses can interact with several ER processes, including the unfolded protein response (UPR), a cellular stress mechanism responsible for managing unfolded protein accumulation and ER stress. The UPR can alter the ER environment in several ways, including increasing ER volume and quantity of available chaperones, both of which can favor viral replication. BiP, a chaperone and master regulator of the UPR, has been demonstrated to play a key role in several flavivirus infections. Here we describe what is known in regard to BiP, its implicated role with flavivirus infection, and what remains to be discovered.
Preparation, Characterization and Application of Optical Switch Probes.
Petchprayoon, Chutima; Marriott, Gerard
2010-08-01
Optical switches represent a new class of molecular probe with applications in high contrast imaging and optical manipulation of protein interactions. Small molecule, organic optical switches based on nitrospirobenzopyran (NitroBIPS) and their reactive derivatives and conjugates undergo efficient, rapid and reversible, orthogonal optically-driven transitions between a colorless spiro (SP) state and a colored merocyanine (MC) state. The excited MC-state also emits fluorescence, which serves as readout of the state of the switch. Defined optical perturbations of SP and MC generate a defined waveform of MC-fluorescence that can be isolated against unmodulated background signals by using a digital optical lock-in detection approach or to control specific dipolar interactions on proteins. The protocols describe general procedures for the synthesis and spectroscopic characterization of NitroBIPS and specifically labeled conjugates along with methods for the manipulation of dipolar interactions on proteins and imaging of the MC-state of NitroBIPS within living cells.
Sigma Receptor 1 Modulates Endoplasmic Reticulum Stress in Retinal Neurons
Ha, Yonju; Dun, Ying; Thangaraju, Muthusamy; Duplantier, Jennifer; Dong, Zheng; Liu, Kebin; Ganapathy, Vadivel
2011-01-01
Purpose. To investigate the mechanism of σ receptor 1 (σR1) neuroprotection in retinal neurons. Methods. Oxidative stress, which is implicated in diabetic retinopathy, was induced in mouse primary ganglion cells (GCs) and RGC-5 cells, and the effect of the σR1 ligand (+)-pentazocine on pro- and anti-apoptotic and endoplasmic reticulum (ER) stress gene expression was examined. Binding of σR1 to BiP, an ER chaperone protein, and σR1 phosphorylation status were examined by immunoprecipitation. Retinas were harvested from Ins2Akita/+ diabetic mice treated with (+)-pentazocine, and the expression of ER stress genes and of the retinal transcriptome was evaluated. Results. Oxidative stress induced the death of primary GCs and RGC-5 cells. The effect was decreased by the application of (+)-pentazocine. Stress increased σR1 binding to BiP and enhanced σR1 phosphorylation in RGC-5 cells. BiP binding was prevented, and σR1 phosphorylation decreased in the presence of (+)-pentazocine. The ER stress proteins PERK, ATF4, ATF6, IRE1α, and CHOP were upregulated in RGC-5 cells during oxidative stress, but decreased in the presence of (+)-pentazocine. A similar phenomenon was observed in retinas of Ins2Akita/+ diabetic mice. Retinal transcriptome analysis of Ins2Akita/+ mice compared with wild-type revealed differential expression of the genes critically involved in oxidative stress, differentiation, and cell death. The expression profile of those genes was reversed when the Ins2Akita/+ mice were treated with (+)-pentazocine. Conclusions. In retinal neurons, the molecular chaperone σR1 binds BiP under stressful conditions; (+)-pentazocine may exert its effects by dissociating σR1 from BiP. As stress in retinal cells increases, phosphorylation of σR1 is increased, which is attenuated when agonists bind to the receptor. PMID:20811050
Male Batterers’ Alcohol Use and Gambling Behavior
Febres, Jeniimarie; Shorey, Ryan; Strong, David; Ninnemann, Andrew; Elmquist, Joanna; Andersen, Shawna M.; Bucossi, Meggan; Schonbrun, Yael C.; Temple, Jeff R.; Stuart, Gregory L.
2012-01-01
Little work has examined the interrelations among intimate partner violence (IPV), alcohol use, and gambling behavior, and no studies have examined these relationships among males court-ordered to batterer intervention programs (BIPs). The aim of the current investigation was to explore the associations between IPV, alcohol use, and gambling behavior among 341 males court-mandated to attend BIPs utilizing self-report measures. Voluntary, anonymous questionnaires were administered and completed during regularly scheduled BIP sessions. Compared to the general population, a higher percentage of the sample met criteria for pathological gambling (9%), and problem gambling (17%). Further, males exhibiting pathological gambling were more likely to be hazardous drinkers, and hazardous drinkers were more likely to exhibit pathological gambling. Additionally, pathological gamblers were at an increased risk for the perpetration of both physical and sexual aggression. Finally, gambling behavior uniquely predicted the perpetration of sexual aggression above and beyond alcohol use, impulsivity, and relationship satisfaction. The implications of these results for future research and intervention are discussed. PMID:21516369
Duran, Ivan; Martin, Jorge H.; Weis, Mary Ann; Krejci, Pavel; Konik, Peter; Li, Bing; Alanay, Yasemin; Lietman, Caressa; Lee, Brendan; Eyre, David; Cohn, Daniel H.; Krakow, Deborah
2017-01-01
Lysine hydroxylation of type I collagen telopeptides varies from tissue to tissue and these distinct hydroxylation patterns modulate collagen crosslinking to generate a unique extracellular matrix. Abnormalities in these patterns contribute to pathologies that include osteogenesis imperfecta (OI), fibrosis and cancer. Telopeptide procollagen modifications are carried out by lysyl hydroxylase 2 (LH2), however, little is known regarding how this enzyme regulates hydroxylation patterns. We identified an ER complex of resident chaperones that includes HSP47, FKBP65 and BiP regulating the activity of LH2. Our findings show that FKBP65 and HSP47 modulate the activity of LH2 to either favor or repress its activity. BiP was also identified as a member of the complex, playing a role in enhancing the formation of the complex. This newly identified ER chaperone complex contributes to our understanding of how LH2 regulates lysyl hydroxylation of type I collagen C-telopeptides to affect the quality of connective tissues. PMID:28177155
Otero, Joel H; Lizák, Beata; Feige, Matthias J; Hendershot, Linda M
2014-10-03
ERdj3, a mammalian endoplasmic reticulum (ER) Hsp40/DnaJ family member, binds unfolded proteins, transfers them to BiP, and concomitantly stimulates BiP ATPase activity. However, the requirements for ERdj3 binding to and release from substrates in cells are not well understood. We found that ERdj3 homodimers that cannot stimulate the ATPase activity of BiP (QPD mutants) bound to unfolded ER proteins under steady state conditions in much greater amounts than wild-type ERdj3. This was due to reduced release from these substrates as opposed to enhanced binding, although in both cases dimerization was strictly required for substrate binding. Conversely, heterodimers consisting of one wild-type and one mutant ERdj3 subunit bound substrates at levels comparable with wild-type ERdj3 homodimers, demonstrating that release requires only one protomer to be functional in stimulating BiP ATPase activity. Co-expressing wild-type ERdj3 and a QPD mutant, which each exclusively formed homodimers, revealed that the release rate of wild-type ERdj3 varied according to the relative half-lives of substrates, suggesting that ERdj3 release is an important step in degradation of unfolded client proteins in the ER. Furthermore, pulse-chase experiments revealed that the binding of QPD mutant homodimers remained constant as opposed to increasing, suggesting that ERdj3 does not normally undergo reiterative binding cycles with substrates. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Otero, Joel H.; Lizák, Beata; Feige, Matthias J.; Hendershot, Linda M.
2014-01-01
ERdj3, a mammalian endoplasmic reticulum (ER) Hsp40/DnaJ family member, binds unfolded proteins, transfers them to BiP, and concomitantly stimulates BiP ATPase activity. However, the requirements for ERdj3 binding to and release from substrates in cells are not well understood. We found that ERdj3 homodimers that cannot stimulate the ATPase activity of BiP (QPD mutants) bound to unfolded ER proteins under steady state conditions in much greater amounts than wild-type ERdj3. This was due to reduced release from these substrates as opposed to enhanced binding, although in both cases dimerization was strictly required for substrate binding. Conversely, heterodimers consisting of one wild-type and one mutant ERdj3 subunit bound substrates at levels comparable with wild-type ERdj3 homodimers, demonstrating that release requires only one protomer to be functional in stimulating BiP ATPase activity. Co-expressing wild-type ERdj3 and a QPD mutant, which each exclusively formed homodimers, revealed that the release rate of wild-type ERdj3 varied according to the relative half-lives of substrates, suggesting that ERdj3 release is an important step in degradation of unfolded client proteins in the ER. Furthermore, pulse-chase experiments revealed that the binding of QPD mutant homodimers remained constant as opposed to increasing, suggesting that ERdj3 does not normally undergo reiterative binding cycles with substrates. PMID:25143379
ERIC Educational Resources Information Center
Camacho, Julian S.
The Compton Community College (CCC) General Education Associate of Arts/Certification Bilingual Immersion Program (BIP) is designed to allow English-as-a-Second-Language (ESL) or limited English proficiency (LEP) students to study subjects beyond ESL in a bilingual setting. Current ESL programs offer students no oppurtunity to take degree/transfer…
Bipyrimidine ruthenium(II) arene complexes: structure, reactivity and cytotoxicity.
Betanzos-Lara, Soledad; Novakova, Olga; Deeth, Robert J; Pizarro, Ana M; Clarkson, Guy J; Liskova, Barbora; Brabec, Viktor; Sadler, Peter J; Habtemariam, Abraha
2012-10-01
The synthesis and characterization of complexes [(η(6)-arene)Ru(N,N')X][PF(6)], where arene is para-cymene (p-cym), biphenyl (bip), ethyl benzoate (etb), hexamethylbenzene (hmb), indane (ind) or 1,2,3,4-tetrahydronaphthalene (thn), N,N' is 2,2'-bipyrimidine (bpm) and X is Cl, Br or I, are reported, including the X-ray crystal structures of [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)I][PF(6)] and [(η(6)-etb)Ru(bpm)Cl][PF(6)]. Complexes in which N,N' is 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione or 4,7-diphenyl-1,10-phenanthroline (bathophen) were studied for comparison. The Ru(II) arene complexes undergo ligand-exchange reactions in aqueous solution at 310 K; their half-lives for hydrolysis range from 14 to 715 min. Density functional theory calculations on [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-p-cym)Ru(bpm)Br][PF(6)], [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)Br][PF(6)] and [(η(6)-bip)Ru(bpm)I][PF(6)] suggest that aquation occurs via an associative pathway and that the reaction is thermodynamically favourable when the leaving ligand is I > Br ≈ Cl. pK (a)* values for the aqua adducts of the complexes range from 6.9 to 7.32. A binding preference for 9-ethylguanine (9-EtG) compared with 9-ethyladenine (9-EtA) was observed for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-hmb)Ru(bpm)Cl](+), [(η(6)-ind)Ru(bpm)Cl](+), [(η(6)-thn)Ru(bpm)Cl](+), [(η(6)-p-cym)Ru(phen)Cl](+) and [(η(6)-p-cym)Ru(bathophen)Cl](+) in aqueous solution at 310 K. The X-ray crystal structure of the guanine complex [(η(6)-p-cym)Ru(bpm)(9-EtG-N7)][PF(6)](2) shows multiple hydrogen bonding. Density functional theory calculations show that the 9-EtG adducts of all complexes are thermodynamically preferred compared with those of 9-EtA. However, the bmp complexes are inactive towards A2780 human ovarian cancer cells. Calf thymus DNA interactions for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)] and [(η(6)-p-cym)Ru(phen)Cl][PF(6)] consist of weak coordinative, intercalative and monofunctional coordination. Binding to biomolecules such as glutathione may play a role in deactivating the bpm complexes.
Zingg, Tobias; Agri, Fabio; Bourgeat, Mylène; Yersin, Bertrand; Romain, Benoît; Schmidt, Sabine; Keller, Nathalie; Demartines, Nicolas
2018-01-01
Significant blunt bowel and mesenteric injuries (sBBMI) are frequently missed despite the widespread use of computed tomography (CT). Early treatment improves the outcome related to these injuries. The aim of this study was to assess the prevalence of sBBMI, the incidence of delayed diagnosis and to test the performance of the Bowel Injury Prediction Score (BIPS), determined by the white blood cell (WBC) count, presence or absence of abdominal tenderness and CT grade of mesenteric injury. Single-centre, registry-based retrospective cohort study, screening all consecutive trauma patients admitted to Lausanne University Hospital Trauma Centre from 2008 to 2015 after a road traffic accident. All patients with reliable information about the presence or absence of sBBMI who underwent abdominal CT and for whom calculation of the BIPS was possible were included for analysis. The incidence of delayed (>24h after admission) diagnosis in the patient group with sBBMI was determined and the diagnostic performance of the BIPS for sBBMI was assessed. For analysis, 766 patients with reliable information about the presence or absence of sBBMI were included. The prevalence of sBBMI was 3.1% (24/766). In 24% (5/21) of stable trauma patients undergoing CT, a diagnostic delay of more than 24h occurred. Abdominal tenderness (p<0.0001) and CT grade ≥4 (p<0.0001) were associated with sBBMI, whereas CT grade 4 alone (p=0.93) and WBC count ≥17G/l (p=0.30) were not. A BIPS ≥2 had a sensitivity of 89% (95% CI, 67-99), specificity of 89% (95% CI, 86-91), positive likelihood ratio of 8 (95% CI, 6.1-10), negative likelihood ratio of 0.12 (95% CI, 0.03-0.44), positive predictive value (PPV) of 19% (95% CI, 15-24) and negative predictive value (NPV) of 99.7% (95% CI, 98.7-99.9). CT alone identified 79% (15/19) and the BIPS 89% (17/19) of patients with sBBMI (p=0.66). Diagnostic delays in patients with sBBMI are common (24%), despite the routine use of abdominal CT. Application of the BIPS on the present cohort would have led to a high number of non-therapeutic abdominal explorations without identifying significantly more sBBMI early than CT alone. Copyright © 2017 Elsevier Ltd. All rights reserved.
Intrarenal renin-angiotensin system mediates fatty acid-induced ER stress in the kidney
Li, Chunling; Lin, Yu; Luo, Renfei; Chen, Shaoming; Zheng, Peili; Levi, Moshe; Yang, Tianxin; Wang, Weidong
2015-01-01
Obesity-related kidney disease is related to caloric excess promoting deleterious cellular responses. Accumulation of saturated free fatty acids in tubular cells produces lipotoxicity involving significant cellular dysfunction and injury. The objectives of this study were to elucidate the role of renin-angiotensin system (RAS) activation in saturated fatty acid-induced endoplasmic reticulum (ER) stress in cultured human proximal tubule epithelial cells (HK2) and in mice fed with a high-fat diet. Treatment with saturated fatty acid palmitic acid (PA; 0.8 mM) for 24 h induced ER stress in HK2, leading to an unfolded protein response as reflected by increased expressions of the ER chaperone binding immunoglobulin protein (BiP) and proapoptotic transcription factor C/EBP homologous protein (CHOP) protein as evaluated by immunoblotting. PA treatment also induced increased protein expression of inositol requiring protein 1α (IRE1α), phosphorylated eukaryotic initiation factor-α (eIF2α), and activating transcription factor 4 (ATF4) as well as activation of caspase-3. PA treatment was associated with increased angiotensin II levels in cultured medium. The angiotensin II type 1 receptor (AT1R) blocker valsartan or renin inhibitor aliskiren dramatically suppressed PA-induced upregulation of BiP, CHOP, IRE1α, p-eIF2α, and ATF4 in HK2 cells. In contrast, valsartan or aliskiren did not prevent ER stress induced by tunicamycin. C57BL/6 mice fed with a high-fat diet for 14 wk exhibited increased protein expressions of BiP and CHOP compared with control mice, which were significantly attenuated by the valsartan treatment. Increased angiotensin II levels in serum and urine were observed in mice fed with a high-fat diet when compared with controls. It is suggested that the intrarenal RAS activation may play an important role in diabetic kidney injury via mediating ER stress induced by saturated fatty acid. PMID:26672616
Martínez, Juan A; Tavárez, José J; Oliveira, Caroline M; Banerjee, Dipak K
2006-05-01
During tumor growth and invasion, the endothelial cells from a relatively quiescent endothelium start proliferating. The exact mechanism of switching to a new angiogenic phenotype is currently unknown. We have examined the role of intracellular cAMP in this process. When a non-transformed capillary endothelial cell line was treated with 2 mM 8Br-cAMP, cell proliferation was enhanced by approximately 70%. Cellular morphology indicated enhanced mitosis after 32-40 h with almost one-half of the cell population in the S phase. Bcl-2 expression and caspase-3, -8, and -9 activity remained unaffected. A significant increase in the Glc(3)Man(9)GlcNAc(2)-PP-Dol biosynthesis and turnover, Factor VIIIC N-glycosylation, and cell surface expression of N-glycans was observed in cells treated with 8Br-cAMP. Dol-P-Man synthase activity in the endoplasmic reticulum membranes also increased. A 1.4-1.6-fold increase in HSP-70 and HSP-90 expression was also observed in 8Br-cAMP treated cells. On the other hand, the expression of GRP-78/Bip was 2.3-fold higher compared to that of GRP-94 in control cells, but after 8Br-cAMP treatment for 32 h, it was reduced by 3-fold. GRP-78/Bip expression in untreated cells was 1.2-1.5-fold higher when compared with HSP-70 and HSP-90, whereas that of the GRP-94 was 1.5-1.8-fold lower. After 8Br-cAMP treatment, GRP-78/Bip expression was reduced 4.5-4.8-fold, but the GRP-94 was reduced by 1.5-1.6-fold only. Upon comparison, a 2.9-fold down-regulation of GRP-78/Bip was observed compared to GRP-94. We, therefore, conclude that a high level of Glc(3)Man(9)GlcNAc(2)-PP-Dol, resulting from 8Br-cAMP stimulation up-regulated HSP-70 expression and down-regulated that of the GRP-78/Bip, maintained adequate protein folding, and reduced endoplasmic reticulum stress. As a result capillary endothelial cell proliferation was induced.
Du, Jingjing; Liu, Chendong; Wu, Xiaoqian; Pu, Qiang; Fu, Yuhua; Tang, Qianzi; Liu, Yuanrui; Li, Qiang; Yang, Runlin; Li, Xuewei; Tang, Guoqing; Jiang, Yanzhi; Li, Mingzhou; Zhang, Shunhua; Zhu, Li
2015-01-01
Animal growth curves can provide essential information for animal breeders to optimize feeding and management strategies. However, the genetic mechanism underlying the phenotypic differentiation between the inflection point and asymptotic stages of the growth curve is not well characterized. Here, we employed Liangshan pigs in stages of growth at the inflection point (under inflection point: UIP) and the two asymptotic stages (before the inflection point: BIP, after the inflection point: AIP) as models to survey global gene expression in the longissimus dorsi muscle using digital gene expression (DGE) tag profiling. We found Liangshan pigs reached maximum growth rate (UIP) at 163.6 days of age and a weight of 134.6 kg. The DGE libraries generated 117 million reads of 5.89 gigabases in length. 21,331, 20,996 and 20,139 expressed transcripts were identified BIP, UIP and AIP, respectively. Among them, we identified 757 differentially expressed genes (DEGs) between BIP and UIP, and 271 DEGs between AIP and UIP. An enrichment analysis of DEGs proved the immune system was strengthened in the AIP stage. Energy metabolism rate, global transcriptional activity and bone development intensity were highest UIP. Meat from Liangshan pigs had the highest intramuscular fat content and most favorable fatty acid composition in the AIP. Three hundred eighty (27.70%) specific expression genes were highly enriched in QTL regions for growth and meat quality traits. This study completed a comprehensive analysis of diverse genetic mechanisms underlying the inflection point and asymptotic stages of growth. Our findings will serve as an important resource in the understanding of animal growth and development in indigenous pig breeds. PMID:26292092
Shen, Linyuan; Luo, Jia; Du, Jingjing; Liu, Chendong; Wu, Xiaoqian; Pu, Qiang; Fu, Yuhua; Tang, Qianzi; Liu, Yuanrui; Li, Qiang; Yang, Runlin; Li, Xuewei; Tang, Guoqing; Jiang, Yanzhi; Li, Mingzhou; Zhang, Shunhua; Zhu, Li
2015-01-01
Animal growth curves can provide essential information for animal breeders to optimize feeding and management strategies. However, the genetic mechanism underlying the phenotypic differentiation between the inflection point and asymptotic stages of the growth curve is not well characterized. Here, we employed Liangshan pigs in stages of growth at the inflection point (under inflection point: UIP) and the two asymptotic stages (before the inflection point: BIP, after the inflection point: AIP) as models to survey global gene expression in the longissimus dorsi muscle using digital gene expression (DGE) tag profiling. We found Liangshan pigs reached maximum growth rate (UIP) at 163.6 days of age and a weight of 134.6 kg. The DGE libraries generated 117 million reads of 5.89 gigabases in length. 21,331, 20,996 and 20,139 expressed transcripts were identified BIP, UIP and AIP, respectively. Among them, we identified 757 differentially expressed genes (DEGs) between BIP and UIP, and 271 DEGs between AIP and UIP. An enrichment analysis of DEGs proved the immune system was strengthened in the AIP stage. Energy metabolism rate, global transcriptional activity and bone development intensity were highest UIP. Meat from Liangshan pigs had the highest intramuscular fat content and most favorable fatty acid composition in the AIP. Three hundred eighty (27.70%) specific expression genes were highly enriched in QTL regions for growth and meat quality traits. This study completed a comprehensive analysis of diverse genetic mechanisms underlying the inflection point and asymptotic stages of growth. Our findings will serve as an important resource in the understanding of animal growth and development in indigenous pig breeds.
Endoplasmic Reticulum Transport of Glutathione by Sec61 Is Regulated by Ero1 and Bip.
Ponsero, Alise J; Igbaria, Aeid; Darch, Maxwell A; Miled, Samia; Outten, Caryn E; Winther, Jakob R; Palais, Gael; D'Autréaux, Benoit; Delaunay-Moisan, Agnès; Toledano, Michel B
2017-09-21
In the endoplasmic reticulum (ER), Ero1 catalyzes disulfide bond formation and promotes glutathione (GSH) oxidation to GSSG. Since GSSG cannot be reduced in the ER, maintenance of the ER glutathione redox state and levels likely depends on ER glutathione import and GSSG export. We used quantitative GSH and GSSG biosensors to monitor glutathione import into the ER of yeast cells. We found that glutathione enters the ER by facilitated diffusion through the Sec61 protein-conducting channel, while oxidized Bip (Kar2) inhibits transport. Increased ER glutathione import triggers H 2 O 2 -dependent Bip oxidation through Ero1 reductive activation, which inhibits glutathione import in a negative regulatory loop. During ER stress, transport is activated by UPR-dependent Ero1 induction, and cytosolic glutathione levels increase. Thus, the ER redox poise is tuned by reciprocal control of glutathione import and Ero1 activation. The ER protein-conducting channel is permeable to small molecules, provided the driving force of a concentration gradient. Copyright © 2017 Elsevier Inc. All rights reserved.
Development and validation of a tailored measure of body image for pregnant women.
Watson, Brittany; Fuller-Tyszkiewicz, Matthew; Broadbent, Jaclyn; Skouteris, Helen
2017-11-01
This study developed and validated a quantitative measure of body image specifically designed for pregnancy-the Body Image in Pregnancy Scale (BIPS). Scale development was guided by qualitative data from a series of studies exploring the meaning of women's body image experiences during pregnancy, and previously established body image measures. Exploratory factor analysis for a sample of pregnant women (n = 251) indicated good fit for a 36-item scale with seven factors: preoccupation with physical appearance, dissatisfaction with physical strength, dissatisfaction with facial features, sexual attractiveness, prioritizing physical appearance over body functioning, appearance-related behavioral avoidance, and dissatisfaction with body parts. BIPS subscale scores demonstrated good internal reliability, test-retest reliability, and both incremental and convergent validity with measures of body image, self-esteem, and depressive symptomatology. Although the pregnancy-focused wording of BIPS items prevents its use for comparisons with nonpregnant populations, further testing of changes in body image throughout pregnancy is an identified area for further research with this measure. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Proton-Coupled Electron Transfer in Artificial Photosynthetic Systems.
Mora, S Jimena; Odella, Emmanuel; Moore, Gary F; Gust, Devens; Moore, Thomas A; Moore, Ana L
2018-02-20
Artificial photosynthetic constructs can in principle operate more efficiently than natural photosynthesis because they can be rationally designed to optimize solar energy conversion for meeting human demands rather than the multiple needs of an organism competing for growth and reproduction in a complex ecosystem. The artificial photosynthetic constructs described in this Account consist primarily of covalently linked synthetic chromophores, electron donors and acceptors, and proton donors and acceptors that carry out the light absorption, electron transfer, and proton-coupled electron transfer (PCET) processes characteristic of photosynthetic cells. PCET is the movement of an electron from one site to another accompanied by proton transfer. PCET and the transport of protons over tens of angstroms are important in all living cells because they are a fundamental link between redox processes and the establishment of transmembrane gradients of proton electrochemical potential, known as proton-motive force (PMF), which is the unifying concept in bioenergetics. We have chosen a benzimidazole phenol (BIP) system as a platform for the study of PCET because with appropriate substitutions it is possible to design assemblies in which one or multiple proton transfers can accompany oxidation of the phenol. In BIP, oxidation of the phenol increases its acidity by more than ten pK a units; thus, electrochemical oxidation of the phenol is associated with a proton transfer to the imidazole. This is an example of a PCET process involving transfer of one electron and one proton, known as electron-proton transfer (EPT). When the benzimidazole moiety of BIP is substituted at the 4-position with good proton acceptor groups such as aliphatic amines, experimental and theoretical results indicate that two proton transfers occur upon one-electron oxidation of the phenol. This phenomenon is described as a one-electron-two-proton transfer (E2PT) process and results in translocation of protons over ∼7 Å via a Grotthuss-type mechanism, where the protons traverse a network of internally H-bonded sites. In the case of the E2TP process involving BIP analogues with amino group substituents, the thermodynamic price paid in redox potential to move a proton to the final proton acceptor is ∼300 mV. In this example, the decrease in redox potential limits the oxidizing power of the resulting phenoxyl radical. Thus, unlike the biological counterpart, the artificial construct is thermodynamically incapable of effectively advancing the redox state of a water oxidation catalyst. The design of systems where multiple proton transfer events are coupled to an oxidation reaction while a relatively high redox potential is maintained remains an outstanding challenge. The ability to control proton transfer and activity at defined distances and times is key to achieving proton management in the vicinity of catalysts operating at low overpotential in myriad biochemically important processes. Artificial photosynthetic constructs with well-defined structures, such as the ones described in this Account, can provide the means for discovering design principles upon which efficient redox catalysts for electrolysis and fuel cells can be based.
Schneider, Markus; Rosam, Mathias; Glaser, Manuel; Patronov, Atanas; Shah, Harpreet; Back, Katrin Christiane; Daake, Marina Angelika; Buchner, Johannes; Antes, Iris
2016-10-01
Substrate binding to Hsp70 chaperones is involved in many biological processes, and the identification of potential substrates is important for a comprehensive understanding of these events. We present a multi-scale pipeline for an accurate, yet efficient prediction of peptides binding to the Hsp70 chaperone BiP by combining sequence-based prediction with molecular docking and MMPBSA calculations. First, we measured the binding of 15mer peptides from known substrate proteins of BiP by peptide array (PA) experiments and performed an accuracy assessment of the PA data by fluorescence anisotropy studies. Several sequence-based prediction models were fitted using this and other peptide binding data. A structure-based position-specific scoring matrix (SB-PSSM) derived solely from structural modeling data forms the core of all models. The matrix elements are based on a combination of binding energy estimations, molecular dynamics simulations, and analysis of the BiP binding site, which led to new insights into the peptide binding specificities of the chaperone. Using this SB-PSSM, peptide binders could be predicted with high selectivity even without training of the model on experimental data. Additional training further increased the prediction accuracies. Subsequent molecular docking (DynaDock) and MMGBSA/MMPBSA-based binding affinity estimations for predicted binders allowed the identification of the correct binding mode of the peptides as well as the calculation of nearly quantitative binding affinities. The general concept behind the developed multi-scale pipeline can readily be applied to other protein-peptide complexes with linearly bound peptides, for which sufficient experimental binding data for the training of classical sequence-based prediction models is not available. Proteins 2016; 84:1390-1407. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Malikowska, Natalia; Sałat, Kinga; Podkowa, Adrian
2017-07-01
Memory disorders accompany numerous diseases and therapies, and this is becoming a growing medical issue worldwide. Currently, various animal models of memory impairments are available; however, many of them require high financial outlay and/or are time-consuming. A simple way to achieve an efficient behavioral model of cognitive disorders is to inject defined drug that has pro-amnesic properties. Since the involvement of cholinergic and glutamatergic neurotransmission in cognition is well established, the utilization of a nonselective muscarinic receptor antagonist, scopolamine (SCOP), a selective M1 muscarinic receptor antagonist, biperiden (BIP), and a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine (PCP) seems to be reliable tools to induce amnesia. As the determination of their effective doses remains vague and the active doses vary significantly in laboratory settings and in mouse species being tested, the aim of this study was to compare these three models of amnesia in CD-1 mice. Male Swiss Albino mice were used in passive avoidance (PA) test. All the compounds were administered intraperitoneally (ip) at doses 1mg/kg, 5mg/kg, and 10mg/kg (SCOP and BIP), and 1mg/kg, 3mg/kg, and 6mg/kg (PCP). In the retention trial of the PA task, SCOP and PCP led to the reduction of step-through latency at all the tested doses as compared to control, but BIP was effective only at the dose of 10mg/kg. This study revealed the effectiveness of SCOP, PCP, and BIP as tools to induce amnesia, with the PCP model being the most efficacious and SCOP being the only model that demonstrates a clear dose-response relationship. Copyright © 2017. Published by Elsevier Inc.
Johnson, Rebecca A; Kierski, Katharine R; Jones, Brian G
2017-05-01
OBJECTIVE To quantify nausea and sedation scores, gastric emptying time, and gastrointestinal transit time after IV administration of a lidocaine hydrochloride bolus followed by a constant rate infusion (CRI) in clinically normal dogs. ANIMALS 6 Beagles. PROCEDURES In a crossover study, dogs were fed thirty 1.5-mm barium-impregnated spheres (BIPS) and received a saline (0.9% NaCl) solution bolus (0.05 mL/kg) IV (time 0) followed by a CRI at 10 mL/h, a lidocaine bolus (1 mg/kg) IV followed by a CRI at 25 μg/kg/min, or a lidocaine bolus (1 mg/kg) IV followed by a CRI at 50 μg/kg/min; CRIs were for 12 hours. Nausea and sedation scores were assessed and abdominal radiographs obtained immediately after feeding of BIPS and every hour for 12 hours and again 16 hours after CRI start. Percentage of BIPSs in the small and large intestines, gastric emptying time, and gastrointestinal transit time were assessed. RESULTS Gastric emptying time did not differ significantly among treatments. Significantly more BIPS were in the large intestine 4 to 7 hours after treatment start for the 50-μg/kg/min treatment than for the other 2 treatments. Six hours after treatment start, significantly more BIPS were in the large intestine for the 25-μg/kg/min treatment than for the saline solution treatment. Higher sedation and nausea scores were associated with the 50-μg/kg/min CRI. CONCLUSIONS AND CLINICAL RELEVANCE In clinically normal dogs, lidocaine CRI did not significantly affect gastric emptying. However, gastrointestinal transit time was mildly decreased and sedation and nausea scores increased in dogs administered a lidocaine CRI at clinically used doses.
Benchmarking in pathology: development of an activity-based costing model.
Burnett, Leslie; Wilson, Roger; Pfeffer, Sally; Lowry, John
2012-12-01
Benchmarking in Pathology (BiP) allows pathology laboratories to determine the unit cost of all laboratory tests and procedures, and also provides organisational productivity indices allowing comparisons of performance with other BiP participants. We describe 14 years of progressive enhancement to a BiP program, including the implementation of 'avoidable costs' as the accounting basis for allocation of costs rather than previous approaches using 'total costs'. A hierarchical tree-structured activity-based costing model distributes 'avoidable costs' attributable to the pathology activities component of a pathology laboratory operation. The hierarchical tree model permits costs to be allocated across multiple laboratory sites and organisational structures. This has enabled benchmarking on a number of levels, including test profiles and non-testing related workload activities. The development of methods for dealing with variable cost inputs, allocation of indirect costs using imputation techniques, panels of tests, and blood-bank record keeping, have been successfully integrated into the costing model. A variety of laboratory management reports are produced, including the 'cost per test' of each pathology 'test' output. Benchmarking comparisons may be undertaken at any and all of the 'cost per test' and 'cost per Benchmarking Complexity Unit' level, 'discipline/department' (sub-specialty) level, or overall laboratory/site and organisational levels. We have completed development of a national BiP program. An activity-based costing methodology based on avoidable costs overcomes many problems of previous benchmarking studies based on total costs. The use of benchmarking complexity adjustment permits correction for varying test-mix and diagnostic complexity between laboratories. Use of iterative communication strategies with program participants can overcome many obstacles and lead to innovations.
Revision of endemic Marquesas Islands Bidens (Asteraceae, Coreopsideae)
Wagner, Warren L.; Clark, John R.; Lorence, David H.
2014-01-01
Abstract During the preparation of the Vascular Flora of the Marquesas Islands four new species of Bidens (Coreopsideae, Asteraceae) have come to light and are described herein: Bidens woodii W.L. Wagner, J.R. Clark & Lorence, sp. nov. from Ua Pou, and Bidens microcephala W.L. Wagner, J.R. Clark & Lorence sp. nov., Bidens evapelliana W.L. Wagner, J.R. Clark & Lorence, sp. nov., and Bidens wichmanii W.L. Wagner, J.R. Clark & Lorence, sp. nov. from the undercollected island of Fatu Hiva. In addition to these new species, we recognize the following six species of Bidens previously described from the Marquesas Islands: Bidens beckiana (F. Br.) Sherff (Eiao and Hatutaa), Bidens bipontina Sherff and Bidens cordifolia Sch. Bip. (both in Nuku Hiva), Bidens henryi Sherff (Hiva Oa, Tahuata), Bidens uapensis (F. Br.) Sherff (Ua Pou), and Bidens polycephala Sch. Bip. (Nuku Hiva, Ua Huku, Hiva Oa, Tahuata, and Mohotani). Two names are reduced to synonymy under Bidens polycephala: Bidens collina Degener & Sherff, syn. nov. and Bidens jardinii Sch. Bip., syn. nov. Bidens polycephala has the widest distribution of the Marquesan species on five of the islands and exhibits considerable variation. PMID:25009437
DOE Office of Scientific and Technical Information (OSTI.GOV)
Harris, L.W.; Anderson, D.R.; Lennox, W.J.
1993-05-13
FDA approved, injectable preparations of candidate compounds BENZTROPINE (BZT), 1.0 mg/ml; biperiden (BIP), 5.0 mg/ml; dicyclomine (DCL), 10 mg/ml; 1-hyoscyamine (HYO), 0.5 mg/ml; orphenadrine (ORP), 30 mg/ml; scopolamine (SCP), 1.0 mg/ml were tested in parallel with diazepam (DZ, the standard) in male guinea pigs against ongoing soman induced convulsive (CV)/sub-CV activity. Three trained graders concurrently assigned CV/sub-CV scores (12 - convulsions; 0 normal) to each animal. Animals received (im) pyridostigmine (PYR; 26 ug/kg) 30 min before soman (56 ug/kg; 2 LD50), atropine (2 mg/kg) admixed with 2-PAM (25 mg/kg) at one min after soman, and the candidate drug preparation atmore » 5.67 min post soman, a time when CV activity is assured. BIP and SCP demonstrated efficacy over dosage ranges between 10 and 0.3 and 1.0 and 0.13 mg/kg, respectively, while the other preparations were less effective at their respective maximum dosages. At optimal dosages of SCP (0.5 mg/kg) and BIP (10 mg/kg), the CV/sub-CV scores were significantly lower (p < 0.05) than those of DZ.« less
Cha-Molstad, Hyunjoo; Sung, Ki Sa; Hwang, Joonsung; Kim, Kyoung A; Yu, Ji Eun; Yoo, Young Dong; Jang, Jun Min; Han, Dong Hoon; Molstad, Michael; Kim, Jung Gi; Lee, Yoon Jee; Zakrzewska, Adriana; Kim, Su-Hyeon; Kim, Sung Tae; Kim, Sun Yong; Lee, Hee Gu; Soung, Nak Kyun; Ahn, Jong Seog; Ciechanover, Aaron; Kim, Bo Yeon; Kwon, Yong Tae
2015-07-01
We show that ATE1-encoded Arg-transfer RNA transferase (R-transferase) of the N-end rule pathway mediates N-terminal arginylation of multiple endoplasmic reticulum (ER)-residing chaperones, leading to their cytosolic relocalization and turnover. N-terminal arginylation of BiP (also known as GRP78), protein disulphide isomerase and calreticulin is co-induced with autophagy during innate immune responses to cytosolic foreign DNA or proteasomal inhibition, associated with increased ubiquitylation. Arginylated BiP (R-BiP) is induced by and associated with cytosolic misfolded proteins destined for p62 (also known as sequestosome 1, SQSTM1) bodies. R-BiP binds the autophagic adaptor p62 through the interaction of its N-terminal arginine with the p62 ZZ domain. This allosterically induces self-oligomerization and aggregation of p62 and increases p62 interaction with LC3, leading to p62 targeting to autophagosomes and selective lysosomal co-degradation of R-BiP and p62 together with associated cargoes. In this autophagic mechanism, Nt-arginine functions as a delivery determinant, a degron and an activating ligand. Bioinformatics analysis predicts that many ER residents use arginylation to regulate non-ER processes.
Stijnen, P; Brouwers, B; Dirkx, E; Ramos-Molina, B; Van Lommel, L; Schuit, F; Thorrez, L; Declercq, J; Creemers, J W M
2016-06-01
The proprotein convertase 1/3 (PC1/3), encoded by proprotein convertase subtilisin/kexin type 1 (PCSK1), cleaves and hence activates several orexigenic and anorexigenic proproteins. Congenital inactivation of PCSK1 leads to obesity in human but not in mice. However, a mouse model harboring the hypomorphic mutation N222D is obese. It is not clear why the mouse models differ in phenotype. Gene expression analysis was performed with pancreatic islets from Pcsk1(N222D/N222D) mice. Subsequently, biosynthesis, maturation, degradation and activity were studied in islets, pituitary, hypothalamus and cell lines. Coimmunoprecipitation of PC1/3-N222D and human PC1/3 variants associated with obesity with the endoplasmic reticulum (ER) chaperone BiP was studied in cell lines. Gene expression analysis of islets of Pcsk1(N222D/N222D) mice showed enrichment of gene sets related to the proteasome and the unfolded protein response. Steady-state levels of PC1/3-N222D and in particular the carboxy-terminally processed form were strongly reduced in islets, pituitary and hypothalamus. However, impairment of substrate cleavage was tissue dependent. Proinsulin processing was drastically reduced, while processing of proopiomelanocortin (POMC) to adrenocorticotropic hormone (ACTH) in pituitary was only mildly impaired. Growth hormone expression and IGF-1 levels were normal, indicating near-normal processing of hypothalamic proGHRH. PC1/3-N222D binds to BiP and is rapidly degraded by the proteasome. Analysis of human PC1/3 obesity-associated mutations showed increased binding to BiP and prolonged intracellular retention for all investigated mutations, in particular for PC1/3-T175M, PC1/3-G226R and PC1/3-G593R. This study demonstrates that the hypomorphic mutation in Pcsk1(N222D) mice has an effect on catalytic activity in pancreatic islets, pituitary and hypothalamus. Reduced substrate processing activity in Pcsk1(N222D/N222D) mice is due to enhanced degradation in addition to reduced catalytic activity of the mutant. PC1/3-N222D binds to BiP, suggesting impaired folding and reduced stability. Enhanced BiP binding is also observed in several human obesity-associated PC1/3 variants, suggesting a common mechanism.
EDI at the Jet Propulsion Laboratory Library
NASA Technical Reports Server (NTRS)
Amago, B.
1994-01-01
The JPL Library and Information Center orders and claims material elecronically whenever feasible. The NASA Aerospace Research Information Network (ARIN) is used to order books for the library collection; BIP Plus on CD-ROM is used to order office copies. Paper copies of invoices are processed when material is received. Subscriptions are ordered using the vendor's online system; monthly and annual invoices are received both in paper and electronic format (diskette of FTP). Library-developed dbase programs complement or duplicate functions available through ARIN and/or the JPL institutional accounting system.
Saito, Momoko; Odanaka, Keita; Otsuka, Nao; Kamachi, Kazunari; Watanabe, Mineo
2016-09-01
Bordetella holmesii is recognized as the third causative agent of pertussis (whooping cough) in addition to Bordetella pertussis and Bordetella parapertussis. Pertussis caused by B. holmesii is not rare around the world. However, to date, there is no effective vaccine against B. holmesii. We examined the protective potency of pertussis vaccines available in Japan and vaccines prepared from B. holmesii. A murine model of respiratory infection was exploited to evaluate protective potency. No Japanese commercial pertussis vaccines were effective against B. holmesii. In contrast, a wBH vaccine and an aBH vaccine prepared from B. holmesii were both protective. Passive immunization with sera from mice immunized with aBH vaccine established protection against B. holmesii, indicating that B. holmesii-specific serum antibodies might play an important role in protection. Immuno-proteomic analysis with sera from mice immunized with aBH vaccine revealed that the sera recognized a BipA-like protein of B. holmesii. An aBH vaccine prepared from a BipA-like protein-deficient mutant strain did not have a protective effect against B. holmesii. Taken together, our results suggest that the BipA-like protein plays an important role in the protective efficacy of aBH vaccine. © 2016 The Societies and John Wiley & Sons Australia, Ltd.
Zhang, Xiao-min; Yan, Xun-yi; Zhang, Bin; Yang, Qian; Ye, Mao; Cao, Wei; Qiang, Wen-bin; Zhu, Li-jun; Du, Yong-lan; Xu, Xing-xing; Wang, Jia-sheng; Xu, Fei; Lu, Wei; Qiu, Shuang; Yang, Wei; Luo, Jian-hong
2015-01-01
The N-methyl-D-aspartate receptor (NMDAR) in adult forebrain is a heterotetramer mainly composed of two GluN1 subunits and two GluN2A and/or GluN2B subunits. The synaptic expression and relative numbers of GluN2A- and GluN2B-containing NMDARs play critical roles in controlling Ca2+-dependent signaling and synaptic plasticity. Previous studies have suggested that the synaptic trafficking of NMDAR subtypes is differentially regulated, but the precise molecular mechanism is not yet clear. In this study, we demonstrated that Bip, an endoplasmic reticulum (ER) chaperone, selectively interacted with GluN2A and mediated the neuronal activity-induced assembly and synaptic incorporation of the GluN2A-containing NMDAR from dendritic ER. Furthermore, the GluN2A-specific synaptic trafficking was effectively disrupted by peptides interrupting the interaction between Bip and GluN2A. Interestingly, fear conditioning in mice was disrupted by intraperitoneal injection of the interfering peptide before training. In summary, we have uncovered a novel mechanism for the activity-dependent supply of synaptic GluN2A-containing NMDARs, and demonstrated its relevance to memory formation. PMID:26088419
Timko, Christine; Valenstein, Helen; Lin, Patricia Y; Moos, Rudolf H; Stuart, Gregory L; Cronkite, Ruth C
2012-09-07
Substance use disorders and perpetration of intimate partner violence (IPV) are interrelated, major public health problems. We surveyed directors of a sample of substance use disorder treatment programs (SUDPs; N=241) and batterer intervention programs (BIPs; N=235) in California (70% response rate) to examine the extent to which SUDPs address IPV, and BIPs address substance abuse. Generally, SUDPs were not addressing co-occurring IPV perpetration in a formal and comprehensive way. Few had a policy requiring assessment of potential clients, or monitoring of admitted clients, for violence perpetration; almost one-quarter did not admit potential clients who had perpetrated IPV, and only 20% had a component or track to address violence. About one-third suspended or terminated clients engaging in violence. The most common barriers to SUDPs providing IPV services were that violence prevention was not part of the program's mission, staff lacked training in violence, and the lack of reimbursement mechanisms for such services. In contrast, BIPs tended to address substance abuse in a more formal and comprehensive way; e.g., one-half had a policy requiring potential clients to be assessed, two-thirds required monitoring of substance abuse among admitted clients, and almost one-half had a component or track to address substance abuse. SUDPs had clients with fewer resources (marriage, employment, income, housing), and more severe problems (both alcohol and drug use disorders, dual substance use and other mental health disorders, HIV + status). We found little evidence that services are centralized for individuals with both substance abuse and violence problems, even though most SUDP and BIP directors agreed that help for both problems should be obtained simultaneously in separate programs. SUDPs may have difficulty addressing violence because they have a clientele with relatively few resources and more complex psychological and medical needs. However, policy change can modify barriers to treatment integration and service linkage, such as reimbursement restrictions and lack of staff training.
Björling, Gunilla; Johansson, Dorota; Bergström, Linda; Jalal, Shah; Kohn, Ivar; Frostell, Claes; Kalman, Sigridur
2015-12-01
Hospital acquired infections worsen the outcome of patients treated in intensive care units and are costly. Coatings with silver or metal alloys may reduce or alter the formation of biofilm on invasive medical devices. An endotracheal tube (ETT) is used to connect the patient to a ventilator and coated tubes have been tested in relation to bacterial colonization and respiratory infection. In the present study, we aimed to evaluate and compare a coated and uncoated ETT for patient symptoms and local tracheal tolerability during short term clinical use. Degree of bacterial colonization was also described. A silver-palladium-gold alloy coating ('Bactiguard®'Infection Protection, BIP) has been extensively used on urinary tract catheters and lately also on central venous catheters. We performed a randomised, single-blinded, controlled, first in man, post Conformité Européenne (EC) certification and CE marking study, focused on Bactiguard® coated ETTs (BIP ETT). Thirty patients at a tertiary university hospital scheduled for upper abdominal elective surgery with an expected duration of anaesthesia of at least 3 h were randomised; BIP ETT (n = 20) or standard ETT (n = 10). The tolerability was assessed with a modified version of Quality of Life Head and Neck Module, QLQ-H&N35 and by inspection of the tracheal mucosa with a fibre-optic bronchoscope before intubation and at extubation. Adverse Events (AE) and bacterial adherence were also studied. Statistical evaluations were carried out with the Fisher's Exact Test, the Clopper-Pearson method, as well as a Proportional Odds Model. Differences between groups were identified in 2 of 8 patient related symptoms with regard to tolerability by QLQ-H&N35 (cough, p = 0.022 and dry mouth, p = 0.014 in the treatment group.). No mucosal damage was identified with bronchoscopy. A low level of bacterial colonization with normal flora, equal between groups, was seen after short-term of intubation (median 5 h). No serious Adverse Events related to the use of an ETT were observed. The results should be treated with caution due to statistical confounders, a small study size and large inter-individual variability in bacterial adhesion. The new device BIP ETT is well tolerated and has good clinical performance during short-term intubation. Studies with larger sample sizes and longer intubation periods (>24 h) in the ICU-setting are needed and can now be planned in order to identify possible differences in clinical outcomes. Registered in ClinicalTrials.gov, NCT01682486 , Date of Registration: August, 30, 2012.
1981-01-09
CHALLENGER for an estimated period of six days. The design for the test Borehole Instrumentation Package (BIP) reentry-sub and associated handling...equipment has been completed ard hmi been submitted for vendor bid. Details of the specialized support equipment for installation on the GLOMAR CHALLENGER ...developed under the direction of the Deep Sea Drilling Project (DSDP) by the dynamically positioned drilling vessel GLOMAR CHALLENGER . Deployment of the
Pathogenic Cx31 is un/misfolded to cause skin abnormality via a Fos/JunB-mediated mechanism.
Tang, Chengyuan; Chen, Xiang; Chi, Jingwei; Yang, Dawei; Liu, Shu; Liu, Mujun; Pan, Qian; Fan, Jianbing; Wang, Danling; Zhang, Zhuohua
2015-11-01
Mutations in connexin-31 (Cx31) are associated with multiple human diseases, including familial erythrokeratodermia variabilis (EKV). The pathogenic mechanism of EKV-associated Cx31 mutants remains largely elusive. Here, we show that EKV-pathogenic Cx31 mutants are un/misfolded and temperature sensitive. In Drosophila, expression of pathogenic Cx31, but not wild-type Cx31, causes depigmentation and degeneration of ommatidia that are rescued by expression of either dBip or dHsp70. Ectopic expression of Cx31 in mouse skin results in skin abnormalities resembling human EKV. The affected tissues show remarkable disrupted gap junction formation and significant upregulation of chaperones Bip and Hsp70 as well as AP-1 proteins c-Fos and JunB, in addition to molecular signatures of skin diseases. Consistently, c-Fos, JunB, Bip and Hsp70 are strikingly higher in keratinocytes of EKV patients than their matched control individuals. Furthermore, a druggable AP-1 inhibitory small molecule suppresses skin phenotype and pathological abnormalities of transgenic Cx31 mice. The study suggests that Cx31 mutant proteins are un/misfolded to cause EKV likely via an AP-1-mediated mechanism and identifies a small molecule with therapeutic potential of the disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
NASA Astrophysics Data System (ADS)
Lalegani, Arash; Khaledi Sardashti, Mohammad; Gajda, Roman; Woźniak, Krzysztof
2017-12-01
Zinc(II) coordination polymers [Zn(bip)2(NCS)2]n (1) and [Zn(μ-bbd)(N3)2]n (2) were synthesized by using the neutral flexible bidentate N-donor ligands 1,4-bis(3,5-dimethylpyrazolyl)butane (bbd) and 1,3-bis(imidazolyl)propane (bip), mono-anionic NCS- or N3-ligand and zinc(II) chloride salts. The results of the X-ray analyses demonstrate that in the structure of 1, the zinc(II) ion is located on an inversion center and exhibits an ZnN6 octahedral arrangement while, in the structure of 2, the zinc(II) ion adopts an ZnN4 tetrahedral geometry. In the polymer 1, the NCS groups are terminally N-bonded to the metal center and the each bip with anti-gauche conformation acts as bridging connecting four zinc(II) ions to form a two-dimensional network with a sql [point symbol (44.62)] topology while, in the polymer 1, the N3 groups are terminally bonded to the metal center and each bbd with anti-anti-anti conformation acts as bridging ligand connecting two zinc(II) ions to form a one-dimensional zig-zag chain. Coordination compounds 1 and 2 have been characterized by infrared spectroscopy, elemental analyses and single-crystal X-ray diffraction. Thermal analyses of polymers were also presented.
Yasuyama, Toshiki; Ohi, Kazutaka; Shimada, Takamitsu; Uehara, Takashi; Kawasaki, Yasuhiro
2017-03-01
Impaired social functioning is a hallmark of major psychiatric disorders. The purpose of this study was to detect a disorder-specific factor of social dysfunction among patients with major psychiatric disorders (PSY), including schizophrenia (SCZ), bipolar disorder (BIP) and major depressive disorder (MDD). Social functioning was assessed in patients with SCZ (n=80), BIP (n=27) or MDD (n=29) and healthy controls (HC, n=68) using the Social Functioning Scale (SFS). Compared to HC, the SCZ, BIP and MDD patient groups showed lower total SFS scores. No differences in the total scores for social functioning were observed between patient groups. We next investigated seven subscales of the SFS among PSY and observed significant diagnostic effects on all subscales of the SFS. Notably, patients with SCZ have poorer interpersonal communication than patients with MDD. Furthermore, the poorer interpersonal communication score was significantly correlated with an increase in schizotypal personality traits, as assessed by the Schizotypal Personality Questionnaire (SPQ) in HC. Although there were no differences in overall social functioning among PSY, disorder-specific factors, such as interpersonal communication, were evident in SCZ. The correlation between poor interpersonal communication and the increase in schizotypal traits suggests that poor interpersonal communication may be an intermediate phenotype of SCZ. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
Shi, M Q; Song, W; Han, T X; Chang, B; Zhang, Y M
2017-02-09
Objective: To explore the activation of endoplasmic reticulum stress (ERS) in bone marrow mesenchymal stem cell (BMMSC) and its effect on osteogenic differentiation induced by micropit/nanotube topography (MNT), so as to provide guidance for the topography design of biomaterials. Methods: Four sample groups were fabricated: polishing control group (polished titanium, PT, no treatment), thapsigargin treatment (TG, 0.1 μmol/L TG treated for 9 h), MNT5 and MNT20 (anodized at 5 V and 20 V after acid etching). Scanning electron microscope (SEM) was used to observe the topography of Ti samples. The alkaline phosphatase (ALP) production, collagen secretion and extracellular matrix (ECM) mineralization of BMMSC (osteogenic induced for 7, 14 and 21 d) on Ti samples were detected to evaluate the osteogenic differentiation. After 12 h incubation, the shape and size of ER was examined using a transmission electron microscope (TEM), and ERS-related genes including immunoglobulin heavy chain binding protein (BiP), protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4) were detected by quantitative real-time PCR (qRT-PCR). Results: After 7, 14 and 21 d of induction, the ALP production, collagen secretion and ECM mineralization in TG and MNT20 all significantly increased compared to PT ( P< 0.05). The cells grown on TG, MNT5 and MNT20 surfaces displayed gross distortions of the ER. Compared to PT, BiP, PERK, ATF4 mRNA expression in TG was respectively 1.87±0.10, 2.24±0.35, 1.85±0.14; BiP, ATF4 mRNA expression in MNT5 were respectively 1.27±0.09, 1.25±0.04; BiP, PERK, ATF4 mRNA expression in MNT20 were respectively 1.44±0.09, 2.40±0.60, 1.48±0.05 ( P< 0.05). Conclusions: MNT triggered different degree of ERS, and the activated ERS may promote MNT-induced osteogenic differentiation.
Katsiougiannis, S; Tenta, R; Skopouli, F N
2015-08-01
The aim of this study was to examine the levels of endoplasmic reticulum (ER) stress in minor salivary glands, to investigate the interplay between ER stress-induced autophagy and apoptosis in human salivary gland (HSG) cells and to test the effect of ER stress-induced apoptosis on the cellular redistribution of the two major Sjögren's syndrome (SS) autoantigens Ro/Sjögren's syndrome-related antigen A (SSA) and La/Sjögren's syndrome-related antigen B (SSB). Minor salivary gland biopsies from SS patients and sicca controls were examined by immunohistochemistry for the expression of 78 kDa glucose-regulated protein/binding immunoglobulin protein (GRP78/BiP) as an indicator of unfolded protein response (UPR). HSG cells were treated with thapsigargin (TG) and cell viability, autophagy and apoptosis were assessed. Immunoblot was applied to detect the conversion of LC3I to LC3II and the protein levels of GRP78/BiP and X-box binding protein-1 (XBP-1). Apoptosis was evaluated by a single-stranded DNA enzyme-linked immunosorbent assay (ELISA). Ro/SSA and La/SSB localization was visualized using immunofluorescence. GRP78/BiP was expressed by acinar and ductal epithelial cells in salivary glands of patients and sicca controls. TG treatment induced autophagy, as indicated by enhanced protein expression of LC3II. The protein levels of UPR marker XBP-1 were increased after TG treatment, while GRP78/BiP levels were decreased. TG treatment resulted in induction of HSG apoptosis. Ro/SSA and La/SSB autoantigens were localized predominantly to the cytoplasm in resting cells, while they were redistributed to cell membrane and blebs in the apoptotic cells. In conclusion, ER stress is activated in minor salivary gland epithelial cells from SS patients and controls. ER stress-induced apoptosis in HSG cells leads to cell surface and apoptotic blebs relocalization of Ro/SSA and La/SSB autoantigens. © 2015 British Society for Immunology.
Briefing on New Zealand Canterbury Earthquake
products laboratories publications nisee b.i.p. members education FAQs links events Calendar of PEER and Inc. Performance of Unreinforced Masonry and Selected Modern Buildings and Port Facilities (pdf file
Temperature increase inside LED-based illuminators for in vitro aPDT photodamage studies
NASA Astrophysics Data System (ADS)
Battisti, A.; Morici, P.; Tortora, G.; Menciassi, A.; Checcucci, G.; Ghetti, F.; Sgarbossa, A.
2018-06-01
Antimicrobial PhotoDynamic Therapy (aPDT) is an emerging strategy aimed at the eradication of bacterial infections, with a special focus on antibiotic-resistant bacteria. This method is easy to apply, not expensive and particularly interesting in case of bacteria that spontaneously produce the required photosensitizers. In the framework of a project aimed at the development of an ingestible pill for the application of aPDT to gastric infections by Helicobacter pylori, a LED-based illuminating prototype (LED-BIP) was purposely designed in order to evaluate the photodamage induced by light of different wavelengths on porphyrin-producing bacteria. This short paper reports about temperature tests performed to assess the maximum exposure time and light dose that can be administered to bacterial cultures inside LED-BIP without reaching temperatures exceeding the physiological range.
Genetic risk scores and family history as predictors of schizophrenia in Nordic registers.
Lu, Y; Pouget, J G; Andreassen, O A; Djurovic, S; Esko, T; Hultman, C M; Metspalu, A; Milani, L; Werge, T; Sullivan, P F
2018-05-01
Family history is a long-standing and readily obtainable risk factor for schizophrenia (SCZ). Low-cost genotyping technologies have enabled large genetic studies of SCZ, and the results suggest the utility of genetic risk scores (GRS, direct assessments of inherited common variant risk). Few studies have evaluated family history and GRS simultaneously to ask whether one can explain away the other. We studied 5959 SCZ cases and 8717 controls from four Nordic countries. All subjects had family history data from national registers and genome-wide genotypes that were processed through the quality control procedures used by the Psychiatric Genomics Consortium. Using external training data, GRS were estimated for SCZ, bipolar disorder (BIP), major depression, autism, educational attainment, and body mass index. Multivariable modeling was used to estimate effect sizes. Using harmonized genomic and national register data from Denmark, Estonia, Norway, and Sweden, we confirmed that family history of SCZ and GRS for SCZ and BIP were risk factors for SCZ. In a joint model, the effects of GRS for SCZ and BIP were essentially unchanged, and the effect of family history was attenuated but remained significant. The predictive capacity of a model including GRS and family history neared the minimum for clinical utility. Combining national register data with measured genetic risk factors represents an important investigative approach for psychotic disorders. Our findings suggest the potential clinical utility of combining GRS and family history for early prediction and diagnostic improvements.
Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L.; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi
2013-01-01
ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra. PMID:23447699
Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi
2013-05-01
ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra.
Systemic effects of AGEs in ER stress induction in vivo.
Adamopoulos, Christos; Mihailidou, Chrysovalantou; Grivaki, Christofora; Papavassiliou, Kostas A; Kiaris, Hippokratis; Piperi, Christina; Papavassiliou, Athanasios G
2016-08-01
Emerging evidence indicates that accumulation of advanced glycation end products (AGEs) in human tissues may contribute to cell injury, inflammation and apoptosis through induction of endoplasmic reticulum (ER) stress. Human metabolism relies on ER homeostasis for the coordinated response of all metabolic organs by controlling the synthesis and catabolism of various nutrients. In vitro studies have demonstrated AGE-induced enhancement of unfolded protein response (UPR) in different cell types including endothelial, neuronal, pancreatic cells and podocytes, suggesting this crosstalk as an underlying pathological mechanism that contributes to metabolic diseases. In this minireview, we describe in vivo studies undertaken by our group and others that demonstrate the diverse systemic effects of AGEs in ER stress induction in major metabolic tissues such as brain, kidney, liver and pancreas of normal mice. Administration of high-AGEs content diet to normal mice for the period of 4 weeks upergulates the mRNA and protein levels of ER chaperone Bip (GRP78) indicative of UPR initiation in all major metabolic organs and induces activation of the pivotal transcription factor XBP1 that regulates glucose and lipid metabolism. Furthermore, animals with genetic ablation of UPR-activated transcription factor C/EBP homologous protein CHOP allocated in high-AGEs diet, exhibited relative resistance to UPR induction (BiP levels) and XBP1 activation in major metabolic organs. Since CHOP presents a critical mediator that links accumulation and aggregation of unfolded proteins with induction of oxidative stress and ER stress-related apoptosis, it is revealed as an important molecular target for the management of metabolic diseases.
Arbel, Yaron; Klempfner, Robert; Erez, Aharon; Goldenberg, Ilan; Benzekry, Sagit; Shlomo, Nir; Fisman, Enrique Z; Tenenbaum, Alexander
2016-01-22
Recent data support the renewed interest in hypertriglyceridemia as a possible important therapeutic target for cardiovascular risk reduction. This study was designed to address the question of all-cause mortality during extended follow-up of the BIP trial in patients stratified by baseline triglyceride levels. In the BIP trial 3090 patients with proven coronary artery disease were randomized to bezafibrate 400 mg/day or placebo. All-cause mortality data after 20 years of follow-up, were obtained from the National Israeli Population Registry. Patients with hypertriglyceridemia (triglycerides ≥200 mg/dL, n = 458) were equally distributed among the study groups (15 % in both placebo and bezafibrate groups). During follow-up 1869 patients died (952 in placebo vs. 917 in bezafibrate group). Following multivariate adjustment allocation to bezafibrate was associated with small but significant 10 % mortality risk reduction (HR 0.90; 95 % CI 0.82-0.98, p = 0.026). Variables associated with significantly increased mortality risk were history of a past MI, NYHA class, diabetes, age, higher BMI and glucose level. In patients with hypertriglyceridemia multivariate analysis demonstrated a 25 % all-cause mortality risk reduction associated with allocation to bezafibrate (HR 0.75, CI 95 % 0.60-0.94; p = 0.012). In patients without hypertriglyceridemia bezafibrate had no significant effect on long-term mortality. During long-term follow-up bezafibrate-allocated patients experienced a modest but significant 10 % reduction in the adjusted risk of mortality. This effect of bezafibrate was more prominent among patients with baseline hypertriglyceridemia (25 % mortality risk reduction).
Materials Data on K9Bi(PS4)4 (SG:18) by Materials Project
Kristin Persson
2014-07-09
Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations
Bednarek, Maria A; MacNeil, Tanya; Tang, Rui; Fong, Tung M; Cabello, M Angeles; Maroto, Marta; Teran, Ana
2007-05-01
Alpha-melanotropin, Ac-Ser(1)-Tyr-Ser-Met-Glu-His(6)-Phe(7)-Arg(8)-Trp(9)-Gly-Lys-Pro-Val(13)-NH(2)(1), is a non-selective endogenous agonist for the melanocortin receptor 5; the receptor present in various peripheral tissues and in the brain, cortex and cerebellum. Most of the synthetic analogs of alphaMSH, including a broadly used and more potent the NDP-alphaMSH peptide, Ac-Ser(1)-Tyr-Ser-Nle(4)-Glu-His(6)-D-Phe(7)-Arg(8)-Trp(9)-Gly-Lys-Pro-Val(13)-NH(2), are also not particularly selective for MC5R. To elucidate physiological functions of the melanocortin receptor 5 in rodents and humans, the receptor subtype selective research tools are needed. We report herein syntheses and pharmacological evaluation in vitro of several analogs of NDP-alphaMSH which are highly potent and specific agonists for the human MC5R. The new linear peptides, of structures and solubility properties similar to those of the endogenous ligand alphaMSH, are exemplified by compound 7, Ac-Ser(1)-Tyr-Ser-Met-Glu-Oic(6)-D-4,4'-Bip(7)-Pip(8)-Trp(9)-Gly-Lys-Pro-Val(13)-NH(2) (Oic: octahydroindole-2-COOH, 4,4'-Bip: 4,4'-biphenylalanine, Pip: pipecolic acid), shortly NODBP-alphaMSH, which has an IC(50)=0.74 nM (binding assay) and EC(50)=0.41 (cAMP production assay) at hMC5R nM and greater than 3500-fold selectivity with respect to the melanocortin receptors 1b, 3 and 4. A shorter peptide derived from NODBP-alphaMSH: Ac-Nle-Glu-Oic(6)-D-4,4'-Bip(7)-Pip(8)-Trp(9) -NH(2) (17) was measured to be an agonist only 10-fold less potent at hMC5R than the full length parent peptide. In the structure of this smaller analog, the Nle-Glu-Oic(6)-D-4,4'-Bip(7)-Pip(8) segment was found to be critical for high agonist potency, while the C-terminal Trp(9) residue was shown to be required for high hMC5R selectivity versus hMC1b,3,4R.
Cánepa, Maria Jesús; Ortega, Nicolás Matías; Monteleone, Melisa Carolina; Mucci, Nicolas; Kaiser, German Gustavo; Brocco, Marcela; Mutto, Adrián
2014-01-01
Reproductive biotechnologies such as in vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT) enable improved reproductive efficiency of animals. However, the birth rate of in vitro-derived embryos still lags behind that of their in vivo counterparts. Thus, it is critical to develop an accurate evaluation and prediction system of embryo competence, both for commercial purposes and for scientific research. Previous works have demonstrated that in vitro culture systems induce alterations in the relative abundance (RA) of diverse transcripts and thus compromise embryo quality. The aim of this work was to analyze the RA of a set of genes involved in cellular stress (heat shock protein 70-kDa, HSP70), endoplasmic reticulum (ER) stress (immunoglobulin heavy chain binding protein, Bip; proteasome subunit β5, PSMB5) and apoptosis (BCL-2 associated X protein, Bax; cysteine aspartate protease-3, Caspase-3) in bovine blastocysts produced by IVF or SCNT and compare it with that of their in vivo counterparts. Poly (A) + mRNA was isolated from three pools of 10 blastocysts per treatment and analyzed by real-time RT-PCR. The RA of three of the stress indicators analyzed (Bax, PSMB5 and Bip) was significantly increased in SCNT embryos as compared with that of in vivo-derived blastocysts. No significant differences were found in the RA of HSP70 and Caspase-3 gene transcripts. This study could potentially complement morphological analyses in the development of an effective and accurate technique for the diagnosis of embryo quality, ultimately aiding to improve the efficiency of assisted reproductive techniques (ART).
Lo Priore, Corrado; Castelnuovo, Gianluca; Liccione, Diego; Liccione, Davide
2003-06-01
The paper discusses the use of immersive virtual reality systems for the cognitive rehabilitation of dysexecutive syndrome, usually caused by prefrontal brain injuries. With respect to classical P&P and flat-screen computer rehabilitative tools, IVR systems might prove capable of evoking a more intense and compelling sense of presence, thanks to the highly naturalistic subject-environment interaction allowed. Within a constructivist framework applied to holistic rehabilitation, we suggest that this difference might enhance the ecological validity of cognitive training, partly overcoming the implicit limits of a lab setting, which seem to affect non-immersive procedures especially when applied to dysexecutive symptoms. We tested presence in a pilot study applied to a new VR-based rehabilitation tool for executive functions, V-Store; it allows patients to explore a virtual environment where they solve six series of tasks, ordered for complexity and designed to stimulate executive functions, programming, categorical abstraction, short-term memory and attention. We compared sense of presence experienced by unskilled normal subjects, randomly assigned to immersive or non-immersive (flat screen) sessions of V-Store, through four different indexes: self-report questionnaire, psychophysiological (GSR, skin conductance), neuropsychological (incidental recall memory test related to auditory information coming from the "real" environment) and count of breaks in presence (BIPs). Preliminary results show in the immersive group a significantly higher GSR response during tasks; neuropsychological data (fewer recalled elements from "reality") and less BIPs only show a congruent but yet non-significant advantage for the immersive condition; no differences were evident from the self-report questionnaire. A larger experimental group is currently under examination to evaluate significance of these data, which also might prove interesting with respect to the question of objective-subjective measures of presence.
Cárdenas, Jorge; Reyes-Pérez, Valeria; Hernández-Navarro, María Dolores; Dorantes-Barrón, Ana María; Almazán, Salvador; Estrada-Reyes, Rosa
2017-03-22
Tanacetum parthenium L. Schultz-Bip (Asteraceae) is widely used worldwide in traditional medicine for the treatment of convulsions and culture-bound syndromes such as susto (fear). The aim of this work was to evaluate the anxiolytic- and antidepressant-like effects of an aqueous extract of T. parthenium in behavioral paradigms in mice. The effects of T. parthenium were compared with those produced by anxiolytic and antidepressant drugs. We carried out the chemical characterization of the main constituents of T. parthenium. The involvement with the GABAergic and serotoninergic neurotransmitter systems were explored be means of synergic and antagonist experiments. The anxiolytic-like effect was evaluated using the Burying Behavior Test (BBT) and the Elevated Plus-Maze Test (PMT). The antidepressant-like effect was evaluated in the Forced Swimming Test (FST), and ambulatory activity was assessed in the Open Field Test (OFT). Employing the behavioral tests, synergism and antagonism experiments with Alprazolam, Muscimol, and Picrotoxin were carried out in the PMT. In a series of independent experiments, concomitant administration of T. parthenium and Alprazolam, Fluoxetine, or p-chlorophenylalanine were conducted in the FST. For chemical characterization, High-Performance Liquid Chromatography-Electro Spray Ionization-Mass Spectrometry (HPLC-ESI-MS) analysis was performed. T. parthenium exerts clear anxiolytic- and antidepressant-like effects in mice, without affecting the ambulatory activity of the experimental subjects. Anxiolytic- and antidepressant-like T. parthenium effects result, at least part from the involvement of the GABAergic system. Our results support the use of Tanacetum parthenium in traditional medicine and suggest its therapeutic potential in the comorbid anxiety and depression. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
75 FR 3820 - Broadband Initiatives Program
Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-22
... DEPARTMENT OF AGRICULTURE Rural Utilities Service RIN 0572-ZA01 Broadband Initiatives Program... policy and application procedures for the second round of funding under the broadband initiatives (the... Act) for the Broadband Initiatives Program (BIP) which provides loans, grants, and loan/grant...
Studies in Ambient Temperature Ionic Liquids.
1987-06-30
by chronoamperometry, chronocoulometrV, linear sweep voltammetry and mediated oxidation of [Fe(2,2’-bipVridine) 5) 2 . Charge transport follows...September 2, 1983. OR. A. Osteryoung, "Introduction to Pulse Voltametry ", Tutorial Session on Electrochemistry, Division of Inorganic Chemistry
ERIC Educational Resources Information Center
Zirkel, Perry A.
2009-01-01
In this article the author provides legal explanations to the following concerns: (1) Free Appropriate Public Education (FAPE) and Individualized Education Programs (IEPs); (2) Functional Behavior Assessments (FBAs) and Behavior Intervention Plans (BIPs); (3) Manifestation Determinations under Individuals with Disabilities Education Act (IDEA);…
75 FR 28778 - Broadband Initiatives Program
Federal Register 2010, 2011, 2012, 2013, 2014
2010-05-24
... DEPARTMENT OF AGRICULTURE Rural Utilities Service RIN 0572-ZA01 Broadband Initiatives Program AGENCY: Rural Utilities Service, Department of Agriculture. ACTION: Notice of Extension of filing Public... Initiatives Program (BIP), published in the Federal Register at 75 FR 3820 (January 22, 2010). Such technical...
home about peer news events research products laboratories publications nisee b.i.p. members Engineering Services is Hiring Bridge Design and Bridge Construction Engineers 05/16/18 - PEER Research Research Project Highlight: "Dissipative Base Connections for Moment Frame Structures in Airports and
NASA Astrophysics Data System (ADS)
Anand, Siddeswaran; Muthusamy, Athianna; Dineshkumar, Sengottuvelu; Chandrasekaran, J.
2017-11-01
A series of polybenzimidazole polymers, poly-2-(1H-benzo[d] imidazole-2-yl) phenol (PBIP2), poly-3-(1H-benzo[d] imidazole-2-yl) phenol (PBIP3) and poly-4-(1H-benzo[d] imidazole-2-yl) phenol (PBIP4) were synthesized by oxidative polycondensation of benzimidazole monomers 2-(1H-benzo [d] imidazole-2-yl) phenol (BIP2), 3-(1H-benzo [d] imidazole-2-yl) phenol (BIP3) and 4-(1H-benzo [d] imidazole-2-yl) phenol (BIP4). The structure of benzimidazoles monomers and polybenzimidazoles (PBI) were confirmed by various spectroscopic techniques. The quantum theoretical calculations of band gap energy values of monomers were done with DFT and are compared with its optical band gap energy values. Fluorescence spectra of these compounds showed maximum emission in blue region. The electrical conductivity of PBIs was measured by four-point probe technique and showed good electrical response on iodine doping and conductivity increases with increase iodine doping time. The differences in conductivities among the three PBIs are in accordance with the charge density on imidazole nitrogens calculated by Huckel method. The high carbines residue (∼40%) at 500 °C in thermo gravimetric analysis shows that the PBIs are having reasonably good thermal stability. Polymers have recorded high dielectric constant at low applied frequency of 50 Hz at 393 K. The I-V characteristics of polybenzimidazoles p-n diodes showed rectifying nature with a typical forward to reverse current in the range -4 to 4 V. The high n values are caused by non homogeneities and effect of series resistance.
Distributing Earthquakes Among California's Faults: A Binary Integer Programming Approach
NASA Astrophysics Data System (ADS)
Geist, E. L.; Parsons, T.
2016-12-01
Statement of the problem is simple: given regional seismicity specified by a Gutenber-Richter (G-R) relation, how are earthquakes distributed to match observed fault-slip rates? The objective is to determine the magnitude-frequency relation on individual faults. The California statewide G-R b-value and a-value are estimated from historical seismicity, with the a-value accounting for off-fault seismicity. UCERF3 consensus slip rates are used, based on geologic and geodetic data and include estimates of coupling coefficients. The binary integer programming (BIP) problem is set up such that each earthquake from a synthetic catalog spanning millennia can occur at any location along any fault. The decision vector, therefore, consists of binary variables, with values equal to one indicating the location of each earthquake that results in an optimal match of slip rates, in an L1-norm sense. Rupture area and slip associated with each earthquake are determined from a magnitude-area scaling relation. Uncertainty bounds on the UCERF3 slip rates provide explicit minimum and maximum constraints to the BIP model, with the former more important to feasibility of the problem. There is a maximum magnitude limit associated with each fault, based on fault length, providing an implicit constraint. Solution of integer programming problems with a large number of variables (>105 in this study) has been possible only since the late 1990s. In addition to the classic branch-and-bound technique used for these problems, several other algorithms have been recently developed, including pre-solving, sifting, cutting planes, heuristics, and parallelization. An optimal solution is obtained using a state-of-the-art BIP solver for M≥6 earthquakes and California's faults with slip-rates > 1 mm/yr. Preliminary results indicate a surprising diversity of on-fault magnitude-frequency relations throughout the state.
Gangloff, Y G; Pointud, J C; Thuault, S; Carré, L; Romier, C; Muratoglu, S; Brand, M; Tora, L; Couderc, J L; Davidson, I
2001-08-01
The RNA polymerase II transcription factor TFIID comprises the TATA binding protein (TBP) and a set of TBP-associated factors (TAF(II)s). TFIID has been extensively characterized for yeast, Drosophila, and humans, demonstrating a high degree of conservation of both the amino acid sequences of the constituent TAF(II)s and overall molecular organization. In recent years, it has been assumed that all the metazoan TAF(II)s have been identified, yet no metazoan homologues of yeast TAF(II)47 (yTAF(II)47) and yTAF(II)65 are known. Both of these yTAF(II)s contain a histone fold domain (HFD) which selectively heterodimerizes with that of yTAF(II)25. We have cloned a novel mouse protein, TAF(II)140, containing an HFD and a plant homeodomain (PHD) finger, which we demonstrated by immunoprecipitation to be a mammalian TFIID component. TAF(II)140 shows extensive sequence similarity to Drosophila BIP2 (dBIP2) (dTAF(II)155), which we also show to be a component of Drosophila TFIID. These proteins are metazoan homologues of yTAF(II)47 as their HFDs selectively heterodimerize with dTAF(II)24 and human TAF(II)30, metazoan homologues of yTAF(II)25. We further show that yTAF(II)65 shares two domains with the Drosophila Prodos protein, a recently described potential dTAF(II). These conserved domains are critical for yTAF(II)65 function in vivo. Our results therefore identify metazoan homologues of yTAF(II)47 and yTAF(II)65.
Concurrent Validity of the Strength-Based "Behavioral Objective Sequence"
ERIC Educational Resources Information Center
Wilder, Lynn K.; Braaten, Sheldon; Wilhite, Kathi; Algozzine, Bob
2006-01-01
An essential task of diagnosticians is the accurate assessment of behavioral skills. Traditionally, deficit-based behavioral assessments have underscored student social skill deficits. Strength-based assessments delineate student competencies and are useful for individualized education program (IEP) and behavioral intervention plan (BIP)…
Currency arbitrage detection using a binary integer programming model
NASA Astrophysics Data System (ADS)
Soon, Wanmei; Ye, Heng-Qing
2011-04-01
In this article, we examine the use of a new binary integer programming (BIP) model to detect arbitrage opportunities in currency exchanges. This model showcases an excellent application of mathematics to the real world. The concepts involved are easily accessible to undergraduate students with basic knowledge in Operations Research. Through this work, students can learn to link several types of basic optimization models, namely linear programming, integer programming and network models, and apply the well-known sensitivity analysis procedure to accommodate realistic changes in the exchange rates. Beginning with a BIP model, we discuss how it can be reduced to an equivalent but considerably simpler model, where an efficient algorithm can be applied to find the arbitrages and incorporate the sensitivity analysis procedure. A simple comparison is then made with a different arbitrage detection model. This exercise helps students learn to apply basic Operations Research concepts to a practical real-life example, and provides insights into the processes involved in Operations Research model formulations.
Pyroelectric effect and lattice thermal conductivity of InN/GaN heterostructures
NASA Astrophysics Data System (ADS)
Hansdah, Gopal; Sahoo, Bijay Kumar
2018-06-01
The built-in-polarization (BIP) of InN/GaN heterostructures enhances Debye temperature, phonon mean free path and thermal conductivity of the heterostructure at room temperature. The variation of thermal conductivities (kp: including polarization mechanism and k: without polarization mechanism) with temperature predicts the existence of a transition temperature (Tp) between primary and secondary pyroelectric effect. Below Tp, kp is lower than k; while above Tp, kp is significantly contributed from BIP mechanism due to thermal expansion. A thermodynamic theory has been proposed to explain the result. The room temperature thermal conductivity of InN/GaN heterostructure with and without polarization is respectively 32 and 48 W m-1 K-1. The temperature Tp and room temperature pyroelectric coefficient of InN has been predicted as 120 K and -8.425 μC m-2 K-1, respectively which are in line with prior literature studies. This study suggests that thermal conductivity measurement in InN/GaN heterostructures can help to understand the role of phonons in pyroelectricity.
Mojarrad, Mehran; Hosseini Sarghein, Siavash; Sonboli, Ali
2018-05-16
Chemical diversity of the essential oils of twenty wild populations of Tanacetum polycephalum Sch. Bip., was investigated. The aerial parts of T. polycephalum were collected at full flowering stage from West Azerbaijan Province of Iran, air-dried; hydrodistilled to produce essential oils. The essential oils were analyzed by GC-FID and GC-MS. A total of forty compounds were identified accounting for 96.4-99.9% of the total oils. The most principal compounds were cis-thujone (0-82.3%), trans-thujone (0-79.8%), camphor (1.3-75.0%), 1,8-cineole (4.5-43.3%), borneol (1.0-36.2%) and bornyl acetate (0-26.8%). Hierarchical cluster analysis based on the percentages (>0.5%) of the essential oils components was carried out to determine the chemical diversity among the populations studied. The cluster analysis resulted in the identification of four main chemotypes namely: 'camphor + 1,8-cineole', 'mixed', 'cis-thujone' and 'trans-thujone'.
PEER logo Pacific Earthquake Engineering Research Center home about peer news events research products laboratories publications nisee b.i.p. members education FAQs links About PEER What is PEER ? Mission and Goals PEER's Benefits to California PEER Core Institutions PEER's Industry Partners PEER's
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Na; Mu, Bao; Lv, Lei
Four new polyoxometalate(POM)–templated metal–organic frameworks based on flexible ligands, namely, [Cu{sub 6}(bip){sub 12}(PMo{sup VI}{sub 12}O{sub 40}){sub 2}(PMo{sup V}Mo{sup VI}{sub 11}O{sub 40}O{sub 2})]·8H{sub 2}O(1), [Cu{sup I}{sub 3}Cu{sup II}{sub 3}(bip){sub 12}(PMo{sup VI}{sub 12}O{sub 40}){sub 2}(PMo{sup V}{sub 12}O{sub 34})]·8H{sub 2}O(2), [Ni{sub 6}(bip){sub 12}(PMo{sup VI}{sub 12}O{sub 40})(PMo{sup VI}{sub 11}Mo{sup V}O{sub 40}){sub 2}]Cl·6H{sub 2}O(3), [Co{sup II}{sub 3}Co{sup III}{sub 2}(H{sub 2}bib){sub 2}(Hbib){sub 2}(PW{sub 9}O{sub 34}){sub 2}(H{sub 2}O){sub 6}]·6H{sub 2}O(4) (bip=1,3-bis(imidazolyl)propane, bib=1,4-bis(imidazolyl)butane) have been obtained under hydrothermal condition and characterized by single-crystal X-ray diffraction analyses, elemental analyses, and thermogravimetric (TG) analyses. The studies of single crystal X-ray indicate that compounds 1–3 crystallize in the trigonal space groupmore » P-3, and compound 4 crystallizes in the triclinic space group P-1. Compounds 1 and 3 represent 3D frameworks, and POMs as the guest molecules are incorporated into the cages which are composed of the ligands and metals, while compounds 2 and 4 show 3D frameworks by hydrogen bonds. This compounds provide new examples of host–guest compounds based on flexible bis(imidazole) ligands. In addition, the electrochemical property and the catalytic property of compound 1 have also been investigated. - Graphical abstract: Four inorganic–organic hybrid compounds based polyoxometalates (POMs) and flexible ligands, namely, have been obtained under hydrothermal conditions and characterized by single-crystal X-ray diffraction analyses, elemental analyses, IR spectra, and thermogravimetric (TG) analyses. Compounds 1–3 are new examples of host–guest compounds based on flexible bis(imidazole) ligands and POMs as the guest molecules are incorporated into the cages which are composed of the ligands and metals. - Highlights: • Polyoxometalate–templated metal–organic frameworks have been prepared. • POMs as the guest molecules are incorporated into the cages. • The cages are flexibility based on flexible bis(imidazole) ligands.« less
Male Parenting Attitudes and Batterer Intervention: Assessing Child Maltreatment Risk
ERIC Educational Resources Information Center
Burnette, Catherine E.; Ferreira, Regardt J.; Buttell, Fred
2017-01-01
Objective: The purpose of the study was to investigate the relationship between parenting attitudes and intimate partner violence (IPV) perpetration and identify factors associated with program completion for a 26-week batterer intervention program (BIP). Method: The study employed a nonequivalent, control-group design (comparing program…
The BASIC Instructional Program: Conversion into MAINSAIL Language.
ERIC Educational Resources Information Center
Dageforde, Mary L.
This report summarizes the rewriting of the BASIC Instructional Program (BIP) (a "hands-on laboratory" that teaches elementary programming in the BASIC language) from SAIL (a programming language available only on PDP-10 computers) into MAINSAIL (a language designed for portability on a broad class of computers). Four sections contain…
PEER logo Pacific Earthquake Engineering Research Center home about peer news events research products laboratories publications nisee b.i.p. members education FAQs links About PEER What is PEER ? Mission and Goals PEER's Benefits to California PEER Core Institutions PEER's Industry Partners PEER's
Using Assessment to Support Basic Instruction Programs in Physical Education
ERIC Educational Resources Information Center
Roberts, Thomas; Evans, Tom; Ormond, Frank
2006-01-01
College/University administrators have, for various reasons, scrutinized Physical Education basic instruction program (BIP) requirements for possible reduction. In an effort to defend these requirements, assessment should be undertaken to obtain objective and subjective data that measure a program's effectiveness. This study was conducted at a…
Exploring Burnout in Batterer Intervention Programs
ERIC Educational Resources Information Center
Bahner, Angela D.; Berkel, LaVerne A.
2007-01-01
This study used the Maslach Burnout Inventory (MBI) to explore burnout in a sample of 115 batterer intervention program (BIP) workers (56% female, 44% male) from four midwestern states. The purpose of this study was to explore the role that demographic variables, job-setting variables, supervisor support, and personality characteristics played in…
Promoting Self-Determination throughout the FBA/BIP Process
ERIC Educational Resources Information Center
Korinek, Lori
2015-01-01
Student behavior that interferes with teaching and learning remains a major concern for educators. In-school and postschool outcomes for students with challenging behaviors are among the poorest. Many of these students require a functional behavioral assessment and intervention plan to become more successful. Externally-driven behavior change…
Reliability of Multi-Category Rating Scales
ERIC Educational Resources Information Center
Parker, Richard I.; Vannest, Kimberly J.; Davis, John L.
2013-01-01
The use of multi-category scales is increasing for the monitoring of IEP goals, classroom and school rules, and Behavior Improvement Plans (BIPs). Although they require greater inference than traditional data counting, little is known about the inter-rater reliability of these scales. This simulation study examined the performance of nine…
Here Comes the Judge: Lessons from the Courts on Behavioral Intervention Plans.
ERIC Educational Resources Information Center
Johns, Bev
This paper reviews provisions of the Individuals with Disabilities Education Act (IDEA) and findings from court cases regarding behavioral intervention plans (BIPs) for students with disabilities. The following eight recommendations are provided for school districts as they strive to implement the behavioral intervention provisions of IDEA and…
Technical and Applied Features of Functional Behavioral Assessments and Behavior Intervention Plans
ERIC Educational Resources Information Center
Hawkins, Shannon M.
2012-01-01
When conducted correctly, functional behavior assessments (FBAs) can help professionals intervene with problem behavior using function-based interventions. Despite the fact that researchers have shown that effective interventions are based on function, recent investigators have found that most behavioral intervention plans (BIPs) are written…
State Special Education Laws for Functional Behavioral Assessment and Behavior Intervention Plans
ERIC Educational Resources Information Center
Zirkel, Perry A.
2011-01-01
A comprehensive search identified 31 state statutes and regulations specific to functional behavioral assessments (FBA) and behavior intervention plans (BIP) in the special education context. A systematic tabulation of the state law provisions that exceed the rather narrow foundation requirements of the Individuals with Disabilities Education Act…
Factors in Teacher Adherence to Treatment.
ERIC Educational Resources Information Center
Gum, Louann
Treatment integrity, a measure of how accurately a treatment is carried out, is integral to the concept of effective behavioral analysis and intervention. This study sought to correlate teachers' perceptions of the functional behavior assessment and behavior intervention process (FBA/BIP) with their confidence that the process is an effective and…
ERIC Educational Resources Information Center
Russell, Jared A.
2009-01-01
For over 100 years, basic instructional programs (BIP) have played a pivotal role in providing undergraduates with opportunities to acquire sport-related skills and conceptual knowledge relevant to promoting their involvement in lifelong physical activity and establishing healthy lifestyle habits. Critical to delivering this instructional content…
ERIC Educational Resources Information Center
Yorke, Nada J.; Friedman, Bruce D.; Hurt, Pat
2010-01-01
This study discusses the pretest and posttest results of a batterer's intervention program (BIP) implemented within a California state prison substance abuse program (SAP), with a recommendation for further programs to be implemented within correctional institutions. The efficacy of utilizing correctional facilities to reach offenders who…
Brown, Marishka K; Strus, Ewa; Naidoo, Nirinjini
2017-07-01
Social isolation has a multitude of negative consequences on human health including the ability to endure challenges to the immune system, sleep amount and efficiency, and general morbidity and mortality. These adverse health outcomes are conserved in other social species. In the fruit fly Drosophila melanogaster, social isolation leads to increased aggression, impaired memory, and reduced amounts of daytime sleep. There is a correlation between molecules affected by social isolation and those implicated in sleep in Drosophila. We previously demonstrated that acute sleep loss in flies and mice induced the unfolded protein response (UPR), an adaptive signaling pathway. One mechanism indicating UPR upregulation is elevated levels of the endoplasmic reticular chaperone BiP/GRP78. We previously showed that BiP overexpression in Drosophila led to increased sleep rebound. Increased rebound sleep has also been demonstrated in socially isolated (SI) flies. D. melanogaster were used to study the effect of social isolation on cellular stress. SI flies displayed an increase in UPR markers; there were higher BiP levels, increased phosphorylation of the translation initiation factor eIF2α, and increased splicing of xbp1. These are all indicators of UPR activation. In addition, the effects of isolation on the UPR were reversible; pharmacologically and genetically altering sleep in the flies modulated the UPR. The reduction in sleep observed in SI flies is a cellular stressor that results in UPR induction. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email: journals.permissions@oup.com
reached out to elementary and high school students to expose them to earthquakes in a hands-on products laboratories publications nisee b.i.p. members education FAQs links education Education Program Internships K-12 Education Contact the PEER Education Program PEER's Educational Affiliates Student Design
Harnessing Novel Secreted Inhibitors of EGF Receptor Signaling for Breast Cancer Treatment
2008-04-01
infected Spodoptera frugiperda Sf9 cells, using the amino-terminal BiP signal sequence to direct 9 secretion of the protein into the medium. The...for crystallization of the Argos/Spitz complex was produced by secretion from Sf9 ( Spodoptera frugiperda ) cells using the Bac- to-Bac baculovirus
Currency Arbitrage Detection Using a Binary Integer Programming Model
ERIC Educational Resources Information Center
Soon, Wanmei; Ye, Heng-Qing
2011-01-01
In this article, we examine the use of a new binary integer programming (BIP) model to detect arbitrage opportunities in currency exchanges. This model showcases an excellent application of mathematics to the real world. The concepts involved are easily accessible to undergraduate students with basic knowledge in Operations Research. Through this…
Adulthood Animal Abuse among Women Court-Referred to Batterer Intervention Programs
ERIC Educational Resources Information Center
Febres, Jeniimarie; Shorey, Ryan C.; Brasfield, Hope; Zucosky, Heather C.; Ninnemann, Andrew; Elmquist, Joanna; Bucossi, Meggan M.; Andersen, Shawna M.; Schonbrun, Yael C.; Stuart, Gregory L.
2012-01-01
The substantial increase in the enrollment of women in batterer intervention programs (BIPs) over the past 30 years has greatly outpaced research on women who perpetrate intimate partner violence (IPV). As a result, it is unknown whether existing programs, which were originally designed to treat male perpetrators, are effective at preventing…
ERIC Educational Resources Information Center
Tucker, Thurman D.
2017-01-01
This research examined attitudes to determine factors influencing teachers' attitudes toward including students with behavior intervention plans in inclusive high-school classrooms. For Research Question 1 one-way ANOVAs analyzed quantitative data with no significant differences found and qualitative data discovered common patterns that BIPs are…
Evaluating Predictors of Program Attrition among Women Mandated into Batterer Intervention Treatment
ERIC Educational Resources Information Center
Buttell, Frederick P.; Powers, Dolores; Wong, Asia
2012-01-01
Objective: The purpose of the present study was to evaluate pretreatment differences between treatment completers and dropouts among a large sample of women ordered into a 26-week batterer intervention program (BIP). Method: The study employed a nonequivalent, control-group design (comparing program completers to dropouts) in a secondary analysis…
Comparing the Effects of Home versus Clinic-Based Parent Training for Children with Autism
ERIC Educational Resources Information Center
Crone, Regina M.
2010-01-01
Research with parents on managing child problem behavior typically measures either child or parent behavior. This study was designed to evaluate the effectiveness of training parents to implement a function-based behavior intervention plan (BIP) in a non-trained natural environment utilizing a Multiple Probe Design across Participants.…
Hayashi, Teruo; Su, Tsung-Ping
2007-11-02
Communication between the endoplasmic reticulum (ER) and mitochondrion is important for bioenergetics and cellular survival. The ER supplies Ca(2+) directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). We found here that the ER protein sigma-1 receptor (Sig-1R), which is implicated in neuroprotection, carcinogenesis, and neuroplasticity, is a Ca(2+)-sensitive and ligand-operated receptor chaperone at MAM. Normally, Sig-1Rs form a complex at MAM with another chaperone, BiP. Upon ER Ca(2+) depletion or via ligand stimulation, Sig-1Rs dissociate from BiP, leading to a prolonged Ca(2+) signaling into mitochondria via IP3Rs. Sig-1Rs can translocate under chronic ER stress. Increasing Sig-1Rs in cells counteracts ER stress response, whereas decreasing them enhances apoptosis. These results reveal that the orchestrated ER chaperone machinery at MAM, by sensing ER Ca(2+) concentrations, regulates ER-mitochondrial interorganellar Ca(2+) signaling and cell survival.
NASA Astrophysics Data System (ADS)
Gupta, Mahima; Mohanty, B. K.
2017-04-01
In this paper, we have developed a methodology to derive the level of compensation numerically in multiple criteria decision-making (MCDM) problems under fuzzy environment. The degree of compensation is dependent on the tranquility and anxiety level experienced by the decision-maker while taking the decision. Higher tranquility leads to the higher realisation of the compensation whereas the increased level of anxiety reduces the amount of compensation in the decision process. This work determines the level of tranquility (or anxiety) using the concept of fuzzy sets and its various level sets. The concepts of indexing of fuzzy numbers, the risk barriers and the tranquility level of the decision-maker are used to derive his/her risk prone or risk averse attitude of decision-maker in each criterion. The aggregation of the risk levels in each criterion gives us the amount of compensation in the entire MCDM problem. Inclusion of the compensation leads us to model the MCDM problem as binary integer programming problem (BIP). The solution to BIP gives us the compensatory decision to MCDM. The proposed methodology is illustrated through a numerical example.
A mega-analysis of genome-wide association studies for major depressive disorder.
Ripke, Stephan; Wray, Naomi R; Lewis, Cathryn M; Hamilton, Steven P; Weissman, Myrna M; Breen, Gerome; Byrne, Enda M; Blackwood, Douglas H R; Boomsma, Dorret I; Cichon, Sven; Heath, Andrew C; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A F; Martin, Nicholas G; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M; Penninx, Brenda P; Pergadia, Michele L; Potash, James B; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H; Preisig, Martin; Smoller, Jordan W; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R; Bettecken, Thomas; Binder, Elisabeth B; Breuer, René; Castro, Victor M; Churchill, Susanne E; Coryell, William H; Craddock, Nick; Craig, Ian W; Czamara, Darina; De Geus, Eco J; Degenhardt, Franziska; Farmer, Anne E; Fava, Maurizio; Frank, Josef; Gainer, Vivian S; Gallagher, Patience J; Gordon, Scott D; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A; Kohane, Isaac S; Kohli, Martin A; Korszun, Ania; Landen, Mikael; Lawson, William B; Lewis, Glyn; Macintyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M; Middleton, Lefkos; Montgomery, Grant M; Murphy, Shawn N; Nauck, Matthias; Nolen, Willem A; Nyholt, Dale R; O'Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A; Schulz, Andrea; Schulze, Thomas G; Shyn, Stanley I; Sigurdsson, Engilbert; Slager, Susan L; Smit, Johannes H; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J C G; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B; Willemsen, Gonneke; Zitman, Frans G; Neale, Benjamin; Daly, Mark; Levinson, Douglas F; Sullivan, Patrick F
2013-04-01
Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.
Effect of microculture on cell metabolism and biochemistry: do cells get stressed in microchannels?
Su, Xiaojing; Theberge, Ashleigh B; January, Craig T; Beebe, David J
2013-02-05
Microfluidics is emerging as a promising platform for cell culture, enabling increased microenvironment control and potential for integrated analysis compared to conventional macroculture systems such as well plates and Petri dishes. To advance the use of microfluidic devices for cell culture, it is necessary to better understand how miniaturization affects cell behavior. In particular, microfluidic devices have significantly higher surface-area-to-volume ratios than conventional platforms, resulting in lower volumes of media per cell, which can lead to cell stress. We investigated cell stress under a variety of culture conditions using three cell lines: parental HEK (human embryonic kidney) cells and transfected HEK cells that stably express wild-type (WT) and mutant (G601S) human ether-a-go-go related gene (hERG) potassium channel protein. These three cell lines provide a unique model system through which to study cell-type-specific responses in microculture because mutant hERG is known to be sensitive to environmental conditions, making its expression a particularly sensitive readout through which to compare macro- and microculture. While expression of WT-hERG was similar in microchannel and well culture, the expression of mutant G601S-hERG was reduced in microchannels. Expression of the endoplasmic reticulum (ER) stress marker immunoglobulin binding protein (BiP) was upregulated in all three cell lines in microculture. Using BiP expression, glucose consumption, and lactate accumulation as readouts we developed methods for reducing ER stress including properly increasing the frequency of media replacement, reducing cell seeding density, and adjusting the serum concentration and buffering capacity of culture medium. Indeed, increasing the buffering capacity of culture medium or frequency of media replacement partially restored the expression of the G601S-hERG in microculture. This work illuminates how biochemical properties of cells differ in macro- and microculture and suggests strategies that can be used to modify cell culture protocols for future studies involving miniaturized culture platforms.
Choi, Seung-Il; Lee, Eunhee; Akuzum, Begum; Jeong, Jang Bin; Maeng, Yong-Sun; Kim, Tae-Im; Kim, Eung Kweon
2017-10-01
Endoplasmic reticulum (ER) stress is emerging as a factor for the pathogenesis of granular corneal dystrophy type 2 (GCD2). This study was designed to investigate the molecular mechanisms underlying the protective effects of melatonin on ER stress in GCD2. Our results showed that GCD2 corneal fibroblasts were more susceptible to ER stress-induced death than were wild-type cells. Melatonin significantly inhibited GCD2 corneal cell death, caspase-3 activation, and poly (ADP-ribose) polymerase 1 cleavage caused by the ER stress inducer, tunicamycin. Under ER stress, melatonin significantly suppressed the induction of immunoglobulin heavy-chain-binding protein (BiP) and activation of inositol-requiring enzyme 1α (IRE1α), and their downstream target, alternative splicing of X-box binding protein 1(XBP1). Notably, the reduction in BiP and IRE1α by melatonin was suppressed by the ubiquitin-proteasome inhibitor, MG132, but not by the autophagy inhibitor, bafilomycin A1, indicating involvement of the ER-associated protein degradation (ERAD) system. Melatonin treatment reduced the levels of transforming growth factor-β-induced protein (TGFBIp) significantly, and this reduction was suppressed by MG132. We also found reduced mRNA expression of the ERAD system components HRD1 and SEL1L, and a reduced level of SEL1L protein in GCD2 cells. Interestingly, melatonin treatments enhanced SEL1L levels and suppressed the inhibition of SEL1L N-glycosylation caused by tunicamycin. In conclusion, this study provides new insights into the mechanisms by which melatonin confers its protective actions during ER stress. The results also indicate that melatonin might have potential as a therapeutic agent for ER stress-related diseases including GCD2. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Fluoride-driven 'turn on' ESPT in the binding with a novel benzimidazole-based sensor.
Liu, Kai; Zhao, Xiaojun; Liu, Qingxiang; Huo, Jianzhong; Zhu, Bolin; Diao, Shihua
2015-01-01
A novel fluorescence sensor (BIP) bearing NH and OH subunits displayed a highly selective and sensitive recognition property for fluoride over other anions. Fluoride-driven ESPT, poorly used in anion recognition and sensing, was suggested to be responsible for the fluorescence enhancement with a blue shift of 35 nm in the emission spectrum.
Can a "Psychosocial Model" Help Explain Violence Perpetrated by Female Batterers?
ERIC Educational Resources Information Center
Ferreira, Regardt J.; Buttell, Frederick P.
2016-01-01
Objective: The purpose of the study was to evaluate the psychosocial predictors of propensity for abusiveness among a large sample of women ordered into a 26-week batterer intervention program (BIP). Method: The study employed a nonequivalent, control group design (comparing program completers to dropouts) in a secondary analysis of 485 women.…
Wilderness Adventure Therapy in Adolescent Psychiatry.
ERIC Educational Resources Information Center
Crisp, Simon; O'Donnell, Matthew
The Brief Intervention Program (BIP) is a mental health day program in Melbourne (Australia) for adolescents with severe mental health problems who are at risk for suicide. The 10-week program serves closed groups of 6-8 adolescents aged 13-18 years and has 3 phases: engagement and orientation (week 1), treatment (weeks 2-9), and integration (week…
Events | Pacific Earthquake Engineering Research Center
home about peer news events research products laboratories publications nisee b.i.p. members education FAQs links Events Calendar of PEER and Other Events PEER Events Archive PEER Annual Meeting 2009 Experimental Structural Engineering PEER Summative Meeting Site Map Search Calendar of PEER and Other Events
Batterer and Facilitator Talk in the Context of a Batterer Intervention Program for Men
ERIC Educational Resources Information Center
Shahane, Amit
2009-01-01
The most common approach to treating male perpetrators of domestic violence has been batterer intervention programs (BIPs) (Aldarondo & Mederos, 2002). In particular, the use of group treatment modalities is due to theoretically-based assumptions that the group treatment context is best for male resocialization, and the most cost effective (Dutton…
When to Use Functional Behavioral Assessment? Best Practice vs. Legal Guidance
ERIC Educational Resources Information Center
von Ravensberg, Heidi; Blakely, Allison
2014-01-01
When to conduct a functional behavioral assessment (FBA) is a question answered by both best practice and the law. The special education field continues to improve the effectiveness and efficiency of the functional behavioral assessment, an evidence-based technology that is the basis of a behavior intervention plan (BIP) and a cornerstone of the…
ERIC Educational Resources Information Center
Killu, Kim; Weber, Kimberly P.; Derby, K. Mark; Barretto, Anjali
2006-01-01
To address the behavioral needs of students with disabilities in school settings, the Individuals with Disabilities Education Improvement Act of 2004 (IDEIA) requires the development and implementation of a behavior intervention plan/positive behavioral support plan (BIP/PBSP) based on positive behavioral interventions and supports (PBIS). Despite…
ERIC Educational Resources Information Center
O'Neill, Sue; Stephenson, Jennifer
2009-01-01
This article examines literature published since 1997 on functional behaviour assessment (FBA) and behaviour intervention plans (BIPs), involving school-based personnel, for children identified as having or being at risk of emotional/behavioural disorder (E/BD) in school settings. Of interest was the level of involvement of school-based personnel…
ERIC Educational Resources Information Center
Rasheed, Saleem A.; Fore, Cecil, III; Jones, Arthur; Smith, Latisha
2012-01-01
The research literature on the use of Functional Behavioral Assessments (FBA) to develop Behavior Intervention Plans (BIP) for students with emotional/behavioral disorders, who present problem classroom behaviors for use in the schools, is well documented. There are school-wide, district-wide, and state-wide plans that are currently being…
Gender and Batterer Intervention: Implications of a Program Evaluation for Policy and Treatment
ERIC Educational Resources Information Center
Hamel, John; Ferreira, Regardt J.; Buttell, Fred
2017-01-01
Objective: The purpose of the present study was to investigate the impact of gender and other variables commonly associated with intimate partner abuse perpetration on program completion and pretreatment abusiveness profiles among a sample of men and women ordered into a 52-week batterer intervention program (BIP). Method: The study employed a…
Exploring the Relevance of Interpersonal Dependency as a Treatment Issue in Batterer Intervention
ERIC Educational Resources Information Center
Carney, Michelle Mohr; Buttell, Fred
2006-01-01
Objective: The purpose of the study was to (a) investigate the pretreatment levels of interpersonal dependency and violence among men entering a 16-week, court-mandated, batterer intervention program (BIP) and determine if there were any associations between interpersonal dependency and violence and (b) evaluate the treatment effect of a standard…
From FBA to Implementation: A Look at What Is Actually Being Delivered
ERIC Educational Resources Information Center
Blood, Erika; Neel, Richard S.
2007-01-01
This study looks at the utilization of assessments on developing behavior intervention plans (BIPs) and their use in designing actual implementation for the children (elementary through high school) labeled EBD in a mid-sized district in eastern Washington. Files were reviewed to determine the types of assessments used, FBA components addressed,…
ERIC Educational Resources Information Center
Mouzakitis, Angela; Codding, Robin S.; Tryon, Georgiana
2015-01-01
Accurate implementation of individualized behavior intervention plans (BIPs) is a critical aspect of evidence-based practice. Research demonstrates that neither training nor consultation is sufficient to improve and maintain high rates of treatment integrity (TI). Therefore, evaluation of ongoing support strategies is needed. The purpose of this…
Cross sections of proton-induced nuclear reactions on bismuth and lead up to 100 MeV
NASA Astrophysics Data System (ADS)
Mokhtari Oranj, L.; Jung, N. S.; Bakhtiari, M.; Lee, A.; Lee, H. S.
2017-04-01
Production cross sections of 209Bi(p , x n )207,206,205,204,203Po, 209Bi(p , pxn) 207,206,205,204,203,202Bi, and natPb(p , x n ) 206,205,204,203,202,201Bi reactions were measured to fill the gap in the excitation functions up to 100 MeV as well as to figure out the effects of different nuclear properties on proton-induced reactions including heavy nuclei. The targets were arranged in two different stacks consisting of Bi, Pb, Al, Au foils and Pb plates. The proton beam intensity was determined by the activation analysis method using 27Al(p ,3 p n )24Na, 197Au(p ,p n )196Au, and 197Au(p , p 3 n )194Au monitor reactions in parallel as well as the Gafchromic film dosimetry method. The activities of produced radionuclei in the foils were measured by the HPGe spectroscopy system. Over 40 new cross sections were measured in the investigated energy range. A satisfactory agreement was observed between the present experimental data and the previously published data. Excitation functions of mentioned reactions were calculated by using the theoretical model based on the latest version of the TALYS code and compared to the new data as well as with other data in the literature. Additionally, the effects of various combinations of the nuclear input parameters of different level density models, optical model potentials, and γ-ray strength functions were considered. It was concluded that if certain level density models are used, the calculated cross sections could be comparable to the measured data. Furthermore, the effects of optical model potential and γ-ray strength functions were considerably lower than that of nuclear level densities.
Design and fabrication of the Mini-Brayton Recuperator (MBR)
NASA Technical Reports Server (NTRS)
Killackey, J. J.; Graves, R.; Mosinskis, G.
1978-01-01
Development of a recuperator for a 2.0 kW closed Brayton space power system is described. The plate-fin heat exchanger is fabricated entirely from Hastelloy X and is designed for 10 years continuous operation at 1000 K (1300 F) with a Xenon-helium working fluid. Special design provisions assure uniform flow distribution, crucial for meeting 0.975 temperature effectiveness. Low-cycle fatigue, resulting from repeated startup and shutdown cycles, was identified as the most critical structural design problem. It is predicted that the unit has a minimum fatigue life of 220 cycles. This is in excess of the BIPS requirement of 100 cycles. Heat transfer performance and thermal cycle testing with air, using a prototype unit, verified that all design objectives can be met.
window. 2018 PEER Annual Meeting, Jan 18-19, 2018 in Berkeley, CA 2016 PEER Annual Meeting, Jan 28-29 home about peer news events research products laboratories publications nisee b.i.p. members education FAQs links Events Calendar of PEER and Other Events PEER Events Archive PEER Annual Meeting 2009
ERIC Educational Resources Information Center
Carney, Michelle Mohr; Buttell, Frederick P.
2005-01-01
Objective: The purpose of the study was to: (a) investigate the pre-treatment levels of interpersonal dependency and violence among women entering a 16-week, court-mandated, batterer intervention program (BIP) and determine if there were any associations between interpersonal dependency and violence; (b) investigate differences in demographic…
Influence of KDEL on the Fate of Trimeric or Assembly-Defective Phaseolin
Frigerio, Lorenzo; Pastres, Alessandra; Prada, Alessandra; Vitale, Alessandro
2001-01-01
The tetrapeptide KDEL is commonly found at the C terminus of soluble proteins of the endoplasmic reticulum (ER), and it contributes to their localization by interacting with a receptor that recycles between the Golgi complex and the ER. We investigated the effects of the addition of KDEL to phaseolin, a protein normally delivered from the ER to storage vacuoles via the Golgi complex. We show that KDEL prevents acquisition of trans-Golgi–specific glycan modifications and causes interactions with the chaperone BiP that are distinct from the ones between BiP and defective proteins. KDEL markedly increases the stability of phaseolin, but a small proportion of phaseolin-KDEL slowly reaches the vacuole without undergoing Golgi-mediated glycan modifications, in a process that can be inhibited by brefeldin A but not monensin. Our results indicate that KDEL can operate with high efficiency before proteins can reach the late Golgi cisternae but allows or promotes delivery to vacuoles via an alternative mechanism. However, addition of KDEL does not alter the destiny of an assembly-defective form of phaseolin, suggesting that the plant ER quality control mechanism is dominant over KDEL effects. PMID:11340185
Frigerio, L; Pastres, A; Prada, A; Vitale, A
2001-05-01
The tetrapeptide KDEL is commonly found at the C terminus of soluble proteins of the endoplasmic reticulum (ER), and it contributes to their localization by interacting with a receptor that recycles between the Golgi complex and the ER. We investigated the effects of the addition of KDEL to phaseolin, a protein normally delivered from the ER to storage vacuoles via the Golgi complex. We show that KDEL prevents acquisition of trans-Golgi-specific glycan modifications and causes interactions with the chaperone BiP that are distinct from the ones between BiP and defective proteins. KDEL markedly increases the stability of phaseolin, but a small proportion of phaseolin-KDEL slowly reaches the vacuole without undergoing Golgi-mediated glycan modifications, in a process that can be inhibited by brefeldin A but not monensin. Our results indicate that KDEL can operate with high efficiency before proteins can reach the late Golgi cisternae but allows or promotes delivery to vacuoles via an alternative mechanism. However, addition of KDEL does not alter the destiny of an assembly-defective form of phaseolin, suggesting that the plant ER quality control mechanism is dominant over KDEL effects.
Lev, Avital; Lulla, Amriti R.; Wagner, Jessica; Ralff, Marie D.; Kiehl, Joshua B.; Zhou, Yan; Benes, Cyril H.; Prabhu, Varun V.; Oster, Wolfgang; Astsaturov, Igor; Dicker, David T.; El-Deiry, Wafik S.
2017-01-01
Pancreatic cancer is chemo-resistant and metastasizes early with an overall five-year survival of ∼8.2%. First-in-class imipridone ONC201 is a small molecule in clinical trials with anti-cancer activity. ONC212, a fluorinated-ONC201 analogue, shows preclinical efficacy in melanoma and hepatocellular-cancer models. We investigated efficacy of ONC201 and ONC212 against pancreatic cancer cell lines (N=16 including 9 PDX-cell lines). We demonstrate ONC212 efficacy in 4 in-vivo models including ONC201-resistant tumors. ONC212 is active in pancreatic cancer as single agent or in combination with 5-fluorouracil, irinotecan, oxaliplatin or RTK inhibitor crizotinib. Based on upregulation of pro-survival IGF1-R in some tumors, we found an active combination of ONC212 with inhibitor AG1024, including in vivo. We show a rationale for targeting pancreatic cancer using ONC212 combined with targeting the unfolded-protein response and ER chaperones such as GRP78/BIP. Our results lay the foundation to test imipridones, anti-cancer agents, in pancreatic cancer, that is refractory to most drugs. PMID:29137221
Lev, Avital; Lulla, Amriti R; Wagner, Jessica; Ralff, Marie D; Kiehl, Joshua B; Zhou, Yan; Benes, Cyril H; Prabhu, Varun V; Oster, Wolfgang; Astsaturov, Igor; Dicker, David T; El-Deiry, Wafik S
2017-10-10
Pancreatic cancer is chemo-resistant and metastasizes early with an overall five-year survival of ∼8.2%. First-in-class imipridone ONC201 is a small molecule in clinical trials with anti-cancer activity. ONC212, a fluorinated-ONC201 analogue, shows preclinical efficacy in melanoma and hepatocellular-cancer models. We investigated efficacy of ONC201 and ONC212 against pancreatic cancer cell lines ( N =16 including 9 PDX-cell lines). We demonstrate ONC212 efficacy in 4 in-vivo models including ONC201-resistant tumors. ONC212 is active in pancreatic cancer as single agent or in combination with 5-fluorouracil, irinotecan, oxaliplatin or RTK inhibitor crizotinib. Based on upregulation of pro-survival IGF1-R in some tumors, we found an active combination of ONC212 with inhibitor AG1024, including in vivo . We show a rationale for targeting pancreatic cancer using ONC212 combined with targeting the unfolded-protein response and ER chaperones such as GRP78/BIP. Our results lay the foundation to test imipridones, anti-cancer agents, in pancreatic cancer, that is refractory to most drugs.
Ahn, Joungjwa; Lee, Jong Suk; Yang, Kyung Mi
2014-06-01
Small-sized particles are more suitable for targeted delivery and are therapeutically more effective than large-sized particles. In this study, we investigated the anticancer effects of ultrafine particles of Ulmus davidiana var. japonica (ufUJ) on human gastric cancer cell lines SNU-1, SNU-216, and SNU-484. ufUJ induced apoptosis by the proteolytic activation of caspase-9, caspase-6, and caspase-3 and cleavage of poly (ADP-ribose) polymerase. The expression levels of the endoplasmic reticulum stress-related protein BiP markedly increased after ufUJ treatment. BiP knockdown decreased ufUJ-induced cell death. ufUJ-induced apoptosis was inhibited by the caspase-3 inhibitor z-DEVD-fmk, caspase-6 inhibitor z-VEID-fmk, and caspase-9 inhibitor z-LEHD-fmk, and by siRNAs against caspases 3, 6, and 9. Gastric cancer cells did not show anchorage-independent growth in the presence of ufUJ. However, cells treated with caspase inhibitors showed an enhanced colony-forming ability. These findings may be helpful in the prevention of gastric cancer and in the development of functional foods.
Li, Zhaohui; Wu, Jia; Sheng, Lei
2018-05-01
The current study mainly aims to evaluate the effects of ibrutinib on endoplasmic reticulum stress (ERS)-induced apoptosis in Reh cells, which may shed light on the treatment of acute lymphoblastic leukemia (ALL) among children. In line with previous studies, our data show that ibrutinib significantly suppressed Reh cell viability in a time- and dose-dependent manner. We further evaluated the role of ibrutinib on Reh cell colony formation and apoptosis. Ibrutinib inhibited clonogenic capacity and induced Reh cell apoptosis, suggesting an anti-tumor effects of ibrutinib in the progression of ALL. Further study showed that ibrutinib treatment increased ERS-related protein expression, including Bip, ATF4 and CHOP, suggesting the induction of ER-stress in Reh cells. More importantly, once ER-stress was suppressed by tauroursodeoxycholic acid (TUDCA), an ER-stress inhibitor, the upregulation of Bip, ATF4, CHOP, cleaved-caspase3 and cleaved-PARP after ibrutinib treatment was partially reversed, suggesting that induction of ALL cell apoptosis by ibrutinib was partially attributed to activation of ER stress. In summary, we showed novel data that ER-stress induced cell apoptosis plays a key role in the therapeutic effects of ibrutinib on ALL cell malignancies.
Delpino, Andrea; Castelli, Mauro
2002-01-01
In human rabdomiosarcoma cells (TE671/RD) chronic exposure to 500 nM thapsigargin (a powerful inhibitor of the endoplasmic reticulum Ca2+-ATPases) resulted in the induction of the stress protein GRP78/BIP. Making use of the surface biotinylation method, followed by the isolation of the GRP78 using ATP-agarose affinity chromatography, it was found that a fraction of the thapsigargin-induced GRP78 is expressed on the cell surface. The presence of GRP78 on the membrane of thapsigargin-treated cells was confirmed by fractionation of cell lysates into a soluble and a membrane fraction, followed by Western blot analysis with an anti-GRP78 antibody. It was also found that conspicuous amounts of GRP78 are present in the culture medium collected from thapsigargin-treated cultures. This extracellular GRP78 originates mostly by an active release from intact cells and does not result solely from the leakage of proteins from dead cells. Moreover, small amounts of circulating, free GRP78 and naturally-occurring anti-GRP78 autoantibodies were detected in the peripheral circulation of healthy human individuals.
NASA Astrophysics Data System (ADS)
Wills, Rebecca H.; Habtemariam, Abraha; Lopez-Clavijo, Andrea F.; Barrow, Mark P.; Sadler, Peter J.; O'Connor, Peter B.
2014-04-01
The binding sites of two ruthenium(II) organometallic complexes of the form [(η6-arene)Ru( N, N)Cl]+, where arene/ N, N = biphenyl (bip)/bipyridine (bipy) for complex AH076, and biphenyl (bip)/ o-phenylenediamine ( o-pda) for complex AH078, on the peptides angiotensin and bombesin have been investigated using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. Fragmentation was performed using collisionally activated dissociation (CAD), with, in some cases, additional data being provided by electron capture dissociation (ECD). The primary binding sites were identified as methionine and histidine, with further coordination to phenylalanine, potentially through a π-stacking interaction, which has been observed here for the first time. This initial peptide study was expanded to investigate protein binding through reaction with insulin, on which the binding sites proposed are histidine, glutamic acid, and tyrosine. Further reaction of the ruthenium complexes with the oxidized B chain of insulin, in which two cysteine residues are oxidized to cysteine sulfonic acid (Cys-SO3H), and glutathione, which had been oxidized with hydrogen peroxide to convert the cysteine to cysteine sulfonic acid, provided further support for histidine and glutamic acid binding, respectively.
Alayed, Mrwan; Deen, M Jamal
2017-09-14
Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are emerging non-invasive imaging modalities that have wide spread potential applications in many fields, particularly for structural and functional imaging in medicine. In this article, we review time-resolved diffuse optical imaging (TR-DOI) systems using solid-state detectors with a special focus on Single-Photon Avalanche Diodes (SPADs) and Silicon Photomultipliers (SiPMs). These TR-DOI systems can be categorized into two types based on the operation mode of the detector (free-running or time-gated). For the TR-DOI prototypes, the physical concepts, main components, figures-of-merit of detectors, and evaluation parameters are described. The performance of TR-DOI prototypes is evaluated according to the parameters used in common protocols to test DOI systems particularly basic instrumental performance (BIP). In addition, the potential features of SPADs and SiPMs to improve TR-DOI systems and expand their applications in the foreseeable future are discussed. Lastly, research challenges and future developments for TR-DOI are discussed for each component in the prototype separately and also for the entire system.
2008-10-01
ER D C/ CR R EL T R -0 8 -1 9 Energetic Residues from Blow-in-Place Detonation of 60-mm and 120-mm Fuzed High-Explosive Mortar Cartridges...Figure 4. Sample filtration setup. ............................................................................................................. 8 ...15 Table 8 . HE munitions BIP and live-fire detonation energetics residues data. .................................. 17 ERDC/CRREL TR-08
Influence of the Solvent on the Thermal Back Reaction of One Spiropyran
ERIC Educational Resources Information Center
Piard, Jonathan
2014-01-01
The solvent influence on the absorption spectra and the kinetics of the back reaction of the 1',3'-dihydro-1',3',3'-trimethyl-6-nitrospiro(2H-1-benzopyran-2,2'-2H-indole) (6-NO2-BIPS) has been investigated by means of temperature-controlled, UV-visible spectroscopic measurements. The back reaction process was proved to follow first-order kinetics…
Maruyama, Daisuke; Yamamoto, Masaya; Endo, Toshiya; Nishikawa, Shuh-ichi
2014-11-01
Angiosperm female gametophytes contain a central cell with two polar nuclei. In many species, including Arabidopsis thaliana, the polar nuclei fuse during female gametogenesis. We previously showed that BiP, an Hsp70 in the endoplasmic reticulum (ER), was essential for membrane fusion during female gametogenesis. Hsp70 function requires partner proteins for full activity. J-domain containing proteins (J-proteins) are the major Hsp70 functional partners. A. thaliana ER contains three soluble J-proteins, AtERdj3A, AtERdj3B, and AtP58(IPK). Here, we analyzed mutants of these proteins and determined that double-mutant ovules lacking AtP58(IPK) and AtERdj3A or AtERdj3B were defective in polar nuclear fusion. Electron microscopy analysis identified that polar nuclei were in close contact, but no membrane fusion occurred in mutant ovules lacking AtP58(IPK) and AtERdj3A. The polar nuclear outer membrane appeared to be connected via the ER remaining at the inner unfused membrane in mutant ovules lacking AtP58(IPK) and AtERdj3B. These results indicate that ER-resident J-proteins, AtP58(IPK)/AtERdj3A and AtP58(IPK)/AtERdj3B, function at distinct steps of polar nuclear-membrane fusion. Similar to the bip1 bip2 double mutant female gametophytes, the aterdj3a atp58(ipk) double mutant female gametophytes defective in fusion of the outer polar nuclear membrane displayed aberrant endosperm proliferation after fertilization with wild-type pollen. However, endosperm proliferated normally after fertilization of the aterdj3b atp58(ipk) double mutant female gametophytes defective in fusion of the inner membrane. Our results indicate that the polar nuclear fusion defect itself does not cause an endosperm proliferation defect. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Zhang, Jintao; Yi, Man; Zha, Longying; Chen, Siqiang; Li, Zhijia; Li, Cheng; Gong, Mingxing; Deng, Hong; Chu, Xinwei; Chen, Jiehua; Zhang, Zheqing; Mao, Limei; Sun, Suxia
2016-01-01
Butyrate, a short-chain fatty acid derived from dietary fiber, inhibits proliferation and induces cell death in colorectal cancer cells. However, clinical trials have shown mixed results regarding the anti-tumor activities of butyrate. We have previously shown that sodium butyrate increases endoplasmic reticulum stress by altering intracellular calcium levels, a well-known autophagy trigger. Here, we investigated whether sodium butyrate-induced endoplasmic reticulum stress mediated autophagy, and whether there was crosstalk between autophagy and the sodium butyrate-induced apoptotic response in human colorectal cancer cells. Human colorectal cancer cell lines (HCT-116 and HT-29) were treated with sodium butyrate at concentrations ranging from 0.5-5mM. Cell proliferation was assessed using MTT tetrazolium salt formation. Autophagy induction was confirmed through a combination of Western blotting for associated proteins, acridine orange staining for acidic vesicles, detection of autolysosomes (MDC staining), and electron microscopy. Apoptosis was quantified by flow cytometry using standard annexinV/propidium iodide staining and by assessing PARP-1 cleavage by Western blot. Sodium butyrate suppressed colorectal cancer cell proliferation, induced autophagy, and resulted in apoptotic cell death. The induction of autophagy was supported by the accumulation of acidic vesicular organelles and autolysosomes, and the expression of autophagy-associated proteins, including microtubule-associated protein II light chain 3 (LC3-II), beclin-1, and autophagocytosis-associated protein (Atg)3. The autophagy inhibitors 3-methyladenine (3-MA) and chloroquine inhibited sodium butyrate induced autophagy. Furthermore, sodium butyrate treatment markedly enhanced the expression of endoplasmic reticulum stress-associated proteins, including BIP, CHOP, PDI, and IRE-1a. When endoplasmic reticulum stress was inhibited by pharmacological (cycloheximide and mithramycin) and genetic (siRNA targeting BIP and CHOP) methods, the induction of BIP, PDI, IRE1a, and LC3-II was blocked, but PARP cleavage was markedly enhanced. Taken together, these results suggested that sodium butyrate-induced autophagy was mediated by endoplasmic reticulum stress, and that preventing autophagy by blocking the endoplasmic reticulum stress response enhanced sodium butyrate-induced apoptosis. These results provide novel insights into the anti-tumor mechanisms of butyric acid.
The Endoplasmic Reticulum Chaperone GRP78/BiP Modulates Prion Propagation in vitro and in vivo.
Park, Kyung-Won; Eun Kim, Gyoung; Morales, Rodrigo; Moda, Fabio; Moreno-Gonzalez, Ines; Concha-Marambio, Luis; Lee, Amy S; Hetz, Claudio; Soto, Claudio
2017-03-23
Prion diseases are fatal neurodegenerative disorders affecting several mammalian species, characterized by the accumulation of the misfolded form of the prion protein, which is followed by the induction of endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR). GRP78, also called BiP, is a master regulator of the UPR, reducing ER stress levels and apoptosis due to an enhancement of the cellular folding capacity. Here, we studied the role of GRP78 in prion diseases using several in vivo and in vitro approaches. Our results show that a reduction in the expression of this molecular chaperone accelerates prion pathogenesis in vivo. In addition, we observed that prion replication in cell culture was inversely related to the levels of expression of GRP78 and that both proteins interact in the cellular context. Finally, incubation of PrP Sc with recombinant GRP78 led to the dose-dependent reduction of protease-resistant PrP Sc in vitro. Our results uncover a novel role of GRP78 in reducing prion pathogenesis, suggesting that modulating its levels/activity may offer a novel opportunity for designing therapeutic approaches for these diseases. These findings may also have implications for other diseases involving the accumulation of misfolded proteins.
Cai, Yanxue; Zhang, Xianwen; Zhou, Xiaoshuang; Wu, Xiaoli; Li, Yanhui; Yao, Jianhua; Bai, Jie
2017-03-01
Parkinson's disease (PD) is a neurodegenerative disease. Nicotine has been reported to have the role in preventing Parkinson's disease. However, its mechanism is still unclear. In present study we found that nicotine suppressed 1-methyl-4-phenylpyridinium ion(MPP + ) toxicity in PC12 cells by MTT assay. The expression of thioredoxin-1(Trx-1) was decreased by MPP + , which was restored by nicotine. The nicotine suppressed expressions of Glucose-regulated protein 78(GRP78/Bip) and C/EBP homologous protein (CHOP) induced by MPP + . The methyllycaconitine (MLA), the inhibitor of α7nAChR and LY294002, the inhibitor of phosphatidylinositol 3-kinase (PI3K) blocked the suppressions of above molecules, respectively. Consistently, pretreatment with nicotine ameliorated the motor ability, restored the declines of Trx-1 and tyrosine hydroxylase (TH), and suppressed the expressions of Bip and CHOP induced by 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Our results suggest that nicotine plays role in resisting MPP + /MPTP neurotoxicity through activating the α7nAChR/PI3K/Trx-1 pathway and suppressing ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.
Liver Inflammation and Metabolic Signaling in ApcMin/+ Mice: The Role of Cachexia Progression
Narsale, Aditi A.; Enos, Reilly T.; Puppa, Melissa J.; Chatterjee, Saurabh; Murphy, E. Angela; Fayad, Raja; Pena, Majorette O’; Durstine, J. Larry; Carson, James A.
2015-01-01
The ApcMin/+ mouse exhibits an intestinal tumor associated loss of muscle and fat that is accompanied by chronic inflammation, insulin resistance and hyperlipidemia. Since the liver governs systemic energy demands through regulation of glucose and lipid metabolism, it is likely that the liver is a pathological target of cachexia progression in the ApcMin/+ mouse. The purpose of this study was to determine if cancer and the progression of cachexia affected liver endoplasmic reticulum (ER)-stress, inflammation, metabolism, and protein synthesis signaling. The effect of cancer (without cachexia) was examined in wild-type and weight-stable ApcMin/+ mice. Cachexia progression was examined in weight-stable, pre-cachectic, and severely-cachectic ApcMin/+ mice. Livers were analyzed for morphology, glycogen content, ER-stress, inflammation, and metabolic changes. Cancer induced hepatic expression of ER-stress markers BiP (binding immunoglobulin protein), IRE-1α (endoplasmic reticulum to nucleus signaling 1), and inflammatory intermediate STAT-3 (signal transducer and activator of transcription 3). While gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was suppressed by cancer, glycogen content or protein synthesis signaling remained unaffected. Cachexia progression depleted liver glycogen content and increased mRNA expression of glycolytic enzyme PFK (phosphofrucktokinase) and gluconeogenic enzyme PEPCK. Cachexia progression further increased pSTAT-3 but suppressed p-65 and JNK (c-Jun NH2-terminal kinase) activation. Interestingly, progression of cachexia suppressed upstream ER-stress markers BiP and IRE-1α, while inducing its downstream target CHOP (DNA-damage inducible transcript 3). Cachectic mice exhibited a dysregulation of protein synthesis signaling, with an induction of p-mTOR (mechanistic target of rapamycin), despite a suppression of Akt (thymoma viral proto-oncogene 1) and S6 (ribosomal protein S6) phosphorylation. Thus, cancer induced ER-stress markers in the liver, however cachexia progression further deteriorated liver ER-stress, disrupted protein synthesis regulation and caused a differential inflammatory response related to STAT-3 and NF-κB (Nuclear factor—κB) signaling. PMID:25789991
Bettaieb, Ahmed; Averill-Bates, Diana A
2015-01-01
Hyperthermia (39-45°C) has emerged as an alternate prospect for cancer therapy in combination with radiation and chemotherapy. Despite promising progress in the clinic, molecular mechanisms involved in hyperthermia-induced cell death are not clear. Hyperthermia causes protein denaturation/aggregation, which results in cell death by apoptosis and/or necrosis. Hyperthermia also induces thermotolerance, which renders cells resistant to subsequent exposure to lethal heat shock. This study investigates the role of both lethal (42-43°C) and mild (40°C) hyperthermia in regulating ER stress and ER stress-induced apoptosis in HeLa cells. The ability of mild thermotolerance induced at 40°C to alleviate either or both of these processes is also determined. Hyperthermia (42-43°C) induced ER stress, revealed by phosphorylation of PERK, eIF2α and IRE1α, cleavage of ATF6 and increased expression of BiP and sXBP1. Real-time PCR revealed that mRNA levels of ATF6, ATF4, BiP, sXBP1 and CHOP increased in cells exposed to hyperthermia. Moreover, hyperthermia caused disruption of calcium homeostasis and activated the calpain-calpastatin proteolytic system and ER resident caspase 4. Pre-exposure to mild hyperthermia (40°C) alleviated the induction of cytotoxicity and ER stress by hyperthermia (42-43°C) and protected cells against ER stress-induced apoptosis. ShRNA-mediated depletion of Hsp72 abrogated protective effects of mild thermotolerance (40°C) against heat-shock induced ER stress and sensitized cells to ER stress-mediated apoptosis. Our findings show that Hsp72 contributes to the protective effects of mild hyperthermia (40°C) against hyperthermia-induced ER stress and apoptosis. Copyright © 2014 Elsevier B.V. All rights reserved.
Mutagen and Oncogen Study on JP-4
1978-09-01
random bred mice were killed by cranial blow , decapitated and bled. The liver was immediately dissected from the animal using aseptic technique and placed...chemical. Positive Controls--N-methylnitrosoguanidine (MNNG) at a concentration of 10 pg/ml was used as the positive control agent in nonactivation tests...The positive control agent in activation tests was 3,4-benzo(u)pyrene (BiP) at a concentration of 10 pg/ml. EXPERIMENTAL DESIGN Cell Preparation
Alayed, Mrwan
2017-01-01
Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are emerging non-invasive imaging modalities that have wide spread potential applications in many fields, particularly for structural and functional imaging in medicine. In this article, we review time-resolved diffuse optical imaging (TR-DOI) systems using solid-state detectors with a special focus on Single-Photon Avalanche Diodes (SPADs) and Silicon Photomultipliers (SiPMs). These TR-DOI systems can be categorized into two types based on the operation mode of the detector (free-running or time-gated). For the TR-DOI prototypes, the physical concepts, main components, figures-of-merit of detectors, and evaluation parameters are described. The performance of TR-DOI prototypes is evaluated according to the parameters used in common protocols to test DOI systems particularly basic instrumental performance (BIP). In addition, the potential features of SPADs and SiPMs to improve TR-DOI systems and expand their applications in the foreseeable future are discussed. Lastly, research challenges and future developments for TR-DOI are discussed for each component in the prototype separately and also for the entire system. PMID:28906462
Sakitani, Kosuke; Hirata, Yoshihiro; Hikiba, Yohko; Hayakawa, Yoku; Ihara, Sozaburo; Suzuki, Hirobumi; Suzuki, Nobumi; Serizawa, Takako; Kinoshita, Hiroto; Sakamoto, Kei; Nakagawa, Hayato; Tateishi, Keisuke; Maeda, Shin; Ikenoue, Tsuneo; Kawazu, Shoji; Koike, Kazuhiko
2015-10-24
Although some molecularly targeted drugs for colorectal cancer are used clinically and contribute to a better prognosis, the current median survival of advanced colorectal cancer patients is not sufficient. Autophagy, a basic cell survival mechanism mediated by recycling of cellular amino acids, plays an important role in cancer. Recently, autophagy has been highlighted as a promising new molecular target. The unfolded protein response (UPR) reportedly act in complementary fashion with autophagy in intestinal homeostasis. However, the roles of UPR in colon cancer under autophagic inhibition remain to be elucidated. We aim to clarify the inhibitory effect of autophagy on colon cancer. We crossed K19 (CreERT) and Atg5 (flox/flox) mice to generate Atg5 (flox/flox)/K19 (CreERT) mice. Atg5 (flox/flox)/K19 (CreERT) mice were first treated with azoxymethane/dextran sodium sulfate and then injected with tamoxifen to inhibit autophagy in CK19-positive epithelial cells. To examine the anti-cancer mechanisms of autophagic inhibition, we used colon cancer cell lines harboring different p53 gene statuses, as well as small interfering RNAs (siRNAs) targeting Atg5 and immunoglobulin heavy-chain binding protein (BiP), a chaperone to aid folding of unfolded proteins. Colon tumors in Atg5 (flox/flox)/K19 (CreERT) mice showed loss of autophagic activity and decreased tumor size (the total tumor diameter was 28.1 mm in the control and 20.7 mm in Atg5 (flox/flox)/K19 (CreERT) mice, p = 0.036). We found that p53 and UPR/endoplasmic reticulum (ER) stress-related proteins, such as cleaved caspase 3, and CAAT/enhancer-binding protein homologous protein, are up-regulated in colon tumors of Atg5 (flox/flox)/K19 (CreERT) mice. Although Atg5 and BiP silencing, respectively, increased apoptosis in p53 wild type cells, Atg5 silencing alone did not show the same effect on apoptosis in p53 mutant cells. However, co-transfection of Atg5 and BiP siRNAs led to increased apoptosis in p53 mutant cells. Blocking autophagy has potential in the treatment of colon cancer by inducing apoptosis via p53 and ER stress, and suppressing the UPR pathway is a valid strategy to overcome resistance to autophagic inhibition.
Jorgensen, Ellen; Stinson, Andy; Shan, Lin; Yang, Jin; Gietl, Diana; Albino, Anthony P
2008-01-01
Background Although lung cancer is among the few malignancies for which we know the primary etiological agent (i.e., cigarette smoke), a precise understanding of the temporal sequence of events that drive tumor progression remains elusive. In addition to finding that cigarette smoke (CS) impacts the functioning of key pathways with significant roles in redox homeostasis, xenobiotic detoxification, cell cycle control, and endoplasmic reticulum (ER) functioning, our data highlighted a defensive role for the unfolded protein response (UPR) program. The UPR promotes cell survival by reducing the accumulation of aberrantly folded proteins through translation arrest, production of chaperone proteins, and increased degradation. Importance of the UPR in maintaining tissue health is evidenced by the fact that a chronic increase in defective protein structures plays a pathogenic role in diabetes, cardiovascular disease, Alzheimer's and Parkinson's syndromes, and cancer. Methods Gene and protein expression changes in CS exposed human cell cultures were monitored by high-density microarrays and Western blot analysis. Tissue arrays containing samples from 110 lung cancers were probed with antibodies to proteins of interest using immunohistochemistry. Results We show that: 1) CS induces ER stress and activates components of the UPR; 2) reactive species in CS that promote oxidative stress are primarily responsible for UPR activation; 3) CS exposure results in increased expression of several genes with significant roles in attenuating oxidative stress; and 4) several major UPR regulators are increased either in expression (i.e., BiP and eIF2α) or phosphorylation (i.e., phospho-eIF2α) in a majority of human lung cancers. Conclusion These data indicate that chronic ER stress and recruitment of one or more UPR effector arms upon exposure to CS may play a pivotal role in the etiology or progression of lung cancers, and that phospho-eIF2α and BiP may have diagnostic and/or therapeutic potential. Furthermore, we speculate that upregulation of UPR regulators (in particular BiP) may provide a pro-survival advantage by increasing resistance to cytotoxic stresses such as hypoxia and chemotherapeutic drugs, and that UPR induction is a potential mechanism that could be attenuated or reversed resulting in a more efficacious treatment strategy for lung cancer. PMID:18694499
Distribution and Fate of Energetics on DoD Test and Training Ranges: Final Report
2006-11-01
tests for unconfined charges........................................................ 106 Table 5-3. Mass (g) of residue generated by BIP of unfuzed anti...Lands Withdrawal Act (Public Law 106 -65). As a portion of this EIS, the Army has pledged to implement a program to identify possible munitions...containing Tritonal, PBXN -109, Composition H-6, and Composition B (Baker et al. 2000). Included in the list of simulated UXOs was the 155-mm, 105-mm, and 8
Rezaiemanesh, Alireza; Mahmoudi, Mahdi; Amirzargar, Ali Akbar; Vojdanian, Mahdi; Jamshidi, Ahmad Reza; Nicknam, Mohammad Hossein
2017-09-01
Interleukin (IL)-23/IL-17 pathway involves in the pathogenesis of ankylosing spondylitis (AS). The exact mechanism implicated in overexpression of IL-23 and activation of the IL-23/IL-17 axis is not clear. The aim of the study was to clarify whether macrophages of AS patients undergo unfolded protein response (UPR) and secret increased IL-23. Peripheral blood monocyte isolated from 10 HLA-B27 + patients and five HLA-B27 + normal subjects were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for seven days. Flow cytometry was used to detect monocyte purity and expression of macrophage markers. Analysis of mRNA expression for HLA-B and B27, UPR-associated proteins (BiP, CHOP, MDG1, and XBP1) and IL-23 was performed by RT-qPCR. RT-qPCR data showed a significant overexpression of HLA-B27, UPR genes (BiP, CHOP, and XBP1), and IL-23 in M-CSF-derived macrophages from AS patients compared to healthy controls. Increased expression of MDG1 was not significant. Our data suggest that UPR activation occurs in M-CSF-derived macrophages of AS patients and is accompanied by overexpression of HLA-B27. UPR appears to be associated with overproduction of IL-23 in AS macrophages.
Li, Kehan; Han, Xuechang
2015-05-01
Lidocaine has been indicated to promote apoptosis and to promote endoplasmic reticulum (ER) stress. However, the mechanism underlining ER stress-mediated apoptosis is unclear. In the present study, we investigated the promotion to ER stress in the lidocaine-induced apoptosis in human neuroblastoma SH-SY5Y cells. Firstly, we confirmed that lidocaine treatment induced apoptosis in SH-SY5Y cells, time-dependently and dose-dependently, via MTT cell viability assay and annexin V/FITC apoptosis detection with a FACScan flow cytometer. And the anti-apoptosis Bcl-2 and Bcl-xL were downregulated, whereas the apoptosis-executive caspase 3 was promoted through Western blot assay and caspase 3 activity assay. Moreover, the ER stress-associated binding immunoglobulin protein (BiP), PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein homologous protein (CHOP) were also upregulated at both mRNA and protein levels by lidocaine treatment. On the other hand, downregulation of the ER stress-associated BiP by RNAi method not only blocked the lidocaine-promoted ER stress but also attenuated the lidocaine-induced SH-SY5Y cell apoptosis. In conclusion, the present study confirmed the involvement of ER stress in the lidocaine-induced apoptosis in human neuroblastoma SH-SY5Y cells. Our study provides a better understanding on the mechanism of lidocaine's neurovirulence.
The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation
Williams, Jeffrey M.; Inoue, Takamasa; Banks, Lindsey; Tsai, Billy
2013-01-01
Cholera toxin (CT) traffics from the host cell surface to the endoplasmic reticulum (ER), where the toxin's catalytic CTA1 subunit retrotranslocates to the cytosol to induce toxicity. In the ER, CT is captured by the E3 ubiquitin ligase Hrd1 via an undefined mechanism to prepare for retrotranslocation. Using loss-of-function and gain-of-function approaches, we demonstrate that the ER-resident factor ERdj5 promotes CTA1 retrotranslocation, in part, via its J domain. This Hsp70 cochaperone regulates binding between CTA and the ER Hsp70 BiP, a chaperone previously implicated in toxin retrotranslocation. Importantly, ERdj5 interacts with the Hrd1 adaptor Sel1L directly through Sel1L's N-terminal lumenal domain, thereby linking ERdj5 to the Hrd1 complex. Sel1L itself also binds CTA and facilitates toxin retrotranslocation. By contrast, EDEM1 and OS-9, two established Sel1L binding partners, do not play significant roles in CTA1 retrotranslocation. Our results thus identify two ER factors that promote ER-to-cytosol transport of CTA1. They also indicate that ERdj5, by binding to Sel1L, triggers BiP–toxin interaction proximal to the Hrd1 complex. We postulate this scenario enables the Hrd1-associated retrotranslocation machinery to capture the toxin efficiently once the toxin is released from BiP. PMID:23363602
Brem, Meagan J; Florimbio, Autumn Rae; Elmquist, JoAnna; Shorey, Ryan C; Stuart, Gregory L
2018-01-01
Men with antisocial personality disorder (ASPD) traits are at an increased risk for consuming alcohol and perpetrating intimate partner violence (IPV). However, previous research has neglected malleable mechanisms potentially responsible for the link between ASPD traits, alcohol problems, and IPV perpetration. Efforts to improve the efficacy of batterer intervention programs (BIPs) would benefit from exploration of such malleable mechanisms. The present study is the first to examine distress tolerance as one such mechanism linking men's ASPD traits to their alcohol problems and IPV perpetration. Using a cross-sectional sample of 331 men arrested for domestic violence and court-referred to BIPs, the present study used structural equation modeling to examine pathways from men's ASPD traits to IPV perpetration directly and indirectly through distress tolerance and alcohol problems. Results supported a two-chain partial mediational model. ASPD traits were related to psychological aggression perpetration directly and indirectly via distress tolerance and alcohol problems. A second pathway emerged by which ASPD traits related to higher levels of alcohol problems, which related to psychological aggression perpetration. Controlling for psychological aggression perpetration, neither distress tolerance nor alcohol problems explained the relation between ASPD traits and physical assault perpetration. These results support and extend existing conceptual models of IPV perpetration. Findings suggest intervention efforts for IPV should target both distress tolerance and alcohol problems.
Blus, Cornelio; Szmukler-Moncler, Serge; Giannelli, Giulio; Denotti, Gloria; Orrù, Germano
2013-01-01
This preliminary work documents the use of a powerful piezosurgery device to treat biphosphonate-related osteonecrosis of the jaw (BRONJ) in combination with classical medication therapy. Eight patients presenting 9 BRONJ sites were treated, 2 in the maxilla and 7 in the mandible. Reason for biphosphonate (BiP) intake was treatment of an oncologic disease for 5 patients and osteoporosis for 3. The oncologic and osteoporosis patients were diagnosed with BRONJ after 35-110 months and 80-183 months of BiP treatment, respectively. BRONJ 2 and 3 was found in 4 patients. Resection of the bone sequestrae was performed with a high power ultrasonic (piezo) surgery and antibiotics were administrated for 2 weeks. Soft tissue healing was incomplete at the 2-week control but it was achieved within 1 month. At the 1-year control, soft tissue healing was maintained at all patients, without symptom recurrence. One patient with paraesthesia had abated; of the 2 pa-tients with trismus, one was healed, severity of the second trismus abated. This case report series suggests that bone resection performed with a high power ultrasonic surgery device combined with antibiotics might lead to BRONJ healing. More patients are warranted to confirm the present findings and assess this treatment approach. PMID:24044030
Large Eddy Simulation of Bubbly Ship Wakes
2005-08-01
as, [Cm +BI(p)+ DE (u)+D,(u,)] (2.28) aRm, =-[E,+FE )(p) (229O•., L pe•,z+_tpjj.( F.(]-](2.29) where Ci and EP represent the convective terms, Bi is the...discrete operator for the pressure gradient term, DE and D, (FE and FI) are discrete operators for the explicitly treated off diagonal terms and the...Bashforth scheme is employed for all the other terms. The off diagonal viscous terms ( DE ) are treated explicitly in order to simplify the LHS matrix of the
2012-02-29
surface and Swiss roll) and real-world data sets (UCI Machine Learning Repository [12] and USPS digit handwriting data). In our experiments, we use...less than µn ( say µ = 0.8), we can first use screening technique to select µn candidate nodes, and then apply BIPS on them for further selection and...identified from node j to node i. So we can say the probability for the existence of this connection is approximately 82%. Given the probability matrix
Kumar, Vinod; Mills, Douglas J.; Anderson, James D.; Mattoo, Autar K.
2004-01-01
Conventional agriculture has relied heavily on chemical inputs that have negatively impacted the environment and increased production costs. Transition to agricultural sustainability is a major challenge and requires that alternative agricultural practices are scientifically analyzed to provide a sufficiently informative knowledge base in favor of alternative farming practices. We show a molecular basis for delayed leaf senescence and tolerance to diseases in tomato plants cultivated in a legume (hairy vetch) mulch-based alternative agricultural system. In the hairy vetch-cultivated plants, expression of specific and select classes of genes is up-regulated compared to those grown on black polyethylene mulch. These include N-responsive genes such as NiR, GS1, rbcL, rbcS, and G6PD; chaperone genes such as hsp70 and BiP; defense genes such as chitinase and osmotin; a cytokinin-responsive gene CKR; and gibberellic acid 20 oxidase. We present a model of how their protein products likely complement one another in a field scenario to effect efficient utilization and mobilization of C and N, promote defense against disease, and enhance longevity. PMID:15249656
Effect of quercetin on apoptosis of PANC-1 cells
Lee, Joo Hyun; Lee, Han-Beom; Jung, Gum O; Oh, Jung Taek; Park, Dong Eun
2013-01-01
Purpose To investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells. Methods Various anticancer drugs including adriamycin, cisplatin, 5-fluorouracil (5-FU) and gemcitabine were used. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphe-nyltetra zolium bromide assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole nuclei staining and flow cytometry in PANC-1 cells treated with 50 µg/mL quercetin for 24 hours. Expression of endoplas mic reticulum (ER) stress mediators including, Grp78/Bip, p-PERK, PERK, ATF4, ATF6 and GADD153/CHOP proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Quercetin induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. But not adriamycin, cisplatin, gemcitabine, and 5-FU. PANC-1 cells were markedly sensitive to quercetin. Results Treatment with quercetin resulted in the increased accumulation of intracellular Ca2+ ion. Treatment with quercetin also increased the expression of Grp78/Bip and GADD153/CHOP protein and induced mitochondrial dysfunction. Quercetin exerted cytotoxicity against human pancreatic cancer cells via ER stress-mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction. Conclusion These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents. PMID:24368982
Effect of quercetin on apoptosis of PANC-1 cells.
Lee, Joo Hyun; Lee, Han-Beom; Jung, Gum O; Oh, Jung Taek; Park, Dong Eun; Chae, Kwon Mook
2013-12-01
To investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells. Various anticancer drugs including adriamycin, cisplatin, 5-fluorouracil (5-FU) and gemcitabine were used. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphe-nyltetra zolium bromide assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole nuclei staining and flow cytometry in PANC-1 cells treated with 50 µg/mL quercetin for 24 hours. Expression of endoplas mic reticulum (ER) stress mediators including, Grp78/Bip, p-PERK, PERK, ATF4, ATF6 and GADD153/CHOP proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Quercetin induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. But not adriamycin, cisplatin, gemcitabine, and 5-FU. PANC-1 cells were markedly sensitive to quercetin. Treatment with quercetin resulted in the increased accumulation of intracellular Ca(2+) ion. Treatment with quercetin also increased the expression of Grp78/Bip and GADD153/CHOP protein and induced mitochondrial dysfunction. Quercetin exerted cytotoxicity against human pancreatic cancer cells via ER stress-mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction. These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents.
Hickman, Gary D; Brown, Mary L
2002-06-07
Two multimetric indices have been developed to help address fish community (reservoir fish assemblage index [RFAI]) and individual population quality (sport fishing index [SFI]) in Tennessee River reservoirs. The RFAI, with characteristics similar to the index of biotic integrity (IBI) used in stream fish community determinations, was developed to monitor the existing condition of resident fish communities. The index, which incorporates standardized electrofishing of littoral areas and experimental gill netting for limnetic bottom-dwelling species, has been used to determine residential fish community response to various anthropogenic impacts in southeastern reservoirs. The SFI is a multimetric index designed to address the quality of the fishery for individual resident sport fish species in a particular lake or reservoir[4]. The SFI incorporates measures of fish population aspects and angler catch and pressure estimates. This paper proposes 70% of the maximum RFAI score and 10% above the average SFI score for individual species as "screening" endpoints for balanced indigenous populations (BIP) or adverse environmental impact (AEI). Endpoints for these indices indicate: (1) communities/populations are obviously balanced indigenous populations (BIP) indicating no adverse environmental impact (AEI), or are "screened out"; (2) communities/populations are considered to be potentially impacted; and (3) where the resident fish community/population should be considered adversely impacted. Suggestions are also made concerning how examination of individual metric scores can help determine the source or cause of the impact.
Arima, Hiroshi; Morishita, Yoshiaki; Hagiwara, Daisuke; Hayashi, Masayuki; Oiso, Yutaka
2014-01-01
The immunoglobulin heavy chain binding protein (BiP) is an endoplasmic reticulum (ER) chaperone, which binds to newly synthesized secretory and transmembrane proteins to facilitate protein folding. BiP mRNA is expressed in the arginine vasopressin (AVP) neurons in the supraoptic nucleus of wild-type mice even in basal conditions, and the expression levels increase in response to dehydration. These data suggest that AVP neurons are subjected to ER stress. Familial neurohypophysial diabetes insipidus (FNDI) is caused by mutations in the gene locus of AVP. The mutant proteins could accumulate in the ER and possibly increase ER stress in the AVP neurons. We bred mice possessing a mutation causing FNDI, which manifested progressive polyuria, as do the patients with FNDI. Electron microscopic analyses demonstrated that aggregates accumulated in the ER of AVP neurons in FNDI mice. Despite polyuria, which could potentially induce dehydration, AVP mRNA expression was decreased in the supraoptic nucleus, and the AVP mRNA poly(A) tail length was shortened in FNDI mice compared with wild-type mice. Incubation of hypothalamic explants of wild-type mice with ER stressors caused shortening of the poly(A) tail length of AVP mRNA, accompanied by decreases in the expression. These data revealed a mechanism by which ER stress decreases poly(A) tail length of AVP mRNA, and this reduces the load of unfolded proteins that form the aggregates in ER of the AVP neurons in FNDI mice.
Morrison, J Kaitlin; Friday, Andrew J; Henderson, Melissa A; Hao, Enhui; Keiper, Brett D
2014-01-01
During apoptosis, activated caspases cleave the translation initiation factor eIF4G. This cleavage disrupts cap-dependent mRNA translation initiation within the cell. However, a specific subset of mRNAs can still be recruited for protein synthesis in a cap-independent manner by the residual initiation machinery. Many of these mRNAs, including cell death related mRNAs, contain internal ribosome entry sites (IRESes) that promote their enhanced translation during apoptosis. Still other mRNAs have little dependence on the cap recognition mechanism. The expression of the encoded proteins, both anti- and pro-apoptotic, allows for an initial period of attempted cell survival, then commitment to cell death when damage is extensive. In this study we address the translational regulation of the stress and apoptosis-related mRNAs in C. elegans: BiP (hsp-3) (hsp-4), Hif-1 (hif-1), p53 (cep-1), Bcl-2 (ced-9) and Apaf-1 (ced-4). Altered translational efficiency of these messages was observed upon depletion of cap-dependent translation and induction of apoptosis within the C. elegans gonad. Our findings suggest a physiological link between the cap-independent mechanism and the enhanced translation of hsp-3 and ced-9. This increase in the efficiency of translation may be integral to the stress response during the induction of physiological apoptosis. PMID:26779406
Lenna, Stefania; Townsend, Danyelle M.; Tan, Filemon K.; Kapanadze, Bagrat; Markiewicz, Malgorzata; Trojanowska, Maria; Scorza, Raffaella
2013-01-01
The presence of the HLA-B35 allele has emerged as an important risk factor for the development of isolated pulmonary hypertension in patients with scleroderma, however the mechanisms underlying this association have not been fully elucidated. The goal of our study was to determine the molecular mechanisms that mediate the biological effects of HLA-B35 in endothelial cells (ECs). Our data demonstrate that HLA-B35 expression at physiological levels via adenoviral vector resulted in significantly increased endothelin-1 (ET-1) and a significantly decreased endothelial NO synthase (eNOS), mRNA, and protein levels. Furthermore, HLA-B35 greatly upregulated expression of chaperones, including heat shock proteins (HSPs) HSP70 (HSPA1A and HSPA1B) and HSP40 (DNAJB1 and DNAJB9), suggesting that HLA-B35 induces the endoplasmic reticulum (ER) stress and unfolded protein response in ECs. Examination of selected mediators of the unfolded protein response, including H chain binding protein (BiP; GRP78), C/Ebp homologous protein (CHOP; GADD153), endoplasmic reticulum oxidase, and protein disulfide isomerase has revealed a consistent increase of BiP expression levels. Accordingly, thapsigargin, a known ER stress inducer, stimulated ET-1mRNAand protein levels in ECs. This study suggests that HLA-B35 could contribute to EC dysfunction via ER stress-mediated induction of ET-1 in patients with pulmonary hypertension. PMID:20335527
Lenna, Stefania; Townsend, Danyelle M; Tan, Filemon K; Kapanadze, Bagrat; Markiewicz, Malgorzata; Trojanowska, Maria; Scorza, Raffaella
2010-05-01
The presence of the HLA-B35 allele has emerged as an important risk factor for the development of isolated pulmonary hypertension in patients with scleroderma, however the mechanisms underlying this association have not been fully elucidated. The goal of our study was to determine the molecular mechanisms that mediate the biological effects of HLA-B35 in endothelial cells (ECs). Our data demonstrate that HLA-B35 expression at physiological levels via adenoviral vector resulted in significantly increased endothelin-1 (ET-1) and a significantly decreased endothelial NO synthase (eNOS), mRNA, and protein levels. Furthermore, HLA-B35 greatly upregulated expression of chaperones, including heat shock proteins (HSPs) HSP70 (HSPA1A and HSPA1B) and HSP40 (DNAJB1 and DNAJB9), suggesting that HLA-B35 induces the endoplasmic reticulum (ER) stress and unfolded protein response in ECs. Examination of selected mediators of the unfolded protein response, including H chain binding protein (BiP; GRP78), C/Ebp homologous protein (CHOP; GADD153), endoplasmic reticulum oxidase, and protein disulfide isomerase has revealed a consistent increase of BiP expression levels. Accordingly, thapsigargin, a known ER stress inducer, stimulated ET-1 mRNA and protein levels in ECs. This study suggests that HLA-B35 could contribute to EC dysfunction via ER stress-mediated induction of ET-1 in patients with pulmonary hypertension.
A novel role for bone-derived cells in ankylosing spondylitis: Focus on IL-23.
Jo, Sungsin; Koo, Bon San; Lee, Bitnara; Kwon, Eunji; Lee, Young Lim; Chung, Heekyoung; Sung, Il-Hoon; Park, Ye-Soo; Kim, Tae-Hwan
2017-09-23
The main aim of this study are to explore the role of bone-derived cells (BdCs) in ankylosing spondylitis (AS) and determine the underlying molecular mechanisms of IL-23 production. Primary BdCs were isolated from diced bone of facet joints obtained during surgery from seven AS patients and seven disease control (Ct) patients. Osteoblastic activity of BdCs was assessed by measuring their alkaline phosphatase activity and by alizarin red staining. Osteoblast and endoplasmic reticulum (ER) stress-related genes were assessed by quantitative PCR, immunoblotting, immunofluorescence, and immunohistochemistry. In addition, expression of IL-23 in response to BIX (selective BIP inducer X)-induced ER stress was evaluated by qPCR and ELISA. Protein interaction and binding to IL-23 promoter were confirmed by Immunoprecipitation and Chromatin immunoprecipitation, respectively. Transcript levels of genes involved in osteoblast function, as well as of the ER stress marker were higher in the AS group than the Ct group, and elevated RUNX2, BiP and IL-23 expression were observed in the BdCs, serum, and bone biopsies from the AS group. BIX-induced ER stress stimulated osteoblastic activity and IL-23 secretion by upregulating RUNX2 expression. Furthermore, in AS BdCs, RUNX2 interacted with C/EBPβ to bind to IL-23 promoter and RUNX2 knockdown suppressed IL-23 secretion. These finding may provide a molecular mechanism involved in sustained ER stress in AS BdCs stimulates the activation of RUNX2 and C/EBPβ genes, leading to IL-23 production. Copyright © 2017 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, Yea-Jin; Kim, Sung-Jo, E-mail: sungjo@hoseo.edu; Heo, Tae-Hwe, E-mail: thhur92@catholic.ac.kr
Highlights: {yields} Catechin reduces the expression level of ER stress marker protein in type I Gaucher disease cells. {yields} Catechin induces the proliferation rate of GD cells similar levels to normal cells. {yields} Catechin improves wound healing activity. {yields} Catechin-mediated reductions in ER stress may be associated with enhanced cell survival. {yields} We identified catechin as a protective agent against ER stress in GD cells. -- Abstract: Gaucher disease (GD) is the most common lysosomal storage disorder (LSD) and is divided into three phenotypes, I, II, and III. Type I is the most prevalent form and has its onset inmore » adulthood. The degree of endoplasmic reticulum (ER) stress is one of the factors that determine GD severity. It has recently been reported that antioxidants reduce ER stress and apoptosis by scavenging the oxidants that cause oxidative stress. For this report, we investigated the possibility that catechin can act on type I GD patient cells to alleviate the pathogenic conditions of GD. We treated GD cells with catechin and examined the expression level of GRP78/BiP (an ER stress marker) by western blots and fluorescence microscopy, the proliferation rate of GD cells, and scratch-induced wound healing activity. Our results show that catechin reduces the expression level of GRP78/BiP, leads to cell proliferation rates of GD cells similar levels to normal cells, and improves wound healing activity. We conclude that catechin protects against ER stress in GD cells and catechin-mediated reductions in ER stress may be associated with enhanced cell survival.« less
Naidoo, Nirinjini; Davis, James G; Zhu, Jingxu; Yabumoto, Maya; Singletary, Kristan; Brown, Marishka; Galante, Raymond; Agarwal, Beamon; Baur, Joseph A
2014-01-01
Sleep disruption has detrimental effects on glucose metabolism through pathways that remain poorly defined. Although numerous studies have examined the consequences of sleep deprivation (SD) in the brain, few have directly tested its effects on peripheral organs. We examined several tissues in mice for induction of the unfolded protein response (UPR) following acute SD. In young animals, we found a robust induction of BiP in the pancreas, indicating an active UPR. At baseline, pancreata from aged animals exhibited a marked increase in a pro-apoptotic transcription factor, CHOP, that was amplified by SD, whereas BiP induction was not observed, suggesting a maladaptive response to cellular stress with age. Acute SD increased plasma glucose levels in both young and old animals. However, this change was not overtly related to stress in the pancreatic beta cells, as plasma insulin levels were not lower following acute SD. Accordingly, animals subjected to acute SD remained tolerant to a glucose challenge. In a chronic SD experiment, young mice were found to be sensitized to insulin and have improved glycemic control, whereas aged animals became hyperglycemic and failed to maintain appropriate plasma insulin concentrations. Our results show that both age and SD cooperate to induce the UPR in pancreatic tissue. While changes in insulin secretion are unlikely to play a major role in the acute effects of SD, CHOP induction in pancreatic tissues suggests that chronic SD may contribute to the loss or dysfunction of endocrine cells and that these effects may be exacerbated by normal aging. PMID:24102714
Absence of BiP co-chaperone DNAJC3 causes diabetes mellitus and multisystemic neurodegeneration.
Synofzik, Matthis; Haack, Tobias B; Kopajtich, Robert; Gorza, Matteo; Rapaport, Doron; Greiner, Markus; Schönfeld, Caroline; Freiberg, Clemens; Schorr, Stefan; Holl, Reinhard W; Gonzalez, Michael A; Fritsche, Andreas; Fallier-Becker, Petra; Zimmermann, Richard; Strom, Tim M; Meitinger, Thomas; Züchner, Stephan; Schüle, Rebecca; Schöls, Ludger; Prokisch, Holger
2014-12-04
Diabetes mellitus and neurodegeneration are common diseases for which shared genetic factors are still only partly known. Here, we show that loss of the BiP (immunoglobulin heavy-chain binding protein) co-chaperone DNAJC3 leads to diabetes mellitus and widespread neurodegeneration. We investigated three siblings with juvenile-onset diabetes and central and peripheral neurodegeneration, including ataxia, upper-motor-neuron damage, peripheral neuropathy, hearing loss, and cerebral atrophy. Exome sequencing identified a homozygous stop mutation in DNAJC3. Screening of a diabetes database with 226,194 individuals yielded eight phenotypically similar individuals and one family carrying a homozygous DNAJC3 deletion. DNAJC3 was absent in fibroblasts from all affected subjects in both families. To delineate the phenotypic and mutational spectrum and the genetic variability of DNAJC3, we analyzed 8,603 exomes, including 506 from families affected by diabetes, ataxia, upper-motor-neuron damage, peripheral neuropathy, or hearing loss. This analysis revealed only one further loss-of-function allele in DNAJC3 and no further associations in subjects with only a subset of the features of the main phenotype. Our findings demonstrate that loss-of-function DNAJC3 mutations lead to a monogenic, recessive form of diabetes mellitus in humans. Moreover, they present a common denominator for diabetes and widespread neurodegeneration. This complements findings from mice in which knockout of Dnajc3 leads to diabetes and modifies disease in a neurodegenerative model of Marinesco-Sjögren syndrome. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Penfluridol induces endoplasmic reticulum stress leading to autophagy in pancreatic cancer.
Ranjan, Alok; German, Nadezhda; Mikelis, Constantinos; Srivenugopal, Kalkunte; Srivastava, Sanjay K
2017-06-01
Pancreatic cancer is one of the most aggressive and difficult to treat cancers. Experimental and clinical evidence suggests that high basal state autophagy in pancreatic tumors could induce resistance to chemotherapy. Recently, we have demonstrated that penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis both in vitro and in vivo; however, the mechanism of autophagy induction by penfluridol was not clear. Several studies have established that endoplasmic reticulum stress could lead to autophagy and inhibit tumor progression. In this study, we demonstrated that penfluridol induced endoplasmic reticulum stress in BxPC-3, AsPC-1, and Panc-1 pancreatic cancer cell lines as indicated by upregulation of endoplasmic reticulum stress markers such as binding protein (BIP), C/EBP homologous protein (CHOP) and inositol requiring 1α (IRE1α) after treatment with penfluridol in a concentration-dependent manner. Inhibiting endoplasmic reticulum stress by pretreatment with pharmacological inhibitors such as sodium phenylbutyrate and mithramycin or by silencing CHOP using CHOP small interfering RNA, blocked penfluridol-induced autophagy. These results clearly indicate that penfluridol-induced endoplasmic reticulum stress lead to autophagy in our model. Western blot analysis of subcutaneously implanted AsPC-1 and BxPC-3 tumors as well as orthotopically implanted Panc-1 tumors demonstrated upregulation of BIP, CHOP, and IRE1α expression in the tumor lysates from penfluridol-treated mice as compared to tumors from control mice. Altogether, our study establishes that penfluridol-induced endoplasmic reticulum stress leads to autophagy resulting in reduced pancreatic tumor growth. Our study opens a new therapeutic target for advanced chemotherapies against pancreatic cancer.
Mutations of NOTCH3 in childhood pulmonary arterial hypertension
Chida, Ayako; Shintani, Masaki; Matsushita, Yoshihisa; Sato, Hiroki; Eitoku, Takahiro; Nakayama, Tomotaka; Furutani, Yoshiyuki; Hayama, Emiko; Kawamura, Yoichi; Inai, Kei; Ohtsuki, Shinichi; Saji, Tsutomu; Nonoyama, Shigeaki; Nakanishi, Toshio
2014-01-01
Mutations of BMPR2 and other TGF-β superfamily genes have been reported in pulmonary arterial hypertension (PAH). However, 60–90% of idiopathic PAH cases have no mutations in these genes. Recently, the expression of NOTCH3 was shown to be increased in the pulmonary artery smooth muscle cells of PAH patients. We sought to investigate NOTCH3 and its target genes in PAH patients and clarify the role of NOTCH3 signaling. We screened for mutations in NOTCH3, HES1, and HES5 in 41 PAH patients who had no mutations in BMPR2, ALK1, endoglin, SMAD1/4/8, BMPR1B, or Caveolin-1. Two novel missense mutations (c.2519 G>A p.G840E, c.2698 A>C p.T900P) in NOTCH3 were identified in two PAH patients. We performed functional analysis using stable cell lines expressing either wild-type or mutant NOTCH3. The protein-folding chaperone GRP78/BiP was colocalized with wild-type NOTCH3 in the endoplasmic reticulum, whereas the majority of GRP78/BiP was translocated into the nuclei of cells expressing mutant NOTCH3. Cell proliferation and viability were higher for cells expressing mutant NOTCH3 than for those expressing wild-type NOTCH3. We identified novel NOTCH3 mutations in PAH patients and revealed that these mutations were involved in cell proliferation and viability. NOTCH3 mutants induced an impairment in NOTCH3-HES5 signaling. The results may contribute to the elucidation of PAH pathogenesis. PMID:24936512
Timko, Christine; Valenstein, Helen; Stuart, Gregory L; Moos, Rudolf H
2015-11-01
The association between substance abuse and intimate partner violence is quite robust. A promising area to improve treatment for the dual problems of substance abuse and violence perpetration is the identification of client characteristics and organisational and programme factors as predictors of health outcomes. Therefore, we examined associations of client, organisational and programme factors with outcomes in community health settings. Directors of 241 substance use disorder programmes (SUDPs) and 235 batterer intervention programmes (BIPs) reported outcomes of programme completion and substance use and violence perpetration rates at discharge; data collection and processing were completed in 2012. SUDPs having more female, non-white, younger, uneducated, unemployed and lower income clients reported lower completion rates. In SUDPs, private, for-profit programmes reported higher completion rates than public or private, non-profit programmes. SUDPs with lower proportions of their budgets from government sources, and higher proportions from client fees, reported better outcomes. Larger SUDPs had poorer programme completion and higher substance use rates. Completion rates in SUDPs were higher when clients could obtain substance- and violence-related help at one location, and programmes integrated violence-prevention contracting into care. In BIPs, few client, organisational and programme factors were associated with outcomes, but the significant factors associated with programme completion were consistent with those for SUDPs. Publicly owned and larger programmes, and SUDPs lacking staff to integrate violence-related treatment, may be at risk of poorer client outcomes, but could learn from programmes that perform well to yield better outcomes. © 2014 John Wiley & Sons Ltd.
Lu, Yuwen; Yin, Mingyuan; Wang, Xiaodan; Chen, Binghua; Yang, Xue; Peng, Jiejun; Zheng, Hongying; Zhao, Jinping; Lin, Lin; Yu, Chulang; MacFarlane, Stuart; He, Jianqing; Liu, Yong; Chen, Jianping; Dai, Liangying; Yan, Fei
2016-06-01
Garlic virus X (GarVX) ORF3 encodes a p11 protein, which contributes to virus cell-to-cell movement and forms granules on the endoplasmic reticulum (ER) in Nicotiana benthamiana. Expression of p11 either from a binary vector, PVX or TMV induced ER stress and the unfolded protein response (UPR), as demonstrated by an increase in transcription of the ER luminal binding protein (BiP) and bZIP60 genes. UPR-related programmed cell death (PCD) was elicited by PVX : p11 or TMV : p11 in systemic infected leaves. Examination of p11 mutants with deletions of two transmembrane domains (TM) revealed that both were required for generating granules and for inducing necrosis. TRV-based VIGS was used to investigate the correlation between bZIP60 expression and p11-induced UPR-related PCD. Less necrosis was observed on local and systemic leaves of bZIP60 knockdown plants when infected with PVXp11, suggesting that bZIP60 plays an important role in the UPR-related PCD response to p11 in N. benthamiana.
Ruetzel, Stefan; Diekmann, Meike; Nuernberger, Patrick; Walter, Christof; Engels, Bernd; Brixner, Tobias
2014-06-14
Upon ultraviolet excitation, photochromic spiropyran compounds can be converted by a ring-opening reaction into merocyanine molecules, which in turn can form several isomers differing by cis and trans configurations in the methine bridge. Whereas the spiropyran-merocyanine conversion reaction of the nitro-substituted indolinobenzopyran 6-nitro-1',3',3'-trimethylspiro[2H-1-benzopyran-2,2'-indoline] (6-nitro BIPS) has been studied extensively in theory and experiments, little is known about photoisomerization among the merocyanine isomers. In this article, we employ femtosecond transient absorption spectroscopy with variable excitation wavelengths to investigate the excited-state dynamics of the merocyanine in acetonitrile at room temperature, where exclusively the trans-trans-cis (TTC) and trans-trans-trans (TTT) isomers contribute. No photochemical ring-closure pathways exist for the two isomers. Instead, we found that (18±4)% of excited TTC isomers undergo an ultrafast excited-state cis→trans photoisomerization to TTT within 200 fs, while the excited-state lifetime of TTC molecules that do not isomerize is 35 ps. No photoisomerization was detected for the TTT isomer, which relaxes to the ground state with a lifetime of roughly 160 ps. Moreover, signal oscillations at 170 cm(-1) and 360 cm(-1) were observed, which can be ascribed to excited-state wave-packet dynamics occurring in the course of the TTC→TTT isomerization. The results of high-level time-dependent density functional theory in conjunction with polarizable continuum models are presented in the subsequent article [C. Walter, S. Ruetzel, M. Diekmann, P. Nuernberger, T. Brixner, and B. Engels, J. Chem. Phys. 140, 224311 (2014)].
NASA Astrophysics Data System (ADS)
Sagar, Elle; Mahesh, R.; Pavan Kumar, N.; Venugopal Reddy, P.
2017-11-01
Electronic band structure, ferroelectric and ferromagnetic properties of Cubic, Tetragonal and Rhombohedral (hexagonal axis) phases of multiferroic BiFeO3 compound has been investigated using first-principles calculations under the generalized gradient (GGA) and TB-mBJ semi local (Tran-Blaha modified Becke-Johnson) potential approximations using WIEN2k code. For this purpose, the total energies were calculated as a function of reduced volumes and the data were fitted to Brich Murnaghan equation. The estimated ground state parameters are found to be comparable with those of experimental ones. The semiconducting behavior of the material was obtained using TB-mBJ method in the spin polarized mode. Analysis of the density of states indicates that the valence band consists of Fe-d and O-p states, while the conduction band is composed of Fe-d and Bi-p states. The analysis of electron localization function shows that stereochemically active lone-pair electrons are present at Bi sites of Rhombohedral and Tetragonal phases and are responsible for the displacements of Bi atoms from the centro-symmetric to the non-centrosymmetric structure leading to the exhibition of ferroelectricity. Further, it has been concluded that the "lone pair" may have been formed due to the hybridization of 6s and 6p atomic orbitals with 6s2 electrons filling one of the resulting orbitals in Bi. The Polarization and the magnetic properties including susceptibility were obtained. The calculated magnetic moments at the iron sites are not integer values, since Fe electrons have a hybridization interaction with the neighboring O ions.
NASA Astrophysics Data System (ADS)
Zhang, Qiangying; He, Man; Chen, Beibei; Hu, Bin
2016-07-01
This paper deals with preparation, characterization and application of the Saussurea tridactyla Sch-Bip (STSB) as a new green adsorbent for separation of matrix elements and preconcentration of rare earth elements (REEs) in environmental water samples. The pretreated STSB adsorbent with 2 mol L- 1 NaOH is characterized with higher surface area and adsorption capacities in comparison with a raw STSB material. The new adsorbent was used for the development of on-line solid phase extraction (SPE) for the determination of REEs by radial viewing 27 MHz inductively coupled plasma optical emission spectrometry (ICP-OES). Various parameters affecting the adsorption/desorption procedure were optimized. The adsorption capacities for the STSB were found to be 62.2 (Y)-153 mg g- 1 (Tm). Under the optimized conditions, the limits of detection (LODs, 3σ) for REEs were in the range of 0.06 (Yb)-8.77 (Sm) ng mL- 1. The relative standard deviations (RSDs) for 7 replicate determinations of target REEs at low concentration level ranged from 2.4 (Yb) to 8.9 (Sm)%. The adsorption isotherm fitted Langmuir model and the adsorption kinetics fitted well with both Pseudo-first order and Pseudo-second order models. The predominant adsorption mechanism is ion exchange. The STSB pretreated with 2 mol L- 1 NaOH has been demonstrated to be low cost, green and environment friendly adsorbent, featuring with high adsorption capacity, wide pH range, and fast adsorption/desorption kinetics for target REEs with long lifetime. The proposed method was applied to the determination of REEs in East Lake, Yangtze River and rain water samples.
Hofer, Patrizia D; Wahl, Karina; Meyer, Andrea H; Miché, Marcel; Beesdo-Baum, Katja; Wong, Shiu F; Grisham, Jessica R; Wittchen, Hans-Ulrich; Lieb, Roselind
2018-04-01
Comorbidity of obsessive-compulsive disorder (OCD) with other mental disorders has been demonstrated repeatedly. Few longitudinal studies, however, have evaluated the temporal association of prior OCD and subsequent mental disorders across the age period of highest risk for first onset of mental disorders. We examined associations between prior OCD and a broad range of subsequent mental disorders and simulated proportions of new onsets of mental disorders that could potentially be attributed to prior OCD, assuming a causal relationship. Data from 3,021 14- to 24-year-old community subjects were prospectively collected for up to 10 years. DSM-IV OCD and other DSM-IV mental disorders were assessed with the Munich-Composite International Diagnostic Interview. We used adjusted time-dependent proportional hazard models to estimate the temporal associations of prior OCD with subsequent mental disorders. Prior OCD was associated with an increased risk of bipolar disorders (BIP; [hazard ratio, HR = 6.9, 95% confidence interval, CI, (2.8,17.3)], bulimia nervosa [HR = 6.8 (1.3,36.6)], dysthymia [HR = 4.4 (2.1,9.0)], generalized anxiety disorder (GAD; [HR = 3.4 (1.1,10.9)], and social phobia [HR = 2.9 (1.1,7.7)]). Of these outcome disorders, between 65 and 85% could be attributed to OCD in the exposed group, whereas between 1.5 and 7.7% could be attributed to OCD in the total sample. This study provides strong evidence that prior OCD is associated with an increased risk of subsequent onset of BIP, bulimia nervosa, dysthymia, GAD, and social phobia among adolescents and young adults. Future studies should evaluate if early treatment of OCD can prevent the onset of these subsequent mental disorders. © 2018 Wiley Periodicals, Inc.
Zhu, Xiaoling; Jiang, Shasha; Hu, Nan; Luo, Fuling; Dong, Hailong; Kang, Yu-Ming; Jones, Kyla R; Zou, Yunzeng; Xiong, Lize; Ren, Jun
2014-07-01
Lenalidomide (Revlimid; Selleck Chemicals, Houston, TX, USA), an analogue of thalidomide, possesses potent cytokine modulatory capacity through inhibition of cytokines such as tumour necrosis factor (TNF)-α, a cytokine pivotal for the onset and development of complications in obesity and diabetes mellitus. The present study was designed to evaluate the effect of lenalidomide on oxidative stress, protein and DNA damage in multiple organs in an ob/ob murine model of obesity. To this end, C57BL/6 lean and ob/ob obese mice were administered lenalidomide (50 mg/kg per day, p.o.) for 5 days. Oxidative stress, protein and DNA damage were assessed using the conversion of reduced glutathione (GSH) to oxidized glutathione (GSSG), carbonyl formation and Comet assay, respectively. Apoptosis was evaluated using caspase 3 activity, and levels of Bax, Bcl-2, Bip, caspase 8, caspase 9 and TNF-α were assessed using western blot analysis. Lenalidomide treatment did not affect glucose clearance in lean or ob/ob mice. Obese mice exhibited a reduced GSH/GSSG ratio in the liver, gastrocnemius skeletal muscle and small intestine, as well as enhanced protein carbonyl formation, DNA damage and caspase 3 activity in the liver, kidney, skeletal muscle and intestine; these effects were alleviated by lenalidomide, with the exception of obesity-associated DNA damage in the liver and kidney. Western blot analysis revealed elevated TNF-α, Bax, Bcl-2, Bip, caspase 8 and caspase 9 in ob/ob mice with various degrees of reversal by lenalidomide treatment. Together, these data indicate that lenalidomide protects against obesity-induced tissue injury and protein damage, possibly in association with antagonism of cytokine production and cytokine-induced apoptosis and oxidative stress. © 2014 Wiley Publishing Asia Pty Ltd.
4-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress.
Zheng, Peili; Lin, Yu; Wang, Feifei; Luo, Renfei; Zhang, Tiezheng; Hu, Shan; Feng, Pinning; Liang, Xinling; Li, Chunling; Wang, Weidong
2016-10-01
Endoplasmic reticulum (ER) stress has been implicated in some types of glomerular and tubular disorders. The objectives of this study were to elucidate the role of ER stress in lithium-induced nephrogenic diabetes insipidus (NDI) and to investigate whether attenuation of ER stress by 4-phenylbutyric acid (4-PBA) improves urinary concentrating defect in lithium-treated rats. Wistar rats received lithium (40 mmol/kg food), 4-PBA (320 mg/kg body wt by gavage every day), or no treatment (control) for 2 wk, and they were dehydrated for 24 h before euthanasia. Lithium treatment resulted in increased urine output and decreased urinary osmolality, which was significantly improved by 4-PBA. 4-PBA also prevented reduced protein expression of aquaporin-2 (AQP2), pS256-AQP2, and pS261-AQP2 in the inner medulla of kidneys from lithium-treated rats after 24-h dehydration. Lithium treatment resulted in increased expression of ER stress markers in the inner medulla, which was associated with dilated cisternae and expansion of ER in the inner medullary collecting duct (IMCD) principal cells. Confocal immunofluorescence studies showed colocalization of a molecular chaperone, binding IgG protein (BiP), with AQP2 in principal cells. Immunohistochemistry demonstrated increased intracellular expression of BiP and decreased AQP2 expression in IMCD principal cells of kidneys from lithium-treated rats. 4-PBA attenuated expression of ER stress markers and recovered ER morphology. In IMCD suspensions isolated from lithium-treated rats, 4-PBA incubation was also associated with increased AQP2 expression and ameliorated ER stress. In conclusion, in experimental lithium-induced NDI, 4-PBA improved the urinary concentrating defect and increased AQP2 expression, likely via attenuating ER stress in IMCD principal cells. Copyright © 2016 the American Physiological Society.
Polatoğlu, Kaan; Karakoç, Ömer Cem; Demirci, Betül; Gören, Nezhun; Can Başer, Kemal Hüsnü
2015-01-01
Insecticides of the natural origin are an important alternative to the synthetic insecticides that are being employed for the preserving stored products. The volatiles obtained from T. cinerariifolium (=Pyrethrum cinerariifolium) is being used for many types of insecticidal applications; however there is a very little information on the insecticidal activity of the essential oils of other Tanacetum species. The main purpose of the present study is to determine the chemical composition of T. macrophyllum (Waldst. & Kit.) Schultz Bip. essential oils and evaluate their insecticidal activity against S. granarius as well as its other beneficial biological activities. Highest contact toxicity was observed in the leaf oil of (88.93%) against S. granarius. The flower oil showed considerable fumigant toxicity against L. minor at 10 mg/mL application concentration (61.86 %) when compared with other samples at the same concentration. The highest DPPH (2,2-Diphenyl-1-picrylhydrazyl) scavenging activity (47.7%) and phosphomolybdenum reducing activity was observed also for the flower oil of T. macrophyllum at 10 mg/mL concentration. The essential oils were analyzed by GC, GC/MS. The flower and leaf oils were characterized with γ-eudesmol 21.5%, (E)-sesquilavandulol 20.3%, copaborneol 8.5% and copaborneol 14.1%, 1,8-cineole 11%, bornyl acetate 9.6%, borneol 6.3% respectively. AHC analysis of the qualitative and quantitative data obtained from the essential oil composition of the T. macrophyllum essential oil from the present research and previous reports pointed out that two different chemotypes could be proposed with current findings which are p-methyl benzyl alcohol/ cadinene and eudesmane chemotypes.
Can Data be Organized for Science and Reuse?
NASA Astrophysics Data System (ADS)
Habermann, T.; Shasharina, S.; Jelenak, A.; Fillmore, D. W.
2015-12-01
The Data Life Cycle is an important general concept for thinking about data collection, management, and preservation practices across the geophysical scientific data community. The cycle generally spans the scientific process from ideation, through experimental design, observation collection, data analysis and visualization, publication, archive, distributions and eventual reuse. During the cycle, the data may change through new analyses, presentations, and responsible parties, but, historically, the format and organization of the data have generally remained the same. Data collected as a time series at a point remains as a time series and data collected/calculated as grids remains as grids. BIP is BIP and BSQ is BSQ. In fact, in many large data centers, the native format remains sacrosanct and, in the scientific community, reformatting is avoided because of fear of losing information or introducing data quality problems and irreproducible results. This traditional approach has worked well in areas where data are collected and used for a single purpose throughout the life cycle and domains where comparisons across different data sets are rare and problematic due to conflicting data organizational structures or incomplete documentation. This is not the world we live in today. Reuse for unexpected purposes and data (and model) comparisons are becoming increasingly common (e.g. climate model / observation comparisons). Data sets are preserved for future global investigators that may be unaware of the original project or purpose of the data. Also, it is becoming more common for data to be restructured and reformatted for particular problem or to support a flexible web service. Unfortunately, many of these efforts do not preserve the metadata that, hopefully, accompanies the data in the original format. In this presentation we will discuss alternative approaches to data management that will facilitate data reuse across teams and disciplines.
Kubisch, Constanze H; Logsdon, Craig D
2007-06-01
Endoplasmic reticulum (ER) stress leads to the accumulation of misfolded proteins in the ER lumen and initiates the unfolded protein response (UPR). Components of the UPR are important in pancreatic development, and recent studies have indicated that the UPR is activated in the arginine model of acute pancreatitis. However, the effects of secretagogues on UPR components in the pancreas are unknown. The present study aimed to examine the effects of different types and concentrations of secretagogues on acinar cell function and specific components of the UPR. Rat pancreatic acini were stimulated with the CCK analogs CCK8 (10 pM-10 nM) or JMV-180 (10 nM-10 microM) or with bombesin (1-100 nM). Components of the UPR, including chaperone BiP expression, PKR-like ER kinase (PERK) phosphorylation, X box-binding protein 1 (XBP1) splicing, and CCAAT/enhancer binding protein homologous protein (CHOP) expression, were measured, as were effects on amylase secretion and intracellular trypsin activation. CCK8 generated a biphasic secretion dose-response curve, and high concentrations increased intracellular active trypsin levels. In contrast, JMV-180 and bombesin secretion dose-response curves were monophasic, and high concentrations did not increase intracellular trypsin activity. All three secretagogues increased BiP levels and XBP1 splicing. However, only supraphysiological levels of CCK8 associated with inhibited amylase secretion and trypsin activation stimulated PERK phosphorylation and expression of CHOP. The effects of CCK8 on UPR components were rapid, occurring within 5-20 min. In conclusion, ER stress response mechanisms appear to be involved in both pancreatic physiology and pathophysiology, and future efforts should be directed at understanding the roles of these mechanisms in the pancreas.
Buffington, Brenda C; Melnyk, Bernadette M; Morales, Shelly; Lords, Amanda; Zupan, Michael R
2016-04-01
Female athletes struggle harder than male athletes to lose body fat and maintain a leaner physique. The purpose of this study was to determine the effects of an educational and cognitive behavioral therapy (CBT)-based intervention on knowledge, body composition, anxiety, stress, and nutritional intake. A randomized controlled trial was conducted with 153 female athletes from the U.S. Air Force Academy (USAFA). Participants were assigned to one of three groups: (a) a combined energy balance and CBT-based intervention (E1); (b) a CBT-based intervention alone (E2); and (c) a control group (C). Main outcomes included a DXA scan for body composition, a knowledge test, the GAD-7 for anxiety, the brief inventory of perceived stress (BIPS) for stress, and a 24-h food recall. Significant improvement on knowledge of energy balance occurred in all three groups E1 (p < .001), E2, and C (p < .05). Significant reductions in percentage of body fat occurred in E1 (p < .001) and E2 (p < .05). There also were significant reductions in the percent of fat consumed by E1 (p < .05) and saturated fat consumed by both E1 and E2 (p < .05). The control group only demonstrated a significant increase in stress as measured by the BIPS (p < .05). A combined energy balance and CBT-based intervention improves knowledge and body fat. The importance to assess knowledge, anxiety, stress, nutrition intake, and percentage of body fat in female athletes and to deliver evidence-based interventions to improve their health outcomes. ©2016 American Association of Nurse Practitioners.
Park, Hyo-Jin; Park, Sun-Ji; Koo, Deog-Bon; Lee, Sang-Rae; Kong, Il-Keun; Ryoo, Jae-Woong; Park, Young-Il; Chang, Kyu-Tae; Lee, Dong-Seok
2014-09-15
We examined whether the three unfolded protein response (UPR) signaling pathways, which are activated in response to endoplasmic reticulum (ER)-stress, are involved in progesterone production in the luteal cells of the corpus luteum (CL) during the mouse estrous cycle. The luteal phase of C57BL/6 female mice (8 weeks old) was divided into two stages: the functional stage (16, 24, and 48 h) and the regression stage (72 and 96 h). Western blotting and reverse transcription (RT)-PCR were performed to analyze UPR protein/gene expression levels in each stage. We investigated whether ER stress affects the progesterone production by using Tm (0.5 μg/g BW) or TUDCA (0.5 μg/g BW) through intra-peritoneal injection. Our results indicate that expressions of Grp78/Bip, p-eIF2α/ATF4, p50ATF6, and p-IRE1/sXBP1 induced by UPR activation were predominantly maintained in functional and early regression stages of the CL. Furthermore, the expression of p-JNK, CHOP, and cleaved caspase3 as ER-stress mediated apoptotic factors increased during the regression stage. Cleaved caspase3 levels increased in the late-regression stage after p-JNK and CHOP expression in the early-regression stage. Additionally, although progesterone secretion and levels of steroidogenic enzymes decreased following intra-peritoneal injection of Tunicamycin, an ER stress inducer, the expression of Grp78/Bip, p50ATF6, and CHOP dramatically increased. These results suggest that the UPR signaling pathways activated in response to ER stress may play important roles in the regulation of the CL function. Furthermore, our findings enhance the understanding of the basic mechanisms affecting the CL life span. Copyright © 2014 Elsevier Inc. All rights reserved.
Sulfur mustard induces an endoplasmic reticulum stress response in the mouse ear vesicant model
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chang, Yoke-Chen; Wang, James D.; Svoboda, Kathy K.
The endoplasmic reticulum (ER) stress response is a cell survival pathway upregulated when cells are under severe stress. Severely damaged mouse ear skin exposed to the vesicant, sulfur mustard (bis-2-chloroethyl sulfide, SM), resulted in increased expression of ER chaperone proteins that accompany misfolded and incorrectly made proteins targeted for degradation. Time course studies with SM using the mouse ear vesicant model (MEVM) showed progressive histopathologic changes including edema, separation of the epidermis from the dermis, persistent inflammation, upregulation of laminin γ2 (one of the chains of laminin-332, a heterotrimeric skin glycoprotein required for wound repair), and delayed wound healing frommore » 24 h to 168 h post exposure. This was associated with time related increased expression of the cell survival ER stress marker, GRP78/BiP, and the ER stress apoptosis marker, GADD153/CHOP, suggesting simultaneous activation of both cell survival and non-mitochondrial apoptosis pathways. Dual immunofluorescence labeling of a keratinocyte migration promoting protein, laminin γ2 and GRP78/BIP, showed colocalization of the two molecules 72 h post exposure indicating that the laminin γ2 was misfolded after SM exposure and trapped within the ER. Taken together, these data show that ER stress is induced in mouse skin within 24 h of vesicant exposure in a defensive response to promote cell survival; however, it appears that this response is rapidly overwhelmed by the apoptotic pathway as a consequence of severe SM-induced injury. - Highlights: ► We demonstrated ER stress response in the mouse ear vesicant model. ► We described the asymmetrical nature of wound repair in the MEVM. ► We identified the distribution of various ER stress markers in the MEVM.« less
Mini-BRU/BIPS foil bearing development
NASA Technical Reports Server (NTRS)
Dobler, F. X.; Miller, L. J.
1978-01-01
The analysis revealed the failure agent to be a combination of poor teflon coating adhesion, a decrease in bearing sway space and, possibly, lack of flushing flow through the bearing. A change in Teflon coating vendors provided substantially improved coating quality and surface finish. The sway space was increased and the cooling bleed flow was adjusted to flush the bearing. These changes were included in a test conducted in the WHL from 6 April to 22 May 1978 which resulted in the completion of 1006.9 hours of operation at temperature and load. Post-test inspection revealed the bearings to be in excellent condition and capable of completing a much longer test.
van Lith, Marcel; Karala, Anna-Riikka; Bown, Dave; Gatehouse, John A.; Ruddock, Lloyd W.; Saunders, Philippa T.K.
2007-01-01
Glycoprotein folding is mediated by lectin-like chaperones and protein disulfide isomerases (PDIs) in the endoplasmic reticulum. Calnexin and the PDI homologue ERp57 work together to help fold nascent polypeptides with glycans located toward the N-terminus of a protein, whereas PDI and BiP may engage proteins that lack glycans or have sugars toward the C-terminus. In this study, we show that the PDI homologue PDILT is expressed exclusively in postmeiotic male germ cells, in contrast to the ubiquitous expression of many other PDI family members in the testis. PDILT is induced during puberty and represents the first example of a PDI family member under developmental control. We find that PDILT is not active as an oxido-reductase, but interacts with the model peptide Δ-somatostatin and nonnative bovine pancreatic trypsin inhibitor in vitro, indicative of chaperone activity. In vivo, PDILT forms a tissue-specific chaperone complex with the calnexin homologue calmegin. The identification of a redox-inactive chaperone partnership defines a new system of testis-specific protein folding with implications for male fertility. PMID:17507649
40 CFR 265.91 - Ground-water monitoring system.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Ground-water monitoring system. 265.91... DISPOSAL FACILITIES Ground-Water Monitoring § 265.91 Ground-water monitoring system. (a) A ground-water monitoring system must be capable of yielding ground-water samples for analysis and must consist of: (1...
40 CFR 265.91 - Ground-water monitoring system.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Ground-water monitoring system. 265.91... DISPOSAL FACILITIES Ground-Water Monitoring § 265.91 Ground-water monitoring system. (a) A ground-water monitoring system must be capable of yielding ground-water samples for analysis and must consist of: (1...
40 CFR 265.91 - Ground-water monitoring system.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Ground-water monitoring system. 265.91... DISPOSAL FACILITIES Ground-Water Monitoring § 265.91 Ground-water monitoring system. (a) A ground-water monitoring system must be capable of yielding ground-water samples for analysis and must consist of: (1...
40 CFR 265.91 - Ground-water monitoring system.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Ground-water monitoring system. 265.91... DISPOSAL FACILITIES Ground-Water Monitoring § 265.91 Ground-water monitoring system. (a) A ground-water monitoring system must be capable of yielding ground-water samples for analysis and must consist of: (1...
Berns, U; Hemprich, L
2001-01-01
In No. 8, 48th year, August 1998, of the journal "Psychotherapie--Psychosomatik--Medizinische Psychologie" the tape recorder transcription of the 290th session of a long-term analysis was studied by three methods (BIP, Frames, ZBKT). The paper presented here was stimulated by this publication. From the author's viewpoint substantial clinical aspects of evaluation could be added by applying a clinical evaluation method developed by R. Langs and his corresponding concept of interpretation. Clinical vignettes exemplify the possibility to resolve pathological countertransference by using this evaluation method. With the help of this method the presented transcription of the 290th session is evaluated partially.
46 CFR 111.05-21 - Ground detection.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 4 2011-10-01 2011-10-01 false Ground detection. 111.05-21 Section 111.05-21 Shipping... REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-21 Ground detection. There must be ground detection for each: (a) Electric propulsion system; (b) Ship's service power system; (c...
46 CFR 111.05-21 - Ground detection.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 4 2010-10-01 2010-10-01 false Ground detection. 111.05-21 Section 111.05-21 Shipping... REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-21 Ground detection. There must be ground detection for each: (a) Electric propulsion system; (b) Ship's service power system; (c...
Facility Systems, Ground Support Systems, and Ground Support Equipment General Design Requirements
NASA Technical Reports Server (NTRS)
Thaxton, Eric A.; Mathews, Roger E.
2014-01-01
This standard establishes requirements and guidance for design and fabrication of ground systems (GS) that includes: ground support equipment (GSE), ground support systems (GSS), and facility ground support systems (F GSS) to provide uniform methods and processes for design and development of robust, safe, reliable, maintainable, supportable, and cost-effective GS in support of space flight and institutional programs and projects.
46 CFR 111.05-13 - Grounding connection.
Code of Federal Regulations, 2010 CFR
2010-10-01
... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-13 Grounding... power sources operating in parallel in the system. ...
46 CFR 129.375 - System grounding.
Code of Federal Regulations, 2014 CFR
2014-10-01
... Power Sources and Distribution Systems § 129.375 System grounding. (a) If a grounded distribution system is provided, there must be only one connection to ground, regardless of the number of power sources. This connection must be at the main switchboard. (b) On each metallic vessel, a grounded distribution...
46 CFR 129.375 - System grounding.
Code of Federal Regulations, 2013 CFR
2013-10-01
... Power Sources and Distribution Systems § 129.375 System grounding. (a) If a grounded distribution system is provided, there must be only one connection to ground, regardless of the number of power sources. This connection must be at the main switchboard. (b) On each metallic vessel, a grounded distribution...
46 CFR 129.375 - System grounding.
Code of Federal Regulations, 2012 CFR
2012-10-01
... Power Sources and Distribution Systems § 129.375 System grounding. (a) If a grounded distribution system is provided, there must be only one connection to ground, regardless of the number of power sources. This connection must be at the main switchboard. (b) On each metallic vessel, a grounded distribution...
46 CFR 111.05-27 - Grounded neutral alternating current systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... the ground connection, is able to withstand the maximum available fault current without damage, and... 46 Shipping 4 2011-10-01 2011-10-01 false Grounded neutral alternating current systems. 111.05-27... Grounded neutral alternating current systems. Grounded neutral and high-impedance grounded neutral...
46 CFR 111.05-27 - Grounded neutral alternating current systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
... the ground connection, is able to withstand the maximum available fault current without damage, and... 46 Shipping 4 2010-10-01 2010-10-01 false Grounded neutral alternating current systems. 111.05-27... Grounded neutral alternating current systems. Grounded neutral and high-impedance grounded neutral...
47 CFR 22.873 - Construction requirements for commercial aviation air-ground systems.
Code of Federal Regulations, 2014 CFR
2014-10-01
... aviation air-ground systems. 22.873 Section 22.873 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... Aviation Air-Ground Systems § 22.873 Construction requirements for commercial aviation air-ground systems. Licensees authorized to use more than one megahertz (1 MHz) of the 800 MHz commercial aviation air-ground...
47 CFR 22.873 - Construction requirements for commercial aviation air-ground systems.
Code of Federal Regulations, 2012 CFR
2012-10-01
... aviation air-ground systems. 22.873 Section 22.873 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... Aviation Air-Ground Systems § 22.873 Construction requirements for commercial aviation air-ground systems. Licensees authorized to use more than one megahertz (1 MHz) of the 800 MHz commercial aviation air-ground...
47 CFR 22.873 - Construction requirements for commercial aviation air-ground systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... aviation air-ground systems. 22.873 Section 22.873 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... Aviation Air-Ground Systems § 22.873 Construction requirements for commercial aviation air-ground systems. Licensees authorized to use more than one megahertz (1 MHz) of the 800 MHz commercial aviation air-ground...
47 CFR 22.873 - Construction requirements for commercial aviation air-ground systems.
Code of Federal Regulations, 2013 CFR
2013-10-01
... aviation air-ground systems. 22.873 Section 22.873 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... Aviation Air-Ground Systems § 22.873 Construction requirements for commercial aviation air-ground systems. Licensees authorized to use more than one megahertz (1 MHz) of the 800 MHz commercial aviation air-ground...
30 CFR 75.705-11 - Use of grounded messenger wires; ungrounded systems.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Use of grounded messenger wires; ungrounded....705-11 Use of grounded messenger wires; ungrounded systems. Solely for purposes of grounding ungrounded high-voltage power systems, grounded messenger wires used to suspend the cables of such systems...
30 CFR 75.705-11 - Use of grounded messenger wires; ungrounded systems.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Use of grounded messenger wires; ungrounded....705-11 Use of grounded messenger wires; ungrounded systems. Solely for purposes of grounding ungrounded high-voltage power systems, grounded messenger wires used to suspend the cables of such systems...
40 CFR 258.51 - Ground-water monitoring systems.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Ground-water monitoring systems. 258... CRITERIA FOR MUNICIPAL SOLID WASTE LANDFILLS Ground-Water Monitoring and Corrective Action § 258.51 Ground-water monitoring systems. (a) A ground-water monitoring system must be installed that consists of a...
40 CFR 258.51 - Ground-water monitoring systems.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Ground-water monitoring systems. 258.51... FOR MUNICIPAL SOLID WASTE LANDFILLS Ground-Water Monitoring and Corrective Action § 258.51 Ground-water monitoring systems. (a) A ground-water monitoring system must be installed that consists of a...
40 CFR 257.22 - Ground-water monitoring systems.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Ground-water monitoring systems. 257... Waste Disposal Units Ground-Water Monitoring and Corrective Action § 257.22 Ground-water monitoring systems. (a) A ground-water monitoring system must be installed that consists of a sufficient number of...
40 CFR 258.51 - Ground-water monitoring systems.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Ground-water monitoring systems. 258... CRITERIA FOR MUNICIPAL SOLID WASTE LANDFILLS Ground-Water Monitoring and Corrective Action § 258.51 Ground-water monitoring systems. (a) A ground-water monitoring system must be installed that consists of a...
40 CFR 257.22 - Ground-water monitoring systems.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Ground-water monitoring systems. 257... Waste Disposal Units Ground-Water Monitoring and Corrective Action § 257.22 Ground-water monitoring systems. (a) A ground-water monitoring system must be installed that consists of a sufficient number of...
30 CFR 77.704-11 - Use of grounded messenger wires; ungrounded systems.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Use of grounded messenger wires; ungrounded... AREAS OF UNDERGROUND COAL MINES Grounding § 77.704-11 Use of grounded messenger wires; ungrounded systems. Solely for purposes of grounding ungrounded high-voltage power systems, grounded messenger wires...
30 CFR 77.704-11 - Use of grounded messenger wires; ungrounded systems.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Use of grounded messenger wires; ungrounded... AREAS OF UNDERGROUND COAL MINES Grounding § 77.704-11 Use of grounded messenger wires; ungrounded systems. Solely for purposes of grounding ungrounded high-voltage power systems, grounded messenger wires...
Hypoxia-inducible factor-1 signalling promotes goblet cell hyperplasia in airway epithelium
Polosukhin, Vasiliy V; Cates, Justin M; Lawson, William E; Milstone, Aaron P; Matafonov, Anton G; Massion, Pierre P; Lee, Jae Woo; Randell, Scott H; Blackwell, Timothy S
2018-01-01
Goblet cell hyperplasia is a common feature of chronic obstructive pulmonary disease (COPD) airways, but the mechanisms that underlie this epithelial remodelling in COPD are not understood. Based on our previous finding of hypoxia-inducible factor-1α (HIF-1α) nuclear localization in large airways from patients with COPD, we investigated whether hypoxia-inducible signalling could influence the development of goblet cell hyperplasia. We evaluated large airway samples obtained from 18 lifelong non-smokers and 13 former smokers without COPD, and 45 former smokers with COPD. In these specimens, HIF-1α nuclear staining occurred almost exclusively in COPD patients in areas of airway remodelling. In COPD patients, 93.2 ± 3.9% (range 65 – 100%) of goblet cells were HIF-1α positive in areas of goblet cell hyperplasia, whereas nuclear HIF-1α was not detected in individuals without COPD or in normal-appearing pseudostratified epithelium from COPD patients. To determine the direct effects of hypoxia-inducible signalling on epithelial cell differentiation in vitro, human bronchial epithelial cells (HBECs) were grown in air-liquid interface cultures under hypoxia (1% O2) or following treatment with a selective HIF-1α stabilizer, (2R)-[(4-biphenylylsulphonyl)amino]-N-hydroxy-3-phenyl-propionamide (BiPS). HBECs grown in hypoxia or with BiPS treatment were characterized by HIF-1α activation, carbonic anhydrase IX expression, mucus-producing cell hyperplasia and increased expression of MUC5AC. Analysis of signal transduction pathways in cells with HIF-1α activation showed increased ERK1/2 phosphorylation without activation of epidermal growth factor receptor, Ras, PI3K-Akt or STAT6. These data indicate an important effect of hypoxia-inducible signalling on airway epithelial cell differentiation and identify a new potential target to limit mucus production in COPD. PMID:21557221
Composite Resin Dosimeters: A New Concept and Design for a Fibrous Color Dosimeter.
Kinashi, Kenji; Iwata, Takato; Tsuchida, Hayato; Sakai, Wataru; Tsutsumi, Naoto
2018-04-11
Polystyrene (PS)-based composite microfibers combined with a photochromic spiropyran dye, 1,3,3-trimethylindolino-6'-nitrobenzopyrylospiran (6-nitro BIPS), and a photostimulable phosphor, europium-doped barium fluorochloride (BaFCl:Eu 2+ ), were developed for the detection of X-ray exposure doses on the order of approximately 1 Gy. To produce the PS-based composite microfibers, we employed a forcespinning method that embeds a high concentration of phosphor in PS in a safe, inexpensive, and simple procedure. On the basis of the optimization of the forcespinning process, fibrous color dosimeters with a high radiation dose sensitivity of 1.2-4.4 Gy were fabricated. The color of the dosimeters was found to transition from white to blue in response to X-ray exposure. The optimized fibrous color dosimeter, made from a solution having a PS/6-nitro BIPS/BaFCl:Eu 2+ /C 2 Cl 4 ratio of 7.0/0.21/28.0/28.0 (wt %) and produced with a 290 mm distance between the needle and collectors, a 0.34 mm 23 G needle nozzle, and a spinneret rotational rate of 3000 rpm, exhibited sensitivity to a dose as low as 1.2 Gy. To realize practical applications, we manufactured the optimized fibrous color dosimeter into a clothlike color dosimeter. The clothlike color dosimeter was mounted on a stuffed bear, and its coloring behavior was demonstrated upon X-ray exposure. After exposure with X-ray, a blue colored and shaped in the form of the letter "[Formula: see text]" clearly appeared on the surface of the clothlike color dosimeter. The proposed fibrous color dosimeters having excellent workability will be an unprecedented dosimetry and contributed to all industries utilizing radiation dosimeters. This new fibrous "composite resin dosimeter" should be able to replace traditional, wearable, and individual radiation dose monitoring devices, such as film badges.
Pybus, Leon P; Dean, Greg; West, Nathan R; Smith, Andrew; Daramola, Olalekan; Field, Ray; Wilkinson, Stephen J; James, David C
2014-02-01
Despite improvements in volumetric titer for monoclonal antibody (MAb) production processes using Chinese hamster ovary (CHO) cells, some "difficult-to-express" (DTE) MAbs inexplicably reach much lower process titers. These DTE MAbs require intensive cell line and process development activity, rendering them more costly or even unsuitable to manufacture. To rapidly and rationally identify an optimal strategy to improve production of DTE MAbs, we have developed an engineering design platform combining high-yielding transient production, empirical modeling of MAb synthesis incorporating an unfolded protein response (UPR) regulatory loop with directed expression and cell engineering approaches. Utilizing a panel of eight IgG1 λ MAbs varying >4-fold in volumetric titer, we showed that MAb-specific limitations on folding and assembly rate functioned to induce a proportionate UPR in host CHO cells with a corresponding reduction in cell growth rate. Derived from comparative empirical modeling of cellular constraints on the production of each MAb we employed two strategies to increase production of DTE MAbs designed to avoid UPR induction through an improvement in the rate/cellular capacity for MAb folding and assembly reactions. Firstly, we altered the transfected LC:HC gene ratio and secondly, we co-expressed a variety of molecular chaperones, foldases or UPR transactivators (BiP, CypB, PDI, and active forms of ATF6 and XBP1) with recombinant MAbs. DTE MAb production was significantly improved by both strategies, although the mode of action was dependent upon the approach employed. Increased LC:HC ratio or CypB co-expression improved cell growth with no effect on qP. In contrast, BiP, ATF6c and XBP1s co-expression increased qP and reduced cell growth. This study demonstrates that expression-engineering strategies to improve production of DTE proteins in mammalian cells should be product specific, and based on rapid predictive tools to assess the relative impact of different engineering interventions. © 2013 Wiley Periodicals, Inc.
Gupta, R S; Aitken, K; Falah, M; Singh, B
1994-01-01
The genes for two different 70-kDa heat shock protein (HSP70) homologs have been cloned and sequenced from the protozoan Giardia lamblia. On the basis of their sequence features, one of these genes corresponds to the cytoplasmic form of HSP70. The second gene, on the basis of its characteristic N-terminal hydrophobic signal sequence and C-terminal endoplasmic reticulum (ER) retention sequence (Lys-Asp-Glu-Leu), is the equivalent of ER-resident GRP78 or the Bip family of proteins. Phylogenetic trees based on HSP70 sequences show that G. lamblia homologs show the deepest divergence among eukaryotic species. The identification of a GRP78 or Bip homolog in G. lamblia strongly suggests the existence of ER in this ancient eukaryote. Detailed phylogenetic analyses of HSP70 sequences by boot-strap neighbor-joining and maximum-parsimony methods show that the cytoplasmic and ER homologs form distinct subfamilies that evolved from a common eukaryotic ancestor by gene duplication that occurred very early in the evolution of eukaryotic cells. It is postulated that because of the essential "molecular chaperone" function of these proteins in translocation of other proteins across membranes, duplication of their genes accompanied the evolution of ER or nucleus in the eukaryotic cell ancestor. The presence in all eukaryotic cytoplasmic HSP70 homologs (including the cognate, heat-induced, and ER forms) of a number of autapomorphic sequence signatures that are not present in any prokaryotic or organellar homologs provides strong evidence regarding the monophyletic nature of eukaryotic lineage. Further, all eukaryotic HSP70 homologs share in common with the Gram-negative group of eubacteria a number of sequence features that are not present in any archaebacterium or Gram-positive bacterium, indicating their evolution from this group of organisms. Some implications of these findings regarding the evolution of eukaryotic cells and ER are discussed. Images PMID:8159675
40 CFR 141.404 - Treatment technique violations for ground water systems.
Code of Federal Regulations, 2011 CFR
2011-07-01
....404 Treatment technique violations for ground water systems. (a) A ground water system with a... ground water system is in violation of the treatment technique requirement if, within 120 days (or...) before or at the first customer for a ground water source is in violation of the treatment technique...
46 CFR 111.05-25 - Ungrounded systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
... REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-25 Ungrounded systems. Each ungrounded system must be provided with a suitably sensitive ground detection system located at the... 46 Shipping 4 2010-10-01 2010-10-01 false Ungrounded systems. 111.05-25 Section 111.05-25 Shipping...
46 CFR 120.376 - Grounded distribution systems (Neutral grounded).
Code of Federal Regulations, 2010 CFR
2010-10-01
... (Neutral grounded). (a) If a grounded distribution system is provided, there must be only one connection to ground, regardless of the number of power sources. This ground connection must be at the switchboard or... ground connection accessible for checking insulation resistance of the generator to ground before the...
46 CFR 120.376 - Grounded distribution systems (Neutral grounded).
Code of Federal Regulations, 2011 CFR
2011-10-01
... (Neutral grounded). (a) If a grounded distribution system is provided, there must be only one connection to ground, regardless of the number of power sources. This ground connection must be at the switchboard or... ground connection accessible for checking insulation resistance of the generator to ground before the...
47 CFR 22.859 - Incumbent commercial aviation air-ground systems.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 47 Telecommunication 2 2014-10-01 2014-10-01 false Incumbent commercial aviation air-ground... CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.859 Incumbent commercial aviation air-ground systems. This section contains rules concerning...
47 CFR 22.859 - Incumbent commercial aviation air-ground systems.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 47 Telecommunication 2 2012-10-01 2012-10-01 false Incumbent commercial aviation air-ground... CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.859 Incumbent commercial aviation air-ground systems. This section contains rules concerning...
47 CFR 22.859 - Incumbent commercial aviation air-ground systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 47 Telecommunication 2 2011-10-01 2011-10-01 false Incumbent commercial aviation air-ground... CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.859 Incumbent commercial aviation air-ground systems. This section contains rules concerning...
47 CFR 22.859 - Incumbent commercial aviation air-ground systems.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 47 Telecommunication 2 2013-10-01 2013-10-01 false Incumbent commercial aviation air-ground... CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.859 Incumbent commercial aviation air-ground systems. This section contains rules concerning...
NASA Technical Reports Server (NTRS)
Pendley, R. D.; Scheidker, E. J.; Levitt, D. S.; Myers, C. R.; Werking, R. D.
1994-01-01
This analysis defines a complete set of ground support functions based on those practiced in real space flight operations during the on-orbit phase of a mission. These functions are mapped against ground support functions currently in use by NASA and DOD. Software components to provide these functions can be hosted on RISC-based work stations and integrated to provide a modular, integrated ground support system. Such modular systems can be configured to provide as much ground support functionality as desired. This approach to ground systems has been widely proposed and prototyped both by government institutions and commercial vendors. The combined set of ground support functions we describe can be used as a standard to evaluate candidate ground systems. This approach has also been used to develop a prototype of a modular, loosely-integrated ground support system, which is discussed briefly. A crucial benefit to a potential user is that all the components are flight-qualified, thus giving high confidence in their accuracy and reliability.
NASA Astrophysics Data System (ADS)
Pendley, R. D.; Scheidker, E. J.; Levitt, D. S.; Myers, C. R.; Werking, R. D.
1994-11-01
This analysis defines a complete set of ground support functions based on those practiced in real space flight operations during the on-orbit phase of a mission. These functions are mapped against ground support functions currently in use by NASA and DOD. Software components to provide these functions can be hosted on RISC-based work stations and integrated to provide a modular, integrated ground support system. Such modular systems can be configured to provide as much ground support functionality as desired. This approach to ground systems has been widely proposed and prototyped both by government institutions and commercial vendors. The combined set of ground support functions we describe can be used as a standard to evaluate candidate ground systems. This approach has also been used to develop a prototype of a modular, loosely-integrated ground support system, which is discussed briefly. A crucial benefit to a potential user is that all the components are flight-qualified, thus giving high confidence in their accuracy and reliability.
NASA Technical Reports Server (NTRS)
Gunn, Jody M.
2006-01-01
The state-of-the-practice for engineering and development of Ground Systems has evolved significantly over the past half decade. Missions that challenge ground system developers with significantly reduced budgets in spite of requirements for greater and previously unimagined functionality are now the norm. Making the right trades early in the mission lifecycle is one of the key factors to minimizing ground system costs. The Mission Operations Strategic Leadership Team at the Jet Propulsion Laboratory has spent the last year collecting and working through successes and failures in ground systems for application to future missions.
46 CFR 111.05-17 - Generation and distribution system grounding.
Code of Federal Regulations, 2013 CFR
2013-10-01
... Section 111.05-17 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-17... must: (a) Be grounded at the generator switchboard, except the neutral of an emergency power generation...
46 CFR 111.05-17 - Generation and distribution system grounding.
Code of Federal Regulations, 2014 CFR
2014-10-01
... Section 111.05-17 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-17... must: (a) Be grounded at the generator switchboard, except the neutral of an emergency power generation...
46 CFR 111.05-17 - Generation and distribution system grounding.
Code of Federal Regulations, 2011 CFR
2011-10-01
... Section 111.05-17 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-17... must: (a) Be grounded at the generator switchboard, except the neutral of an emergency power generation...
On the Isolation of Halophilic Microorganisms from Salt Deposits of Great Geological Age
NASA Technical Reports Server (NTRS)
Stan-Lotter, Helga; Denner, Ewald; Orans, Robin (Editor)
1993-01-01
From salt sediments of Triassic or Permian ace from various locations in the world halophilic microorganisms were isolated. Molecular characteristics of several of the isolates suggested they belong to the archaebacteriae. One group appears to represent novel strains; several properties or one such isolate, strain BIp, are described here. The existence of viable microorganisms in ancient sediments would have great implications with respect to our notions on evolution, the search for life in extraterrestrial environments and the long- term survival of functional biological structures. Of crucial importance is thus the question if these microorganisms existed in the salt since the time of deposition or invaded at some later date. Some suggestions to address these issues experimentally are discussed.
On the isolation of halophilic microorganisms from salt deposits of great geological age
NASA Technical Reports Server (NTRS)
Stan-Lotter, Helga; Denner, Ewald
1993-01-01
From salt sediments of Triassic or Permian age from various locations in the world halophilic microorganisms were isolated. Molecular characteristics of several of the isolates suggested they belong to the archaebacteria. One group appears to represent novel strains; several properties of one such isolate, strain BIp, are described here. The existence of viable microorganisms in ancient sediment would have great implications with respect to our notions on evolution, the research for life in extraterrestrial environments, and the longterm survival of functional biological structures. Of crucial importance is thus the question if these microorganisms existed in the salt since the time of deposition or invaded at some later date. Some suggestions to address these issues experimentally are discussed.
Modernization of the Cassini Ground System
NASA Technical Reports Server (NTRS)
Razo, Gus; Fujii, Tammy J.
2014-01-01
The Cassini Spacecraft and its ground system have been operational for over 16 years. Modernization presents several challenges due to the personnel, processes, and tools already invested and embedded into the current ground system structure. Every mission's ground system has its own unique complexities and challenges, involving various organizational units. As any mission from its inception to its execution, schedules are always tight. This forces GDS engineers to implement a working ground system that is not necessarily fully optimized. Ground system challenges increase as technology evolves and cyber threats become more sophisticated. Cassini's main challenges were due to its ground system existing before many security requirements were levied on the multi-mission tools and networks. This caused a domino effect on Cassini GDS tools that relied on outdated technological features. In the aerospace industry reliable and established technology is preferred over innovative yet less proven technology. Loss of data for a spacecraft mission can be catastrophic; therefore, there is a reluctance to make changes and updates to the ground system. Nevertheless, all missions and associated teams face the need to modernize their processes and tools. Systems development methods from well-known system analysis and design principles can be applied to many missions' ground systems. Modernization should always be considered, but should be done in such a way that it does not affect flexibility nor interfere with established practices. Cassini has accomplished a secure and efficient ground data system through periodic updates. The obstacles faced while performing the modernization of the Cassini ground system will be outlined, as well as the advantages and challenges that were encountered.
46 CFR 111.05-33 - Equipment safety grounding (bonding) conductors.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 4 2012-10-01 2012-10-01 false Equipment safety grounding (bonding) conductors. 111.05... ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-33 Equipment safety grounding (bonding) conductors. (a) Each equipment-grounding conductor must...
46 CFR 111.05-33 - Equipment safety grounding (bonding) conductors.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 4 2014-10-01 2014-10-01 false Equipment safety grounding (bonding) conductors. 111.05... ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-33 Equipment safety grounding (bonding) conductors. (a) Each equipment-grounding conductor must...
46 CFR 111.05-33 - Equipment safety grounding (bonding) conductors.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 4 2013-10-01 2013-10-01 false Equipment safety grounding (bonding) conductors. 111.05... ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-33 Equipment safety grounding (bonding) conductors. (a) Each equipment-grounding conductor must...
An intelligent position-specific training system for mission operations
NASA Technical Reports Server (NTRS)
Schneider, M. P.
1992-01-01
Marshall Space Flight Center's (MSFC's) payload ground controller training program provides very good generic training; however, ground controller position-specific training can be improved by including position-specific training systems in the training program. This report explains why MSFC needs to improve payload ground controller position-specific training. The report describes a generic syllabus for position-specific training systems, a range of system designs for position-specific training systems, and a generic development process for developing position-specific training systems. The report also describes a position-specific training system prototype that was developed for the crew interface coordinator payload operations control center ground controller position. The report concludes that MSFC can improve the payload ground controller training program by incorporating position-specific training systems for each ground controller position; however, MSFC should not develop position-specific training systems unless payload ground controller position experts will be available to participate in the development process.
40 CFR 141.401 - Sanitary surveys for ground water systems.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Sanitary surveys for ground water...) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Ground Water Rule § 141.401 Sanitary surveys for ground water systems. (a) Ground water systems must provide the State, at the State's...
14 CFR 135.153 - Ground proximity warning system.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Ground proximity warning system. 135.153... Equipment § 135.153 Ground proximity warning system. (a) No person may operate a turbine-powered airplane... equipped with an approved ground proximity warning system. (b) [Reserved] (c) For a system required by this...
14 CFR 135.153 - Ground proximity warning system.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Ground proximity warning system. 135.153... Equipment § 135.153 Ground proximity warning system. (a) No person may operate a turbine-powered airplane... equipped with an approved ground proximity warning system. (b) [Reserved] (c) For a system required by this...
47 CFR 22.857 - Channel plan for commercial aviation air-ground systems.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 47 Telecommunication 2 2013-10-01 2013-10-01 false Channel plan for commercial aviation air-ground... CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.857 Channel plan for commercial aviation air-ground systems. The 849-851 MHz and 894-896 MHz...
47 CFR 22.857 - Channel plan for commercial aviation air-ground systems.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 47 Telecommunication 2 2014-10-01 2014-10-01 false Channel plan for commercial aviation air-ground... CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.857 Channel plan for commercial aviation air-ground systems. The 849-851 MHz and 894-896 MHz...
47 CFR 22.857 - Channel plan for commercial aviation air-ground systems.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 47 Telecommunication 2 2012-10-01 2012-10-01 false Channel plan for commercial aviation air-ground... CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.857 Channel plan for commercial aviation air-ground systems. The 849-851 MHz and 894-896 MHz...
47 CFR 22.857 - Channel plan for commercial aviation air-ground systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 47 Telecommunication 2 2011-10-01 2011-10-01 false Channel plan for commercial aviation air-ground... CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.857 Channel plan for commercial aviation air-ground systems. The 849-851 MHz and 894-896 MHz...
46 CFR 111.05-31 - Grounding conductors for systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 4 2010-10-01 2010-10-01 false Grounding conductors for systems. 111.05-31 Section 111... Grounding conductors for systems. (a) A conductor for grounding a direct-current system must be the larger of: (1) The largest conductor supplying the system; or (2) No. 8 AWG (8.4mm2). (b) A conductor for...
46 CFR 111.05-31 - Grounding conductors for systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 4 2011-10-01 2011-10-01 false Grounding conductors for systems. 111.05-31 Section 111... Grounding conductors for systems. (a) A conductor for grounding a direct-current system must be the larger of: (1) The largest conductor supplying the system; or (2) No. 8 AWG (8.4mm2). (b) A conductor for...
46 CFR 183.376 - Grounded distribution systems (neutral grounded).
Code of Federal Regulations, 2013 CFR
2013-10-01
... VESSELS (UNDER 100 GROSS TONS) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.376... propulsion, power, lighting, or distribution system having a neutral bus or conductor must have the neutral... 46 Shipping 7 2013-10-01 2013-10-01 false Grounded distribution systems (neutral grounded). 183...
40 CFR 141.404 - Treatment technique violations for ground water systems.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Treatment technique violations for ground water systems. 141.404 Section 141.404 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....404 Treatment technique violations for ground water systems. (a) A ground water system with a...
Sail GTS ground system analysis: Avionics system engineering
NASA Technical Reports Server (NTRS)
Lawton, R. M.
1977-01-01
A comparison of two different concepts for the guidance, navigation and control test set signal ground system is presented. The first is a concept utilizing a ground plate to which crew station, avionics racks, electrical power distribution system, master electrical common connection assembly and marshall mated elements system grounds are connected by 4/0 welding cable. An alternate approach has an aluminum sheet interconnecting the signal ground reference points between the crew station and avionics racks. The comparison analysis quantifies the differences between the two concepts in terms of dc resistance, ac resistance and inductive reactance. These parameters are figures of merit for ground system conductors in that the system with the lowest impedance is the most effective in minimizing noise voltage. Although the welding cable system is probably adequate, the aluminum sheet system provides a higher probability of a successful system design.
Regional hydrology of the Blanding-Durango area, southern Paradox Basin, Utah and Colorado
DOE Office of Scientific and Technical Information (OSTI.GOV)
Whitfield, M.S. Jr.; Thordarson, W.; Oatfield, W.J.
1983-01-01
Principal findings of this study that are pertinent to an assessment of suitability of the hydrogeologic systems to store and contain radioactive waste in salt anticlines of adjacent areas are: water in the upper ground-water flow system discharges to the San Juan River - a major tributary of the Colorado River. Discharge of water from the upper aquifer system to streambed channels of the San Juan River and its tributaries during low-flow periods primarily is through evapotranspiration from areas on flood plains and maintenance of streamflow; the lower ground-water system does not have known recharge or discharge areas within themore » study area; subsurface inflow to this system comes from recharge areas located north and northeast of the study area; the upper and lower ground-water systems are separated regionally by thick salt deposits in the Blanding-Durango study area of the Paradox basin; potential exists in mountainous areas for downward leakage between the upper and lower ground-water systems, where salt deposits are thin, absent, or faulted; no brines were found in this study area with outflow to the biosphere; water in the upper ground-water system generally is fresh. Water in the lower ground-water system generally is brackish or saline; and ground-water flow disruptions by contiguous faults probably are common in the upper ground-water system. These disruptions of flow are not apparent in the lower ground-water system, perhaps because available hydrologic data for the lower ground-water system are scarce. The above major findings do not preclude the potential for waste storage in salt; however, they do not allow the prediction of detailed ground-water flow rates and directions through this area. 55 references, 13 figures, 15 tables.« less
Opportunistic MSPA Demonstration #1: Final Report
NASA Astrophysics Data System (ADS)
Abraham, D. S.; Finley, S. G.; Heckman, D. P.; Lay, N. E.; Lush, C. M.; MacNeal, B. E.
2015-02-01
The Opportunistic Multiple Spacecraft Per Antenna (OMSPA) concept seeks to provide smallsat missions with a low-attributed-aperture-fee technique for obtaining routine downlink in a manner that is very low cost to the Deep Space Network (DSN). Unlike traditional MSPA in which the number of spacecraft that can be supported is limited by the number of available receivers, OMSPA makes use of a digital recorder at each station that is capable of capturing IF signals from every spacecraft in the antenna beam within the frequency bands of interest. When smallsat missions see one or more opportunities to intercept the traditionally scheduled antenna beam of a "host" spacecraft, they can transmit open loop during those opportunities. Via a secure Internet site, the smallsat mission operators can then retrieve relevant portions of the digital recording for subsequent demodulation and decoding or subscribe to a service that does it for them. The demonstration discussed in this article was intended to provide prospective smallsat users and the DSN, as the prospective service provider, with demonstrable proof that the OMSPA concept is, in fact, an operationally viable means for obtaining routine downlink telemetry. To do this, the demonstration began by treating Mars Odyssey as a "smallsat" and Mars Reconnaissance Orbiter (MRO) as the "host" spacecraft. Using a specially created Beam Intercept Planning System (BIPS) and a DSN 7-Day Schedule Cross-Comparison (7-DSC) tool, opportunities were identified when Mars Odyssey would be transmitting while in MRO's ground antenna beam. Existing Very Long Baseline Interferometry (VLBI) Science Receivers (VSRs) were used to record the Mars Odyssey downlink telemetry during these opportunities. The recordings were played back to a secure server outside the Flight Operations Network firewall, but inside the JPL firewall. The demonstration team's signal processing personnel retrieved the recordings from this secure server and downloaded them to a workstation containing an OMSPA Software Demodulator (OSD) tool that was developed to demodulate and decode the Mars Odyssey signal. Validation of the recovered data was then accomplished by comparing the transfer frames obtained through OMSPA with those recovered via Mars Odyssey's formally scheduled downlink. The demonstration successfully achieved its intended purpose. All of the above steps were accomplished within an operationally viable timeframe, with at least 99.95 percent of the transfer frames being successfully recovered from each demonstration recording.
NASA Technical Reports Server (NTRS)
Mata, Carlos T.; Rakov, V. A.; Mata, Angel G.
2010-01-01
A new Lightning Protection System (LPS) was designed and built at Launch Complex 39B (LC39B), at the Kennedy Space Center (KSC), Florida, which consists of a catenary wire system (at a height of about 181 meters above ground level) supported by three insulators installed atop three towers in a triangular configuration. A total of nine downconductors (each about 250 meters long, on average) are connected to the catenary wire system. Each of the nine downconductors is connected to a 7.62-meter radius circular counterpoise conductor with six equally spaced 6-meter long vertical grounding rods. Grounding requirements at LC39B call for all underground and above ground metallic piping, enclosures, raceways, and cable trays, within 7.62 meters of the counterpoise, to be bounded to the counterpoise, which results in a complex interconnected grounding system, given the many metallic piping, raceways, and cable trays that run in multiple direction around LC39B. The complexity of this grounding system makes the fall of potential method, which uses multiple metallic rods or stakes, unsuitable for measuring the grounding impedances of the downconductors. To calculate the downconductors grounding impedance, an Earth Ground Clamp (a stakeless grounding resistance measuring device) and a LPS Alternative Transient Program (ATP) model are used. The Earth Ground Clamp is used to measure the loop impedance plus the grounding impedance of each downconductor and the ATP model is used to calculate the loop impedance of each downconductor circuit. The grounding impedance of the downconductors is then calculated by subtracting the ATP calculated loop impedances from the Earth Ground Clamp measurements.
NASA Technical Reports Server (NTRS)
1972-01-01
The design and verification tests for the biomedical ground lead system of Apollo biomedical monitors are presented. Major efforts were made to provide a low impedance path to ground, reduce noise and artifact of ECG signals, and limit the current flowing in the ground electrode of the system.
Grounding and lightning protection. Volume 5
DOE Office of Scientific and Technical Information (OSTI.GOV)
Robinson, M.D.
1987-12-31
Grounding systems protect personnel and equipment by isolating faulted systems and dissipating transient currents. Lightning protection systems minimize the possible consequences of a direct strike by lightning. This volume focuses on design requirements of the grounding system and on present-day concepts used in the design of lightning protection systems. Various types of grounding designs are presented, and their advantages and disadvantages discussed. Safety, of course, is the primary concern of any grounding system. Methods are shown for grounding the non-current-carrying parts of electrical equipment to reduce shock hazards to personnel. Lightning protection systems are installed on tall structures (such asmore » chimneys and cooling towers) to minimize the possibility of structural damage caused by direct lightning strokes. These strokes may carry currents of 200,000 A or more. The volume examines the formation and characteristics of lightning strokes and the way stroke characteristics influence the design of lightning protection systems. Because a large portion of the grounding system is buried in soil or concrete, it is not readily accessible for inspection or repair after its installation. The volume details the careful selection and sizing of materials needed to ensure a long, maintenance-free life for the system. Industry standards and procedures for testing the adequacy of the grounding system are also discussed.« less
Manufacturing Methods and Technology Project Summary Reports
1986-07-01
Yuma Proving Ground in January 1985. The ARBAT system provides a unique real-time computer capability to identify all critical flight...cheaper tnaii the existing radar system. This prototype is expected to save over ^1 million per year at Yuma Proving Grounds . TECOM is planning to...purchase 4 production ballistic radar systems to be installed at Yuma Proving Grounds , Dugway Proving Grounds , and Jefferson Proving Grounds at a
NASA Technical Reports Server (NTRS)
1981-01-01
The software developed to simulate the ground control point navigation system is described. The Ground Control Point Simulation Program (GCPSIM) is designed as an analysis tool to predict the performance of the navigation system. The system consists of two star trackers, a global positioning system receiver, a gyro package, and a landmark tracker.
Code of Federal Regulations, 2010 CFR
2010-07-01
... SAFETY BOATS AND ASSOCIATED EQUIPMENT Fuel Systems Manufacturer Requirements § 183.572 Grounding. Each metallic component of the fuel fill system and fuel tank which is in contact with fuel must be statically grounded so that the resistance between the ground and each metallic component of the fuel fill system and...
40 CFR 258.51 - Ground-water monitoring systems.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Ground-water monitoring systems. 258.51 Section 258.51 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES CRITERIA FOR MUNICIPAL SOLID WASTE LANDFILLS Ground-Water Monitoring and Corrective Action § 258.51 Ground-water monitoring systems. (a) A...
NASA Astrophysics Data System (ADS)
Rao, Mandava Mohana
2017-10-01
Ground resistance of high voltage substations must be as low as possible for safe grounding of their equipment both during normal and fault conditions. However, in gas insulated substations (GIS), even though resistance is low, it does not ensure the step and touch potentials of the grounding system within permissible levels. In the present study, an analytical model has been developed to calculate ground resistance, step and touch potentials of a grounding system used for GIS. Different models have been proposed for the evaluation of number of grounding rods to be inserted in to the ground. The effect of concrete foundations on above performance parameters has been analyzed by considering various fault currents, soil/earth resistivities and number of grounding rods. Finally, design optimization of GIS grounding system has been reported for fault currents in the order of 63 kA located in earth resistivity of 100Ω-m and above.
Wireless remote monitoring of myocardial ischemia using reconstructed 12-lead ECGs.
Vukcevic, Vladan; Panescu, Dorin; Bojovic, Bosko; George, Samuel; Gussak, Ihor; Giga, Vojislav; Stankovic, Ivana
2010-01-01
CardioBip (CB) is a hand-held patient-activated device for recording and wireless transmission of reconstructed 12-lead ECG (12CB) based on patient specific matrices. It has 5 contact points: 3 precordial and 2 on the device top serving as limb leads when touched by index fingers. To determine whether CB could be used to monitor coronary disease (CAD) patients, we compared 12CB to simultaneous 12-lead ECGs (12L) in patients with CAD, pre-and post-exercise treadmill testing (ETT). The study goals were to assess: (1) whether 12CB can accurately reconstruct and wirelessly transmit 12-lead ECGs in CAD patients during ETT recovery; (2) whether 12CB can be used to evaluate ST segment changes in patients with exercise-induced ischemia.
NASA Astrophysics Data System (ADS)
Choi, M. K.; Morehouse, J. H.; Hughes, P. J.
1981-07-01
An analysis is performed of ground-coupled stand-alone and series configured solar-assisted liquid-to-air heat pump systems for residences. The year-round thermal performance of these systems for space heating, space cooling, and water heating is determined by simulation and compared against non-ground-coupled solar heat pump systems as well as conventional heating and cooling systems in three geographic locations: Washington, DC; Fort Worth, Texas; and Madison, Wisconsin. The results indicate that without tax credits a combined solar/ground-coupled heat pump system for space heating and cooling is not cost competitive with conventional systems. Its thermal performance is considerably better than non-ground-coupled solar heat pumps in Fort Worth. Though the ground-coupled stand-alone heat pump provides 51 percent of the heating and cooling load with non-purchased energy in Fort Worth, its thermal performance in Washington and Madison is poor.
Tethered Vehicle Control and Tracking System
NASA Technical Reports Server (NTRS)
North, David D. (Inventor); Aull, Mark J. (Inventor)
2017-01-01
A kite system includes a kite and a ground station. The ground station includes a sensor that can be utilized to determine an angular position and velocity of the kite relative to the ground station. A controller utilizes a fuzzy logic control system to autonomously fly the kite. The system may include a ground station having powered winding units that generate power as the lines to the kite are unreeled. The control system may be configured to fly the kite in a crosswind trajectory to increase line tension for power generation. The sensors for determining the position of the kite are preferably ground-based.
Tethered Vehicle Control and Tracking System
NASA Technical Reports Server (NTRS)
North, David D. (Inventor); Aull, Mark J. (Inventor)
2014-01-01
A kite system includes a kite and a ground station. The ground station includes a sensor that can be utilized to determine an angular position and velocity of the kite relative to the ground station. A controller utilizes a fuzzy logic control system to autonomously fly the kite. The system may include a ground station having powered winding units that generate power as the lines to the kite are unreeled. The control system may be configured to fly the kite in a crosswind trajectory to increase line tension for power generation. The sensors for determining the position of the kite are preferably ground-based.
Proven Innovations and New Initiatives in Ground System Development
NASA Technical Reports Server (NTRS)
Gunn, Jody M.
2006-01-01
The state-of-the-practice for engineering and development of Ground Systems has evolved significantly over the past half decade. Missions that challenge ground system developers with significantly reduced budgets in spite of requirements for greater and previously unimagined functionality are now the norm. Making the right trades early in the mission lifecycle is one of the key factors to minimizing ground system costs. The Mission Operations Strategic Leadership Team at the Jet Propulsion Laboratory has spent the last year collecting and working through successes and failures in ground systems for application to future missions.
30 CFR 77.704-1 - Work on high-voltage lines.
Code of Federal Regulations, 2011 CFR
2011-07-01
... grounded or solid wye-connected systems, the neutral wire is the system grounding medium. In the case of an ungrounded power system, either the steel armor or conduit enclosing the system or a surface grounding field...
30 CFR 77.704-1 - Work on high-voltage lines.
Code of Federal Regulations, 2010 CFR
2010-07-01
... grounded or solid wye-connected systems, the neutral wire is the system grounding medium. In the case of an ungrounded power system, either the steel armor or conduit enclosing the system or a surface grounding field...
Ground/bonding for Large Space System Technology (LSST). [of metallic and nonmetallic structures
NASA Technical Reports Server (NTRS)
Dunbar, W. G.
1980-01-01
The influence of the environment and extravehicular activity remote assembly operations on the grounding and bonding of metallic and nonmetallic structures is discussed. Grounding and bonding philosophy is outlined for the electrical systems and electronic compartments which contain high voltage, high power electrical and electronic equipment. The influence of plasma and particulate on the system was analyzed and the effects of static buildup on the spacecraft electrical system discussed. Conceptual grounding bonding designs are assessed for capability to withstand high current arcs to ground from a high voltage conductor and electromagnetic interference. Also shown were the extravehicular activities required of the space station and or supply spacecraft crew members to join and inspect the ground system using manual on remote assembly construction.
Ground/bonding for Large Space System Technology (LSST)
NASA Astrophysics Data System (ADS)
Dunbar, W. G.
1980-04-01
The influence of the environment and extravehicular activity remote assembly operations on the grounding and bonding of metallic and nonmetallic structures is discussed. Grounding and bonding philosophy is outlined for the electrical systems and electronic compartments which contain high voltage, high power electrical and electronic equipment. The influence of plasma and particulate on the system was analyzed and the effects of static buildup on the spacecraft electrical system discussed. Conceptual grounding bonding designs are assessed for capability to withstand high current arcs to ground from a high voltage conductor and electromagnetic interference. Also shown were the extravehicular activities required of the space station and or supply spacecraft crew members to join and inspect the ground system using manual on remote assembly construction.
Perl Tools for Automating Satellite Ground Systems
NASA Technical Reports Server (NTRS)
McLean, David; Haar, Therese; McDonald, James
2000-01-01
The freeware scripting language Pert offers many opportunities for automating satellite ground systems for new satellites as well as older, in situ systems. This paper describes a toolkit that has evolved from of the experiences gained by using Pert to automate the ground system for the Compton Gamma Ray Observatory (CGRO) and for automating some of the elements in the Earth Observing System Data and Operations System (EDOS) ground system at Goddard Space Flight Center (GSFC). CGRO is an older ground system that was forced to automate because of fund cuts. Three 8 hour shifts were cut back to one 8 hour shift, 7 days per week. EDOS supports a new mission called Terra, launched December 1999 that requires distribution and tracking of mission-critical reports throughout the world. Both of these ground systems use Pert scripts to process data and display it on the Internet as well as scripts to coordinate many of the other systems that make these ground systems work as a coherent whole. Another task called Automated Multimodal Trend Analysis System (AMTAS) is looking at technology for isolation and recovery of spacecraft problems. This effort has led to prototypes that seek to evaluate various tools and technology that meet at least some of the AMTAS goals. The tools, experiences, and lessons learned by implementing these systems are described here.
A Proven Methodology for Developing Secure Software and Applying It to Ground Systems
NASA Technical Reports Server (NTRS)
Bailey, Brandon
2016-01-01
Part Two expands upon Part One in an attempt to translate the methodology for ground system personnel. The goal is to build upon the methodology presented in Part One by showing examples and details on how to implement the methodology. Section 1: Ground Systems Overview; Section 2: Secure Software Development; Section 3: Defense in Depth for Ground Systems; Section 4: What Now?
The effects of large-scale pumping and diversion on the water resources of Dane County, Wisconsin
Hunt, Randall J.; Bradbury, Kenneth R.; Krohelski, James T.
2001-01-01
Throughout many parts of the U.S., there is growing concern over the effects of rapid urban growth and development on water resources. Ground- water and surface-water systems (which comprise the hydrologic system) are linked in much of Wisconsin, and ground water can be utilized both for drinking water and as a source of water for sustaining lakes, streams, springs, and wetlands. Ground water is important for surface-water systems because it commonly has greater dissolved solids and more acid-neutraliz- ing capacity than surface water or precipitation. The supplies of ground water are finite, however, and, in many cases ground water used for one purpose cannot be used for another. Moreover, ground-water use and withdrawal patterns may not be easy to alter once established. Thus, urban and rural planners are faced with decisions that balance the need for ground- water withdrawals while maintaining the quantity and quality of ground water for sustaining surface-water resources. Science-based information on the ground-water system and the connections to surface-water systems provides valuable insight for such decisions.
30 CFR 77.803 - Fail safe ground check circuits on high-voltage resistance grounded systems.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Fail safe ground check circuits on high-voltage... WORK AREAS OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.803 Fail safe ground check..., resistance grounded systems shall include a fail safe ground check circuit or other no less effective device...
30 CFR 77.803 - Fail safe ground check circuits on high-voltage resistance grounded systems.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Fail safe ground check circuits on high-voltage... WORK AREAS OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.803 Fail safe ground check..., resistance grounded systems shall include a fail safe ground check circuit or other no less effective device...
30 CFR 77.803 - Fail safe ground check circuits on high-voltage resistance grounded systems.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Fail safe ground check circuits on high-voltage... WORK AREAS OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.803 Fail safe ground check..., resistance grounded systems shall include a fail safe ground check circuit or other no less effective device...
30 CFR 77.803 - Fail safe ground check circuits on high-voltage resistance grounded systems.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Fail safe ground check circuits on high-voltage... WORK AREAS OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.803 Fail safe ground check..., resistance grounded systems shall include a fail safe ground check circuit or other no less effective device...
Code of Federal Regulations, 2014 CFR
2014-10-01
...-cellular 800 MHz licensees from commercial aviation air-ground systems. 22.877 Section 22.877...-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.877 Unacceptable interference to part 90 non-cellular 800 MHz licensees from commercial aviation air-ground systems. The definition...
Code of Federal Regulations, 2012 CFR
2012-10-01
...-cellular 800 MHz licensees from commercial aviation air-ground systems. 22.877 Section 22.877...-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.877 Unacceptable interference to Part 90 non-cellular 800 MHz licensees from commercial aviation air-ground systems. The definition...
Code of Federal Regulations, 2011 CFR
2011-10-01
...-cellular 800 MHz licensees from commercial aviation air-ground systems. 22.877 Section 22.877...-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.877 Unacceptable interference to Part 90 non-cellular 800 MHz licensees from commercial aviation air-ground systems. The definition...
Code of Federal Regulations, 2013 CFR
2013-10-01
...-cellular 800 MHz licensees from commercial aviation air-ground systems. 22.877 Section 22.877...-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.877 Unacceptable interference to Part 90 non-cellular 800 MHz licensees from commercial aviation air-ground systems. The definition...
40 CFR 141.401 - Sanitary surveys for ground water systems.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Sanitary surveys for ground water systems. 141.401 Section 141.401 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Ground Water Rule § 141.401 Sanitary surveys for ground water systems. (a)...
46 CFR 111.05-25 - Ungrounded systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 4 2011-10-01 2011-10-01 false Ungrounded systems. 111.05-25 Section 111.05-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-25 Ungrounded systems. Each...
46 CFR 111.05-25 - Ungrounded systems.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 4 2013-10-01 2013-10-01 false Ungrounded systems. 111.05-25 Section 111.05-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-25 Ungrounded systems. Each...
46 CFR 111.05-25 - Ungrounded systems.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 4 2012-10-01 2012-10-01 false Ungrounded systems. 111.05-25 Section 111.05-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Equipment Ground, Ground Detection, and Grounded Systems § 111.05-25 Ungrounded systems. Each...
Thermal and economic assessment of ground-coupled storage for residential solar heat pump systems
NASA Astrophysics Data System (ADS)
Choi, M. K.; Morehouse, J. H.
1980-11-01
This study performed an analysis of ground-coupled stand-alone and series configured solar-assisted liquid-to-air heat pump systems for residences. The year-round thermal performance of these systems for space heating, space cooling, and water heating were determined by simulation and compared against non-ground-coupled solar heat pump systems as well as conventional heating and cooling systems in three geographic locations: Washington, D.C., Fort Worth, Tex., and Madison, Wis. The results indicate that without tax credits a combined solar/ground-coupled heat pump system for space heating and cooling is not cost competitive with conventional systems. Its thermal performance is considerably better than non-ground-coupled solar heat pumps in Forth Worth. Though the ground-coupled stand-alone heat pump provides 51% of the heating and cooling load with non-purchased energy in Forth Worth, its thermal performance in Washington and Madison is poor.
Multimission Software Reuse in an Environment of Large Paradigm Shifts
NASA Technical Reports Server (NTRS)
Wilson, Robert K.
1996-01-01
The ground data systems provided for NASA space mission support are discussed. As space missions expand, the ground systems requirements become more complex. Current ground data systems provide for telemetry, command, and uplink and downlink processing capabilities. The new millennium project (NMP) technology testbed for 21st century NASA missions is discussed. The program demonstrates spacecraft and ground system technologies. The paradigm shift from detailed ground sequencing to a goal oriented planning approach is considered. The work carried out to meet this paradigm for the Deep Space-1 (DS-1) mission is outlined.
Analysis of ER Resident Proteins in S. cerevisiae: Implementation of H/KDEL Retrieval Sequences
Young, Carissa L.; Raden, David L.; Robinson, Anne S.
2013-01-01
An elaborate quality control system regulates ER homeostasis by ensuring the fidelity of protein synthesis and maturation. In budding yeast, genomic analyses and high-throughput proteomic studies have identified ER resident proteins that restore homeostasis following local perturbations. Yet, how these folding factors modulate stress has been largely unexplored. In this study, we designed a series of PCR-based modules including codon-optimized epitopes and FP variants complete with C-terminal H/KDEL retrieval motifs. These conserved sequences are inherent to most soluble ER resident proteins. To monitor multiple proteins simultaneously, H/KDEL cassettes are available with six different selection markers, providing optimal flexibility for live-cell imaging and multicolor labeling in vivo. A single pair of PCR primers can be used for the amplification of these 26 modules, enabling numerous combinations of tags and selection markers. The versatility of pCY H/KDEL cassettes was demonstrated by labeling BiP/Kar2p, Pdi1p, and Scj1p with all novel tags, thus providing a direct comparison among FP variants. Furthermore, to advance in vitro studies of yeast ER proteins, Strep-tag II was engineered with a C-terminal retrieval sequence. Here, an efficient purification strategy was established for BiP under physiological conditions. PMID:23324027
NASA Astrophysics Data System (ADS)
Liu, Junzi; Cheng, Lan
2018-04-01
An atomic mean-field (AMF) spin-orbit (SO) approach within exact two-component theory (X2C) is reported, thereby exploiting the exact decoupling scheme of X2C, the one-electron approximation for the scalar-relativistic contributions, the mean-field approximation for the treatment of the two-electron SO contribution, and the local nature of the SO interactions. The Hamiltonian of the proposed SOX2CAMF scheme comprises the one-electron X2C Hamiltonian, the instantaneous two-electron Coulomb interaction, and an AMF SO term derived from spherically averaged Dirac-Coulomb Hartree-Fock calculations of atoms; no molecular relativistic two-electron integrals are required. Benchmark calculations for bond lengths, harmonic frequencies, dipole moments, and electric-field gradients for a set of diatomic molecules containing elements across the periodic table show that the SOX2CAMF scheme offers a balanced treatment for SO and scalar-relativistic effects and appears to be a promising candidate for applications to heavy-element containing systems. SOX2CAMF coupled-cluster calculations of molecular properties for bismuth compounds (BiN, BiP, BiF, BiCl, and BiI) are also presented and compared with experimental results to further demonstrate the accuracy and applicability of the SOX2CAMF scheme.
Simple system for locating ground loops.
Bellan, P M
2007-06-01
A simple low-cost system for rapid identification of the cables causing ground loops in complex instrumentation configurations is described. The system consists of an exciter module that generates a 100 kHz ground loop current and a detector module that determines which cable conducts this test current. Both the exciter and detector are magnetically coupled to the ground circuit so there is no physical contact to the instrumentation system under test.
2010-08-19
UNCLASSIFIED Systems Engineering Processes Applied To Ground Vehicle Integration at US Army Tank Automotive Research, Development, and Engineering...DATES COVERED - 4. TITLE AND SUBTITLE Systems Engineering Processes Applied To Ground Vehicle Integration at US Army Tank Automotive Research...release, distribution unlimited 13. SUPPLEMENTARY NOTES Presented at NDIAs Ground Vehicle Systems Engineering and Technology Symposium (GVSETS), 17 22
Using NASA's Reference Architecture: Comparing Polar and Geostationary Data Processing Systems
NASA Technical Reports Server (NTRS)
Ullman, Richard; Burnett, Michael
2013-01-01
The JPSS and GOES-R programs are housed at NASA GSFC and jointly implemented by NASA and NOAA to NOAA requirements. NASA's role in the JPSS Ground System is to develop and deploy the system according to NOAA requirements. NASA's role in the GOES-R ground segment is to provide Systems Engineering expertise and oversight for NOAA's development and deployment of the system. NASA's Earth Science Data Systems Reference Architecture is a document developed by NASA's Earth Science Data Systems Standards Process Group that describes a NASA Earth Observing Mission Ground system as a generic abstraction. The authors work within the respective ground segment projects and are also separately contributors to the Reference Architecture document. Opinions expressed are the author's only and are not NOAA, NASA or the Ground Projects' official positions.
Code of Federal Regulations, 2011 CFR
2011-07-01
..., casings and other enclosures of electric equipment receiving power from direct current power systems with... equipment receiving power from direct current power systems with one polarity grounded. For the purpose of... direct-current power system with one polarity grounded, the following methods of grounding will be...
Code of Federal Regulations, 2010 CFR
2010-07-01
..., casings and other enclosures of electric equipment receiving power from direct current power systems with... equipment receiving power from direct current power systems with one polarity grounded. For the purpose of... direct-current power system with one polarity grounded, the following methods of grounding will be...
Code of Federal Regulations, 2013 CFR
2013-07-01
..., casings and other enclosures of electric equipment receiving power from direct current power systems with... equipment receiving power from direct current power systems with one polarity grounded. For the purpose of... direct-current power system with one polarity grounded, the following methods of grounding will be...
Code of Federal Regulations, 2014 CFR
2014-07-01
..., casings and other enclosures of electric equipment receiving power from direct current power systems with... equipment receiving power from direct current power systems with one polarity grounded. For the purpose of... direct-current power system with one polarity grounded, the following methods of grounding will be...
Code of Federal Regulations, 2012 CFR
2012-07-01
..., casings and other enclosures of electric equipment receiving power from direct current power systems with... equipment receiving power from direct current power systems with one polarity grounded. For the purpose of... direct-current power system with one polarity grounded, the following methods of grounding will be...
NASA Technical Reports Server (NTRS)
Mata, Carlos T.; Mata, Angel G.
2012-01-01
A new Lightning Protection System (LPS) was designed and built at Launch Complex 39B (LC39B), at the Kennedy Space Center (KSC), Florida, which consists of a catenary wire system (at a height of about 181 meters above ground level) supported by three insulators installed atop three towers in a triangular configuration. Nine downconductors (each about 250 meters long) are connected to the catenary wire system. Each downconductor is connected to a 7.62-meter-radius circular counterpoise conductor with six equally spaced, 6-meter-long vertical grounding rods. Grounding requirements at LC39B call for all underground and aboveground metallic piping, enclosures, raceways, and cable trays, within 7.62 meters of the counterpoise, to be bonded to the counterpoise, which results in a complex interconnected grounding system, given the many metallic piping, raceways, and cable trays that run in multiple directions around LC39B. The complexity of this grounding system makes the fall-of-potential method, which uses multiple metallic rods or stakes, unsuitable for measuring the grounding impedances of the downconductors. To calculate the grounding impedance of the downconductors, an Earth Ground Clamp (EGC) (a stakeless device for measuring grounding impedance) and an Alternative Transient Program (ATP) model of the LPS are used. The EGC is used to measure the loop impedance plus the grounding impedance of each downconductor, and the ATP model is used to calculate the loop impedance of each downconductor circuit. The grounding resistance of the downconductors is then calculated by subtracting the ATP calculated loop impedances from the EGC measurements.
Ground Data System Risk Mitigation Techniques for Faster, Better, Cheaper Missions
NASA Technical Reports Server (NTRS)
Catena, John J.; Saylor, Rick; Casasanta, Ralph; Weikel, Craig; Powers, Edward I. (Technical Monitor)
2000-01-01
With the advent of faster, cheaper, and better missions, NASA Projects acknowledged that a higher level of risk was inherent and accepted with this approach. It was incumbent however upon each component of the Project whether spacecraft, payload, launch vehicle, or ground data system to ensure that the mission would nevertheless be an unqualified success. The Small Explorer (SMEX) program's ground data system (GDS) team developed risk mitigation techniques to achieve these goals starting in 1989. These techniques have evolved through the SMEX series of missions and are practiced today under the Triana program. These techniques are: (1) Mission Team Organization--empowerment of a closeknit ground data system team comprising system engineering, software engineering, testing, and flight operations personnel; (2) Common Spacecraft Test and Operational Control System--utilization of the pre-launch spacecraft integration system as the post-launch ground data system on-orbit command and control system; (3) Utilization of operations personnel in pre-launch testing--making the flight operations team an integrated member of the spacecraft testing activities at the beginning of the spacecraft fabrication phase; (4) Consolidated Test Team--combined system, mission readiness and operations testing to optimize test opportunities with the ground system and spacecraft; and (5). Reuse of Spacecraft, Systems and People--reuse of people, software and on-orbit spacecraft throughout the SMEX mission series. The SMEX ground system development approach for faster, cheaper, better missions has been very successful. This paper will discuss these risk management techniques in the areas of ground data system design, implementation, test, and operational readiness.
Facility Systems, Ground Support Systems, and Ground Support Equipment General Design Requirements
NASA Technical Reports Server (NTRS)
Thaxton, Eric A.
2014-01-01
KSC-DE-512-SM establishes overall requirements and best design practices to be used at the John F. Kennedy Space Center (KSC) for the development of ground systems (GS) in support of operations at launch, landing, and retrieval sites. These requirements apply to the design and development of hardware and software for ground support equipment (GSE), ground support systems (GSS), and facility ground support systems (F-GSS) used to support the KSC mission for transportation, receiving, handling, assembly, test, checkout, servicing, and launch of space vehicles and payloads and selected flight hardware items for retrieval. This standards manual supplements NASA-STD-5005 by including KSC-site-specific and local environment requirements. These requirements and practices are optional for equipment used at manufacturing, development, and test sites.
Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish
DOE Office of Scientific and Technical Information (OSTI.GOV)
Christen, Verena; Capelle, Martinus; Fent, Karl, E-mail: karl.fent@fhnw.ch
2013-10-15
Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120 nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplasmatic reticulum (ER) stress response, and TNF-α. Transcriptional alterations also occur in pro-apoptotic genes p53 and Bax. The transcriptional profile differed in ZFL andmore » Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6 h and 24 h exposure to 0.5 g/L and 0.05 g/L AgNPs, respectively. This indicates the induction of different pathways of the ER stress response. Moreover, AgNPs induce TNF-α. In zebrafish embryos exposed to 0.01, 0.1, 1 and 5 mg/L AgNPs hatching was affected and morphological defects occurred at high concentrations. ER stress related gene transcripts BiP and Synv are significantly up-regulated after 24 h at 0.1 and 5 mg/L AgNPs. Furthermore, transcriptional alterations occurred in the pro-apoptotic genes Noxa and p21. The ER stress response was strong in ZFL cells and occurred in zebrafish embryos as well. Our data demonstrate for the first time that AgNPs lead to induction of ER stress in zebrafish. The induction of ER stress can have several consequences including the activation of apoptotic and inflammatory pathways. - Highlights: • Effects of silver nanoparticles (120 nm AgNPs) are investigated in zebrafish. • AgNPs induce all ER stress reponses in vitro in zebrafish liver cells. • AgNPs induce weak ER stress in zebrafish embryos. • AgNPs induce oxidative stress and transcripts of pro-apoptosis genes.« less
Karlshøj, Stefanie; Amarandi, Roxana Maria; Larsen, Olav; Daugvilaite, Viktorija; Steen, Anne; Brvar, Matjaž; Pui, Aurel; Frimurer, Thomas Michael; Ulven, Trond; Rosenkilde, Mette Marie
2016-12-23
The small molecule metal ion chelators bipyridine and terpyridine complexed with Zn 2+ (ZnBip and ZnTerp) act as CCR5 agonists and strong positive allosteric modulators of CCL3 binding to CCR5, weak modulators of CCL4 binding, and competitors for CCL5 binding. Here we describe their binding site using computational modeling, binding, and functional studies on WT and mutated CCR5. The metal ion Zn 2+ is anchored to the chemokine receptor-conserved Glu-283 VII:06/7.39 Both chelators interact with aromatic residues in the transmembrane receptor domain. The additional pyridine ring of ZnTerp binds deeply in the major binding pocket and, in contrast to ZnBip, interacts directly with the Trp-248 VI:13/6.48 microswitch, contributing to its 8-fold higher potency. The impact of Trp-248 was further confirmed by ZnClTerp, a chloro-substituted version of ZnTerp that showed no inherent agonism but maintained positive allosteric modulation of CCL3 binding. Despite a similar overall binding mode of all three metal ion chelator complexes, the pyridine ring of ZnClTerp blocks the conformational switch of Trp-248 required for receptor activation, thereby explaining its lack of activity. Importantly, ZnClTerp becomes agonist to the same extent as ZnTerp upon Ala mutation of Ile-116 III:16/3.40 , a residue that constrains the Trp-248 microswitch in its inactive conformation. Binding studies with 125 I-CCL3 revealed an allosteric interface between the chemokine and the small molecule binding site, including residues Tyr-37 I:07/1.39 , Trp-86 II:20/2.60 , and Phe-109 III:09/3.33 The small molecules and CCL3 approach this interface from opposite directions, with some residues being mutually exploited. This study provides new insight into the molecular mechanism of CCR5 activation and paves the way for future allosteric drugs for chemokine receptors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Hylin, Michael J; Holden, Ryan C; Smith, Aidan C; Logsdon, Aric F; Qaiser, Rabia; Lucke-Wold, Brandon P
2018-05-22
The leading cause of death in the juvenile population is trauma, and in particular neurotrauma. The juvenile brain response to neurotrauma is not completely understood. Endoplasmic reticulum (ER) stress has been shown to contribute to injury expansion and behavioral deficits in adult rodents and furthermore has been seen in adult postmortem human brains diagnosed with chronic traumatic encephalopathy. Whether endoplasmic reticulum stress is increased in juveniles with traumatic brain injury (TBI) is poorly delineated. We investigated this important topic using a juvenile rat controlled cortical impact (CCI) model. We proposed that ER stress would be significantly increased in juvenile rats following TBI and that this would correlate with behavioral deficits using a juvenile rat model. A juvenile rat (postnatal day 28) CCI model was used. Binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP) were measured at 4 h in the ipsilateral pericontusion cortex. Hypoxia-inducible factor (HIF)-1α was measured at 48 h and tau kinase measured at 1 week and 30 days. At 4 h following injury, BiP and CHOP (markers of ER stress) were significantly elevated in rats exposed to TBI. We also found that HIF-1α was significantly upregulated 48 h following TBI showing delayed hypoxia. The early ER stress activation was additionally asso-ciated with the activation of a known tau kinase, glycogen synthase kinase-3β (GSK-3β), by 1 week. Tau oligomers measured by R23 were significantly increased by 30 days following TBI. The biochemical changes following TBI were associated with increased impulsive-like or anti-anxiety behavior measured with the elevated plus maze, deficits in short-term memory measured with novel object recognition, and deficits in spatial memory measured with the Morris water maze in juvenile rats exposed to TBI. These results show that ER stress was increased early in juvenile rats exposed to TBI, that these rats developed tau oligomers over the course of 30 days, and that they had significant short-term and spatial memory deficits following injury. © 2018 S. Karger AG, Basel.
den Hollander, Martha W; Westerink, Nico-Derk L; Lubberts, Sjoukje; Bongaerts, Alfons H H; Wolf, Rienhart F E; Altena, Renska; Nuver, Janine; Oosting, Sjoukje F; de Vries, Elisabeth G E; Walenkamp, Anna M E; Meijer, Coby; Gietema, Jourik A
2016-08-01
In metastatic testicular cancer patients treated with bleomycin, etoposide, and cisplatin (BEP) chemotherapy, bleomycin-induced pneumonitis is a well-known and potentially fatal side effect. We sought to determine the prevalence of lesions as signs of bleomycin-induced pulmonary changes on restaging computed tomography (CT) scans after treatment and to ascertain whether fibrosis markers were predictive of these changes. This prospective nonrandomized cohort study included metastatic testicular cancer patients, 18-50 years of age, treated with BEP chemotherapy. Restaging CT scans were examined for lesions as signs of bleomycin-induced pulmonary changes by two independent radiologists and graded as minor, moderate, or severe. Plasma samples were collected before, during, and after treatment and were quantified for transforming growth factor-β1 (TGF-β1), growth differentiation factor-15 (GDF-15), and high-sensitivity C-reactive protein (hs-CRP). In total, 66 patients were included: forty-five (68%) showed signs of bleomycin-induced pulmonary changes on the restaging CT scan, 37 of which were classified as minor and 8 as moderate. No differences in TGF-β1, GDF-15, or hs-CRP plasma levels were found between these groups. Bleomycin-induced pulmonary changes are common on restaging CT scans after BEP chemotherapy for metastatic testicular cancer. Changes in TGF-β1, GDF-15, and hs-CRP plasma levels do not differ between patients with and without radiological lesions as signs of bleomycin-induced pulmonary changes and are therefore not helpful as predictive biomarkers. Bleomycin-induced pneumonitis (BIP) is a well-known and potentially fatal side effect in metastatic testicular cancer patients treated with bleomycin, etoposide, and cisplatin chemotherapy. Currently, the decision to discontinue bleomycin administration is made during treatment and is based on clinical signs. An upfront or early marker or biomarker that identifies patients likely to develop BIP would be preferable. This study found that bleomycin-induced pulmonary changes are common on restaging computed tomography scans and mostly resolve. No correlation was seen between these changes and fibrosis or inflammation markers (transforming growth factor-β1, growth differentiation factor-15, and high-sensitivity C-reactive protein). ©AlphaMed Press.
Air Ground Data Link VHF Airline Communications and Reporting System (ACARS) Preliminary Test Report
DOT National Transportation Integrated Search
1995-02-01
An effort was conducted to determine actual ground-to-air, and air-to-ground : performance of the Airline Communications and Reporting system (ACARS), Very : High Frequency (VHF) Data Link System. Parameters of system throughput, error : rates, and a...
14 CFR 417.405 - Ground safety analysis.
Code of Federal Regulations, 2011 CFR
2011-01-01
... hazard from affecting the public. A launch operator must incorporate the launch site operator's systems... personnel who are knowledgeable of launch vehicle systems, launch processing, ground systems, operations...) Begin a ground safety analysis by identifying the systems and operations to be analyzed; (2) Define the...
14 CFR 417.405 - Ground safety analysis.
Code of Federal Regulations, 2010 CFR
2010-01-01
... hazard from affecting the public. A launch operator must incorporate the launch site operator's systems... personnel who are knowledgeable of launch vehicle systems, launch processing, ground systems, operations...) Begin a ground safety analysis by identifying the systems and operations to be analyzed; (2) Define the...
Blainey, Joan B.; Faunt, Claudia C.; Hill, Mary C.
2006-01-01
This report is a guide for executing numerical simulations with the transient ground-water flow model of the Death Valley regional ground-water flow system, Nevada and California using the U.S. Geological Survey modular finite-difference ground-water flow model, MODFLOW-2000. Model inputs, including observations of hydraulic head, discharge, and boundary flows, are summarized. Modification of the DVRFS transient ground-water model is discussed for two common uses of the Death Valley regional ground-water flow system model: predictive pumping scenarios that extend beyond the end of the model simulation period (1998), and model simulations with only steady-state conditions.
Advanced Ground Systems Maintenance Functional Fault Models For Fault Isolation Project
NASA Technical Reports Server (NTRS)
Perotti, Jose M. (Compiler)
2014-01-01
This project implements functional fault models (FFM) to automate the isolation of failures during ground systems operations. FFMs will also be used to recommend sensor placement to improve fault isolation capabilities. The project enables the delivery of system health advisories to ground system operators.
47 CFR 22.859 - Incumbent commercial aviation air-ground systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 47 Telecommunication 2 2010-10-01 2010-10-01 false Incumbent commercial aviation air-ground systems. 22.859 Section 22.859 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground...
Movable Ground Based Recovery System for Reuseable Space Flight Hardware
NASA Technical Reports Server (NTRS)
Sarver, George L. (Inventor)
2013-01-01
A reusable space flight launch system is configured to eliminate complex descent and landing systems from the space flight hardware and move them to maneuverable ground based systems. Precision landing of the reusable space flight hardware is enabled using a simple, light weight aerodynamic device on board the flight hardware such as a parachute, and one or more translating ground based vehicles such as a hovercraft that include active speed, orientation and directional control. The ground based vehicle maneuvers itself into position beneath the descending flight hardware, matching its speed and direction and captures the flight hardware. The ground based vehicle will contain propulsion, command and GN&C functionality as well as space flight hardware landing cushioning and retaining hardware. The ground based vehicle propulsion system enables longitudinal and transverse maneuverability independent of its physical heading.
47 CFR 15.509 - Technical requirements for ground penetrating radars and wall imaging systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 47 Telecommunication 1 2011-10-01 2011-10-01 false Technical requirements for ground penetrating radars and wall imaging systems. 15.509 Section 15.509 Telecommunication FEDERAL COMMUNICATIONS... ground penetrating radars and wall imaging systems. (a) The UWB bandwidth of an imaging system operating...
47 CFR 15.509 - Technical requirements for ground penetrating radars and wall imaging systems.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 47 Telecommunication 1 2013-10-01 2013-10-01 false Technical requirements for ground penetrating radars and wall imaging systems. 15.509 Section 15.509 Telecommunication FEDERAL COMMUNICATIONS... ground penetrating radars and wall imaging systems. (a) The UWB bandwidth of an imaging system operating...
47 CFR 15.509 - Technical requirements for ground penetrating radars and wall imaging systems.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 47 Telecommunication 1 2012-10-01 2012-10-01 false Technical requirements for ground penetrating radars and wall imaging systems. 15.509 Section 15.509 Telecommunication FEDERAL COMMUNICATIONS... ground penetrating radars and wall imaging systems. (a) The UWB bandwidth of an imaging system operating...
47 CFR 15.509 - Technical requirements for ground penetrating radars and wall imaging systems.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 47 Telecommunication 1 2014-10-01 2014-10-01 false Technical requirements for ground penetrating radars and wall imaging systems. 15.509 Section 15.509 Telecommunication FEDERAL COMMUNICATIONS... ground penetrating radars and wall imaging systems. (a) The UWB bandwidth of an imaging system operating...
47 CFR 15.509 - Technical requirements for ground penetrating radars and wall imaging systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 47 Telecommunication 1 2010-10-01 2010-10-01 false Technical requirements for ground penetrating radars and wall imaging systems. 15.509 Section 15.509 Telecommunication FEDERAL COMMUNICATIONS... ground penetrating radars and wall imaging systems. (a) The UWB bandwidth of an imaging system operating...
Franke, O. Lehn; Reilly, Thomas E.; Bennett, Gordon D.
1987-01-01
Accurate definition of boundary and initial conditions is an essential part of conceptualizing and modeling ground-water flow systems. This report describes the properties of the seven most common boundary conditions encountered in ground-water systems and discusses major aspects of their application. It also discusses the significance and specification of initial conditions and evaluates some common errors in applying this concept to ground-water-system models. An appendix is included that discusses what the solution of a differential equation represents and how the solution relates to the boundary conditions defining the specific problem. This report considers only boundary conditions that apply to saturated ground-water systems.
Safety policy and requirements for payloads using the space transportation system
NASA Technical Reports Server (NTRS)
1989-01-01
The safety policy and requirements are established applicable to the Space Transportation System (STS) payloads and their ground support equipment (GSE). The requirements are intended to protect flight and ground personnel, the STS, other payloads, GSE, the general public, public-private property, and the environment from payload-related hazards. The technical and system safety requirements applicable to STS payloads (including payload-provided ground and flight supports systems) during ground and flight operations are contained.
Ground truth management system to support multispectral scanner /MSS/ digital analysis
NASA Technical Reports Server (NTRS)
Coiner, J. C.; Ungar, S. G.
1977-01-01
A computerized geographic information system for management of ground truth has been designed and implemented to relate MSS classification results to in situ observations. The ground truth system transforms, generalizes and rectifies ground observations to conform to the pixel size and shape of high resolution MSS aircraft data. These observations can then be aggregated for comparison to lower resolution sensor data. Construction of a digital ground truth array allows direct pixel by pixel comparison between classification results of MSS data and ground truth. By making comparisons, analysts can identify spatial distribution of error within the MSS data as well as usual figures of merit for the classifications. Use of the ground truth system permits investigators to compare a variety of environmental or anthropogenic data, such as soil color or tillage patterns, with classification results and allows direct inclusion of such data into classification operations. To illustrate the system, examples from classification of simulated Thematic Mapper data for agricultural test sites in North Dakota and Kansas are provided.
Autonomic Computing for Spacecraft Ground Systems
NASA Technical Reports Server (NTRS)
Li, Zhenping; Savkli, Cetin; Jones, Lori
2007-01-01
Autonomic computing for spacecraft ground systems increases the system reliability and reduces the cost of spacecraft operations and software maintenance. In this paper, we present an autonomic computing solution for spacecraft ground systems at NASA Goddard Space Flight Center (GSFC), which consists of an open standard for a message oriented architecture referred to as the GMSEC architecture (Goddard Mission Services Evolution Center), and an autonomic computing tool, the Criteria Action Table (CAT). This solution has been used in many upgraded ground systems for NASA 's missions, and provides a framework for developing solutions with higher autonomic maturity.
The Advanced Orbiting Systems Testbed Program: Results to date
NASA Technical Reports Server (NTRS)
Otranto, John F.; Newsome, Penny A.
1994-01-01
The Consultative Committee for Space Data Systems (CCSDS) Recommendations for Packet Telemetry (PT) and Advanced Orbiting Systems (AOS) propose standard solutions to data handling problems common to many types of space missions. The Recommendations address only space/ground and space/space data handling systems. Goddard Space Flight Center's (GSFC's) AOS Testbed (AOST) Program was initiated to better understand the Recommendations and their impact on real-world systems, and to examine the extended domain of ground/ground data handling systems. The results and products of the Program will reduce the uncertainties associated with the development of operational space and ground systems that implement the Recommendations.
Benefits Derived From Laser Ranging Measurements for Orbit Determination of the GPS Satellite Orbit
NASA Technical Reports Server (NTRS)
Welch, Bryan W.
2007-01-01
While navigation systems for the determination of the orbit of the Global Position System (GPS) have proven to be very effective, the current research is examining methods to lower the error in the GPS satellite ephemerides below their current level. Two GPS satellites that are currently in orbit carry retro-reflectors onboard. One notion to reduce the error in the satellite ephemerides is to utilize the retro-reflectors via laser ranging measurements taken from multiple Earth ground stations. Analysis has been performed to determine the level of reduction in the semi-major axis covariance of the GPS satellites, when laser ranging measurements are supplemented to the radiometric station keeping, which the satellites undergo. Six ground tracking systems are studied to estimate the performance of the satellite. The first system is the baseline current system approach which provides pseudo-range and integrated Doppler measurements from six ground stations. The remaining five ground tracking systems utilize all measurements from the current system and laser ranging measurements from the additional ground stations utilized within those systems. Station locations for the additional ground sites were taken from a listing of laser ranging ground stations from the International Laser Ranging Service. Results show reductions in state covariance estimates when utilizing laser ranging measurements to solve for the satellite s position component of the state vector. Results also show dependency on the number of ground stations providing laser ranging measurements, orientation of the satellite to the ground stations, and the initial covariance of the satellite's state vector.
Grünberger, Tanja; Laireiter, Anton-Rupert
2014-01-01
In an online-survey 152 psychotherapists were asked about their subjectively perceived effects of therapeutic practice on personality and experience in private context. Changes were retrospectively measured by changes in subscales of NEO-FFI and BIP and a newly developed scale. The changes were tested for significance and influences by demographic factors. Compared to the beginning of their professional careers therapists perceived significant increases in agree-ableness, openness, self-confidence and sensitivity, and significant decreases in neuroticism and social isolation. Changes in extraversion were not significant. Demographic factors did not show any significant influence on the perceived changes. Therapeutic practice therefore seems to have a positive influence on the perceived development of personality in psychotherapists by their professional practice. © Georg Thieme Verlag KG Stuttgart · New York.
NASA Astrophysics Data System (ADS)
Kore, Ashish; Singh, Poorva
2018-05-01
We have studied the heterostructure of BaBi3 (superconductor) and stanene (topological insulator) with the aim of inducing topological superconductivity in stanene, due to proximity with superconductor BaBi3. The density functional theory calculations have been done for 2D structure of BaBi3 as well as for monolayer of stanene, separately. We find that compared to bulk BaBi3, the 2D bandstructure has contributions coming from both Ba and Bi atoms, unlike bulk where only Bi-p states are contributing to the bandstructure. Surface reconstruction of surface and sub-surface layer of 2D BaBi3 is also evident. The bandstructure of heterostructure of BaBi3-stanene is expected to bring out explicit features of topological superconductivity and indicating the presence of Majorana fermions.
van Anken, Eelco; Pena, Florentina; Hafkemeijer, Nicole; Christis, Chantal; Romijn, Edwin P.; Grauschopf, Ulla; Oorschot, Viola M. J.; Pertel, Thomas; Engels, Sander; Ora, Ari; Lástun, Viorica; Glockshuber, Rudi; Klumperman, Judith; Heck, Albert J. R.; Luban, Jeremy; Braakman, Ineke
2009-01-01
Plasma cells daily secrete their own mass in antibodies, which fold and assemble in the endoplasmic reticulum (ER). To reach these levels, cells require pERp1, a novel lymphocyte-specific small ER-resident protein, which attains expression levels as high as BiP when B cells differentiate into plasma cells. Although pERp1 has no homology with known ER proteins, it does contain a CXXC motif typical for oxidoreductases. In steady state, the CXXC cysteines are locked by two parallel disulfide bonds with a downstream C(X)6C motif, and pERp1 displays only modest oxidoreductase activity. pERp1 emerged as a dedicated folding factor for IgM, associating with both heavy and light chains and promoting assembly and secretion of mature IgM. PMID:19805154
Matrix evaluation of science objectives
NASA Technical Reports Server (NTRS)
Wessen, Randii R.
1994-01-01
The most fundamental objective of all robotic planetary spacecraft is to return science data. To accomplish this, a spacecraft is fabricated and built, software is planned and coded, and a ground system is designed and implemented. However, the quantitative analysis required to determine how the collection of science data drives ground system capabilities has received very little attention. This paper defines a process by which science objectives can be quantitatively evaluated. By applying it to the Cassini Mission to Saturn, this paper further illustrates the power of this technique. The results show which science objectives drive specific ground system capabilities. In addition, this process can assist system engineers and scientists in the selection of the science payload during pre-project mission planning; ground system designers during ground system development and implementation; and operations personnel during mission operations.
47 CFR 22.857 - Channel plan for commercial aviation air-ground systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 47 Telecommunication 2 2010-10-01 2010-10-01 false Channel plan for commercial aviation air-ground systems. 22.857 Section 22.857 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground...
30 CFR 77.902-2 - Approved ground check systems not employing pilot check wires.
Code of Federal Regulations, 2010 CFR
2010-07-01
... pilot check wires. 77.902-2 Section 77.902-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Approved ground check systems not employing pilot check wires. Ground check systems not employing pilot check wires shall be approved by the Secretary only after it has been determined that the system...
30 CFR 77.902-2 - Approved ground check systems not employing pilot check wires.
Code of Federal Regulations, 2011 CFR
2011-07-01
... pilot check wires. 77.902-2 Section 77.902-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Approved ground check systems not employing pilot check wires. Ground check systems not employing pilot check wires shall be approved by the Secretary only after it has been determined that the system...
14 CFR 23.415 - Ground gust conditions.
Code of Federal Regulations, 2010 CFR
2010-01-01
... and System Loads § 23.415 Ground gust conditions. (a) The control system must be investigated as... control system for ground gust loads is not required by paragraph (a)(2) of this section, but the applicant elects to design a part of the control system of these loads, these loads need only be carried...
30 CFR 77.902-2 - Approved ground check systems not employing pilot check wires.
Code of Federal Regulations, 2012 CFR
2012-07-01
... pilot check wires. 77.902-2 Section 77.902-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Approved ground check systems not employing pilot check wires. Ground check systems not employing pilot check wires shall be approved by the Secretary only after it has been determined that the system...
30 CFR 77.902-2 - Approved ground check systems not employing pilot check wires.
Code of Federal Regulations, 2013 CFR
2013-07-01
... pilot check wires. 77.902-2 Section 77.902-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Approved ground check systems not employing pilot check wires. Ground check systems not employing pilot check wires shall be approved by the Secretary only after it has been determined that the system...
30 CFR 77.902-2 - Approved ground check systems not employing pilot check wires.
Code of Federal Regulations, 2014 CFR
2014-07-01
... pilot check wires. 77.902-2 Section 77.902-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Approved ground check systems not employing pilot check wires. Ground check systems not employing pilot check wires shall be approved by the Secretary only after it has been determined that the system...
49 CFR 236.107 - Ground tests.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 4 2014-10-01 2014-10-01 false Ground tests. 236.107 Section 236.107...: All Systems Inspections and Tests; All Systems § 236.107 Ground tests. (a) Except as provided in paragraph (b) of this section, a test for grounds on each energy bus furnishing power to circuits, the...
49 CFR 236.107 - Ground tests.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Ground tests. 236.107 Section 236.107...: All Systems Inspections and Tests; All Systems § 236.107 Ground tests. (a) Except as provided in paragraph (b) of this section, a test for grounds on each energy bus furnishing power to circuits, the...
14 CFR 25.415 - Ground gust conditions.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground gust conditions. 25.415 Section 25... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Control Surface and System Loads § 25.415 Ground... ground gusts and taxiing downwind: (1) The control system between the stops nearest the surfaces and the...
14 CFR 25.415 - Ground gust conditions.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Ground gust conditions. 25.415 Section 25... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Control Surface and System Loads § 25.415 Ground... ground gusts and taxiing downwind: (1) The control system between the stops nearest the surfaces and the...
Landon, M.K.; Delin, G.N.; Nelson, K.J.; Regan, C.P.; Lamb, J.A.; Larson, S.J.; Capel, P.D.; Anderson, J.L.; Dowdy, R.H.
1997-01-01
The Minnesota Management Systems Evaluation Area (MSEA) project was part of a multi-scale, inter-agency initiative to evaluate the effects of agricultural management systems on water quality in the midwest corn belt. The research area was located in the Anoka Sand Plain about 5 kilometers southwest of Princeton, Minnesota. The ground-water-quality monitoring network within and immediately surrounding the research area consisted of 73 observation wells and 25 multiport wells. The primary objectives of the ground-water monitoring program at the Minnesota MSEA were to: (1) determine the effects of three farming systems on ground-water quality, and (2) understand the processes and factors affecting the loading, transport, and fate of agricultural chemicals in ground water at the site. This report presents well construction, geologic, water-level, chemical application, water-quality, and quality-assurance data used to evaluate the effects of farming systems on ground-water quality during 1991-95.
Launch and Landing Effects Ground Operations (LLEGO) Model
NASA Technical Reports Server (NTRS)
2008-01-01
LLEGO is a model for understanding recurring launch and landing operations costs at Kennedy Space Center for human space flight. Launch and landing operations are often referred to as ground processing, or ground operations. Currently, this function is specific to the ground operations for the Space Shuttle Space Transportation System within the Space Shuttle Program. The Constellation system to follow the Space Shuttle consists of the crewed Orion spacecraft atop an Ares I launch vehicle and the uncrewed Ares V cargo launch vehicle. The Constellation flight and ground systems build upon many elements of the existing Shuttle flight and ground hardware, as well as upon existing organizations and processes. In turn, the LLEGO model builds upon past ground operations research, modeling, data, and experience in estimating for future programs. Rather than to simply provide estimates, the LLEGO model s main purpose is to improve expenses by relating complex relationships among functions (ground operations contractor, subcontractors, civil service technical, center management, operations, etc.) to tangible drivers. Drivers include flight system complexity and reliability, as well as operations and supply chain management processes and technology. Together these factors define the operability and potential improvements for any future system, from the most direct to the least direct expenses.
James Webb Space Telescope: Supporting Multiple Ground System Transitions in One Year
NASA Technical Reports Server (NTRS)
Detter, Ryan; Fatig, Curtis; Steck, Jane
2004-01-01
Ideas, requirements, and concepts developed during the very early phases of the mission design often conflict with the reality of a situation once the prime contractors are awarded. This happened for the James Webb Space Telescope (JWST) as well. The high level requirement of a common real-time ground system for both the Integration and Test (I&T), as well as the Operation phase of the mission is meant to reduce the cost and time needed later in the mission development for re-certification of databases, command and control systems, scripts, display pages, etc. In the case of JWST, the early Phase A flight software development needed a real-time ground system and database prior to the spacecraft prime contractor being selected. To compound the situation, the very low level requirements for the real-time ground system were not well defined. These two situations caused the initial real-time ground system to be switched out for a system that was previously used by the Bight software development team. To meet the high-!evel requirement, a third ground system was selected based on the prime spacecraft contractor needs and JWST Project decisions. The JWST ground system team has responded to each of these changes successfully. The lessons learned from each transition have not only made each transition smoother, but have also resolved issues earlier in the mission development than what would normally occur.
Thomas, B.E.; Cox, S.E.
1998-01-01
This report describes the results of two related studies: a study of ground-water age, flow, and quality near a landfill in the south-central part of the Swinomish Indian Reservation; and a study of changes in ground-water conditions for the entire reservation from 1976 to 1996. The Swinomish Indian Reservation is a 17-square-mile part of Fidalgo Island in northwestern Washington. The groundwater flow system in the reservation is probably independent of other flow systems in the area because it is almost completely surrounded by salt water. There has been increasing stress on the ground-water resources of the reservation because the population has almost tripled during the past 20 years, and 65 percent of the population obtain their domestic water supply from the local ground-water system. The Swinomish Tribe is concerned that increased pumping of ground water might have caused decreased ground-water discharge into streams, declines in ground-water levels, and seawater intrusion into the ground-water system. There is also concern that leachate from an inactive landfill containing mostly household and wood-processing wastes may be contaminating the ground water. The study area is underlain by unconsolidated glacial and interglacial deposits of Quaternary age that range from about 300 to 900 feet thick. Five hydrogeologic units have been defined in the unconsolidated deposits. From top to bottom, the hydrogeologic units are a till confining bed, an outwash aquifer, a clay confining bed, a sea-level aquifer, and an undifferentiated unit. The ground-water flow system of the reservation is similar to other island-type flow systems. Water enters the system through the water table as infiltration and percolation of precipitation (recharge), then the water flows downward and radially outward from the center of the island. At the outside edges of the system, ground water flows upward to discharge into the surrounding saltwater bodies. Average annual recharge is estimated to be about 3 inches, or 12 percent of the average annual precipitation. Ground water in the outwash aquifer near the landfill is estimated to be between 15 and 43 years old. Some deeper ground waters and ground water near the discharge areas close to the shoreline are older than 43 years. Analysis of water-quality data collected for this study and review of existing data indicate that material in the landfill has had no appreciable impact on the current quality of ground water outside of the landfill. The water quality of samples from seven wells near to and downgradient from the landfill appears to be similar to the ground-water quality throughout the entire study area. The high iron and manganese concentrations found in most of the samples from wells near the landfill are probably within the range of natural concentrations for the study area. Ground-water pumping during the past 20 years has not caused any large changes in ground-water discharge to streams, ground-water levels, or seawater intrusion into the ground-water system. Ground-water discharge into Snee-oosh Creek and Munks Creek had similar magnitudes in the summers of 1976 and 1996; flows in both creeks during those summers ranged from 0.07 t 0.15 cubic feet per second. Ground-water levels changed minimally between 1976 and 1996. The average water-level change for 20 wells with more than 10 years between measurements was -0.7 feet and the two largest waterlevel declines were 6 and 9 feet. No appreciable seawater intrusion was found in the ground water in 1996, and there was no significant increase in the extent of seawater intrusion from 1976 to 1996. Median chloride concentrations of water samples collected from wells were 22 milligrams per liter in 1976 and 18 milligrams per liter in 1996.
Kollipara, Laxmikanth; Buchkremer, Stephan; Coraspe, José Andrés González; Hathazi, Denisa; Senderek, Jan; Weis, Joachim; Zahedi, René P.; Roos, Andreas
2017-01-01
SIL1 is a ubiquitous protein of the Endoplasmic Reticulum (ER) acting as a co-chaperone for the ER-resident chaperone, BiP. Recessive mutations of the corresponding gene lead to vulnerability of skeletal muscle and central nervous system in man (Marinesco-Sjögren syndrome; MSS) and mouse. However, it is still unclear how loss of ubiquitous SIL1 leads to selective vulnerability of the nervous system and skeletal muscle whereas other cells and organs are protected from clinical manifestations. In this study we aimed to disentangle proteins participating in selective vulnerability of SIL1-deficient cells and tissues: morphological examination of MSS patient-derived lymphoblastoid cells revealed altered organelle structures (ER, nucleus and mitochondria) thus showing subclinical vulnerability. To correlate structural perturbations with biochemical changes and to identify proteins potentially preventing phenotypical manifestation, proteomic studies have been carried out. Results of proteomic profiling are in line with the morphological findings and show affection of nuclear, mitochondrial and cytoskeletal proteins as well as of such responsible for cellular viability. Moreover, expression patterns of proteins known to be involved in neuromuscular disorders or in development and function of the nervous system were altered. Paradigmatic findings were confirmed by immunohistochemistry of splenic lymphocytes and the cerebellum of SIL1-deficient mice. Ataxin-10, identified with increased abundance in our proteome profile, is necessary for the neuronal survival but also controls muscle fiber apoptosis, thus declaring this protein as a plausible candidate for selective tissue vulnerability. Our combined results provide first insights into the molecular causes of selective cell and tissue vulnerability defining the MSS phenotype. PMID:28978133
Ulbrich, Lisa; Favaloro, Flores Lietta; Trobiani, Laura; Marchetti, Valentina; Patel, Vruti; Pascucci, Tiziana; Comoletti, Davide; Marciniak, Stefan J.; De Jaco, Antonella
2015-01-01
Several forms of monogenic heritable autism spectrum disorders are associated with mutations in the neuroligin genes. The autism-linked substitution R451C in neuroligin3 induces local misfolding of its extracellular domain, causing partial retention in the ER (endoplasmic reticulum) of expressing cells. We have generated a PC12 Tet-On cell model system with inducible expression of wild-type or R451C neuroligin3 to investigate whether there is activation of the UPR (unfolded protein response) as a result of misfolded protein retention. As a positive control for protein misfolding, we also expressed the mutant G221R neuroligin3, which is known to be completely retained within the ER. Our data show that overexpression of either R451C or G221R mutant proteins leads to the activation of all three signalling branches of the UPR downstream of the stress sensors ATF6 (activating transcription factor 6), IRE1 (inositol-requiring enzyme 1) and PERK [PKR (dsRNA-dependent protein kinase)-like endoplasmic reticulum kinase]. Each branch displayed different activation profiles that partially correlated with the degree of misfolding caused by each mutation. We also show that up-regulation of BiP (immunoglobulin heavy-chain-binding protein) and CHOP [C/EBP (CCAAT/enhancer-binding protein)-homologous protein] was induced by both mutant proteins but not by wild-type neuroligin3, both in proliferative cells and cells differentiated to a neuron-like phenotype. Collectively, our data show that mutant R451C neuroligin3 activates the UPR in a novel cell model system, suggesting that this cellular response may have a role in monogenic forms of autism characterized by misfolding mutations. PMID:26621873
2014-01-01
Background Grain chalkiness is a complex trait adversely affecting appearance and milling quality, and therefore has been one of principal targets for rice improvement. Eliminating chalkiness from rice has been a daunting task due to the complex interaction between genotype and environment and the lack of molecular markers. In addition, the molecular mechanisms underlying grain chalkiness formation are still imperfectly understood. Results We identified a notched-belly mutant (DY1102) with high percentage of white-belly, which only occurs in the bottom part proximal to the embryo. Using this mutant, a novel comparison system that can minimize the effect of genetic background and growing environment was developed. An iTRAQ-based comparative display of the proteins between the bottom chalky part and the upper translucent part of grains of DY1102 was performed. A total of 113 proteins responsible for chalkiness formation was identified. Among them, 70 proteins are up-regulated and 43 down-regulated. Approximately half of these differentially expressed proteins involved in central metabolic or regulatory pathways including carbohydrate metabolism (especially cell wall synthesis) and protein synthesis, folding and degradation, providing proteomic confirmation of the notion that chalkiness formation involves diverse but delicately regulated pathways. Protein metabolism was the most abundant category, accounting for 27.4% of the total differentially expressed proteins. In addition, down regulation of PDIL 2–3 and BiP was detected in the chalky tissue, indicating the important role of protein metabolism in grain chalkiness formation. Conclusions Using this novel comparison system, our comprehensive survey of endosperm proteomics in the notched-belly mutant provides a valuable proteomic resource for the characterization of pathways contributing to chalkiness formation at molecular and biochemical levels. PMID:24924297
2010-01-01
Background Burkholderia pseudomallei is the causative agent of melioidosis where the highest reported incidence world wide is in the Northeast of Thailand, where saline soil and water are prevalent. Moreover, recent reports indicate a potential pathogenic role for B. pseudomallei in cystic fibrosis lung disease, where an increased sodium chloride (NaCl) concentration in airway surface liquid has been proposed. These observations raise the possibility that high salinity may represent a favorable niche for B. pseudomallei. We therefore investigated the global transcriptional response of B. pseudomallei to increased salinity using microarray analysis. Results Transcriptome analysis of B. pseudomallei under salt stress revealed several genes significantly up-regulated in the presence of 320 mM NaCl including genes associated with the bsa-derived Type III secretion system (T3SS). Microarray data were verified by reverse transcriptase-polymerase chain reactions (RT-PCR). Western blot analysis confirmed the increased expression and secretion of the invasion-associated type III secreted proteins BipD and BopE in B. pseudomallei cultures at 170 and 320 mM NaCl relative to salt-free medium. Furthermore, salt-treated B. pseudomallei exhibited greater invasion efficiency into the lung epithelial cell line A549 in a manner partly dependent on a functional Bsa system. Conclusions B. pseudomallei responds to salt stress by modulating the transcription of a relatively small set of genes, among which is the bsa locus associated with invasion and virulence. Expression and secretion of Bsa-secreted proteins was elevated in the presence of exogenous salt and the invasion efficiency was enhanced. Our data indicate that salinity has the potential to influence the virulence of B. pseudomallei. PMID:20540813
Simulation-Based Acceptance Testing for Unmanned Ground Vehicles
2011-05-12
Ground Robotic Reliability Center (GRRC) at the University of Michigan in 2010, the focus of his research has been on unmanned ground vehicles...Jong Lee is a former student of the University of Michigan’s Ground Robotics Reliability Center (GRRC). He received his Bachelor’s and Master’s degree...methods to improve reliability of Unmanned Ground Vehicle (UGV) systems. His primary research interests include robotic systems and control
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Grounding frames of stationary high-voltage...-UNDERGROUND COAL MINES Grounding § 75.704 Grounding frames of stationary high-voltage equipment receiving power from ungrounded delta systems. [Statutory Provisions] The frames of all stationary high-voltage...
40 CFR 141.405 - Reporting and recordkeeping for ground water systems.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Reporting and recordkeeping for ground water systems. 141.405 Section 141.405 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Ground Water Rule § 141.405 Reporting and recordkeeping for ground...
14 CFR 23.415 - Ground gust conditions.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Ground gust conditions. 23.415 Section 23... and System Loads § 23.415 Ground gust conditions. (a) The control system must be investigated as follows for control surface loads due to ground gusts and taxiing downwind: (1) If an investigation of the...
Current Thrusts in Ground Robotics: Programs, Systems, Technologies, Issues
2000-03-01
MPRS – Demo III – MDARS-E and MDARS-I – JAUGS SPAWAR Systems Center, San Diego San Diego CA 92152-7383 Basic UXO Gathering System (BUGS) Use tens of...processing resources • Modularity improves sensor fusion for alarms and alerts • Joint Architecture for Unmanned Ground Systems ( JAUGS ) SPAWAR Systems...pp lic at io ns 1996 1998 2000 2002 SPAWAR Systems Center, San Diego San Diego CA 92152-7383 JAUGS : Joint Architecture for Unmanned Ground Systems
Snyder, D.T.; Wilkinson, J.M.; Orzol, L.L.
1996-01-01
A ground-water flow model was used in conjunction with particle tracking to evaluate ground-water vulnerability in Clark County, Washington. Using the particle-tracking program, particles were placed in every cell of the flow model (about 60,000 particles) and tracked backwards in time and space upgradient along flow paths to their recharge points. A new computer program was developed that interfaces the results from a particle-tracking program with a geographic information system (GIS). The GIS was used to display and analyze the particle-tracking results. Ground-water vulnerability was evaluated by selecting parts of the ground-water flow system and combining the results with ancillary information stored in the GIS to determine recharge areas, characteristics of recharge areas, downgradient impact of land use at recharge areas, and age of ground water. Maps of the recharge areas for each hydrogeologic unit illustrate the presence of local, intermediate, or regional ground-water flow systems and emphasize the three-dimensional nature of the ground-water flow system in Clark County. Maps of the recharge points for each hydrogeologic unit were overlaid with maps depicting aquifer sensitivity as determined by DRASTIC (a measure of the pollution potential of ground water, based on the intrinsic characteristics of the near-surface unsaturated and saturated zones) and recharge from on-site waste-disposal systems. A large number of recharge areas were identified, particularly in southern Clark County, that have a high aquifer sensitivity, coincide with areas of recharge from on-site waste-disposal systems, or both. Using the GIS, the characteristics of the recharge areas were related to the downgradient parts of the ground-water system that will eventually receive flow that has recharged through these areas. The aquifer sensitivity, as indicated by DRASTIC, of the recharge areas for downgradient parts of the flow system was mapped for each hydrogeologic unit. A number of public-supply wells in Clark County may be receiving a component of water that recharged in areas that are more conducive to contaminant entry. The aquifer sensitivity maps illustrate a critical deficiency in the DRASTIC methodology: the failure to account for the dynamics of the ground-water flow system. DRASTIC indices calculated for a particular location thus do not necessarily reflect the conditions of the ground-water resources at the recharge areas to that particular location. Each hydrogeologic unit was also mapped to highlight those areas that will eventually receive flow from recharge areas with on-site waste-disposal systems. Most public-supply wells in southern Clark County may eventually receive a component of water that was recharged from on-site waste-disposal systems.Traveltimes from particle tracking were used to estimate the minimum and maximum age of ground water within each model-grid cell. Chlorofluorocarbon (CFC)-age dating of ground water from 51 wells was used to calibrate effective porosity values used for the particle- tracking program by comparison of ground-water ages determined through the use of the CFC-age dating with those calculated by the particle- tracking program. There was a 76 percent agreement in predicting the presence of modern water in the 51 wells as determined using CFCs and calculated by the particle-tracking program. Maps showing the age of ground water were prepared for all the hydrogeologic units. Areas with the youngest ground-water ages are expected to be at greatest risk for contamination from anthropogenic sources. Comparison of these maps with maps of public- supply wells in Clark County indicates that most of these wells may withdraw ground water that is, in part, less than 100 years old, and in many instances less than 10 years old. Results of the analysis showed that a single particle-tracking analysis simulating advective transport can be used to evaluate ground-water vulnerability for any part of a ground-wate
Application of an adaptive neuro-fuzzy inference system to ground subsidence hazard mapping
NASA Astrophysics Data System (ADS)
Park, Inhye; Choi, Jaewon; Jin Lee, Moung; Lee, Saro
2012-11-01
We constructed hazard maps of ground subsidence around abandoned underground coal mines (AUCMs) in Samcheok City, Korea, using an adaptive neuro-fuzzy inference system (ANFIS) and a geographical information system (GIS). To evaluate the factors related to ground subsidence, a spatial database was constructed from topographic, geologic, mine tunnel, land use, and ground subsidence maps. An attribute database was also constructed from field investigations and reports on existing ground subsidence areas at the study site. Five major factors causing ground subsidence were extracted: (1) depth of drift; (2) distance from drift; (3) slope gradient; (4) geology; and (5) land use. The adaptive ANFIS model with different types of membership functions (MFs) was then applied for ground subsidence hazard mapping in the study area. Two ground subsidence hazard maps were prepared using the different MFs. Finally, the resulting ground subsidence hazard maps were validated using the ground subsidence test data which were not used for training the ANFIS. The validation results showed 95.12% accuracy using the generalized bell-shaped MF model and 94.94% accuracy using the Sigmoidal2 MF model. These accuracy results show that an ANFIS can be an effective tool in ground subsidence hazard mapping. Analysis of ground subsidence with the ANFIS model suggests that quantitative analysis of ground subsidence near AUCMs is possible.
46 CFR 169.676 - Grounded electrical systems.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 7 2013-10-01 2013-10-01 false Grounded electrical systems. 169.676 Section 169.676... Machinery and Electrical Electrical Installations Operating at Potentials of 50 Volts Or More on Vessels of Less Than 100 Gross Tons § 169.676 Grounded electrical systems. (a) Except as provided in paragraph (b...
46 CFR 169.676 - Grounded electrical systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 7 2010-10-01 2010-10-01 false Grounded electrical systems. 169.676 Section 169.676... Machinery and Electrical Electrical Installations Operating at Potentials of 50 Volts Or More on Vessels of Less Than 100 Gross Tons § 169.676 Grounded electrical systems. (a) Except as provided in paragraph (b...
46 CFR 169.676 - Grounded electrical systems.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 7 2012-10-01 2012-10-01 false Grounded electrical systems. 169.676 Section 169.676... Machinery and Electrical Electrical Installations Operating at Potentials of 50 Volts Or More on Vessels of Less Than 100 Gross Tons § 169.676 Grounded electrical systems. (a) Except as provided in paragraph (b...
46 CFR 169.676 - Grounded electrical systems.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 7 2014-10-01 2014-10-01 false Grounded electrical systems. 169.676 Section 169.676... Machinery and Electrical Electrical Installations Operating at Potentials of 50 Volts Or More on Vessels of Less Than 100 Gross Tons § 169.676 Grounded electrical systems. (a) Except as provided in paragraph (b...
46 CFR 169.676 - Grounded electrical systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 7 2011-10-01 2011-10-01 false Grounded electrical systems. 169.676 Section 169.676... Machinery and Electrical Electrical Installations Operating at Potentials of 50 Volts Or More on Vessels of Less Than 100 Gross Tons § 169.676 Grounded electrical systems. (a) Except as provided in paragraph (b...
30 CFR 77.700-1 - Approved methods of grounding.
Code of Federal Regulations, 2014 CFR
2014-07-01
... in resistance grounded systems, where the enclosed conductors are a part of the system, will be approved if a solid connection is made to the neutral conductor; in all other systems, the following... earth; (b) A solid connection to a grounding conductor, other than the neutral conductor of a resistance...
30 CFR 77.700-1 - Approved methods of grounding.
Code of Federal Regulations, 2012 CFR
2012-07-01
... in resistance grounded systems, where the enclosed conductors are a part of the system, will be approved if a solid connection is made to the neutral conductor; in all other systems, the following... earth; (b) A solid connection to a grounding conductor, other than the neutral conductor of a resistance...
Fio, John L.; Leighton, David A.
1994-01-01
Chemical and geohydrologic data were used to assess the effects of regional ground-water flow on the quality of on-farm drainflows in a part of the western San Joaquin Valley, California. Shallow ground water beneath farm fields has been enriched in stable isotopes and salts by partial evaporation from the shallow water table and is being displaced by irrigation, drainage, and regional ground-water flow. Ground-water flow is primarily downward in the study area but can flow upward in some down- slope areas. Transitional areas exist between the downward and upward flow zones, where ground water can move substantial horizontal distances (0.3 to 3.6 kilometers) and can require 10 to 90 years to reach the downslope drainage systems. Simulation of ground-water flow to drainage systems indicates that regional ground water contributes to about 11 percent of annual drainflow. Selenium concentrations in ground water and drainwater are affected by geologic source materials, partial evaporation from a shallow water table, drainage-system, and regional ground-water flow. Temporal variability in drainflow quality is affected in part by the distribution of chemical constituents in ground water and the flow paths to the drainage systems. The mass flux of selenium in drainflows, or load, generally is proportional to flow, and reductions in drainflow quantity should reduce selenium loads over the short-term. Uncertain changes in the distribution of ground-water quality make future changes in drainflow quality difficult to quantify.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Shuo; Maillet, Yoann; Wang, Fei
2010-01-01
High-frequency common-mode (CM) electromagnetic-interference (EMI) noise is difficult to suppress in electronics systems. EMI filters are used to suppress CM noise, but their performance is greatly affected by the parasitic effects of the grounding paths. In this paper, the parasitic effects of the grounding paths on an EMI filter's performance are investigated in a motor-drive system. The effects of the mutual inductance between two grounding paths are explored. Guidelines for the grounding of CM EMI filters are derived. Simulations and experiments are finally carried out to verify the theoretical analysis.
Advanced Ground Systems Maintenance Physics Models For Diagnostics Project
NASA Technical Reports Server (NTRS)
Perotti, Jose M.
2015-01-01
The project will use high-fidelity physics models and simulations to simulate real-time operations of cryogenic and systems and calculate the status/health of the systems. The project enables the delivery of system health advisories to ground system operators. The capability will also be used to conduct planning and analysis of cryogenic system operations. This project will develop and implement high-fidelity physics-based modeling techniques tosimulate the real-time operation of cryogenics and other fluids systems and, when compared to thereal-time operation of the actual systems, provide assessment of their state. Physics-modelcalculated measurements (called “pseudo-sensors”) will be compared to the system real-timedata. Comparison results will be utilized to provide systems operators with enhanced monitoring ofsystems' health and status, identify off-nominal trends and diagnose system/component failures.This capability can also be used to conduct planning and analysis of cryogenics and other fluidsystems designs. This capability will be interfaced with the ground operations command andcontrol system as a part of the Advanced Ground Systems Maintenance (AGSM) project to helpassure system availability and mission success. The initial capability will be developed for theLiquid Oxygen (LO2) ground loading systems.
Zero to Integration in Eight Months, the Dawn Ground Data System Engineering Challange
NASA Technical Reports Server (NTRS)
Dubon, Lydia P.
2006-01-01
The Dawn Project has presented the Ground Data System (GDS) with technical challenges driven by cost and schedule constraints commonly associated with National Aeronautics and Space Administration (NASA) Discovery Projects. The Dawn mission consists of a new and exciting Deep Space partnership among: the Jet Propulsion Laboratory (JPL), responsible for project management and flight operations; Orbital Sciences Corporation (OSC), spacecraft builder and responsible for flight system test and integration; and the University of California, at Los Angeles (UCLA), responsible for science planning and operations. As a cost-capped mission, one of Dawn s implementation strategies is to leverage from both flight and ground heritage. OSC's ground data system is used for flight system test and integration as part of the flight heritage strategy. Mission operations, however, are to be conducted with JPL s ground system. The system engineering challenge of dealing with two heterogeneous ground systems emerged immediately. During the first technical interchange meeting between the JPL s GDS Team and OSC's Flight Software Team, August 2003, the need to integrate the ground system with the flight software was brought to the table. This need was driven by the project s commitment to enable instrument engineering model integration in a spacecraft simulator environment, for both demonstration and risk mitigation purposes, by April 2004. This paper will describe the system engineering approach that was undertaken by JPL's GDS Team in order to meet the technical challenge within a non-negotiable eight-month schedule. Key to the success was adherence to an overall systems engineering process and fundamental systems engineering practices: decomposition of the project request into manageable requirements; definition of a structured yet flexible development process; integration of multiple ground disciplines and experts into a focused team effort; in-process risk management; and aggregation of the intermediate products to an integrated final product. In addition, this paper will highlight the role of lessons learned from the integration experience. The lessons learned from an early GDS deployment have served as the foundation for the design and implementation of the Dawn Ground Data System.
Juckem, Paul F.
2009-01-01
A regional, two-dimensional, areal ground-water-flow model was developed to simulate the ground-water-flow system and ground-water/surface-water interaction in the Rock River Basin. The model was developed by the U.S. Geological Survey (USGS), in cooperation with the Rock River Coalition. The objectives of the regional model were to improve understanding of the ground-water-flow system and to develop a tool suitable for evaluating the effects of potential regional water-management programs. The computer code GFLOW was used because of the ease with which the model can simulate ground-water/surface-water interactions, provide a framework for simulating regional ground-water-flow systems, and be refined in a stepwise fashion to incorporate new data and simulate ground-water-flow patterns at multiple scales. The ground-water-flow model described in this report simulates the major hydrogeologic features of the modeled area, including bedrock and surficial aquifers, ground-water/surface-water interactions, and ground-water withdrawals from high-capacity wells. The steady-state model treats the ground-water-flow system as a single layer with hydraulic conductivity and base elevation zones that reflect the distribution of lithologic groups above the Precambrian bedrock and a regionally significant confining unit, the Maquoketa Formation. In the eastern part of the Basin where the shale-rich Maquoketa Formation is present, deep ground-water flow in the sandstone aquifer below the Maquoketa Formation was not simulated directly, but flow into this aquifer was incorporated into the GFLOW model from previous work in southeastern Wisconsin. Recharge was constrained primarily by stream base-flow estimates and was applied uniformly within zones guided by regional infiltration estimates for soils. The model includes average ground-water withdrawals from 1997 to 2006 for municipal wells and from 1997 to 2005 for high-capacity irrigation, industrial, and commercial wells. In addition, the model routes tributary base flow through the river network to the Rock River. The parameter-estimation code PEST was linked to the GFLOW model to select the combination of parameter values best able to match more than 8,000 water-level measurements and base-flow estimates at 9 streamgages. Results from the calibrated GFLOW model show simulated (1) ground-water-flow directions, (2) ground-water/surface-water interactions, as depicted in a map of gaining and losing river and lake sections, (3) ground-water contributing areas for selected tributary rivers, and (4) areas of relatively local ground water captured by rivers. Ground-water flow patterns are controlled primarily by river geometries, with most river sections gaining water from the ground-water-flow system; losing sections are most common on the downgradient shore of lakes and reservoirs or near major pumping centers. Ground-water contributing areas to tributary rivers generally coincide with surface watersheds; however the locations of ground-water divides are controlled by the water table, whereas surface-water divides are controlled by surface topography. Finally, areas of relatively local ground water captured by rivers generally extend upgradient from rivers but are modified by the regional flow pattern, such that these areas tend to shift toward regional ground-water divides for relatively small rivers. It is important to recognize the limitations of this regional-scale model. Heterogeneities in subsurface properties and in recharge rates are considered only at a very broad scale (miles to tens of miles). No account is taken of vertical variations in properties or pumping rates, and no provision is made to account for stacked ground-water-flow systems that have different flow patterns at different depths. Small-scale flow systems (hundreds to thousands of feet) associated with minor water bodies are not considered; as a result, the model is not currently designed for simulating site-specifi
Storage, retrieval, and analysis of ST data
NASA Technical Reports Server (NTRS)
Albrecht, R.
1984-01-01
Space Telescope can generate multidimensional image data, very similar in nature to data produced with microdensitometers. An overview is presented of the ST science ground system between carrying out the observations and the interactive analysis of preprocessed data. The ground system elements used in data archival and retrieval are described and operational procedures are discussed. Emphasis is given to aspects of the ground system that are relevant to the science user and to general principles of system software development in a production environment. While the system being developed uses relatively conservative concepts for the launch baseline, concepts were developed to enhance the ground system. This includes networking, remote access, and the utilization of alternate data storage technologies.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Grounding frames of stationary high-voltage..., SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Grounding § 77.703 Grounding frames of stationary high-voltage equipment receiving power from ungrounded delta systems. The frames of all stationary...
Technology Transfer Opportunities: Automated Ground-Water Monitoring, A Proven Technology
Smith, Kirk P.; Granato, Gregory E.
1998-01-01
Introduction The U.S. Geological Survey (USGS) has developed and tested an automated ground-water monitoring system that measures and records values of selected water-quality properties and constituents using protocols approved for manual sampling. Prototypes using the automated process have demonstrated the ability to increase the quantity and quality of data collected and have shown the potential for reducing labor and material costs for ground-water quality data collection. Automated ground-water monitoring systems can be used to monitor known or potential contaminant sites, such as near landfills, underground storage tanks, or other facilities where potential contaminants are stored, to serve as early warning systems monitoring ground-water quality near public water-supply wells, and for ground-water quality research.
NASA Technical Reports Server (NTRS)
Gernand, Jeffrey L.; Gillespie, Amanda M.; Monaghan, Mark W.; Cummings, Nicholas H.
2010-01-01
Success of the Constellation Program's lunar architecture requires successfully launching two vehicles, Ares I/Orion and Ares V/Altair, in a very limited time period. The reliability and maintainability of flight vehicles and ground systems must deliver a high probability of successfully launching the second vehicle in order to avoid wasting the on-orbit asset launched by the first vehicle. The Ground Operations Project determined which ground subsystems had the potential to affect the probability of the second launch and allocated quantitative availability requirements to these subsystems. The Ground Operations Project also developed a methodology to estimate subsystem reliability, availability and maintainability to ensure that ground subsystems complied with allocated launch availability and maintainability requirements. The verification analysis developed quantitative estimates of subsystem availability based on design documentation; testing results, and other information. Where appropriate, actual performance history was used for legacy subsystems or comparative components that will support Constellation. The results of the verification analysis will be used to verify compliance with requirements and to highlight design or performance shortcomings for further decision-making. This case study will discuss the subsystem requirements allocation process, describe the ground systems methodology for completing quantitative reliability, availability and maintainability analysis, and present findings and observation based on analysis leading to the Ground Systems Preliminary Design Review milestone.
NASA Technical Reports Server (NTRS)
Spencer, M. M.; Wolf, J. M.; Schall, M. A.
1974-01-01
A system of computer programs were developed which performs geometric rectification and line-by-line mapping of airborne multispectral scanner data to ground coordinates and estimates ground area. The system requires aircraft attitude and positional information furnished by ancillary aircraft equipment, as well as ground control points. The geometric correction and mapping procedure locates the scan lines, or the pixels on each line, in terms of map grid coordinates. The area estimation procedure gives ground area for each pixel or for a predesignated parcel specified in map grid coordinates. The results of exercising the system with simulated data showed the uncorrected video and corrected imagery and produced area estimates accurate to better than 99.7%.
High Power Microwave Tube Reliability Study
1976-08-01
Factors . . . . . ................ 67 1. Environmental Factors . . . . . . . . . a. Ground Fixed ...... .......... 67 b. Ground Mobile ...including cube structure and operating parameters as factors in the models but also environment and aplication . Initially, the tubes to be included in...instLllations. Mobile ground based and seagoing systems have minimum restrictions, spacecraft systems the maximum and airborne system Y 6 .*.. restrictionts
Code of Federal Regulations, 2013 CFR
2013-07-01
... receiving power from ungrounded alternating current power systems. 77.701-1 Section 77.701-1 Mineral... power systems. For purposes of grounding metallic frames, casings and other enclosures of equipment receiving power from ungrounded alternating current power systems, the following methods of grounding will...
Code of Federal Regulations, 2012 CFR
2012-07-01
... receiving power from ungrounded alternating current power systems. 77.701-1 Section 77.701-1 Mineral... power systems. For purposes of grounding metallic frames, casings and other enclosures of equipment receiving power from ungrounded alternating current power systems, the following methods of grounding will...
Code of Federal Regulations, 2014 CFR
2014-07-01
... receiving power from ungrounded alternating current power systems. 77.701-1 Section 77.701-1 Mineral... power systems. For purposes of grounding metallic frames, casings and other enclosures of equipment receiving power from ungrounded alternating current power systems, the following methods of grounding will...
NASA Technical Reports Server (NTRS)
Jackson, Mariea Dunn; Dischinger, Charles; Stambolian, Damon; Henderson, Gena
2012-01-01
Spacecraft and launch vehicle ground processing activities require a variety of unique human activities. These activities are being documented in a Primitive motion capture library. The Library will be used by the human factors engineering in the future to infuse real to life human activities into the CAD models to verify ground systems human factors requirements. As the Primitive models are being developed for the library the project has selected several current human factors issues to be addressed for the SLS and Orion launch systems. This paper explains how the Motion Capture of unique ground systems activities are being used to verify the human factors analysis requirements for ground system used to process the STS and Orion vehicles, and how the primitive models will be applied to future spacecraft and launch vehicle processing.
Postures and Motions Library Development for Verification of Ground Crew Human Factors Requirements
NASA Technical Reports Server (NTRS)
Stambolian, Damon; Henderson, Gena; Jackson, Mariea Dunn; Dischinger, Charles
2013-01-01
Spacecraft and launch vehicle ground processing activities require a variety of unique human activities. These activities are being documented in a primitive motion capture library. The library will be used by human factors engineering analysts to infuse real to life human activities into the CAD models to verify ground systems human factors requirements. As the primitive models are being developed for the library, the project has selected several current human factors issues to be addressed for the Space Launch System (SLS) and Orion launch systems. This paper explains how the motion capture of unique ground systems activities is being used to verify the human factors engineering requirements for ground systems used to process the SLS and Orion vehicles, and how the primitive models will be applied to future spacecraft and launch vehicle processing.
New developments in ground probing radar for Earth resource mapping and planetology
NASA Astrophysics Data System (ADS)
Cattermole, P. J.; Junkin, G.; Finkelstein, M. I.; Kingsley, S. P.
1992-07-01
Ground probing radar is a well established technique for locating buried objects and has found application in resource mapping. The development of this technology for the Mars exploration programme has lead to lightweight systems with potential applications for investigating shallow geological structures on Earth, Mars and Venus. Recent advances in ground probing radar technology for planetary exploration include the development of single-antenna systems with improved beam focussing into the ground and a move to lower frequencies which considerably extends the depth penetration in dry ground. These systems are designed for mobility and could form the basis of autonomous mapping systems for terrestrial exploration. Such systems would be particularly valuable for water resource surveying in arid and semi-arid regions, where there is a need to have lightweight instrumentation that can be moved into sometimes inhospitable terrain.
Re-Engineering of the Hubble Space Telescope (HST) to Reduce Operational Costs
NASA Technical Reports Server (NTRS)
Garvis, Michael; Dougherty, Andrew; Whittier, Wallace
1996-01-01
Satellite telemetry processing onboard the Hubble Space Telescope (HST) is carried out using dedicated software and hardware. The current ground system is expensive to operate and maintain. The mandate to reduce satellite ground system operations and maintenance costs by the year 2000 led NASA to upgrade the command and control systems in order to improve the data processing capabilities, reduce operator experience levels and increase system standardization. As a result, a command and control system product development team was formed to redesign and develop the HST ground system. The command and control system ground system development consists of six elements. The results of the prototyping phase carried out for the following of these elements are presented: the front end processor; middleware, and the graphical user interface.
Zero to Integration in Eight Months, the Dawn Ground Data System Engineering Challenge
NASA Technical Reports Server (NTRS)
Dubon, Lydia P.
2006-01-01
The Dawn Project has presented the Ground Data System (GDS) with technical challenges driven by cost and schedule constraints commonly associated with National Aeronautics and Space Administration (NASA) Discovery Projects. The Dawn mission consists of a new and exciting Deep Space partnership among: the Jet Propulsion Laboratory (JPL), manages the project and is responsible for flight operation; Orbital Sciences Corporation (OSC), is the spacecraft builder and is responsible for flight system test and integration; and the University of California, at Los Angeles (UCLA), is responsible for science planning and operations. As a cost-capped mission, one of Dawn's implementation strategies is to leverage from both flight and ground heritage. OSC's ground data system is used for flight system test and integration as part of the flight heritage strategy. Mission operations, however, are to be conducted with JPL's ground system. The system engineering challenge of dealing with two heterogeneous ground systems emerged immediately. During the first technical interchange meeting between the JPL's GDS Team and OSC's Flight Software Team, August 2003, the need to integrate the ground system with the flight software was brought to the table. This need was driven by the project's commitment to enable instrument engineering model integration in a spacecraft simulator environment, for both demonstration and risk mitigation purposes, by April 2004. This paper will describe the system engineering approach that was undertaken by JPL's GDS Team in order to meet the technical challenge within a non-negotiable eight-month schedule. Key to the success was adherence to fundamental systems engineering practices: decomposition of the project request into manageable requirements; integration of multiple ground disciplines and experts into a focused team effort; definition of a structured yet flexible development process; definition of an in-process risk reduction plan; and aggregation of the intermediate products to an integrated final product. In addition, this paper will highlight the role of lessons learned from the integration experience. The lessons learned from an early GDS deployment have served as the foundation for the design and implementation of the Dawn Ground Data System.
Automated Ground Umbilical Systems (AGUS) Project
NASA Technical Reports Server (NTRS)
Gosselin, Armand M.
2007-01-01
All space vehicles require ground umbilical systems for servicing. Servicing requirements can include, but are not limited to, electrical power and control, propellant loading and venting, pneumatic system supply, hazard gas detection and purging as well as systems checkout capabilities. Of the various types of umbilicals, all require several common subsystems. These typically include an alignment system, mating and locking system, fluid connectors, electrical connectors and control !checkout systems. These systems have been designed to various levels of detail based on the needs for manual and/or automation requirements. The Automated Ground Umbilical Systems (AGUS) project is a multi-phase initiative to develop design performance requirements and concepts for launch system umbilicals. The automation aspect minimizes operational time and labor in ground umbilical processing while maintaining reliability. This current phase of the project reviews the design, development, testing and operations of ground umbilicals built for the Saturn, Shuttle, X-33 and Atlas V programs. Based on the design and operations lessons learned from these systems, umbilicals can be optimized for specific applications. The product of this study is a document containing details of existing systems and requirements for future automated umbilical systems with emphasis on design-for-operations (DFO).
47 CFR 22.880 - Information exchange.
Code of Federal Regulations, 2010 CFR
2010-10-01
... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.880 Information exchange. (a) Prior notification. Public safety/CII licensees may notify a commercial aviation air-ground system...
Potential effects of the Hawaii Geothermal Project on ground-water resources on the island of Hawaii
Sorey, M.L.; Colvard, E.M.
1994-01-01
In 1990, the State of Hawaii proposed the Hawaii Geothermal Project for the development of as much as 500 MW of electric power from the geothermal system in the East Rift Zone of Kilauea Volcano. This report uses data from 31 wells and 8 springs to describe the properties of the ground-water system in and adjacent to the East Rift Zone. Potential effects of this project on ground-water resources are also discussed. Data show differences in ground-water chemistry and heads within the study area that appear to be related to mixing of waters of different origins and ground-water impoundment by volcanic dikes. East of Pahoa, the ground-water system within the rift is highly transmissive and receives abundant recharge from precipitation; therefore, the pumping of freshwater to support geothermal development in that part of the rift zone would have a minimal effect on ground-water levels. To the southwest of Pahoa, dike impoundment reduces the transmissivity of the ground-water system to such an extent that wells might not be capable of supplying sufficient fresh water to support geothermal operations. Contamination of ground-water resources by accidental release of geothermal fluids into shallow aquifers is possible because of corrosive conditions in the geothermal wells, potential well blowouts, and high ground-water velocities in parts of the region. Hydrologic monitoring of water level, temperature, and chemistry in observation wells should continue throughout development of geothermal resources for the Hawaii Geothermal Project for early detection of leakage and migration of geothermal fluids within the groundwater system.
Sepúlveda, Nicasio
2002-01-01
A numerical model of the intermediate and Floridan aquifer systems in peninsular Florida was used to (1) test and refine the conceptual understanding of the regional ground-water flow system; (2) develop a data base to support subregional ground-water flow modeling; and (3) evaluate effects of projected 2020 ground-water withdrawals on ground-water levels. The four-layer model was based on the computer code MODFLOW-96, developed by the U.S. Geological Survey. The top layer consists of specified-head cells simulating the surficial aquifer system as a source-sink layer. The second layer simulates the intermediate aquifer system in southwest Florida and the intermediate confining unit where it is present. The third and fourth layers simulate the Upper and Lower Floridan aquifers, respectively. Steady-state ground-water flow conditions were approximated for time-averaged hydrologic conditions from August 1993 through July 1994 (1993-94). This period was selected based on data from Upper Floridan a quifer wells equipped with continuous water-level recorders. The grid used for the ground-water flow model was uniform and composed of square 5,000-foot cells, with 210 columns and 300 rows.
Configurable technology development for reusable control and monitor ground systems
NASA Technical Reports Server (NTRS)
Uhrlaub, David R.
1994-01-01
The control monitor unit (CMU) uses configurable software technology for real-time mission command and control, telemetry processing, simulation, data acquisition, data archiving, and ground operations automation. The base technology is currently planned for the following control and monitor systems: portable Space Station checkout systems; ecological life support systems; Space Station logistics carrier system; and the ground system of the Delta Clipper (SX-2) in the Single-Stage Rocket Technology program. The CMU makes extensive use of commercial technology to increase capability and reduce development and life-cycle costs. The concepts and technology are being developed by McDonnell Douglas Space and Defense Systems for the Real-Time Systems Laboratory at NASA's Kennedy Space Center under the Payload Ground Operations Contract. A second function of the Real-Time Systems Laboratory is development and utilization of advanced software development practices.
Electrical Grounding Architecture for Unmanned Spacecraft
NASA Technical Reports Server (NTRS)
1998-01-01
This handbook is approved for use by NASA Headquarters and all NASA Centers and is intended to provide a common framework for consistent practices across NASA programs. This handbook was developed to describe electrical grounding design architecture options for unmanned spacecraft. This handbook is written for spacecraft system engineers, power engineers, and electromagnetic compatibility (EMC) engineers. Spacecraft grounding architecture is a system-level decision which must be established at the earliest point in spacecraft design. All other grounding design must be coordinated with and be consistent with the system-level architecture. This handbook assumes that there is no one single 'correct' design for spacecraft grounding architecture. There have been many successful satellite and spacecraft programs from NASA, using a variety of grounding architectures with different levels of complexity. However, some design principles learned over the years apply to all types of spacecraft development. This handbook summarizes those principles to help guide spacecraft grounding architecture design for NASA and others.
Moreo, Michael T.; Justet, Leigh
2008-01-01
Ground-water withdrawal estimates from 1913 through 2003 for the Death Valley regional ground-water flow system are compiled in an electronic database to support a regional, three-dimensional, transient ground-water flow model. This database updates a previously published database that compiled estimates of ground-water withdrawals for 1913-1998. The same methodology is used to construct each database. Primary differences between the 2 databases are an additional 5 years of ground-water withdrawal data, well locations in the updated database are restricted to Death Valley regional ground-water flow system model boundary, and application rates are from 0 to 1.5 feet per year lower than original estimates. The lower application rates result from revised estimates of crop consumptive use, which are based on updated estimates of potential evapotranspiration. In 2003, about 55,700 acre-feet of ground water was pumped in the DVRFS, of which 69 percent was used for irrigation, 13 percent for domestic, and 18 percent for public supply, commercial, and mining activities.
Millimeter Wave Radar Applications to Weapons Systems
1976-06-01
meter wave region compared with the high attenuation in the optical region. It is this unique characteristic of millimeter waves to penetrate fog...miiliaeter wave radars in graund-to-- air , ground-to-ground, and air -to-ground weapons systems aye presented. The advantages and limitation~s¶ of operating...MILLIMETER WAVE RADAR CHARACTERISTICS ..... ............ .. 27 A, General ................ ......................... ... 27 B. Ground-to- Air Millimeter
TRACTS: a program to map oligopurine.oligopyrimidine and other binary DNA tracts
Gal, Moshe; Katz, Tzvi; Ovadia, Amir; Yagil, Gad
2003-01-01
A program to map the locations and frequencies of DNA tracts composed of only two bases (‘Binary DNA’) is described. The program, TRACTS (URL http://bioportal.weizmann.ac.il/tracts/tracts.html and/or http://bip.weizmann.ac.il/miwbin/servers/tracts) is of interest because long tracts composed of only two bases are highly over-represented in most genomes. In eukaryotes, oligopurine.oligopyrimidine tracts (‘R.Y tracts’) are found in the highest excess. In prokaryotes, W tracts predominate (A,T ‘rich’). A pre-program, ANEX, parses database annotation files of GenBank and EMBL, to produce a convenient one-line list of every gene (exon, intron) in a genome. The main unit lists and analyzes tracts of the three possible binary pairs (R.Y, K.M and S;W). As an example, the results of R.Y tract mapping of mammalian gene p53 is described. PMID:12824393
Identification of Nanocrystalline Inclusions in Bismuth-Doped Silica Fibers and Preforms.
Iskhakova, Liudmila D; Milovich, Filipp O; Mashinsky, Valery M; Zlenko, Alexander S; Borisovsky, Sergey E; Dianov, Evgeny M
2016-10-01
The nature of nanocrystalline inclusions and dopant distribution in bismuth-doped silicate fibers and preforms are studied by scanning and transmission electron microscopy, and energy and wavelength-dispersive X-ray microanalysis. The core compositions are Bi:SiO2, Bi:Al2O3-SiO2, Bi:GeO2-SiO2, Bi:Al2O3-GeO2-SiO2, and Bi:P2O5-Al2O3-GeO2-SiO2. Nanocrystals of metallic Bi, Bi2O3, SiO2, GeO2, and Bi4(GeO4)3 are observed in these glasses. These inclusions can be the reason for the background optical loss in bismuth-doped optical fibers. The bismuth concentration of 0.0048±0.0006 at% is directly measured in aluminosilicate optical fibers with effective laser generation (slope efficiency of 27% at room temperature).
Effect of ultrasonic cavitation on measurement of sound pressure using hydrophone
NASA Astrophysics Data System (ADS)
Thanh Nguyen, Tam; Asakura, Yoshiyuki; Okada, Nagaya; Koda, Shinobu; Yasuda, Keiji
2017-07-01
Effect of ultrasonic cavitation on sound pressure at the fundamental, second harmonic, and first ultraharmonic frequencies was investigated from low to high ultrasonic intensities. The driving frequencies were 22, 304, and 488 kHz. Sound pressure was measured using a needle-type hydrophone and ultrasonic cavitation was estimated from the broadband integrated pressure (BIP). With increasing square root of electric power applied to a transducer, the sound pressure at the fundamental frequency linearly increased initially, dropped at approximately the electric power of cavitation inception, and afterward increased again. The sound pressure at the second harmonic frequency was detected just below the electric power of cavitation inception. The first ultraharmonic component appeared at around the electric power of cavitation inception at 304 and 488 kHz. However, at 22 kHz, the first ultraharmonic component appeared at a higher electric power than that of cavitation inception.
30 CFR 75.902-2 - Approved ground check systems not employing pilot check wires.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Approved ground check systems not employing pilot check wires. 75.902-2 Section 75.902-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... employing pilot check wires. Ground check systems not employing pilot check wires will be approved only if...
30 CFR 75.902-2 - Approved ground check systems not employing pilot check wires.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Approved ground check systems not employing pilot check wires. 75.902-2 Section 75.902-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... employing pilot check wires. Ground check systems not employing pilot check wires will be approved only if...
NASA Technical Reports Server (NTRS)
Truszkowski, Walt; Obenschain, Arthur F. (Technical Monitor)
2002-01-01
Currently, spacecraft ground systems have a well defined and somewhat standard architecture and operations concept. Based on domain analysis studies of various control centers conducted over the years it is clear that ground systems have core capabilities and functionality that are common across all ground systems. This observation alone supports the realization of reuse. Additionally, spacecraft ground systems are increasing in their ability to do things autonomously. They are being engineered using advanced expert systems technology to provide automated support for operators. A clearer understanding of the possible roles of agent technology is advancing the prospects of greater autonomy for these systems. Many of their functional and management tasks are or could be supported by applied agent technology, the dynamics of the ground system's infrastructure could be monitored by agents, there are intelligent agent-based approaches to user-interfaces, etc. The premise of this paper is that the concepts associated with software reuse, applicable in consideration of classically-engineered ground systems, can be updated to address their application in highly agent-based realizations of future ground systems. As a somewhat simplified example consider the following situation, involving human agents in a ground system context. Let Group A of controllers be working on Mission X. They are responsible for the command, control and health and safety of the Mission X spacecraft. Let us suppose that mission X successfully completes it mission and is turned off. Group A could be dispersed or perhaps move to another Mission Y. In this case there would be reuse of the human agents from Mission X to Mission Y. The Group A agents perform their well-understood functions in a somewhat but related context. There will be a learning or familiarization process that the group A agents go through to make the new context, determined by the new Mission Y, understood. This simplified scenario highlights some of the major issues that need to be addressed when considering the situation where Group A is composed of software-based agents (not their human counterparts) and they migrate from one mission support system to another. This paper will address: - definition of an agent architecture appropriate to support reuse; - identification of non-mission-specific agent capabilities required; - appropriate knowledge representation schemes for mission-specific knowledge; - agent interface with mission-specific knowledge (a type of Learning); development of a fully-operational group of cooperative software agents for ground system support; architecture and operation of a repository of reusable agents that could be the source of intelligent components for realizing an autonomous (or nearly autonomous) agent-based ground system, and an agent-based approach to repository management and operation (an intelligent interface for human use of the repository in a ground-system development activity).
47 CFR 22.879 - Interference resolution procedures.
Code of Federal Regulations, 2010 CFR
2010-10-01
... communications on these systems are not safety related. (b) Interference analysis. Commercial aviation air-ground... Section 22.879 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial Aviation Air-Ground Systems § 22.879...
COMPILATION OF GROUND-WATER MODELS
Ground-water modeling is a computer-based methodology for mathematical analysis of the mechanisms and controls of ground-water systems for the evaluation of policies, action, and designs that may affect such systems. n addition to satisfying scientific interest in the workings of...
2005-08-01
the Office of the Secretary of Defense chartered the Joint Architecture for Unmanned Ground Systems ( JAUGS ) Working Group to address these concerns...The JAUGS Working Group was tasked with developing an initial standard for interoperable unmanned ground systems. In 2002, the charter of the... JAUGS Working Group was 1 2 modified such that their efforts would extend to all unmanned systems, not only ground systems. The standard was
Fox, Jessica L.; Aptekar, Jacob W.; Zolotova, Nadezhda M.; Shoemaker, Patrick A.; Frye, Mark A.
2014-01-01
The behavioral algorithms and neural subsystems for visual figure–ground discrimination are not sufficiently described in any model system. The fly visual system shares structural and functional similarity with that of vertebrates and, like vertebrates, flies robustly track visual figures in the face of ground motion. This computation is crucial for animals that pursue salient objects under the high performance requirements imposed by flight behavior. Flies smoothly track small objects and use wide-field optic flow to maintain flight-stabilizing optomotor reflexes. The spatial and temporal properties of visual figure tracking and wide-field stabilization have been characterized in flies, but how the two systems interact spatially to allow flies to actively track figures against a moving ground has not. We took a systems identification approach in flying Drosophila and measured wing-steering responses to velocity impulses of figure and ground motion independently. We constructed a spatiotemporal action field (STAF) – the behavioral analog of a spatiotemporal receptive field – revealing how the behavioral impulse responses to figure tracking and concurrent ground stabilization vary for figure motion centered at each location across the visual azimuth. The figure tracking and ground stabilization STAFs show distinct spatial tuning and temporal dynamics, confirming the independence of the two systems. When the figure tracking system is activated by a narrow vertical bar moving within the frontal field of view, ground motion is essentially ignored despite comprising over 90% of the total visual input. PMID:24198267
Cooperative heat transfer and ground coupled storage system
Metz, Philip D.
1982-01-01
A cooperative heat transfer and ground coupled storage system wherein collected solar heat energy is ground stored and permitted to radiate into the adjacent ground for storage therein over an extended period of time when such heat energy is seasonally maximally available. Thereafter, when said heat energy is seasonally minimally available and has propagated through the adjacent ground a substantial distance, the stored heat energy may be retrieved by a circumferentially arranged heat transfer means having a high rate of heat transfer.
Cooperative heat transfer and ground coupled storage system
Metz, P.D.
A cooperative heat transfer and ground coupled storage system wherein collected solar heat energy is ground stored and permitted to radiate into the adjacent ground for storage therein over an extended period of time when such heat energy is seasonally maximally available. Thereafter, when said heat energy is seasonally minimally available and has propagated through the adjacent ground a substantial distance, the stored heat energy may be retrieved by a circumferentially arranged heat transfer means having a high rate of heat transfer.
Geology and ground-water resources of Dane County, Wisconsin
Cline, Denzel R.
1965-01-01
The purpose of the ground-water investigation of Dane County, Wis., was to determine the occurrence, movement, quantity, quality, and availability of ground water in the unconsolidated deposits and the underlying bedrock. The relationships between ground water and surface water were studied in general in Dane County and in detail in the Madison metropolitan area. An analysis was made of the hydrologic system of the Yahara River valley and of the effects of ground-water pumpage on that system.
Batista, A R; Gianni, D; Ventosa, M; Coelho, A V; Almeida, M R; Sena-Esteves, M; Saraiva, M J
2014-12-01
Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by extracellular deposition of amyloid fibrils composed by mutated transthyretin (TTR) mainly in the peripheral nervous system. At present, liver transplantation is still the standard treatment to halt the progression of clinical symptoms in FAP, but new therapeutic strategies are emerging, including the use of TTR stabilizers. Here we propose to establish a new gene therapy approach using adeno-associated virus (AAV) vectors to deliver the trans-suppressor TTR T119M variant to the liver of transgenic TTR V30M mice at different ages. This TTR variant is known for its ability to stabilize the tetrameric protein. Analysis of the gastrointestinal tract of AAV-treated animals revealed a significant reduction in deposition of TTR non-fibrillar aggregates in as much as 34% in stomach and 30% in colon, as well as decreased levels of biomarkers associated with TTR deposition, namely the endoplasmic reticulum stress marker BiP and the extracellular matrix protein MMP-9. Moreover, we showed with different studies that our approach leads to an increase in tetrameric and more stable forms of TTR, in favor of destabilized monomers. Altogether our data suggest the possibility to use this gene therapy approach in a prophylactic manner to prevent FAP pathology.
Liang, Zhongxiu; Liu, Rui; Zhao, Depeng; Wang, Lingling; Sun, Mingzhe; Wang, Mengqiang; Song, Linsheng
2016-07-01
Ammonia is one of major environmental pollutants in the aquatic system that poses a great threat to the survival of shrimp. In the present study, the mRNA expression of endoplasmic reticulum (ER) stress marker and unfolded protein response (UPR) related genes, as well as the change of redox enzyme and apoptosis were investigated in hepatopancreas of the pacific white shrimp, Litopenaeus vannamei after the exposure of 20 mg L(-1) total ammonia nitrogen (TAN). Compared with the control group, the superoxide dismutase (SOD) activity in hepatopancreas decreased significantly (p < 0.05) at 96 h, whereas the malonyldialdehyde (MDA) concentration increased significantly (p < 0.05). The mRNA expression levels of ER stress marker-immunoglobulin heavy chain binding protein (Bip) gene and key UPR related genes including activating transcription factor 4 (ATF4) and the spliced form of X box binding protein 1 (XBP1) increased significantly (p < 0.05) in hepatopancreas at 96 h after exposure to ammonia. In addition, apoptosis was observed obviously in the hepatopancreas of L. vannamei after exposure to ammonia by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The results indicated that ammonia exposure could induce oxidative stress, which further caused ER stress and apoptosis in hepatopancreas of L. vannamei. Copyright © 2016 Elsevier Ltd. All rights reserved.
Achieving Operability via the Mission System Paradigm
NASA Technical Reports Server (NTRS)
Hammer, Fred J.; Kahr, Joseph R.
2006-01-01
In the past, flight and ground systems have been developed largely-independently, with the flight system taking the lead, and dominating the development process. Operability issues have been addressed poorly in planning, requirements, design, I&T, and system-contracting activities. In many cases, as documented in lessons-learned, this has resulted in significant avoidable increases in cost and risk. With complex missions and systems, operability is being recognized as an important end-to-end design issue. Never-the-less, lessons-learned and operability concepts remain, in many cases, poorly understood and sporadically applied. A key to effective application of operability concepts is adopting a 'mission system' paradigm. In this paradigm, flight and ground systems are treated, from an engineering and management perspective, as inter-related elements of a larger mission system. The mission system consists of flight hardware, flight software, telecom services, ground data system, testbeds, flight teams, science teams, flight operations processes, procedures, and facilities. The system is designed in functional layers, which span flight and ground. It is designed in response to project-level requirements, mission design and an operations concept, and is developed incrementally, with early and frequent integration of flight and ground components.
Photovoltaic central station step and touch potential considerations in grounding system design
NASA Technical Reports Server (NTRS)
Engmann, G.
1983-01-01
The probability of hazardous step and touch potentials is an important consideration in central station grounding system design. Steam turbine generating station grounding system design is based on accepted industry practices and there is extensive in-service experience with these grounding systems. A photovoltaic (PV) central station is a relatively new concept and there is limited experience with PV station grounding systems. The operation and physical configuration of a PV central station is very different from a steam electric station. A PV station bears some similarity to a substation and the PV station step and touch potentials might be addressed as they are in substation design. However, the PV central station is a generating station and it is appropriate to examine the effect that the differences and similarities of the two types of generating stations have on step and touch potential considerations.
NASA Astrophysics Data System (ADS)
Nakayama, Tomoko; Takayama, Yoshihisa; Fujikawa, Chiemi; Watanabe, Eriko; Kodate, Kashiko
2014-09-01
In recent years, there has been considerable interest in satellite-ground laser communication due to an increase in the quantity of data exchanged between satellites and the ground. However, improving the quality of this data communication is necessary as laser communication is vulnerable to air fluctuation. We first verify the spatial and temporal averaging effects using light beam intensity images acquired from middle-range transmission experiments between two ground positions and the superposition of these images using simulations. Based on these results, we propose a compact and lightweight optical duplicate system as a multi-beam generation device with which it is easy to apply the spatial averaging effect. Although an optical duplicate system is already used for optical correlation operations, we present optimum design solutions, design a compact optical duplicate system for satellite-ground laser communications, and demonstrate the efficacy of this system using simulations.
Space/ground systems as cooperating agents
NASA Technical Reports Server (NTRS)
Grant, T. J.
1994-01-01
Within NASA and the European Space Agency (ESA) it is agreed that autonomy is an important goal for the design of future spacecraft and that this requires on-board artificial intelligence. NASA emphasizes deep space and planetary rover missions, while ESA considers on-board autonomy as an enabling technology for missions that must cope with imperfect communications. ESA's attention is on the space/ground system. A major issue is the optimal distribution of intelligent functions within the space/ground system. This paper describes the multi-agent architecture for space/ground systems (MAASGS) which would enable this issue to be investigated. A MAASGS agent may model a complete spacecraft, a spacecraft subsystem or payload, a ground segment, a spacecraft control system, a human operator, or an environment. The MAASGS architecture has evolved through a series of prototypes. The paper recommends that the MAASGS architecture should be implemented in the operational Dutch Utilization Center.
SHARP: Automated monitoring of spacecraft health and status
NASA Technical Reports Server (NTRS)
Atkinson, David J.; James, Mark L.; Martin, R. Gaius
1991-01-01
Briefly discussed here are the spacecraft and ground systems monitoring process at the Jet Propulsion Laboratory (JPL). Some of the difficulties associated with the existing technology used in mission operations are highlighted. A new automated system based on artificial intelligence technology is described which seeks to overcome many of these limitations. The system, called the Spacecraft Health Automated Reasoning Prototype (SHARP), is designed to automate health and status analysis for multi-mission spacecraft and ground data systems operations. The system has proved to be effective for detecting and analyzing potential spacecraft and ground systems problems by performing real-time analysis of spacecraft and ground data systems engineering telemetry. Telecommunications link analysis of the Voyager 2 spacecraft was the initial focus for evaluation of the system in real-time operations during the Voyager spacecraft encounter with Neptune in August 1989.
SHARP - Automated monitoring of spacecraft health and status
NASA Technical Reports Server (NTRS)
Atkinson, David J.; James, Mark L.; Martin, R. G.
1990-01-01
Briefly discussed here are the spacecraft and ground systems monitoring process at the Jet Propulsion Laboratory (JPL). Some of the difficulties associated with the existing technology used in mission operations are highlighted. A new automated system based on artificial intelligence technology is described which seeks to overcome many of these limitations. The system, called the Spacecraft Health Automated Reasoning Prototype (SHARP), is designed to automate health and status analysis for multi-mission spacecraft and ground data systems operations. The system has proved to be effective for detecting and analyzing potential spacecraft and ground systems problems by performing real-time analysis of spacecraft and ground data systems engineering telemetry. Telecommunications link analysis of the Voyager 2 spacecraft was the initial focus for evaluation of the system in real-time operations during the Voyager spacecraft encounter with Neptune in August 1989.
47 CFR 22.873 - Construction requirements for commercial aviation air-ground systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 47 Telecommunication 2 2010-10-01 2010-10-01 false Construction requirements for commercial aviation air-ground systems. 22.873 Section 22.873 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Air-Ground Radiotelephone Service Commercial...
49 CFR 236.107 - Ground tests.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 4 2011-10-01 2011-10-01 false Ground tests. 236.107 Section 236.107 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION...: All Systems Inspections and Tests; All Systems § 236.107 Ground tests. (a) Except as provided in...
Enhanced networks operations using the X Window System
NASA Technical Reports Server (NTRS)
Linares, Irving
1993-01-01
We propose an X Window Graphical User Interface (GUI) which is tailored to the operations of NASA GSFC's Network Control Center (NCC), the NASA Ground Terminal (NGT), the White Sands Ground Terminal (WSGT), and the Second Tracking and Data Relay Satellite System (TDRSS) Ground Terminal (STGT). The proposed GUI can also be easily extended to other Ground Network (GN) Tracking Stations due to its standardized nature.