Molecular cloning, phylogenetic analysis, and expression profiling of endoplasmic reticulum molecular chaperone BiP genes from bread wheat (Triticum aestivum L.).

PubMed

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...

High expression of GRP78/BiP as a novel predictor of favorable outcomes in patients with advanced thymic carcinoma.

PubMed

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.

The binding protein BiP attenuates stress-induced cell death in soybean via modulation of the N-rich protein-mediated signaling pathway.

PubMed

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.

The Binding Protein BiP Attenuates Stress-Induced Cell Death in Soybean via Modulation of the N-Rich Protein-Mediated Signaling Pathway1[C][W][OA

PubMed Central

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

The Road to Prison is Paved with Bad Evaluations: The Case for Functional Behavioral Assessments and Behavior Intervention Plans.

PubMed

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.

Evaluation of gastrointestinal tract transit times using barium-impregnated polyethylene spheres and barium sulfate suspension in a domestic pigeon (Columba livia) model.

PubMed

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.

PubMed

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▿ †

PubMed Central

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.

PubMed

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.

Biophysical analysis of the effect of chemical modification by 4-oxononenal on the structure, stability, and function of binding immunoglobulin protein (BiP)

PubMed Central

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

Bleep me up scotty!

PubMed

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

PubMed Central

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

Introducing the Brassica Information Portal: Towards integrating genotypic and phenotypic Brassica crop data

PubMed Central

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

Screening of the antioxidative properties and total phenolic contents of three endemic Tanacetum subspecies from Turkish flora.

PubMed

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.

76 FR 18552 - Seeking Public Comment on Two Draft Chapters of the National Health Security Strategy Biennial...

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.

Intervention and societal costs of residential community reintegration for patients with acquired brain injury: a cost-analysis of the Brain Integration Programme.

PubMed

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. :

Biomedical Interdisciplinary Curriculum Project: BIP (Biomedical Instrumentation Package) User's Manual.

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.

PubMed

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.

PubMed

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

PubMed Central

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

Three d10 coordination polymers assembled from 3,5-bis(imidazole-1-yl)pyridine and different polycarboxylates: Syntheses, structures and luminescence properties

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.

Conformational stability and differential structural analysis of LcrV, PcrV, BipD, and SipD from type III secretion systems

PubMed Central

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

PubMed Central

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.

PubMed

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.

Bax-inhibiting peptide protects glutamate-induced cerebellar granule cell death by blocking Bax translocation.

PubMed

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.

PubMed

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.

75 FR 62096 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-07

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77 FR 66433 - Information Collection Activity; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-05

... appropriated $2.5 billion of budget authority for establishing the Broadband Initiatives Program (BIP) which... Program (BIP). OMB Control Number: 0572-0142. Type of Request: Revision of a currently approved...

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Alternative Fuels Data Center

Science.gov Websites

Biofuels Infrastructure Partnership (BIP) grant program. The BIP program works with retailers and state and eligible applicants in the following amounts: Infrastructure Grant Amount E15 Pumps 50% of the costs of

Endoplasmic reticulum proteins SDF2 and SDF2L1 act as components of the BiP chaperone cycle to prevent protein aggregation.

PubMed

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.

RCAD/BiP pathway is necessary for the proper synthesis of digestive enzymes and secretory function of the exocrine pancreas.

PubMed

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.

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.

PubMed

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.

Machine health prognostics using the Bayesian-inference-based probabilistic indication and high-order particle filtering framework

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.

Larger low voltage zone in endocardial unipolar map compared with that in epicardial bipolar map indicates difficulty in eliminating ventricular tachycardia by catheter ablation.

PubMed

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.

A Peptidic Unconjugated GRP78/BiP Ligand Modulates the Unfolded Protein Response and Induces Prostate Cancer Cell Death

PubMed Central

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

Saussurea tridactyla Sch. Bip.-derived polysaccharides and flavones reduce oxidative damage in ultraviolet B-irradiated HaCaT cells via a p38MAPK-independent mechanism

PubMed Central

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

PubMed Central

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.

PubMed

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.

Similarity and diversity of translational GTPase factors EF-G, EF4, and BipA: From structure to function.

PubMed

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.

Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress

PubMed Central

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].

PubMed

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.

Roles of silkworm endoplasmic reticulum chaperones in the secretion of recombinant proteins expressed by baculovirus system.

PubMed

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)

Science.gov Websites

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.

PubMed

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.

PubMed

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.

Early Childhood Practitioner Involvement in Functional Behavioral Assessment and Function-Based Interventions: A Literature Review

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…

Functional Behavior Assessments and Behavior Intervention Plans: Legal Requirements and Professional Recommendations

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

PubMed Central

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

Experimental reconstitution of chronic ER stress in the liver reveals feedback suppression of BiP mRNA expression

PubMed Central

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

BiP and Multiple DNAJ Molecular Chaperones in the Endoplasmic Reticulum Are Required for Efficient Simian Virus 40 Infection

PubMed Central

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.

PubMed

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.

Endoplasmic reticulum stress responses function in the HRT-mediated hypersensitive response in Nicotiana benthamiana.

PubMed

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.

Mimotopes for Api g 5, a Relevant Cross-reactive Allergen, in the Celery-Mugwort-Birch-Spice Syndrome.

PubMed

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.

PubMed

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…

Exploring the Link among Behavior Intervention Plans, Treatment Integrity, and Student Outcomes under Natural Educational Conditions

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…

Format of Basic Instruction Program Resistance Training Classes: Effect on Fitness Change in College Students

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…

Special Considerations for Using Functional Behavior Assessment and Functionally-Indicated Interventions with Students in Alternative Educational Settings

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…

Behavioral Intervention Plans: Legal and Practical Considerations for Students with Emotional and Behavioral Disorders

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…

Integrating the Principles of Effective Intervention into Batterer Intervention Programming: The Case for Moving Toward More Evidence-Based Programming.

PubMed

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.

Long-term sensitization training in Aplysia leads to an increase in the expression of BiP, the major protein chaperon of the ER.

PubMed

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

DTIC Science & Technology

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

Commentary on Zirkel: Judicial Rulings Specific to FBAs or BIPs under the IDEA and Corollary State Laws--An Update

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…

Extending human perception of electromagnetic radiation to the UV region through biologically inspired photochromic fuzzy logic (BIPFUL) systems.

PubMed

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.

Primer to Design Safe School Projects in Case of Terrorist Attacks and School Shootings. Buildings and Infrastructure Protection Series. FEMA-428/BIPS-07/January 2012. Edition 2

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

PubMed Central

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

Variation in the HFE gene is associated with the development of bleomycin-induced pulmonary toxicity in testicular cancer patients.

PubMed

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.

PubMed

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.

Structural and electronic properties of the V-V compounds isoelectronic to GaN and isostructural to gray arsenic

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.

Tracking Behavior Assessment Methodology and Support Strategies: A National Survey of How Schools Utilize Functional Behavioral Assessments and Behavior Intervention Plans

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

APPLICATION OF A BIP CONSTRAINED OPTIMIZATION MODEL COMBINED WITH NASA's ATLAS MODEL TO OPTIMIZE THE SOCIETAL BENEFITS OF THE USA's INTERNATIONAL SPACE EXPLORATION AND UTILIZATION INITIATIVE OF 1/14/04

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


PubMed Central

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
.

PubMed

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.

PubMed

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

PubMed Central

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

PubMed Central

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

A Chaperone Complex Formed by HSP47, FKBP65 and BiP Modulates Telopeptide Lysyl Hydroxylation of Type I Procollagen

PubMed Central

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

Dissection of structural and functional requirements that underlie the interaction of ERdj3 protein with substrates in the endoplasmic reticulum.

PubMed

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.

Dissection of Structural and Functional Requirements That Underlie the Interaction of ERdj3 Protein with Substrates in the Endoplasmic Reticulum*

PubMed Central

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

Compton Community College General Education Associate of Arts/Certification, Bilingual Immersion Program for the California State University System.

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.

PubMed

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.

Avoiding delayed diagnosis of significant blunt bowel and mesenteric injuries: Can a scoring tool make the difference? A 7-year retrospective cohort study.

PubMed

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

PubMed Central

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

Leaf-traits and growth allometry explain competition and differences in response to climatic change in a temperate forest landscape: a simulation study

PubMed Central

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

Potentiation of angiogenic switch in capillary endothelial cells by cAMP: A cross-talk between up-regulated LLO biosynthesis and the HSP-70 expression.

PubMed

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.

Transcriptome Analysis of Liangshan Pig Muscle Development at the Growth Curve Inflection Point and Asymptotic Stages Using Digital Gene Expression Profiling

PubMed Central

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

Transcriptome Analysis of Liangshan Pig Muscle Development at the Growth Curve Inflection Point and Asymptotic Stages Using Digital Gene Expression Profiling.

PubMed

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.

PubMed

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.

PubMed

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.

PubMed

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.

BiPPred: Combined sequence- and structure-based prediction of peptide binding to the Hsp70 chaperone BiP.

PubMed

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.

Comparison of pro-amnesic efficacy of scopolamine, biperiden, and phencyclidine by using passive avoidance task in CD-1 mice.

PubMed

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.

Evaluation of gastric emptying time, gastrointestinal transit time, sedation score, and nausea score associated with intravenous constant rate infusion of lidocaine hydrochloride in clinically normal dogs.

PubMed

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.

PubMed

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)

PubMed Central

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

Effects of injectable anticholinergic drugs on soman-induced lethality and convulsant/subconvulsant activity

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

Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding.

PubMed

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.

Endoplasmic reticulum-associated degradation of the mouse PC1/3-N222D hypomorph and human PCSK1 mutations contributes to obesity.

PubMed

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.

Development of vaccines against pertussis caused by Bordetella holmesii using a mouse intranasal challenge model.

PubMed

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.

Activity-induced synaptic delivery of the GluN2A-containing NMDA receptor is dependent on endoplasmic reticulum chaperone Bip and involved in fear memory

PubMed Central

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

Addressing substance abuse and violence in substance use disorder treatment and batterer intervention programs.

PubMed

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.

Tolerability and performance of BIP endotracheal tubes with noble metal alloy coating--a randomized clinical evaluation study.

PubMed

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.

Marine Seismic System Deployment (MSS). Phase 2. Investigation of Techniques and Deployment Scenarios for Installation of Triaxial Seismometer in a Borehole in the Deep Ocean

DTIC Science & Technology

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.

PubMed

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.

Synthesis and characterization of two new zinc(II) coordination polymers with bidentate flexible ligands: Formation of a 2D structure with (44.62)-sql topology

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.

Differences in social functioning among patients with major psychiatric disorders: Interpersonal communication is impaired in patients with schizophrenia and correlates with an increase in schizotypal traits.

PubMed

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.

Trends in Ground-State Entropies for Transition Metal Based Hydrogen Atom Transfer Reactions

PubMed Central

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

[Activation of endoplasmic reticulum stress and its effect on osteogenic differentiation induced by micropit/nanotube topography].

PubMed

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.

Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular redistribution of the autoantigens Ro/Sjögren's syndrome-related antigen A (SSA) and La/SSB in salivary gland epithelial cells.

PubMed

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

Science.gov Websites

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.

PubMed

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.

ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish

PubMed Central

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

ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish.

PubMed

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.

PubMed

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.

Bezafibrate for the treatment of dyslipidemia in patients with coronary artery disease: 20-year mortality follow-up of the BIP randomized control trial.

PubMed

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

DOE Data Explorer

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

Potent and selective agonists of alpha-melanotropin (alphaMSH) action at human melanocortin receptor 5; linear analogs of alpha-melanotropin.

PubMed

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.

Expression profile of genes as indicators of developmental competence and quality of in vitro fertilization and somatic cell nuclear transfer bovine embryos.

PubMed

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).

Experience with V-STORE: considerations on presence in virtual environments for effective neuropsychological rehabilitation of executive functions.

PubMed

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.

Anxiolytic- and antidepressant-like effects of an aqueous extract of Tanacetum parthenium L. Schultz-Bip (Asteraceae) in mice.

PubMed

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.

DTIC Science & Technology

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

What Does the Law Say?

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...

PEER News

Science.gov Websites

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

Oxidative polycondensation of benzimidazole using NaOCl: Synthesis, characterization, optical, thermal and electrical properties of polybenzimidazoles

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.

The TFIID components human TAF(II)140 and Drosophila BIP2 (TAF(II)155) are novel metazoan homologues of yeast TAF(II)47 containing a histone fold and a PHD finger.

PubMed

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.

Chemical diversity of the essential oils of twenty populations of Tanacetum polycephalum Sch. Bip. from Iran.

PubMed

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'.

Directions

Science.gov Websites

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…

What is PEER?

Science.gov Websites

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…

A Survey of Basic Instructional Program Graduate Teaching Assistant Development and Support Processes

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…

Implementing a Batterer's Intervention Program in a Correctional Setting: A Tertiary Prevention Model

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…

Reduced Sleep During Social Isolation Leads to Cellular Stress and Induction of the Unfolded Protein Response.

PubMed

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

K-12 Education

Science.gov Websites

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

DTIC Science & Technology

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…

Teacher Attitudes on Including Students with Behavior Intervention Plans in a High-School Inclusive Classroom

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.…

Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival.

PubMed

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.

Finding the numerical compensation in multiple criteria decision-making problems under fuzzy environment

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.

PubMed

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?

PubMed

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.

Melatonin reduces endoplasmic reticulum stress and corneal dystrophy-associated TGFBIp through activation of endoplasmic reticulum-associated protein degradation.

PubMed

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.

PubMed

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

Science.gov Websites

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…

Behavior Intervention Planning and Implementation of Positive Behavioral Support Plans: An Examination of States' Adherence to Standards for Practice

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…

Teacher Involvement in the Development of Function-Based Behaviour Intervention Plans for Students with Challenging Behaviour

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…

The Use of a Functional Behavioral Assessment-Based Self Management Intervention for Students with Emotional/Behavioral Disorders

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,…

The Effects of Self-Monitoring and Performance Feedback on the Treatment Integrity of Behavior Intervention Plan Implementation and Generalization

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.

PEER Annual Meeting | Events

Science.gov Websites

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

Exploring the Relevance of Attachment Theory as a Dependent Variable in the Treatment of Women Mandated into Treatment for Domestic Violence Offenses

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

PubMed Central

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

Influence of KDEL on the fate of trimeric or assembly-defective phaseolin: selective use of an alternative route to vacuoles.

PubMed

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.

Anti-pancreatic cancer activity of ONC212 involves the unfolded protein response (UPR) and is reduced by IGF1-R and GRP78/BIP

PubMed Central

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

Anti-pancreatic cancer activity of ONC212 involves the unfolded protein response (UPR) and is reduced by IGF1-R and GRP78/BIP.

PubMed

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.

Ultrafine particles of Ulmus davidiana var. japonica induce apoptosis of gastric cancer cells via activation of caspase and endoplasmic reticulum stress.

PubMed

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.

Ibrutinib improves the development of acute lymphoblastic leukemia by activating endoplasmic reticulum stress-induced cell death.

PubMed

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.

The 78 kDa glucose-regulated protein (GRP78/BIP) is expressed on the cell membrane, is released into cell culture medium and is also present in human peripheral circulation.

PubMed

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.

Insights into the Binding Sites of Organometallic Ruthenium Anticancer Compounds on Peptides Using Ultra-High Resolution Mass Spectrometry

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.

Time-Resolved Diffuse Optical Spectroscopy and Imaging Using Solid-State Detectors: Characteristics, Present Status, and Research Challenges.

PubMed

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.

Energetic Residues from Blow-in-Place Detonation of 60-mm and 120-mm Fuzed High-Explosive Mortar Cartridges

DTIC Science & Technology

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…

Different sets of ER-resident J-proteins regulate distinct polar nuclear-membrane fusion events in Arabidopsis thaliana.

PubMed

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.

Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells: Implications for Apoptosis.

PubMed

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.

PubMed

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.

Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress.

PubMed

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

PubMed Central

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

Thermotolerance induced at a mild temperature of 40°C alleviates heat shock-induced ER stress and apoptosis in HeLa cells.

PubMed

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

DTIC Science & Technology

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

Time-Resolved Diffuse Optical Spectroscopy and Imaging Using Solid-State Detectors: Characteristics, Present Status, and Research Challenges

PubMed Central

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

Inhibition of autophagy exerts anti-colon cancer effects via apoptosis induced by p53 activation and ER stress.

PubMed

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.

Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells

PubMed Central

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

DTIC Science & Technology

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

Ankylosing spondylitis M-CSF-derived macrophages are undergoing unfolded protein response (UPR) and express higher levels of interleukin-23.

PubMed

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.

Endoplasmic reticulum stress is involved in the lidocaine-induced apoptosis in SH-SY5Y neuroblastoma cells.

PubMed

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

PubMed Central

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

Antisocial Traits, Distress Tolerance, and Alcohol Problems as Predictors of Intimate Partner Violence in Men Arrested for Domestic Violence.

PubMed

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.

Use of Ultrasonic Bone Surgery (Piezosurgery) to Surgically Treat Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ). A Case Series Report with at Least 1 Year of Follow-Up

PubMed Central

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

Vision based flight procedure stereo display system

NASA Astrophysics Data System (ADS)

Shen, Xiaoyun; Wan, Di; Ma, Lan; He, Yuncheng

2008-03-01

A virtual reality flight procedure vision system is introduced in this paper. The digital flight map database is established based on the Geographic Information System (GIS) and high definitions satellite remote sensing photos. The flight approaching area database is established through computer 3D modeling system and GIS. The area texture is generated from the remote sensing photos and aerial photographs in various level of detail. According to the flight approaching procedure, the flight navigation information is linked to the database. The flight approaching area vision can be dynamic displayed according to the designed flight procedure. The flight approaching area images are rendered in 2 channels, one for left eye images and the others for right eye images. Through the polarized stereoscopic projection system, the pilots and aircrew can get the vivid 3D vision of the flight destination approaching area. Take the use of this system in pilots preflight preparation procedure, the aircrew can get more vivid information along the flight destination approaching area. This system can improve the aviator's self-confidence before he carries out the flight mission, accordingly, the flight safety is improved. This system is also useful in validate the visual flight procedure design, and it helps to the flight procedure design.

Large Eddy Simulation of Bubbly Ship Wakes

DTIC Science & Technology

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

Joint Information Theoretic and Differential Geometrical Approach for Robust Automated Target Recognition

DTIC Science & Technology

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

14 CFR 415.127 - Flight safety system design and operation data.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Expendable Launch Vehicle From a Non-Federal Launch Site § 415.127 Flight safety system design and operation...: flight termination system; command control system; tracking; telemetry; communications; flight safety... control system. (7) Flight termination system component storage, operating, and service life. A listing of...

Automated flight test management system

NASA Technical Reports Server (NTRS)

Hewett, M. D.; Tartt, D. M.; Agarwal, A.

1991-01-01

The Phase 1 development of an automated flight test management system (ATMS) as a component of a rapid prototyping flight research facility for artificial intelligence (AI) based flight concepts is discussed. The ATMS provides a flight engineer with a set of tools that assist in flight test planning, monitoring, and simulation. The system is also capable of controlling an aircraft during flight test by performing closed loop guidance functions, range management, and maneuver-quality monitoring. The ATMS is being used as a prototypical system to develop a flight research facility for AI based flight systems concepts at NASA Ames Dryden.

Advanced Transport Operating System (ATOPS) Flight Management/Flight Controls (FM/FC) software description

NASA Technical Reports Server (NTRS)

Wolverton, David A.; Dickson, Richard W.; Clinedinst, Winston C.; Slominski, Christopher J.

1993-01-01

The flight software developed for the Flight Management/Flight Controls (FM/FC) MicroVAX computer used on the Transport Systems Research Vehicle for Advanced Transport Operating Systems (ATOPS) research is described. The FM/FC software computes navigation position estimates, guidance commands, and those commands issued to the control surfaces to direct the aircraft in flight. Various modes of flight are provided for, ranging from computer assisted manual modes to fully automatic modes including automatic landing. A high-level system overview as well as a description of each software module comprising the system is provided. Digital systems diagrams are included for each major flight control component and selected flight management functions.

Development and Flight Test of an Augmented Thrust-Only Flight Control System on an MD-11 Transport Airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Maine, Trindel A.; Burken, John J.; Pappas, Drew

1996-01-01

An emergency flight control system using only engine thrust, called Propulsion-Controlled Aircraft (PCA), has been developed and flight tested on an MD-11 airplane. In this thrust-only control system, pilot flight path and track commands and aircraft feedback parameters are used to control the throttles. The PCA system was installed on the MD-11 airplane using software modifications to existing computers. Flight test results show that the PCA system can be used to fly to an airport and safely land a transport airplane with an inoperative flight control system. In up-and-away operation, the PCA system served as an acceptable autopilot capable of extended flight over a range of speeds and altitudes. The PCA approaches, go-arounds, and three landings without the use of any non-nal flight controls have been demonstrated, including instrument landing system-coupled hands-off landings. The PCA operation was used to recover from an upset condition. In addition, PCA was tested at altitude with all three hydraulic systems turned off. This paper reviews the principles of throttles-only flight control; describes the MD-11 airplane and systems; and discusses PCA system development, operation, flight testing, and pilot comments.

An alternative agriculture system is defined by a distinct expression profile of select gene transcripts and proteins

PubMed Central

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

Development and Flight Evaluation of an Emergency Digital Flight Control System Using Only Engine Thrust on an F-15 Airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Maine, Trindel A.; Fullerton, C. Gordon; Webb, Lannie Dean

1996-01-01

A propulsion-controlled aircraft (PCA) system for emergency flight control of aircraft with no flight controls was developed and flight tested on an F-15 aircraft at the NASA Dryden Flight Research Center. The airplane has been flown in a throttles-only manual mode and with an augmented system called PCA in which pilot thumbwheel commands and aircraft feedback parameters were used to drive the throttles. Results from a 36-flight evaluation showed that the PCA system can be used to safety land an airplane that has suffered a major flight control system failure. The PCA system was used to recover from a severe upset condition, descend, and land. Guest pilots have also evaluated the PCA system. This paper describes the principles of throttles-only flight control; a history of loss-of-control accidents; a description of the F-15 aircraft; the PCA system operation, simulation, and flight testing; and the pilot comments.

Effect of quercetin on apoptosis of PANC-1 cells

PubMed Central

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.

PubMed

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.

Proposed methods and endpoints for defining and assessing adverse environmental impact (AEI) on fish communities/populations in Tennessee River reservoirs.

PubMed

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.

Endoplasmic reticulum stress in vasopressin neurons of familial diabetes insipidus model mice: aggregate formation and mRNA poly(A) tail shortening.

PubMed

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.

Induction of cap-independent BiP (hsp-3) and Bcl-2 (ced-9) translation in response to eIF4G (IFG-1) depletion in C. elegans

PubMed Central

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

HLA-B35 Upregulates Endothelin-1 and Downregulates Endothelial Nitric Oxide Synthase via Endoplasmic Reticulum Stress Response in Endothelial Cells

PubMed Central

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

HLA-B35 upregulates endothelin-1 and downregulates endothelial nitric oxide synthase via endoplasmic reticulum stress response in endothelial cells.

PubMed

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.

The use of an automated flight test management system in the development of a rapid-prototyping flight research facility

NASA Technical Reports Server (NTRS)

Duke, Eugene L.; Hewett, Marle D.; Brumbaugh, Randal W.; Tartt, David M.; Antoniewicz, Robert F.; Agarwal, Arvind K.

1988-01-01

An automated flight test management system (ATMS) and its use to develop a rapid-prototyping flight research facility for artificial intelligence (AI) based flight systems concepts are described. The ATMS provides a flight test engineer with a set of tools that assist in flight planning and simulation. This system will be capable of controlling an aircraft during the flight test by performing closed-loop guidance functions, range management, and maneuver-quality monitoring. The rapid-prototyping flight research facility is being developed at the Dryden Flight Research Facility of the NASA Ames Research Center (Ames-Dryden) to provide early flight assessment of emerging AI technology. The facility is being developed as one element of the aircraft automation program which focuses on the qualification and validation of embedded real-time AI-based systems.

Orion Launch Abort System Jettison Motor Performance During Exploration Flight Test 1

NASA Technical Reports Server (NTRS)

McCauley, Rachel J.; Davidson, John B.; Winski, Richard G.

2015-01-01

This paper presents an overview of the flight test objectives and performance of the Orion Launch Abort System during Exploration Flight Test-1. Exploration Flight Test-1, the first flight test of the Orion spacecraft, was managed and led by the Orion prime contractor, Lockheed Martin, and launched atop a United Launch Alliance Delta IV Heavy rocket. This flight test was a two-orbit, high-apogee, high-energy entry, low-inclination test mission used to validate and test systems critical to crew safety. This test included the first flight test of the Launch Abort System performing Orion nominal flight mission critical objectives. Although the Orion Program has tested a number of the critical systems of the Orion spacecraft on the ground, the launch environment cannot be replicated completely on Earth. Data from this flight will be used to verify the function of the jettison motor to separate the Launch Abort System from the crew module so it can continue on with the mission. Selected Launch Abort System flight test data is presented and discussed in the paper. Through flight test data, Launch Abort System performance trends have been derived that will prove valuable to future flights as well as the manned space program.

Development and Flight Test of an Emergency Flight Control System Using Only Engine Thrust on an MD-11 Transport Airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Burken, John J.; Maine, Trindel A.; Fullerton, C. Gordon

1997-01-01

An emergency flight control system that uses only engine thrust, called the propulsion-controlled aircraft (PCA) system, was developed and flight tested on an MD-11 airplane. The PCA system is a thrust-only control system, which augments pilot flightpath and track commands with aircraft feedback parameters to control engine thrust. The PCA system was implemented on the MD-11 airplane using only software modifications to existing computers. Results of a 25-hr flight test show that the PCA system can be used to fly to an airport and safely land a transport airplane with an inoperative flight control system. In up-and-away operation, the PCA system served as an acceptable autopilot capable of extended flight over a range of speeds, altitudes, and configurations. PCA approaches, go-arounds, and three landings without the use of any normal flight controls were demonstrated, including ILS-coupled hands-off landings. PCA operation was used to recover from an upset condition. The PCA system was also tested at altitude with all three hydraulic systems turned off. This paper reviews the principles of throttles-only flight control, a history of accidents or incidents in which some or all flight controls were lost, the MD-11 airplane and its systems, PCA system development, operation, flight testing, and pilot comments.

Experience with synchronous and asynchronous digital control systems. [for flight

NASA Technical Reports Server (NTRS)

Regenie, Victoria A.; Chacon, Claude V.; Lock, Wilton P.

1986-01-01

Flight control systems have undergone a revolution since the days of simple mechanical linkages; presently the most advanced systems are full-authority, full-time digital systems controlling unstable aircraft. With the use of advanced control systems, the aerodynamic design can incorporate features that allow greater performance and fuel savings, as can be seen on the new Airbus design and advanced tactical fighter concepts. These advanced aircraft will be and are relying on the flight control system to provide the stability and handling qualities required for safe flight and to allow the pilot to control the aircraft. Various design philosophies have been proposed and followed to investigate system architectures for these advanced flight control systems. One major area of discussion is whether a multichannel digital control system should be synchronous or asynchronous. This paper addressed the flight experience at the Dryden Flight Research Facility of NASA's Ames Research Center with both synchronous and asynchronous digital flight control systems. Four different flight control systems are evaluated against criteria such as software reliability, cost increases, and schedule delays.

Initial flight qualification and operational maintenance of X-29A flight software

NASA Technical Reports Server (NTRS)

Earls, Michael R.; Sitz, Joel R.

1989-01-01

A discussion is presented of some significant aspects of the initial flight qualification and operational maintenance of the flight control system softward for the X-29A technology demonstrator. Flight qualification and maintenance of complex, embedded flight control system software poses unique problems. The X-29A technology demonstrator aircraft has a digital flight control system which incorporates functions generally considered too complex for analog systems. Organizational responsibilities, software assurance issues, tools, and facilities are discussed.

Mission Control Center (MCC) system specification for the shuttle Orbital Flight Test (OFT) timeframe

NASA Technical Reports Server (NTRS)

1978-01-01

The Mission Control Center Shuttle (MCC) Shuttle Orbital Flight Test (OFT) Data System (OFTDS) provides facilities for flight control and data systems personnel to monitor and control the Shuttle flights from launch (tower clear) to rollout (wheels stopped on runway). It also supports the preparation for flight (flight planning, flight controller and crew training, and integrated vehicle and network testing activities). The MCC Shuttle OFTDS is described in detail. Three major support systems of the OFTDS and the data types and sources of data entering or exiting the MCC were illustrated. These systems are the communication interface system, the data computation complex, and the display and control system.

Design of an expert-system flight status monitor

NASA Technical Reports Server (NTRS)

Regenie, V. A.; Duke, E. L.

1985-01-01

The modern advanced avionics in new high-performance aircraft strains the capability of current technology to safely monitor these systems for flight test prior to their generalized use. New techniques are needed to improve the ability of systems engineers to understand and analyze complex systems in the limited time available during crucial periods of the flight test. The Dryden Flight Research Facility of NASA's Ames Research Center is involved in the design and implementation of an expert system to provide expertise and knowledge to aid the flight systems engineer. The need for new techniques in monitoring flight systems and the conceptual design of an expert-system flight status monitor is discussed. The status of the current project and its goals are described.

From an automated flight-test management system to a flight-test engineer's workstation

NASA Technical Reports Server (NTRS)

Duke, E. L.; Brumbaugh, R. W.; Hewett, M. D.; Tartt, D. M.

1992-01-01

Described here are the capabilities and evolution of a flight-test engineer's workstation (called TEST PLAN) from an automated flight-test management system. The concept and capabilities of the automated flight-test management system are explored and discussed to illustrate the value of advanced system prototyping and evolutionary software development.

14 CFR 23.1335 - Flight director systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Flight director systems. 23.1335 Section 23...: Installation § 23.1335 Flight director systems. If a flight director system is installed, means must be provided to indicate to the flight crew its current mode of operation. Selector switch position is not...

14 CFR 23.1335 - Flight director systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Flight director systems. 23.1335 Section 23...: Installation § 23.1335 Flight director systems. If a flight director system is installed, means must be provided to indicate to the flight crew its current mode of operation. Selector switch position is not...

From an automated flight-test management system to a flight-test engineer's workstation

NASA Technical Reports Server (NTRS)

Duke, E. L.; Brumbaugh, Randal W.; Hewett, M. D.; Tartt, D. M.

1991-01-01

The capabilities and evolution is described of a flight engineer's workstation (called TEST-PLAN) from an automated flight test management system. The concept and capabilities of the automated flight test management systems are explored and discussed to illustrate the value of advanced system prototyping and evolutionary software development.

Experience with synchronous and asynchronous digital control systems

NASA Technical Reports Server (NTRS)

Regenie, V. A.; Chacon, C. V.; Lock, W. P.

1986-01-01

Flight control systems have undergone a revolution since the days of simple mechanical linkages; presently the most advanced systems are full-authority, full-time digital systems controlling unstable aircraft. With the use of advanced control systems, the aerodynamic design can incorporate features that allow greater performance and fuel savings, as can be seen on the new Airbus design and advanced tactical fighter concepts. These advanced aircraft will be and are relying on the flight control system to provide the stability and handling qualities required for safe flight and to allow the pilot to control the aircraft. Various design philosophies have been proposed and followed to investigate system architectures for these advanced flight control systems. One major area of discussion is whether a multichannel digital control system should be synchronous or asynchronous. This paper addressed the flight experience at the Dryden Flight Research Facility of NASA's Ames Research Center with both synchronous and asynchronous digital flight control systems. Four different flight control systems are evaluated against criteria such as software reliability, cost increases, and schedule delays.

cFE/CFS (Core Flight Executive/Core Flight System)

NASA Technical Reports Server (NTRS)

Wildermann, Charles P.

2008-01-01

This viewgraph presentation describes in detail the requirements and goals of the Core Flight Executive (cFE) and the Core Flight System (CFS). The Core Flight Software System is a mission independent, platform-independent, Flight Software (FSW) environment integrating a reusable core flight executive (cFE). The CFS goals include: 1) Reduce time to deploy high quality flight software; 2) Reduce project schedule and cost uncertainty; 3) Directly facilitate formalized software reuse; 4) Enable collaboration across organizations; 5) Simplify sustaining engineering (AKA. FSW maintenance); 6) Scale from small instruments to System of Systems; 7) Platform for advanced concepts and prototyping; and 7) Common standards and tools across the branch and NASA wide.

75 FR 38863 - Tenth Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems...

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2010-07-06

... Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY...-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing...: Enhanced Flight [[Page 38864

78 FR 16756 - Twenty-Second Meeting: RTCA Special Committee 213, Enhanced Flight Vision Systems/Synthetic...

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2013-03-18

... Committee 213, Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY: Federal Aviation... 213, Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing..., Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). DATES: The meeting will be held April...

77 FR 16890 - Eighteenth Meeting: RTCA Special Committee 213, Enhanced Flight Visions Systems/Synthetic Vision...

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2012-03-22

... Committee 213, Enhanced Flight Visions Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY: Federal Aviation... 213, Enhanced Flight Visions Systems/Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing... Flight Visions Systems/Synthetic Vision Systems (EFVS/SVS). DATES: The meeting will be held April 17-19...

78 FR 5557 - Twenty-First Meeting: RTCA Special Committee 213, Enhanced Flight Vision Systems/Synthetic Vision...

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2013-01-25

... Committee 213, Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY: Federal Aviation... 213, Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing..., Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). DATES: The meeting will be held...

78 FR 55774 - Twenty Fourth Meeting: RTCA Special Committee 213, Enhanced Flight Vision Systems/Synthetic...

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2013-09-11

... Committee 213, Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY: Federal Aviation... 213, Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing..., Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). DATES: The meeting will be held October...

75 FR 17202 - Eighth Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-05

... Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY...-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing...: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). DATES: The meeting will be held April...

77 FR 56254 - Twentieth Meeting: RTCA Special Committee 213, Enhanced Flight Vision Systems/Synthetic Vision...

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2012-09-12

... Committee 213, Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY: Federal Aviation... 213, Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing... Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). DATES: The meeting will be held October 2-4...

75 FR 44306 - Eleventh Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems...

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2010-07-28

... Committee 213: EUROCAE WG- 79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY... Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS... 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). DATES: The...

75 FR 71183 - Twelfth Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems...

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2010-11-22

... Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY... Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). SUMMARY...: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). DATES: The meeting will...

Flight demonstration of a self repairing flight control system in a NASA F-15 fighter aircraft

NASA Technical Reports Server (NTRS)

Urnes, James M.; Stewart, James; Eslinger, Robert

1990-01-01

Battle damage causing loss of control capability can compromise mission objectives and even result in aircraft loss. The Self Repairing Flight Control System (SRFCS) flight development program directly addresses this issue with a flight control system design that measures the damage and immediately refines the control system commands to preserve mission potential. The system diagnostics process detects in flight the type of faults that are difficult to isolate post flight, and thus cause excessive ground maintenance time and cost. The control systems of fighter aircraft have the control power and surface displacement to maneuver the aircraft in a very large flight envelope with a wide variation in airspeed and g maneuvering conditions, with surplus force capacity available from each control surface. Digital flight control processors are designed to include built-in status of the control system components, as well as sensor information on aircraft control maneuver commands and response. In the event of failure or loss of a control surface, the SRFCS utilizes this capability to reconfigure control commands to the remaining control surfaces, thus preserving maneuvering response. Correct post-flight repair is the key to low maintainability support costs and high aircraft mission readiness. The SRFCS utilizes the large data base available with digital flight control systems to diagnose faults. Built-in-test data and sensor data are used as inputs to an Onboard Expert System process to accurately identify failed components for post-flight maintenance action. This diagnostic technique has the advantage of functioning during flight, and so is especially useful in identifying intermittent faults that are present only during maneuver g loads or high hydraulic flow requirements. A flight system was developed to test the reconfiguration and onboard maintenance diagnostics concepts on a NASA F-15 fighter aircraft.

Optimum Strategies for Selecting Descent Flight-Path Angles

NASA Technical Reports Server (NTRS)

Wu, Minghong G. (Inventor); Green, Steven M. (Inventor)

2016-01-01

An information processing system and method for adaptively selecting an aircraft descent flight path for an aircraft, are provided. The system receives flight adaptation parameters, including aircraft flight descent time period, aircraft flight descent airspace region, and aircraft flight descent flyability constraints. The system queries a plurality of flight data sources and retrieves flight information including any of winds and temperatures aloft data, airspace/navigation constraints, airspace traffic demand, and airspace arrival delay model. The system calculates a set of candidate descent profiles, each defined by at least one of a flight path angle and a descent rate, and each including an aggregated total fuel consumption value for the aircraft following a calculated trajectory, and a flyability constraints metric for the calculated trajectory. The system selects a best candidate descent profile having the least fuel consumption value while the fly ability constraints metric remains within aircraft flight descent flyability constraints.

Flight Test Implementation of a Second Generation Intelligent Flight Control System

NASA Technical Reports Server (NTRS)

Williams-Hayes, Peggy S.

2005-01-01

The NASA F-15 Intelligent Flight Control System project team has developed a series of flight control concepts designed to demonstrate the benefits of a neural network-based adaptive controller. The objective of the team was to develop and flight-test control systems that use neural network technology, to optimize the performance of the aircraft under nominal conditions, and to stabilize the aircraft under failure conditions. Failure conditions include locked or failed control surfaces as well as unforeseen damage that might occur to the aircraft in flight. The Intelligent Flight Control System team is currently in the process of implementing a second generation control scheme, collectively known as Generation 2 or Gen 2, for flight testing on the NASA F-15 aircraft. This report describes the Gen 2 system as implemented by the team for flight test evaluation. Simulation results are shown which describe the experiment to be performed in flight and highlight the ways in which the Gen 2 system meets the defined objectives.

Software control and system configuration management: A systems-wide approach

NASA Technical Reports Server (NTRS)

Petersen, K. L.; Flores, C., Jr.

1984-01-01

A comprehensive software control and system configuration management process for flight-crucial digital control systems of advanced aircraft has been developed and refined to insure efficient flight system development and safe flight operations. Because of the highly complex interactions among the hardware, software, and system elements of state-of-the-art digital flight control system designs, a systems-wide approach to configuration control and management has been used. Specific procedures are implemented to govern discrepancy reporting and reconciliation, software and hardware change control, systems verification and validation testing, and formal documentation requirements. An active and knowledgeable configuration control board reviews and approves all flight system configuration modifications and revalidation tests. This flexible process has proved effective during the development and flight testing of several research aircraft and remotely piloted research vehicles with digital flight control systems that ranged from relatively simple to highly complex, integrated mechanizations.

14 CFR 121.127 - Flight following system; requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Flight following system; requirements. 121... Supplemental Operations § 121.127 Flight following system; requirements. (a) Each certificate holder conducting supplemental operations using a flight following system must show that— (1) The system has adequate facilities...

14 CFR 121.127 - Flight following system; requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Flight following system; requirements. 121... Supplemental Operations § 121.127 Flight following system; requirements. (a) Each certificate holder conducting supplemental operations using a flight following system must show that— (1) The system has adequate facilities...

14 CFR 121.127 - Flight following system; requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Flight following system; requirements. 121... Supplemental Operations § 121.127 Flight following system; requirements. (a) Each certificate holder conducting supplemental operations using a flight following system must show that— (1) The system has adequate facilities...

14 CFR 121.127 - Flight following system; requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Flight following system; requirements. 121... Supplemental Operations § 121.127 Flight following system; requirements. (a) Each certificate holder conducting supplemental operations using a flight following system must show that— (1) The system has adequate facilities...

14 CFR 121.127 - Flight following system; requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Flight following system; requirements. 121... Supplemental Operations § 121.127 Flight following system; requirements. (a) Each certificate holder conducting supplemental operations using a flight following system must show that— (1) The system has adequate facilities...

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.

76 FR 11847 - Thirteenth Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-03

... Special Committee 213: EUROCAE WG- 79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS... Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems... Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS...

76 FR 20437 - Fourteenth Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-12

... Special Committee 213: EUROCAE WG- 79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS... Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems... Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS...

Flight control system design factors for applying automated testing techniques

NASA Technical Reports Server (NTRS)

Sitz, Joel R.; Vernon, Todd H.

1990-01-01

Automated validation of flight-critical embedded systems is being done at ARC Dryden Flight Research Facility. The automated testing techniques are being used to perform closed-loop validation of man-rated flight control systems. The principal design features and operational experiences of the X-29 forward-swept-wing aircraft and F-18 High Alpha Research Vehicle (HARV) automated test systems are discussed. Operationally applying automated testing techniques has accentuated flight control system features that either help or hinder the application of these techniques. The paper also discusses flight control system features which foster the use of automated testing techniques.

Software control and system configuration management - A process that works

NASA Technical Reports Server (NTRS)

Petersen, K. L.; Flores, C., Jr.

1983-01-01

A comprehensive software control and system configuration management process for flight-crucial digital control systems of advanced aircraft has been developed and refined to insure efficient flight system development and safe flight operations. Because of the highly complex interactions among the hardware, software, and system elements of state-of-the-art digital flight control system designs, a systems-wide approach to configuration control and management has been used. Specific procedures are implemented to govern discrepancy reporting and reconciliation, software and hardware change control, systems verification and validation testing, and formal documentation requirements. An active and knowledgeable configuration control board reviews and approves all flight system configuration modifications and revalidation tests. This flexible process has proved effective during the development and flight testing of several research aircraft and remotely piloted research vehicles with digital flight control systems that ranged from relatively simple to highly complex, integrated mechanizations.

Spacecraft Design Thermal Control Subsystem

NASA Technical Reports Server (NTRS)

Miyake, Robert N.

2008-01-01

The Thermal Control Subsystem engineers task is to maintain the temperature of all spacecraft components, subsystems, and the total flight system within specified limits for all flight modes from launch to end-of-mission. In some cases, specific stability and gradient temperature limits will be imposed on flight system elements. The Thermal Control Subsystem of "normal" flight systems, the mass, power, control, and sensing systems mass and power requirements are below 10% of the total flight system resources. In general the thermal control subsystem engineer is involved in all other flight subsystem designs.

14 CFR 417.311 - Flight safety crew roles and qualifications.

Code of Federal Regulations, 2012 CFR

2012-01-01

... crew roles and qualifications. (a) A flight safety crew must operate the flight safety system hardware... the knowledge, skills, and abilities needed to operate the flight safety system hardware in accordance... rules. (3) An individual who operates flight safety support systems must have knowledge of and be...

14 CFR 417.311 - Flight safety crew roles and qualifications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... crew roles and qualifications. (a) A flight safety crew must operate the flight safety system hardware... the knowledge, skills, and abilities needed to operate the flight safety system hardware in accordance... rules. (3) An individual who operates flight safety support systems must have knowledge of and be...

14 CFR 417.311 - Flight safety crew roles and qualifications.

Code of Federal Regulations, 2014 CFR

2014-01-01

... crew roles and qualifications. (a) A flight safety crew must operate the flight safety system hardware... the knowledge, skills, and abilities needed to operate the flight safety system hardware in accordance... rules. (3) An individual who operates flight safety support systems must have knowledge of and be...

Initial Flight Test of the Production Support Flight Control Computers at NASA Dryden Flight Research Center

NASA Technical Reports Server (NTRS)

Carter, John; Stephenson, Mark

1999-01-01

The NASA Dryden Flight Research Center has completed the initial flight test of a modified set of F/A-18 flight control computers that gives the aircraft a research control law capability. The production support flight control computers (PSFCC) provide an increased capability for flight research in the control law, handling qualities, and flight systems areas. The PSFCC feature a research flight control processor that is "piggybacked" onto the baseline F/A-18 flight control system. This research processor allows for pilot selection of research control law operation in flight. To validate flight operation, a replication of a standard F/A-18 control law was programmed into the research processor and flight-tested over a limited envelope. This paper provides a brief description of the system, summarizes the initial flight test of the PSFCC, and describes future experiments for the PSFCC.

Air traffic management evaluation tool

NASA Technical Reports Server (NTRS)

Sridhar, Banavar (Inventor); Chatterji, Gano Broto (Inventor); Schipper, John F. (Inventor); Bilimoria, Karl D. (Inventor); Grabbe, Shon (Inventor); Sheth, Kapil S. (Inventor)

2012-01-01

Methods for evaluating and implementing air traffic management tools and approaches for managing and avoiding an air traffic incident before the incident occurs. A first system receives parameters for flight plan configurations (e.g., initial fuel carried, flight route, flight route segments followed, flight altitude for a given flight route segment, aircraft velocity for each flight route segment, flight route ascent rate, flight route descent route, flight departure site, flight departure time, flight arrival time, flight destination site and/or alternate flight destination site), flight plan schedule, expected weather along each flight route segment, aircraft specifics, airspace (altitude) bounds for each flight route segment, navigational aids available. The invention provides flight plan routing and direct routing or wind optimal routing, using great circle navigation and spherical Earth geometry. The invention provides for aircraft dynamics effects, such as wind effects at each altitude, altitude changes, airspeed changes and aircraft turns to provide predictions of aircraft trajectory (and, optionally, aircraft fuel use). A second system provides several aviation applications using the first system. Several classes of potential incidents are analyzed and averted, by appropriate change en route of one or more parameters in the flight plan configuration, as provided by a conflict detection and resolution module and/or traffic flow management modules. These applications include conflict detection and resolution, miles-in trail or minutes-in-trail aircraft separation, flight arrival management, flight re-routing, weather prediction and analysis and interpolation of weather variables based upon sparse measurements. The invention combines these features to provide an aircraft monitoring system and an aircraft user system that interact and negotiate changes with each other.

Advanced Command Destruct System (ACDS) Enhanced Flight Termination System (EFTS)

NASA Technical Reports Server (NTRS)

Tow, David K.

2011-01-01

This presentation provides information on the development, integration, and operational usage of the Enhanced Flight Termination System (EFTS) at NASA Dryden Flight Research Center and Air Force Flight Test Center. The presentation will describe the efforts completed to certify the system and acquire approval for operational usage, the efforts to integrate the system into the NASA Dryden existing flight termination infrastructure, and the operational support of aircraft with EFTS at Edwards AFB.

The development of an automated flight test management system for flight test planning and monitoring

NASA Technical Reports Server (NTRS)

Hewett, Marle D.; Tartt, David M.; Duke, Eugene L.; Antoniewicz, Robert F.; Brumbaugh, Randal W.

1988-01-01

The development of an automated flight test management system (ATMS) as a component of a rapid-prototyping flight research facility for AI-based flight systems concepts is described. The rapid-prototyping facility includes real-time high-fidelity simulators, numeric and symbolic processors, and high-performance research aircraft modified to accept commands for a ground-based remotely augmented vehicle facility. The flight system configuration of the ATMS includes three computers: the TI explorer LX and two GOULD SEL 32/27s.

What can formal methods offer to digital flight control systems design

NASA Technical Reports Server (NTRS)

Good, Donald I.

1990-01-01

Formal methods research begins to produce methods which will enable mathematic modeling of the physical behavior of digital hardware and software systems. The development of these methods directly supports the NASA mission of increasing the scope and effectiveness of flight system modeling capabilities. The conventional, continuous mathematics that is used extensively in modeling flight systems is not adequate for accurate modeling of digital systems. Therefore, the current practice of digital flight control system design has not had the benefits of extensive mathematical modeling which are common in other parts of flight system engineering. Formal methods research shows that by using discrete mathematics, very accurate modeling of digital systems is possible. These discrete modeling methods will bring the traditional benefits of modeling to digital hardware and hardware design. Sound reasoning about accurate mathematical models of flight control systems can be an important part of reducing risk of unsafe flight control.

An American knowledge base in England - Alternate implementations of an expert system flight status monitor

NASA Technical Reports Server (NTRS)

Butler, G. F.; Graves, A. T.; Disbrow, J. D.; Duke, E. L.

1989-01-01

A joint activity between the Dryden Flight Research Facility of the NASA Ames Research Center (Ames-Dryden) and the Royal Aerospace Establishment (RAE) on knowledge-based systems has been agreed. Under the agreement, a flight status monitor knowledge base developed at Ames-Dryden has been implemented using the real-time AI (artificial intelligence) toolkit MUSE, which was developed in the UK. Here, the background to the cooperation is described and the details of the flight status monitor and a prototype MUSE implementation are presented. It is noted that the capabilities of the expert-system flight status monitor to monitor data downlinked from the flight test aircraft and to generate information on the state and health of the system for the test engineers provides increased safety during flight testing of new systems. Furthermore, the expert-system flight status monitor provides the systems engineers with ready access to the large amount of information required to describe a complex aircraft system.

Flight testing a propulsion-controlled aircraft emergency flight control system on an F-15 airplane

NASA Technical Reports Server (NTRS)

Burcham, F. W., Jr.; Burken, John; Maine, Trindel A.

1994-01-01

Flight tests of a propulsion-controlled aircraft (PCA) system on an F-15 airplane have been conducted at the NASA Dryden Flight Research Center. The airplane was flown with all flight control surfaces locked both in the manual throttles-only mode and in an augmented system mode. In the latter mode, pilot thumbwheel commands and aircraft feedback parameters were used to position the throttles. Flight evaluation results showed that the PCA system can be used to land an airplane that has suffered a major flight control system failure safely. The PCA system was used to recover the F-15 airplane from a severe upset condition, descend, and land. Pilots from NASA, U.S. Air Force, U.S. Navy, and McDonnell Douglas Aerospace evaluated the PCA system and were favorably impressed with its capability. Manual throttles-only approaches were unsuccessful. This paper describes the PCA system operation and testing. It also presents flight test results and pilot comments.

High-speed flight propulsion systems. Progress in Astronautics and Aeronautics. Vol. 137

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murthy, S.N.B.; Curran, E.T.

1991-01-01

Various papers on high-speed flight propulsion systems are presented. The topics addressed are: propulsion systems from takeoff to high-speed flight, propulsion system performance and integration for high Mach air-breathing flight, energy analysis of high-speed flight systems, waves and thermodynamics in high Mach number propulsive ducts, turbulent free shear layer mixing and combustion, turbulent mixing in supersonic combustion systems, mixing and mixing enhancement in supersonic reacting flowfields, study of combustion and heat-exchange processes in high-enthalpy short-duration facilities, and facility requirements for hypersonic propulsion system testing.

MMW radar enhanced vision systems: the Helicopter Autonomous Landing System (HALS) and Radar-Enhanced Vision System (REVS) are rotary and fixed wing enhanced flight vision systems that enable safe flight operations in degraded visual environments

NASA Astrophysics Data System (ADS)

Cross, Jack; Schneider, John; Cariani, Pete

2013-05-01

Sierra Nevada Corporation (SNC) has developed rotary and fixed wing millimeter wave radar enhanced vision systems. The Helicopter Autonomous Landing System (HALS) is a rotary-wing enhanced vision system that enables multi-ship landing, takeoff, and enroute flight in Degraded Visual Environments (DVE). HALS has been successfully flight tested in a variety of scenarios, from brown-out DVE landings, to enroute flight over mountainous terrain, to wire/cable detection during low-level flight. The Radar Enhanced Vision Systems (REVS) is a fixed-wing Enhanced Flight Vision System (EFVS) undergoing prototype development testing. Both systems are based on a fast-scanning, threedimensional 94 GHz radar that produces real-time terrain and obstacle imagery. The radar imagery is fused with synthetic imagery of the surrounding terrain to form a long-range, wide field-of-view display. A symbology overlay is added to provide aircraft state information and, for HALS, approach and landing command guidance cuing. The combination of see-through imagery and symbology provides the key information a pilot needs to perform safe flight operations in DVE conditions. This paper discusses the HALS and REVS systems and technology, presents imagery, and summarizes the recent flight test results.

14 CFR 29.1335 - Flight director systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Flight director systems. 29.1335 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Equipment Instruments: Installation § 29.1335 Flight director systems. If a flight director system is installed, means must be provided to indicate to the...

14 CFR 27.1335 - Flight director systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Flight director systems. 27.1335 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Equipment Instruments: Installation § 27.1335 Flight director systems. If a flight director system is installed, means must be provided to indicate to the...

14 CFR 27.1335 - Flight director systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Flight director systems. 27.1335 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Equipment Instruments: Installation § 27.1335 Flight director systems. If a flight director system is installed, means must be provided to indicate to the...

14 CFR 29.1335 - Flight director systems.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Flight director systems. 29.1335 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Equipment Instruments: Installation § 29.1335 Flight director systems. If a flight director system is installed, means must be provided to indicate to the...

14 CFR 29.1335 - Flight director systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Flight director systems. 29.1335 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Equipment Instruments: Installation § 29.1335 Flight director systems. If a flight director system is installed, means must be provided to indicate to the...

Overview of a Proposed Flight Validation of Aerocapture System Technology for Planetary Missions

NASA Technical Reports Server (NTRS)

Keys, Andrew S.; Hall, Jeffery L.; Oh, David; Munk, Michelle M.

2006-01-01

Aerocapture System Technology for Planetary Missions is being proposed to NASA's New Millennium Program for flight aboard the Space Technology 9 (ST9) flight opportunity. The proposed ST9 aerocapture mission is a system-level flight validation of the aerocapture maneuver as performed by an instrumented, high-fidelity flight vehicle within a true in-space and atmospheric environment. Successful validation of the aerocapture maneuver will be enabled through the flight validation of an advanced guidance, navigation, and control system as developed by Ball Aerospace and two advanced Thermal Protection System (TPS) materials, Silicon Refined Ablative Material-20 (SRAM-20) and SRAM-14, as developed by Applied Research Associates (ARA) Ablatives Laboratory. The ST9 aerocapture flight validation will be sufficient for immediate infusion of these technologies into NASA science missions being proposed for flight to a variety of Solar System destinations possessing a significant planetary atmosphere.

L(sub 1) Adaptive Flight Control System: Flight Evaluation and Technology Transition

NASA Technical Reports Server (NTRS)

Xargay, Enric; Hovakimyan, Naira; Dobrokhodov, Vladimir; Kaminer, Isaac; Gregory, Irene M.; Cao, Chengyu

2010-01-01

Certification of adaptive control technologies for both manned and unmanned aircraft represent a major challenge for current Verification and Validation techniques. A (missing) key step towards flight certification of adaptive flight control systems is the definition and development of analysis tools and methods to support Verification and Validation for nonlinear systems, similar to the procedures currently used for linear systems. In this paper, we describe and demonstrate the advantages of L(sub l) adaptive control architectures for closing some of the gaps in certification of adaptive flight control systems, which may facilitate the transition of adaptive control into military and commercial aerospace applications. As illustrative examples, we present the results of a piloted simulation evaluation on the NASA AirSTAR flight test vehicle, and results of an extensive flight test program conducted by the Naval Postgraduate School to demonstrate the advantages of L(sub l) adaptive control as a verifiable robust adaptive flight control system.

Stability and control flight test results of the space transportation system's orbiter

NASA Technical Reports Server (NTRS)

Culp, M. A.; Cooke, D. R.

1982-01-01

Flight testing of the Space Shuttle Orbiter is in progress and current results of the post-flight aerodynamic analyses are discussed. The purpose of these analyses is to reduce the pre-flight aerodynamic uncertainties, thereby leading to operational certification of the Orbiter flight envelope relative to the integrated airframe and flight control system. Primary data reduction is accomplished with a well documented maximum likelihood system identification techniques.

Information Display System for Atypical Flight Phase

NASA Technical Reports Server (NTRS)

Statler, Irving C. (Inventor); Ferryman, Thomas A. (Inventor); Amidan, Brett G. (Inventor); Whitney, Paul D. (Inventor); White, Amanda M. (Inventor); Willse, Alan R. (Inventor); Cooley, Scott K. (Inventor); Jay, Joseph Griffith (Inventor); Lawrence, Robert E. (Inventor); Mosbrucker, Chris J. (Inventor);

14 CFR 121.125 - Flight following system.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Flight following system. 121.125 Section... Operations § 121.125 Flight following system. (a) Each certificate holder conducting supplemental operations must show that it has— (1) An approved flight following system established in accordance with subpart U...

14 CFR 121.125 - Flight following system.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Flight following system. 121.125 Section... Operations § 121.125 Flight following system. (a) Each certificate holder conducting supplemental operations must show that it has— (1) An approved flight following system established in accordance with subpart U...

14 CFR 121.125 - Flight following system.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Flight following system. 121.125 Section... Operations § 121.125 Flight following system. (a) Each certificate holder conducting supplemental operations must show that it has— (1) An approved flight following system established in accordance with subpart U...

14 CFR 121.125 - Flight following system.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Flight following system. 121.125 Section... Operations § 121.125 Flight following system. (a) Each certificate holder conducting supplemental operations must show that it has— (1) An approved flight following system established in accordance with subpart U...

14 CFR 121.125 - Flight following system.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Flight following system. 121.125 Section... Operations § 121.125 Flight following system. (a) Each certificate holder conducting supplemental operations must show that it has— (1) An approved flight following system established in accordance with subpart U...

76 FR 9265 - Special Conditions: Gulfstream Model GVI Airplane; Electronic Flight Control System: Control...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-17

... for transport category airplanes. These design features include an electronic flight control system... Design Features The GVI has an electronic flight control system and no direct coupling from the cockpit...: Gulfstream Model GVI Airplane; Electronic Flight Control System: Control Surface Position Awareness AGENCY...

Design and utilization of a Flight Test Engineering Database Management System at the NASA Dryden Flight Research Facility

NASA Technical Reports Server (NTRS)

Knighton, Donna L.

1992-01-01

A Flight Test Engineering Database Management System (FTE DBMS) was designed and implemented at the NASA Dryden Flight Research Facility. The X-29 Forward Swept Wing Advanced Technology Demonstrator flight research program was chosen for the initial system development and implementation. The FTE DBMS greatly assisted in planning and 'mass production' card preparation for an accelerated X-29 research program. Improved Test Plan tracking and maneuver management for a high flight-rate program were proven, and flight rates of up to three flights per day, two times per week were maintained.

A novel role for bone-derived cells in ankylosing spondylitis: Focus on IL-23.

PubMed

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.

Protective effect of catechin in type I Gaucher disease cells by reducing endoplasmic reticulum stress

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

Aging and sleep deprivation induce the unfolded protein response in the pancreas: implications for metabolism

PubMed Central

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.

PubMed

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.

PubMed

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

PubMed Central

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

Substance abuse and batterer programmes in California, USA: factors associated with treatment outcomes.

PubMed

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.

Development of Autonomous Optimal Cooperative Control in Relay Rover Configured Small Unmanned Aerial Systems

DTIC Science & Technology

2013-03-01

Unmanned Aircraft Systems Flight Plan that identified small unmanned aerial systems ( SUAS ) as “a profound technological...advances in small unmanned aerial systems ( SUAS ) cooperative control. The end state objective of the research effort was to flight test an autonomous...requirements were captured in the Unmanned Aircraft Systems Flight Plan . The flight plan

Flight-determined benefits of integrated flight-propulsion control systems

NASA Technical Reports Server (NTRS)

Stewart, James F.; Burcham, Frank W., Jr.; Gatlin, Donald H.

1992-01-01

Over the last two decades, NASA has conducted several experiments in integrated flight-propulsion control. Benefits have included improved maneuverability; increased thrust, range, and survivability; reduced fuel consumption; and reduced maintenance. This paper presents the basic concepts for control integration, examples of implementation, and benefits. The F-111E experiment integrated the engine and inlet control systems. The YF-12C incorporated an integral control system involving the inlet, autopilot, autothrottle, airdata, navigation, and stability augmentation systems. The F-15 research involved integration of the engine, flight, and inlet control systems. Further extension of the integration included real-time, onboard optimization of engine, inlet, and flight control variables; a self-repairing flight control system; and an engines-only control concept for emergency control. The F-18A aircraft incorporated thrust vectoring integrated with the flight control system to provide enhanced maneuvering at high angles of attack. The flight research programs and the resulting benefits of each program are described.

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.

AGARD Flight Test Techniques Series. Volume 18. Flight Testing of Radio Navigation Systems. (Les Essais en Vol des Systemes de Radionavigation)

DTIC Science & Technology

2000-04-01

18 Flight Testing of Radio Navigation Systems (les Essais en vol des systemes de radionavigation) This AGARDograph has been sponsored by the Systems...Techniques Series - Volume 18 Flight Testing of Radio Navigation Systems (les Essais en vol des syst~mes de radionavigation) Edited by H. Bothe H.J...Landing Test and Other Short-Range 19853 Applications by P. de Benquoe D’Agut, H. Rieheek and A. Pool 17. Analogue Signal Conditioning for Flight Test

A neural based intelligent flight control system for the NASA F-15 flight research aircraft

NASA Technical Reports Server (NTRS)

Urnes, James M.; Hoy, Stephen E.; Ladage, Robert N.; Stewart, James

1993-01-01

A flight control concept that can identify aircraft stability properties and continually optimize the aircraft flying qualities has been developed by McDonnell Aircraft Company under a contract with the NASA-Dryden Flight Research Facility. This flight concept, termed the Intelligent Flight Control System, utilizes Neural Network technology to identify the host aircraft stability and control properties during flight, and use this information to design on-line the control system feedback gains to provide continuous optimum flight response. This self-repairing capability can provide high performance flight maneuvering response throughout large flight envelopes, such as needed for the National Aerospace Plane. Moreover, achieving this response early in the vehicle's development schedule will save cost.

Development of a simple, self-contained flight test data acquisition system

NASA Technical Reports Server (NTRS)

Clarke, R.; Shane, D.; Roskam, J.; Rummer, D. I.

1982-01-01

The flight test system described combines state-of-the-art microprocessor technology and high accuracy instrumentation with parameter identification technology which minimize data and flight time requirements. The system was designed to avoid permanent modifications of the test airplane and allow quick installation. It is capable of longitudinal and lateral-directional stability and control derivative estimation. Details of this system, calibration and flight test procedures, and the results of the Cessna 172 flight test program are presented. The system proved easy to install, simple to operate, and capable of accurate estimation of stability and control parameters in the Cessna 172 flight tests.

14 CFR 415.131 - Flight safety system crew data.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Flight safety system crew data. 415.131... Launch Vehicle From a Non-Federal Launch Site § 415.131 Flight safety system crew data. (a) An applicant's safety review document must identify each flight safety system crew position and the role of that...

14 CFR Appendix D to Part 417 - Flight Termination Systems, Components, Installation, and Monitoring

Code of Federal Regulations, 2013 CFR

2013-01-01

... other propulsion system. D417.5Flight termination system design (a) Reliability prediction. A flight... design margin required by this appendix. As an alternative to subjecting the flight termination system to... the component is heated or cooled to achieve the required dwell time at one extreme of the required...

14 CFR Appendix D to Part 417 - Flight Termination Systems, Components, Installation, and Monitoring

Code of Federal Regulations, 2011 CFR

2011-01-01

... other propulsion system. D417.5Flight termination system design (a) Reliability prediction. A flight... design margin required by this appendix. As an alternative to subjecting the flight termination system to... the component is heated or cooled to achieve the required dwell time at one extreme of the required...

14 CFR Appendix D to Part 417 - Flight Termination Systems, Components, Installation, and Monitoring

Code of Federal Regulations, 2012 CFR

2012-01-01

... other propulsion system. D417.5Flight termination system design (a) Reliability prediction. A flight... design margin required by this appendix. As an alternative to subjecting the flight termination system to... the component is heated or cooled to achieve the required dwell time at one extreme of the required...

14 CFR Appendix D to Part 417 - Flight Termination Systems, Components, Installation, and Monitoring

Code of Federal Regulations, 2014 CFR

2014-01-01

... other propulsion system. D417.5Flight termination system design (a) Reliability prediction. A flight... design margin required by this appendix. As an alternative to subjecting the flight termination system to... the component is heated or cooled to achieve the required dwell time at one extreme of the required...

In-Flight Suppression of an Unstable F/A-18 Structural Mode Using the Space Launch System Adaptive Augmenting Control System

NASA Technical Reports Server (NTRS)

VanZwieten, Tannen S.; Gilligan, Eric T.; Wall, John H.; Miller, Christopher J.; Hanson, Curtis E.; Orr, Jeb S.

2015-01-01

NASA's Space Launch System (SLS) Flight Control System (FCS) includes an Adaptive Augmenting Control (AAC) component which employs a multiplicative gain update law to enhance the performance and robustness of the baseline control system for extreme off-nominal scenarios. The SLS FCS algorithm including AAC has been flight tested utilizing a specially outfitted F/A-18 fighter jet in which the pitch axis control of the aircraft was performed by a Non-linear Dynamic Inversion (NDI) controller, SLS reference models, and the SLS flight software prototype. This paper describes test cases from the research flight campaign in which the fundamental F/A-18 airframe structural mode was identified using post-flight frequency-domain reconstruction, amplified to result in closed loop instability, and suppressed in-flight by the SLS adaptive control system.

Man-vehicle systems research facility advanced aircraft flight simulator throttle mechanism

NASA Technical Reports Server (NTRS)

Kurasaki, S. S.; Vallotton, W. C.

1985-01-01

The Advanced Aircraft Flight Simulator is equipped with a motorized mechanism that simulates a two engine throttle control system that can be operated via a computer driven performance management system or manually by the pilots. The throttle control system incorporates features to simulate normal engine operations and thrust reverse and vary the force feel to meet a variety of research needs. While additional testing to integrate the work required is principally now in software design, since the mechanical aspects function correctly. The mechanism is an important part of the flight control system and provides the capability to conduct human factors research of flight crews with advanced aircraft systems under various flight conditions such as go arounds, coupled instrument flight rule approaches, normal and ground operations and emergencies that would or would not normally be experienced in actual flight.

Optical Air Flow Measurements for Flight Tests and Flight Testing Optical Air Flow Meters

NASA Technical Reports Server (NTRS)

Jentink, Henk W.; Bogue, Rodney K.

2005-01-01

Optical air flow measurements can support the testing of aircraft and can be instrumental to in-flight investigations of the atmosphere or atmospheric phenomena. Furthermore, optical air flow meters potentially contribute as avionics systems to flight safety and as air data systems. The qualification of these instruments for the flight environment is where we encounter the systems in flight testing. An overview is presented of different optical air flow measurement techniques applied in flight and what can be achieved with the techniques for flight test purposes is reviewed. All in-flight optical airflow velocity measurements use light scattering. Light is scattered on both air molecules and aerosols entrained in the air. Basic principles of making optical measurements in flight, some basic optical concepts, electronic concepts, optoelectronic interfaces, and some atmospheric processes associated with natural aerosols are reviewed. Safety aspects in applying the technique are shortly addressed. The different applications of the technique are listed and some typical examples are presented. Recently NASA acquired new data on mountain rotors, mountain induced turbulence, with the ACLAIM system. Rotor position was identified using the lidar system and the potentially hazardous air flow profile was monitored by the ACLAIM system.

Navigation and flight director guidance for the NASA/FAA helicopter MLS curved approach flight test program

NASA Technical Reports Server (NTRS)

Phatak, A. V.; Lee, M. G.

1985-01-01

The navigation and flight director guidance systems implemented in the NASA/FAA helicopter microwave landing system (MLS) curved approach flight test program is described. Flight test were conducted at the U.S. Navy's Crows Landing facility, using the NASA Ames UH-lH helicopter equipped with the V/STOLAND avionics system. The purpose of these tests was to investigate the feasibility of flying complex, curved and descending approaches to a landing using MLS flight director guidance. A description of the navigation aids used, the avionics system, cockpit instrumentation and on-board navigation equipment used for the flight test is provided. Three generic reference flight paths were developed and flown during the test. They were as follows: U-Turn, S-turn and Straight-In flight profiles. These profiles and their geometries are described in detail. A 3-cue flight director was implemented on the helicopter. A description of the formulation and implementation of the flight director laws is also presented. Performance data and analysis is presented for one pilot conducting the flight director approaches.

Research flight-control system development for the F-18 high alpha research vehicle

NASA Technical Reports Server (NTRS)

Pahle, Joseph W.; Powers, Bruce; Regenie, Victoria; Chacon, Vince; Degroote, Steve; Murnyak, Steven

1991-01-01

The F-18 high alpha research vehicle was recently modified by adding a thrust vectoring control system. A key element in the modification was the development of a research flight control system integrated with the basic F-18 flight control system. Discussed here are design requirements, system development, and research utility of the resulting configuration as an embedded system for flight research in the high angle of attack regime. Particular emphasis is given to control system modifications and control law features required for high angle of attack flight. Simulation results are used to illustrate some of the thrust vectoring control system capabilities and predicted maneuvering improvements.

Digital Fly-By-Wire Flight Control Validation Experience

NASA Technical Reports Server (NTRS)

Szalai, K. J.; Jarvis, C. R.; Krier, G. E.; Megna, V. A.; Brock, L. D.; Odonnell, R. N.

1978-01-01

The experience gained in digital fly-by-wire technology through a flight test program being conducted by the NASA Dryden Flight Research Center in an F-8C aircraft is described. The system requirements are outlined, along with the requirements for flight qualification. The system is described, including the hardware components, the aircraft installation, and the system operation. The flight qualification experience is emphasized. The qualification process included the theoretical validation of the basic design, laboratory testing of the hardware and software elements, systems level testing, and flight testing. The most productive testing was performed on an iron bird aircraft, which used the actual electronic and hydraulic hardware and a simulation of the F-8 characteristics to provide the flight environment. The iron bird was used for sensor and system redundancy management testing, failure modes and effects testing, and stress testing in many cases with the pilot in the loop. The flight test program confirmed the quality of the validation process by achieving 50 flights without a known undetected failure and with no false alarms.

Innovative use of global navigation satellite systems for flight inspection

NASA Astrophysics Data System (ADS)

Kim, Eui-Ho

The International Civil Aviation Organization (ICAO) mandates flight inspection in every country to provide safety during flight operations. Among many criteria of flight inspection, airborne inspection of Instrument Landing Systems (ILS) is very important because the ILS is the primary landing guidance system worldwide. During flight inspection of the ILS, accuracy in ILS landing guidance is checked by using a Flight Inspection System (FIS). Therefore, a flight inspection system must have high accuracy in its positioning capability to detect any deviation so that accurate guidance of the ILS can be maintained. Currently, there are two Automated Flight Inspection Systems (AFIS). One is called Inertial-based AFIS, and the other one is called Differential GPS-based (DGPS-based) AFIS. The Inertial-based AFIS enables efficient flight inspection procedures, but its drawback is high cost because it requires a navigation-grade Inertial Navigation System (INS). On the other hand, the DGPS-based AFIS has relatively low cost, but flight inspection procedures require landing and setting up a reference receiver. Most countries use either one of the systems based on their own preferences. There are around 1200 ILS in the U.S., and each ILS must be inspected every 6 to 9 months. Therefore, it is important to manage the airborne inspection of the ILS in a very efficient manner. For this reason, the Federal Aviation Administration (FAA) mainly uses the Inertial-based AFIS, which has better efficiency than the DGPS-based AFIS in spite of its high cost. Obviously, the FAA spends tremendous resources on flight inspection. This thesis investigates the value of GPS and the FAA's augmentation to GPS for civil aviation called the Wide Area Augmentation System (or WAAS) for flight inspection. Because standard GPS or WAAS position outputs cannot meet the required accuracy for flight inspection, in this thesis, various algorithms are developed to improve the positioning ability of Flight Inspection Systems (FIS) by using GPS and WAAS in novel manners. The algorithms include Adaptive Carrier Smoothing (ACS), optimizing WAAS accuracy and stability, and reference point-based precise relative positioning for real-time and near-real-time applications. The developed systems are WAAS-aided FIS, WAAS-based FIS, and stand-alone GPS-based FIS. These systems offer both high efficiency and low cost, and they have different advantages over one another in terms of accuracy, integrity, and worldwide availability. The performance of each system is tested with experimental flight test data and shown to have accuracy that is sufficient for flight inspection and superior to the current Inertial-based AFIS.

Flight-testing of the self-repairing flight control system using the F-15 highly integrated digital electronic control flight research facility

NASA Technical Reports Server (NTRS)

Stewart, James F.; Shuck, Thomas L.

1990-01-01

Flight tests conducted with the self-repairing flight control system (SRFCS) installed on the NASA F-15 highly integrated digital electronic control aircraft are described. The development leading to the current SRFCS configuration is highlighted. Key objectives of the program are outlined: (1) to flight-evaluate a control reconfiguration strategy with three types of control surface failure; (2) to evaluate a cockpit display that will inform the pilot of the maneuvering capacity of the damage aircraft; and (3) to flight-evaluate the onboard expert system maintenance diagnostics process using representative faults set to occur only under maneuvering conditions. Preliminary flight results addressing the operation of the overall system, as well as the individual technologies, are included.

Autonomous Flight Safety System

NASA Technical Reports Server (NTRS)

Ferrell, Bob; Santuro, Steve; Simpson, James; Zoerner, Roger; Bull, Barton; Lanzi, Jim

2004-01-01

Autonomous Flight Safety System (AFSS) is an independent flight safety system designed for small to medium sized expendable launch vehicles launching from or needing range safety protection while overlying relatively remote locations. AFSS replaces the need for a man-in-the-loop to make decisions for flight termination. AFSS could also serve as the prototype for an autonomous manned flight crew escape advisory system. AFSS utilizes onboard sensors and processors to emulate the human decision-making process using rule-based software logic and can dramatically reduce safety response time during critical launch phases. The Range Safety flight path nominal trajectory, its deviation allowances, limit zones and other flight safety rules are stored in the onboard computers. Position, velocity and attitude data obtained from onboard global positioning system (GPS) and inertial navigation system (INS) sensors are compared with these rules to determine the appropriate action to ensure that people and property are not jeopardized. The final system will be fully redundant and independent with multiple processors, sensors, and dead man switches to prevent inadvertent flight termination. AFSS is currently in Phase III which includes updated algorithms, integrated GPS/INS sensors, large scale simulation testing and initial aircraft flight testing.

Design and Development of a Flight Route Modification, Logging, and Communication Network

NASA Technical Reports Server (NTRS)

Merlino, Daniel K.; Wilson, C. Logan; Carboneau, Lindsey M.; Wilder, Andrew J.; Underwood, Matthew C.

2016-01-01

There is an overwhelming desire to create and enhance communication mechanisms between entities that operate within the National Airspace System. Furthermore, airlines are always extremely interested in increasing the efficiency of their flights. An innovative system prototype was developed and tested that improves collaborative decision making without modifying existing infrastructure or operational procedures within the current Air Traffic Management System. This system enables collaboration between flight crew and airline dispatchers to share and assess optimized flight routes through an Internet connection. Using a sophisticated medium-fidelity flight simulation environment, a rapid-prototyping development, and a unified modeling language, the software was designed to ensure reliability and scalability for future growth and applications. Ensuring safety and security were primary design goals, therefore the software does not interact or interfere with major flight control or safety systems. The system prototype demonstrated an unprecedented use of in-flight Internet to facilitate effective communication with Airline Operations Centers, which may contribute to increased flight efficiency for airlines.

The development of a Flight Test Engineer's Workstation for the Automated Flight Test Management System

NASA Technical Reports Server (NTRS)

Tartt, David M.; Hewett, Marle D.; Duke, Eugene L.; Cooper, James A.; Brumbaugh, Randal W.

1989-01-01

The Automated Flight Test Management System (ATMS) is being developed as part of the NASA Aircraft Automation Program. This program focuses on the application of interdisciplinary state-of-the-art technology in artificial intelligence, control theory, and systems methodology to problems of operating and flight testing high-performance aircraft. The development of a Flight Test Engineer's Workstation (FTEWS) is presented, with a detailed description of the system, technical details, and future planned developments. The goal of the FTEWS is to provide flight test engineers and project officers with an automated computer environment for planning, scheduling, and performing flight test programs. The FTEWS system is an outgrowth of the development of ATMS and is an implementation of a component of ATMS on SUN workstations.

Propulsion system-flight control integration-flight evaluation and technology transition

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Gilyard, Glenn B.; Myers, Lawrence P.

1990-01-01

Integration of propulsion and flight control systems and their optimization offering significant performance improvement are assessed. In particular, research programs conducted by NASA on flight control systems and propulsion system-flight control interactions on the YF-12 and F-15 aircraft are addressed; these programs have demonstrated increased thrust, reduced fuel consumption, increased engine life, and improved aircraft performance. Focus is placed on altitude control, speed-Mach control, integrated controller design, as well as flight control systems and digital electronic engine control. A highly integrated digital electronic control program is analyzed and compared with a performance seeking control program. It is shown that the flight evaluation and demonstration of these technologies have been a key part in the transition of the concepts to production and operational use on a timely basis.

The unfolded protein response and programmed cell death are induced by expression of Garlic virus X p11 in Nicotiana benthamiana.

PubMed

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.

ACES: Space shuttle flight software analysis expert system

NASA Technical Reports Server (NTRS)

Satterwhite, R. Scott

1990-01-01

The Analysis Criteria Evaluation System (ACES) is a knowledge based expert system that automates the final certification of the Space Shuttle onboard flight software. Guidance, navigation and control of the Space Shuttle through all its flight phases are accomplished by a complex onboard flight software system. This software is reconfigured for each flight to allow thousands of mission-specific parameters to be introduced and must therefore be thoroughly certified prior to each flight. This certification is performed in ground simulations by executing the software in the flight computers. Flight trajectories from liftoff to landing, including abort scenarios, are simulated and the results are stored for analysis. The current methodology of performing this analysis is repetitive and requires many man-hours. The ultimate goals of ACES are to capture the knowledge of the current experts and improve the quality and reduce the manpower required to certify the Space Shuttle onboard flight software.

Operational viewpoint of the X-29A digital flight control system

NASA Technical Reports Server (NTRS)

Chacon, Vince; Mcbride, David

1988-01-01

In the past few years many flight control systems have been implemented as full-authority, full-time digital systems. The digital design has allowed flight control systems to make use of many enhanced elements that are generally considered too complex to implement in an analog system. Examples of these elements are redundant information exchanged between channels to allow for continued operation after multiple failures and multiple variable gain schedules to optimize control of the aircraft throughout its flight envelope and in all flight modes. The introduction of the digital system for flight control also created the problem of obtaining information from the system in an understandable and useful format. This paper presents how the X-29A was dealt with during its operations at NASA Ames-Dryden Flight Research Facility. A brief description of the X-29A control system, a discussion of the tools developed to aid in daily operations, and the troubleshooting of the aircraft are included.

Implementation of the Enhanced Flight Termination System at National Aeronautics and Space Administration Dryden Flight Research Center

NASA Technical Reports Server (NTRS)

Tow, David

2010-01-01

This paper discusses the methodology, requirements, tests, and results of the implementation of the current operating capability for the Enhanced Flight Termination System (EFTS) at the National Aeronautics and Space Administration (NASA) Dryden Flight Research Center (DFRC). The implementation involves the development of the EFTS at NASA DFRC starting from the requirements to system safety review to full end to end system testing, and concluding with the acceptance of the system as an operational system. The paper discusses the first operational usage and subsequent flight utilizing EFTS successfully.

UAVSAR Flight-Planning System

NASA Technical Reports Server (NTRS)

2008-01-01

A system of software partly automates planning of a flight of the Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) -- a polarimetric synthetic-aperture radar system aboard an unpiloted or minimally piloted airplane. The software constructs a flight plan that specifies not only the intended flight path but also the setup of the radar system at each point along the path.

URV Flight Test of an ADA Implemented Self-Repairing Flight Control System

DTIC Science & Technology

1992-08-01

USE ONLY(Leave blank) I2. REPORT DATE j3.REOTYPANDTSCVRD JAUG 1992 j FINAL 01/01/85--08/31/92 4. TITLE AND SUBTITLE URV FL GHT TEST OF AN ADA IMPLEMESNT...History of the XBQM-106 2 2.0 Self-Repairing Flight Control System 4 Introduction 2.1 Control System Reconfiguration 5 Strategy 2.2 Failure Detection...ji * Ill ’ha A GJ s.d I I I C S U L 3 2.0 Self-Repairing Flight Control System Introduction Self-Repairing Flight Control Systems (SRFCS) are an

Advanced flight control system study

NASA Technical Reports Server (NTRS)

Mcgough, J.; Moses, K.; Klafin, J. F.

1982-01-01

The architecture, requirements, and system elements of an ultrareliable, advanced flight control system are described. The basic criteria are functional reliability of 10 to the minus 10 power/hour of flight and only 6 month scheduled maintenance. A distributed system architecture is described, including a multiplexed communication system, reliable bus controller, the use of skewed sensor arrays, and actuator interfaces. Test bed and flight evaluation program are proposed.

Design and Manufacturing of Extremely Low Mass Flight Systems

NASA Technical Reports Server (NTRS)

Johnson, Michael R.

2002-01-01

Extremely small flight systems pose some unusual design and manufacturing challenges. The small size of the components that make up the system generally must be built with extremely tight tolerances to maintain the functionality of the assembled item. Additionally, the total mass of the system is extremely sensitive to what would be considered small perturbations in a larger flight system. The MUSES C mission, designed, built, and operated by Japan, has a small rover provided by NASA that falls into this small flight system category. This NASA-provided rover is used as a case study of an extremely small flight system design. The issues that were encountered with the rover portion of the MUSES C program are discussed and conclusions about the recommended mass margins at different stages of a small flight system project are presented.

Flight Results of the NF-15B Intelligent Flight Control System (IFCS) Aircraft with Adaptation to a Longitudinally Destabilized Plant

NASA Technical Reports Server (NTRS)

Bosworth, John T.

2008-01-01

Adaptive flight control systems have the potential to be resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. The goal for the adaptive system is to provide an increase in survivability in the event that these extreme changes occur. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane. The adaptive element was incorporated into a dynamic inversion controller with explicit reference model-following. As a test the system was subjected to an abrupt change in plant stability simulating a destabilizing failure. Flight evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to stabilize the vehicle and reestablish good onboard reference model-following. Flight evaluation with the simulated destabilizing failure and adaptation engaged showed improvement in the vehicle stability margins. The convergent properties of this initial system warrant additional improvement since continued maneuvering caused continued adaptation change. Compared to the non-adaptive system the adaptive system provided better closed-loop behavior with improved matching of the onboard reference model. A detailed discussion of the flight results is presented.

Orion Launch Abort System Performance During Exploration Flight Test 1

NASA Technical Reports Server (NTRS)

McCauley, Rachel; Davidson, John; Gonzalez, Guillo

2015-01-01

The Orion Launch Abort System Office is taking part in flight testing to enable certification that the system is capable of delivering the astronauts aboard the Orion Crew Module to a safe environment during both nominal and abort conditions. Orion is a NASA program, Exploration Flight Test 1 is managed and led by the Orion prime contractor, Lockheed Martin, and launched on a United Launch Alliance Delta IV Heavy rocket. Although the Launch Abort System Office has tested the critical systems to the Launch Abort System jettison event on the ground, the launch environment cannot be replicated completely on Earth. During Exploration Flight Test 1, the Launch Abort System was to verify the function of the jettison motor to separate the Launch Abort System from the crew module so it can continue on with the mission. Exploration Flight Test 1 was successfully flown on December 5, 2014 from Cape Canaveral Air Force Station's Space Launch Complex 37. This was the first flight test of the Launch Abort System preforming Orion nominal flight mission critical objectives. The abort motor and attitude control motors were inert for Exploration Flight Test 1, since the mission did not require abort capabilities. Exploration Flight Test 1 provides critical data that enable engineering to improve Orion's design and reduce risk for the astronauts it will protect as NASA continues to move forward on its human journey to Mars. The Exploration Flight Test 1 separation event occurred at six minutes and twenty seconds after liftoff. The separation of the Launch Abort System jettison occurs once Orion is safely through the most dynamic portion of the launch. This paper will present a brief overview of the objectives of the Launch Abort System during a nominal Orion flight. Secondly, the paper will present the performance of the Launch Abort System at it fulfilled those objectives. The lessons learned from Exploration Flight Test 1 and the other Flight Test Vehicles will certainly contribute to the vehicle architecture of a human-rated space launch vehicle.

The X-43A Flush Airdata Sensing System Flight Test Results

NASA Technical Reports Server (NTRS)

Baumann, Ethan; Pahle, Joseph W.; Davis, Mark; White, John Terry

2008-01-01

The National Aeronautics and Space Administration (NASA) has flight-tested a flush airdata sensing (FADS) system on the Hyper-X Research Vehicle (X-43A) at hypersonic speeds during the course of two successful flights. For this series of tests, the FADS system was calibrated to operate between Mach 3 and Mach 8, and flight test data was collected between Mach 1 and Mach 10. The FADS system acquired pressure data from surface-mounted ports and generated a real-time angle-of-attack (alpha) estimate on board the X-43A. The collected data were primarily intended to evaluate the FADS system performance, and the estimated alpha was used by the flight control algorithms on the X-43A for only a portion of the first successful flight. This paper provides an overview of the FADS system and alpha estimation algorithms, presents the in-flight alpha estimation algorithm performance, and provides comparisons to wind tunnel results and theory. Results indicate that the FADS system adequately estimated the alpha of the vehicle during the hypersonic portions of the two flights.

Flight Test Results from the NF-15B Intelligent Flight Control System (IFCS) Project with Adaptation to a Simulated Stabilator Failure

NASA Technical Reports Server (NTRS)

Bosworth, John T.; Williams-Hayes, Peggy S.

2007-01-01

Adaptive flight control systems have the potential to be more resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane and subjected to an inflight simulation of a failed (frozen) (unmovable) stabilator. Formation flight handling qualities evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to decouple the roll and pitch response and reestablish good onboard model tracking. Flight evaluation with the simulated stabilator failure and adaptation engaged showed that there was generally improvement in the pitch response; however, a tendency for roll pilot-induced oscillation was experienced. A detailed discussion of the cause of the mixed results is presented.

Flight Test Results from the NF-15B Intelligent Flight Control System (IFCS) Project with Adaptation to a Simulated Stabilator Failure

NASA Technical Reports Server (NTRS)

Bosworth, John T.; Williams-Hayes, Peggy S.

2010-01-01

Adaptive flight control systems have the potential to be more resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane and subjected to an inflight simulation of a failed (frozen) (unmovable) stabilator. Formation flight handling qualities evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to decouple the roll and pitch response and reestablish good onboard model tracking. Flight evaluation with the simulated stabilator failure and adaptation engaged showed that there was generally improvement in the pitch response; however, a tendency for roll pilot-induced oscillation was experienced. A detailed discussion of the cause of the mixed results is presented.

In-Flight Suppression of a Destabilized F/A-18 Structural Mode Using the Space Launch System Adaptive Augmenting Control System

NASA Technical Reports Server (NTRS)

Wall, John H.; VanZwieten, Tannen S.; Gilligan, Eric T.; Miller, Christopher J.; Hanson, Curtis E.; Orr, Jeb S.

2015-01-01

NASA's Space Launch System (SLS) Flight Control System (FCS) includes an Adaptive Augmenting Control (AAC) component which employs a multiplicative gain update law to enhance the performance and robustness of the baseline control system for extreme off nominal scenarios. The SLS FCS algorithm including AAC has been flight tested utilizing a specially outfitted F/A-18 fighter jet in which the pitch axis control of the aircraft was performed by a Non-linear Dynamic Inversion (NDI) controller, SLS reference models, and the SLS flight software prototype. This paper describes test cases from the research flight campaign in which the fundamental F/A-18 airframe structural mode was identified using frequency-domain reconstruction of flight data, amplified to result in closed loop instability, and suppressed in-flight by the SLS adaptive control system.

Development of U.S. Government General Technical Requirements for UAS Flight Safety Systems Utilizing the Iridium Satellite Constellation

NASA Technical Reports Server (NTRS)

Murray, Jennifer; Birr, Richard

2010-01-01

This slide presentation reviews the development of technical requirements for Unmanned Aircraft Systems (UAS) utilization of the Iridium Satellite Constellation to provide flight safety. The Federal Aviation Authority (FAA) required an over-the-horizon communication standard to guarantee flight safety before permitting widespread UAS flights in the National Air Space (NAS). This is important to ensure reliable control of UASs during loss-link and over-the-horizon scenarios. The core requirement was to utilize a satellite system to send GPS tracking data and other telemetry from a flight vehicle down to the ground. Iridium was chosen as the system because it is one of the only true satellite systems that has world wide coverage, and the service has a highly reliable link margin. The Iridium system, the flight modems, and the test flight are described.

Armstrong Flight Research Center Flight Test Capabilities and Opportunities for the Applications of Wireless Data Acquisition Systems

NASA Technical Reports Server (NTRS)

Hang, Richard

2015-01-01

The presentation will overview NASA Armstrong Flight Research Centers flight test capabilities, which can provide various means for flight testing of passive and active wireless sensor systems, also, it will address the needs of the wireless data acquisition solutions for the centers flight instrumentation issues such as additional weight caused by added instrumentation wire bundles, connectors, wire cables routing, moving components, etc., that the Passive Wireless Sensor Technology Workshop may help. The presentation shows the constraints and requirements that the wireless sensor systems will face in the flight test applications.

Applying Ada to Beech Starship avionics

NASA Technical Reports Server (NTRS)

Funk, David W.

1986-01-01

As Ada solidified in its development, it became evident that it offered advantages for avionics systems because of it support for modern software engineering principles and real time applications. An Ada programming support environment was developed for two major avionics subsystems in the Beech Starship. The two subsystems include electronic flight instrument displays and the flight management computer system. Both of these systems use multiple Intel 80186 microprocessors. The flight management computer provides flight planning, navigation displays, primary flight display of checklists and other pilot advisory information. Together these systems represent nearly 80,000 lines of Ada source code and to date approximately 30 man years of effort. The Beech Starship avionics systems are in flight testing.

Digital flight control actuation system study

NASA Technical Reports Server (NTRS)

Rossing, R.; Hupp, R.

1974-01-01

Flight control actuators and feedback sensors suitable for use in a redundant digital flight control system were examined. The most appropriate design approach for an advanced digital flight control actuation system for development and use in a fly-by-wire system was selected. The concept which was selected consisted of a PM torque motor direct drive. The selected system is compatible with concurrent and independent development efforts on the computer system and the control law mechanizations.

Determination of UAV pre-flight Checklist for flight test purpose using qualitative failure analysis

NASA Astrophysics Data System (ADS)

Hendarko; Indriyanto, T.; Syardianto; Maulana, F. A.

2018-05-01

Safety aspects are of paramount importance in flight, especially in flight test phase. Before performing any flight tests of either manned or unmanned aircraft, one should include pre-flight checklists as a required safety document in the flight test plan. This paper reports on the development of a new approach for determination of pre-flight checklists for UAV flight test based on aircraft’s failure analysis. The Lapan’s LSA (Light Surveillance Aircraft) is used as a study case, assuming this aircraft has been transformed into the unmanned version. Failure analysis is performed on LSA using fault tree analysis (FTA) method. Analysis is focused on propulsion system and flight control system, which fail of these systems will lead to catastrophic events. Pre-flight checklist of the UAV is then constructed based on the basic causes obtained from failure analysis.

77 FR 2342 - Seventeenth Meeting: RTCA Special Committee 213, Enhanced Flight Vision/Synthetic Vision Systems...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-17

... Committee 213, Enhanced Flight Vision/Synthetic Vision Systems (EFVS/SVS) AGENCY: Federal Aviation..., Enhanced Flight Vision/ Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing this notice to advise the public of the seventeenth meeting of RTCA Special Committee 213, Enhanced Flight Vision...

14 CFR Appendix E to Part 60 - Qualification Performance Standards for Quality Management Systems for Flight Simulation Training...

Code of Federal Regulations, 2010 CFR

2010-01-01

... Quality Management Systems for Flight Simulation Training Devices E Appendix E to Part 60 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN FLIGHT SIMULATION...—Qualification Performance Standards for Quality Management Systems for Flight Simulation Training Devices Begin...

14 CFR 91.1415 - CAMP: Mechanical reliability reports.

Code of Federal Regulations, 2013 CFR

2013-01-01

... failure, malfunction, or defect in an aircraft concerning— (1) Fires during flight and whether the related fire-warning system functioned properly; (2) Fires during flight not protected by related fire-warning system; (3) False fire-warning during flight; (4) An exhaust system that causes damage during flight to...

14 CFR 91.1415 - CAMP: Mechanical reliability reports.

Code of Federal Regulations, 2011 CFR

2011-01-01

... failure, malfunction, or defect in an aircraft concerning— (1) Fires during flight and whether the related fire-warning system functioned properly; (2) Fires during flight not protected by related fire-warning system; (3) False fire-warning during flight; (4) An exhaust system that causes damage during flight to...

Mechanization of and experience with a triplex fly-by-wire backup control system

NASA Technical Reports Server (NTRS)

Lock, W. P.; Petersen, W. R.; Whitman, G. B.

1975-01-01

A redundant three-axis analog control system was designed and developed to back up a digital fly-by-wire control system for an F-8C airplane. Forty-two flights, involving 58 hours of flight time, were flown by six pilots. The mechanization and operational experience with the backup control system, the problems involved in synchronizing it with the primary system, and the reliability of the system are discussed. The backup control system was dissimilar to the primary system, and it provided satisfactory handling through the flight envelope evaluated. Limited flight tests of a variety of control tasks showed that control was also satisfactory when the backup control system was controlled by a minimum-displacement (force) side stick. The operational reliability of the F-8 digital fly-by-wire control system was satisfactory, with no unintentional downmodes to the backup control system in flight. The ground and flight reliability of the system's components is discussed.

STS-1 operational flight profile. Volume 5: Descent, cycle 3. Appendix C: Monte Carlo dispersion analysis

NASA Technical Reports Server (NTRS)

1980-01-01

The results of three nonlinear the Monte Carlo dispersion analyses for the Space Transportation System 1 Flight (STS-1) Orbiter Descent Operational Flight Profile, Cycle 3 are presented. Fifty randomly selected simulation for the end of mission (EOM) descent, the abort once around (AOA) descent targeted line are steep target line, and the AOA descent targeted to the shallow target line are analyzed. These analyses compare the flight environment with system and operational constraints on the flight environment and in some cases use simplified system models as an aid in assessing the STS-1 descent flight profile. In addition, descent flight envelops are provided as a data base for use by system specialists to determine the flight readiness for STS-1. The results of these dispersion analyses supersede results of the dispersion analysis previously documented.

Integrated Flight Path Planning System and Flight Control System for Unmanned Helicopters

PubMed Central

Jan, Shau Shiun; Lin, Yu Hsiang

2011-01-01

This paper focuses on the design of an integrated navigation and guidance system for unmanned helicopters. The integrated navigation system comprises two systems: the Flight Path Planning System (FPPS) and the Flight Control System (FCS). The FPPS finds the shortest flight path by the A-Star (A*) algorithm in an adaptive manner for different flight conditions, and the FPPS can add a forbidden zone to stop the unmanned helicopter from crossing over into dangerous areas. In this paper, the FPPS computation time is reduced by the multi-resolution scheme, and the flight path quality is improved by the path smoothing methods. Meanwhile, the FCS includes the fuzzy inference systems (FISs) based on the fuzzy logic. By using expert knowledge and experience to train the FIS, the controller can operate the unmanned helicopter without dynamic models. The integrated system of the FPPS and the FCS is aimed at providing navigation and guidance to the mission destination and it is implemented by coupling the flight simulation software, X-Plane, and the computing software, MATLAB. Simulations are performed and shown in real time three-dimensional animations. Finally, the integrated system is demonstrated to work successfully in controlling the unmanned helicopter to operate in various terrains of a digital elevation model (DEM). PMID:22164029

Integrated flight path planning system and flight control system for unmanned helicopters.

PubMed

Jan, Shau Shiun; Lin, Yu Hsiang

2011-01-01

This paper focuses on the design of an integrated navigation and guidance system for unmanned helicopters. The integrated navigation system comprises two systems: the Flight Path Planning System (FPPS) and the Flight Control System (FCS). The FPPS finds the shortest flight path by the A-Star (A*) algorithm in an adaptive manner for different flight conditions, and the FPPS can add a forbidden zone to stop the unmanned helicopter from crossing over into dangerous areas. In this paper, the FPPS computation time is reduced by the multi-resolution scheme, and the flight path quality is improved by the path smoothing methods. Meanwhile, the FCS includes the fuzzy inference systems (FISs) based on the fuzzy logic. By using expert knowledge and experience to train the FIS, the controller can operate the unmanned helicopter without dynamic models. The integrated system of the FPPS and the FCS is aimed at providing navigation and guidance to the mission destination and it is implemented by coupling the flight simulation software, X-Plane, and the computing software, MATLAB. Simulations are performed and shown in real time three-dimensional animations. Finally, the integrated system is demonstrated to work successfully in controlling the unmanned helicopter to operate in various terrains of a digital elevation model (DEM).

Total energy based flight control system

NASA Technical Reports Server (NTRS)

Lambregts, Antonius A. (Inventor)

1985-01-01

An integrated aircraft longitudinal flight control system uses a generalized thrust and elevator command computation (38), which accepts flight path angle, longitudinal acceleration command signals, along with associated feedback signals, to form energy rate error (20) and energy rate distribution error (18) signals. The engine thrust command is developed (22) as a function of the energy rate distribution error and the elevator position command is developed (26) as a function of the energy distribution error. For any vertical flight path and speed mode the outerloop errors are normalized (30, 34) to produce flight path angle and longitudinal acceleration commands. The system provides decoupled flight path and speed control for all control modes previously provided by the longitudinal autopilot, autothrottle and flight management systems.

Conduct and Results of YF-16 RPRV Stall/Spin Drop Model Tests

DTIC Science & Technology

1977-04-01

Bomb Recovery System Tests Iron Bird Recovery System Tests Captive Flights Typical Flight Operations Flight Planning and Pilot Training...helicopter tow qualification test, one model tow qualification test, three Iron Bird parachute recovery system verification tests, three captive tests...Corresponding Full-Scale YF-16 Altitude -Reference 1: Woodcock , Robert J., Some Notes on Free-Flight Model Seal- ing, AFFDL-TM-73-123-FCC, Air Force Flight

Flight evaluation of a computer aided low-altitude helicopter flight guidance system

NASA Technical Reports Server (NTRS)

Swenson, Harry N.; Jones, Raymond D.; Clark, Raymond

1993-01-01

The Flight Systems Development branch of the U.S. Army's Avionics Research and Development Activity (AVRADA) and NASA Ames Research Center developed for flight testing a Computer Aided Low-Altitude Helicopter Flight (CALAHF) guidance system. The system includes a trajectory-generation algorithm which uses dynamic programming and a helmet-mounted display (HMD) presentation of a pathway-in-the-sky, a phantom aircraft, and flight-path vector/predictor guidance symbology. The trajectory-generation algorithm uses knowledge of the global mission requirements, a digital terrain map, aircraft performance capabilities, and precision navigation information to determine a trajectory between mission waypoints that seeks valleys to minimize threat exposure. This system was developed and evaluated through extensive use of piloted simulation and has demonstrated a 'pilot centered' concept of automated and integrated navigation and terrain mission planning flight guidance. This system has shown a significant improvement in pilot situational awareness, and mission effectiveness as well as a decrease in training and proficiency time required for a near terrain, nighttime, adverse weather system.

Flight Design System-1 System Design Document. Volume 9: Executive logic flow, program design language

NASA Technical Reports Server (NTRS)

1979-01-01

The detailed logic flow for the Flight Design System Executive is presented. The system is designed to provide the hardware/software capability required for operational support of shuttle flight planning.

SSI-ARC Flight Test 3 Data Review

NASA Technical Reports Server (NTRS)

Gong, Chester; Wu, Minghong G.

2015-01-01

The "Unmanned Aircraft System (UAS) Integration into the National Airspace System (NAS)" Project conducted flight test program, referred to as Flight Test 3, at Armstrong Flight Research Center from June - August 2015. Four flight test days were dedicated to the NASA Ames-developed Detect and Avoid (DAA) System referred to as Autoresolver. The encounter scenarios, which involved NASA's Ikhana UAS and a manned intruder aircraft, were designed to collect data on DAA system performance in real-world conditions and uncertainties with four different surveillance sensor systems. Resulting flight test data and analysis results will be used to evaluate the DAA system performance (e.g., trajectory prediction accuracy, threat detection) and to add fidelity to simulation models used to inform Minimum Operating Performance Standards (MOPS) for integrating UAS into routine NAS operations.

NASA TSRV essential flight control system requirements via object oriented analysis

NASA Technical Reports Server (NTRS)

Duffy, Keith S.; Hoza, Bradley J.

1992-01-01

The objective was to analyze the baseline flight control system of the Transport Systems Research Vehicle (TSRV) and to develop a system specification that offers high visibility of the essential system requirements in order to facilitate the future development of alternate, more advanced software architectures. The flight control system is defined to be the baseline software for the TSRV research flight deck, including all navigation, guidance, and control functions, and primary pilot displays. The Object Oriented Analysis (OOA) methodology developed is used to develop a system requirement definition. The scope of the requirements definition contained herein is limited to a portion of the Flight Management/Flight Control computer functionality. The development of a partial system requirements definition is documented, and includes a discussion of the tasks required to increase the scope of the requirements definition and recommendations for follow-on research.

Description and Flight Test Results of the NASA F-8 Digital Fly-by-Wire Control System

NASA Technical Reports Server (NTRS)

1975-01-01

A NASA program to develop digital fly-by-wire (DFBW) technology for aircraft applications is discussed. Phase I of the program demonstrated the feasibility of using a digital fly-by-wire system for aircraft control through developing and flight testing a single channel system, which used Apollo hardware, in an F-8C airplane. The objective of Phase II of the program is to establish a technology base for designing practical DFBW systems. It will involve developing and flight testing a triplex digital fly-by-wire system using state-of-the-art airborne computers, system hardware, software, and redundancy concepts. The papers included in this report describe the Phase I system and its development and present results from the flight program. Man-rated flight software and the effects of lightning on digital flight control systems are also discussed.

Advanced flight control system study

NASA Technical Reports Server (NTRS)

Hartmann, G. L.; Wall, J. E., Jr.; Rang, E. R.; Lee, H. P.; Schulte, R. W.; Ng, W. K.

1982-01-01

A fly by wire flight control system architecture designed for high reliability includes spare sensor and computer elements to permit safe dispatch with failed elements, thereby reducing unscheduled maintenance. A methodology capable of demonstrating that the architecture does achieve the predicted performance characteristics consists of a hierarchy of activities ranging from analytical calculations of system reliability and formal methods of software verification to iron bird testing followed by flight evaluation. Interfacing this architecture to the Lockheed S-3A aircraft for flight test is discussed. This testbed vehicle can be expanded to support flight experiments in advanced aerodynamics, electromechanical actuators, secondary power systems, flight management, new displays, and air traffic control concepts.

HIDEC F-15 adaptive engine control system flight test results

NASA Technical Reports Server (NTRS)

Smolka, James W.

1987-01-01

NASA-Ames' Highly Integrated Digital Electronic Control (HIDEC) flight test program aims to develop fully integrated airframe, propulsion, and flight control systems. The HIDEC F-15 adaptive engine control system flight test program has demonstrated that significant performance improvements are obtainable through the retention of stall-free engine operation throughout the aircraft flight and maneuver envelopes. The greatest thrust increase was projected for the medium-to-high altitude flight regime at subsonic speed which is of such importance to air combat. Adaptive engine control systems such as the HIDEC F-15's can be used to upgrade the performance of existing aircraft without resort to expensive reengining programs.

Preliminary Flight Results of a Fly-by-throttle Emergency Flight Control System on an F-15 Airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Maine, Trindel A.; Fullerton, C. Gordon; Wells, Edward A.

1993-01-01

A multi-engine aircraft, with some or all of the flight control system inoperative, may use engine thrust for control. NASA Dryden has conducted a study of the capability and techniques for this emergency flight control method for the F-15 airplane. With an augmented control system, engine thrust, along with appropriate feedback parameters, is used to control flightpath and bank angle. Extensive simulation studies were followed by flight tests. The principles of throttles only control, the F-15 airplane, the augmented system, and the flight results including actual landings with throttles-only control are discussed.

Summary of NASA Aerospace Flight Battery Systems Program activities

NASA Technical Reports Server (NTRS)

Manzo, Michelle; Odonnell, Patricia

1994-01-01

A summary of NASA Aerospace Flight Battery Systems Program Activities is presented. The NASA Aerospace Flight Battery Systems Program represents a unified NASA wide effort with the overall objective of providing NASA with the policy and posture which will increase the safety, performance, and reliability of space power systems. The specific objectives of the program are to: enhance cell/battery safety and reliability; maintain current battery technology; increase fundamental understanding of primary and secondary cells; provide a means to bring forth advanced technology for flight use; assist flight programs in minimizing battery technology related flight risks; and ensure that safe, reliable batteries are available for NASA's future missions.

Propulsion system/flight control integration for supersonic aircraft

NASA Technical Reports Server (NTRS)

Reukauf, P. J.; Burcham, F. W., Jr.

1976-01-01

Digital integrated control systems are studied. Such systems allow minimization of undesirable interactions while maximizing performance at all flight conditions. One such program is the YF-12 cooperative control program. The existing analog air data computer, autothrottle, autopilot, and inlet control systems are converted to digital systems by using a general purpose airborne computer and interface unit. Existing control laws are programed and tested in flight. Integrated control laws, derived using accurate mathematical models of the airplane and propulsion system in conjunction with modern control techniques, are tested in flight. Analysis indicates that an integrated autothrottle autopilot gives good flight path control and that observers are used to replace failed sensors.

Crew Exploration Vehicle Launch Abort System Flight Test Overview

NASA Technical Reports Server (NTRS)

Williams-Hayes, Peggy S.

2007-01-01

The Constellation program is an organization within NASA whose mission is to create the new generation of spacecraft that will replace the Space Shuttle after its planned retirement in 2010. In the event of a catastrophic failure on the launch pad or launch vehicle during ascent, the successful use of the launch abort system will allow crew members to escape harm. The Flight Test Office is the organization within the Constellation project that will flight-test the launch abort system on the Orion crew exploration vehicle. The Flight Test Office has proposed six tests that will demonstrate the use of the launch abort system. These flight tests will be performed at the White Sands Missile Range in New Mexico and are similar in nature to the Apollo Little Joe II tests performed in the 1960s. An overview of the launch abort system flight tests for the Orion crew exploration vehicle is given. Details on the configuration of the first pad abort flight test are discussed. Sample flight trajectories for two of the six flight tests are shown.

Effects of the space flight environment on the immune system

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald; Butel, Janet S.; Shearer, William T.

2003-01-01

Space flight conditions have a dramatic effect on a variety of physiologic functions of mammals, including muscle, bone, and neurovestibular function. Among the physiological functions that are affected when humans or animals are exposed to space flight conditions is the immune response. The focus of this review is on the function of the immune system in space flight conditions during actual space flights, as well as in models of space flight conditions on the earth. The experiments were carried out in tissue culture systems, in animal models, and in human subjects. The results indicate that space flight conditions alter cell-mediated immune responses, including lymphocyte proliferation and subset distribution, and cytokine production. The mechanism(s) of space flight-induced alterations in immune system function remain(s) to be established. It is likely, however, that multiple factors, including microgravity, stress, neuroendocrine factors, sleep disruption, and nutritional factors, are involved in altering certain functions of the immune system. Such alterations could lead to compromised defenses against infections and tumors.

ACAS-Xu Initial Self-Separation Flight Tests

NASA Technical Reports Server (NTRS)

Marston, Mike; Baca, Gabe

2015-01-01

The purpose of this flight test report is to document and report the details of the ACAS Xu (Airborne Collision Avoidance System For Unmanned Aircraft) / Self-Separation flight test series performed at Edwards AFB from November to December of 2014. Included in this document are details about participating aircraft, aircrew, mission crew, system configurations, flight data, flight execution, flight summary, test results, and lessons learned.

Feasibility of using a knowledge-based system concept for in-flight primary flight display research

NASA Technical Reports Server (NTRS)

Ricks, Wendell R.

1991-01-01

A study was conducted to determine the feasibility of using knowledge-based systems architectures for inflight research of primary flight display information management issues. The feasibility relied on the ability to integrate knowledge-based systems with existing onboard aircraft systems. And, given the hardware and software platforms available, the feasibility also depended on the ability to use interpreted LISP software with the real time operation of the primary flight display. In addition to evaluating these feasibility issues, the study determined whether the software engineering advantages of knowledge-based systems found for this application in the earlier workstation study extended to the inflight research environment. To study these issues, two integrated knowledge-based systems were designed to control the primary flight display according to pre-existing specifications of an ongoing primary flight display information management research effort. These two systems were implemented to assess the feasibility and software engineering issues listed. Flight test results were successful in showing the feasibility of using knowledge-based systems inflight with actual aircraft data.

Descent and Landing Triggers for the Orion Multi-Purpose Crew Vehicle Exploration Flight Test-1

NASA Technical Reports Server (NTRS)

Bihari, Brian D.; Semrau, Jeffrey D.; Duke, Charity J.

2013-01-01

The Orion Multi-Purpose Crew Vehicle (MPCV) will perform a flight test known as Exploration Flight Test-1 (EFT-1) currently scheduled for 2014. One of the primary functions of this test is to exercise all of the important Guidance, Navigation, Control (GN&C), and Propulsion systems, along with the flight software for future flights. The Descent and Landing segment of the flight is governed by the requirements levied on the GN&C system by the Landing and Recovery System (LRS). The LRS is a complex system of parachutes and flight control modes that ensure that the Orion MPCV safely lands at its designated target in the Pacific Ocean. The Descent and Landing segment begins with the jettisoning of the Forward Bay Cover and concludes with sensing touchdown. This paper discusses the requirements, design, testing, analysis and performance of the current EFT-1 Descent and Landing Triggers flight software.

Development and flight test experiences with a flight-crucial digital control system

NASA Technical Reports Server (NTRS)

Mackall, Dale A.

1988-01-01

Engineers and scientists in the advanced fighter technology integration (AFTI) F-16 program investigated the integration of emerging technologies into an advanced fighter aircraft. AFTI's three major technologies included: flight-crucial digital control, decoupled aircraft flight control, and integration of avionics, flight control, and pilot displays. In addition to investigating improvements in fighter performance, researchers studied the generic problems confronting the designers of highly integrated flight-crucial digital control. An overview is provided of both the advantages and problems of integration digital control systems. Also, an examination of the specification, design, qualification, and flight test life-cycle phase is provided. An overview is given of the fault-tolerant design, multimoded decoupled flight control laws, and integrated avionics design. The approach to qualifying the software and system designs is discussed, and the effects of design choices on system qualification are highlighted.

Flight control systems development and flight test experience with the HiMAT research vehicles

NASA Technical Reports Server (NTRS)

Kempel, Robert W.; Earls, Michael R.

1988-01-01

Two highly maneuverable aircraft technology (HiMAT) remotely piloted vehicles were flown a total of 26 flights. These subscale vehicles were of advanced aerodynamic configuration with advanced technology concepts such as composite and metallic structures, digital integrated propulsion control, and ground (primary) and airborne (backup) relaxed static stability, digital fly-by-wire control systems. Extensive systems development, checkout, and flight qualification were required to conduct the flight test program. The design maneuver goal was to achieve a sustained 8-g turn at Mach 0.9 at an altitude of 25,000 feet. This goal was achieved, along with the acquisition of high-quality flight data at subsonic and supersonic Mach numbers. Control systems were modified in a variety of ways using the flight-determined aerodynamic characteristics. The HiMAT program was successfully completed with approximately 11 hours of total flight time.

A Comprehensive Analysis of the X-15 Flight 3-65 Accident

NASA Technical Reports Server (NTRS)

Dennehy, Cornelius J.; Orr, Jeb S.; Barshi, Immanuel; Statler, Irving C.

2014-01-01

The November 15, 1967, loss of X-15 Flight 3-65-97 (hereafter referred to as Flight 3-65) was a unique incident in that it was the first and only aerospace flight accident involving loss of crew on a vehicle with an adaptive flight control system (AFCS). In addition, Flight 3-65 remains the only incidence of a single-pilot departure from controlled flight of a manned entry vehicle in a hypersonic flight regime. To mitigate risk to emerging aerospace systems, the NASA Engineering and Safety Center (NESC) proposed a comprehensive review of this accident. The goal of the assessment was to resolve lingering questions regarding the failure modes of the aircraft systems (including the AFCS) and thoroughly analyze the interactions among the human agents and autonomous systems that contributed to the loss of the pilot and aircraft. This document contains the outcome of the accident review.

Flight Validation of a Metrics Driven L(sub 1) Adaptive Control

NASA Technical Reports Server (NTRS)

Dobrokhodov, Vladimir; Kitsios, Ioannis; Kaminer, Isaac; Jones, Kevin D.; Xargay, Enric; Hovakimyan, Naira; Cao, Chengyu; Lizarraga, Mariano I.; Gregory, Irene M.

2008-01-01

The paper addresses initial steps involved in the development and flight implementation of new metrics driven L1 adaptive flight control system. The work concentrates on (i) definition of appropriate control driven metrics that account for the control surface failures; (ii) tailoring recently developed L1 adaptive controller to the design of adaptive flight control systems that explicitly address these metrics in the presence of control surface failures and dynamic changes under adverse flight conditions; (iii) development of a flight control system for implementation of the resulting algorithms onboard of small UAV; and (iv) conducting a comprehensive flight test program that demonstrates performance of the developed adaptive control algorithms in the presence of failures. As the initial milestone the paper concentrates on the adaptive flight system setup and initial efforts addressing the ability of a commercial off-the-shelf AP with and without adaptive augmentation to recover from control surface failures.

The flight planning - flight management connection

NASA Technical Reports Server (NTRS)

Sorensen, J. A.

1984-01-01

Airborne flight management systems are currently being implemented to minimize direct operating costs when flying over a fixed route between a given city pair. Inherent in the design of these systems is that the horizontal flight path and wind and temperature models be defined and input into the airborne computer before flight. The wind/temperature model and horizontal path are products of the flight planning process. Flight planning consists of generating 3-D reference trajectories through a forecast wind field subject to certain ATC and transport operator constraints. The interrelationships between flight management and flight planning are reviewed, and the steps taken during the flight planning process are summarized.

Flight Research Using F100 Engine P680063 in the NASA F-15 Airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Conners, Timothy R.; Maxwell, Michael D.

1994-01-01

The value of flight research in developing and evaluating gas turbine engines is high. NASA Dryden Flight Research Center has been conducting flight research on propulsion systems for many years. The F100 engine has been tested in the NASA F-15 research airplane in the last three decades. One engine in particular, S/N P680063, has been used for the entire program and has been flown in many pioneering propulsion flight research activities. Included are detailed flight-to-ground facility tests; tests of the first production digital engine control system, the first active stall margin control system, the first performance-seeking control system; and the first use of computer-controlled engine thrust for emergency flight control. The flight research has been supplemented with altitude facility tests at key times. This paper presents a review of the tests of engine P680063, the F-15 airplanes in which it flew, and the role of the flight test in maturing propulsion technology.

Synthetic and Enhanced Vision Systems for NextGen (SEVS) Simulation and Flight Test Performance Evaluation

NASA Technical Reports Server (NTRS)

Shelton, Kevin J.; Kramer, Lynda J.; Ellis,Kyle K.; Rehfeld, Sherri A.

2012-01-01

The Synthetic and Enhanced Vision Systems for NextGen (SEVS) simulation and flight tests are jointly sponsored by NASA's Aviation Safety Program, Vehicle Systems Safety Technology project and the Federal Aviation Administration (FAA). The flight tests were conducted by a team of Honeywell, Gulfstream Aerospace Corporation and NASA personnel with the goal of obtaining pilot-in-the-loop test data for flight validation, verification, and demonstration of selected SEVS operational and system-level performance capabilities. Nine test flights (38 flight hours) were conducted over the summer and fall of 2011. The evaluations were flown in Gulfstream.s G450 flight test aircraft outfitted with the SEVS technology under very low visibility instrument meteorological conditions. Evaluation pilots flew 108 approaches in low visibility weather conditions (600 ft to 2400 ft visibility) into various airports from Louisiana to Maine. In-situ flight performance and subjective workload and acceptability data were collected in collaboration with ground simulation studies at LaRC.s Research Flight Deck simulator.

Development and Flight Testing of a Neural Network Based Flight Control System on the NF-15B Aircraft

NASA Technical Reports Server (NTRS)

Bomben, Craig R.; Smolka, James W.; Bosworth, John T.; Silliams-Hayes, Peggy S.; Burken, John J.; Larson, Richard R.; Buschbacher, Mark J.; Maliska, Heather A.

2006-01-01

The Intelligent Flight Control System (IFCS) project at the NASA Dryden Flight Research Center, Edwards AFB, CA, has been investigating the use of neural network based adaptive control on a unique NF-15B test aircraft. The IFCS neural network is a software processor that stores measured aircraft response information to dynamically alter flight control gains. In 2006, the neural network was engaged and allowed to learn in real time to dynamically alter the aircraft handling qualities characteristics in the presence of actual aerodynamic failure conditions injected into the aircraft through the flight control system. The use of neural network and similar adaptive technologies in the design of highly fault and damage tolerant flight control systems shows promise in making future aircraft far more survivable than current technology allows. This paper will present the results of the IFCS flight test program conducted at the NASA Dryden Flight Research Center in 2006, with emphasis on challenges encountered and lessons learned.

A pilot rating scale for evaluating failure transients in electronic flight control systems

NASA Technical Reports Server (NTRS)

Hindson, William S.; Schroeder, Jeffery A.; Eshow, Michelle M.

1990-01-01

A pilot rating scale was developed to describe the effects of transients in helicopter flight-control systems on safety-of-flight and on pilot recovery action. The scale was applied to the evaluation of hardovers that could potentially occur in the digital flight-control system being designed for a variable-stability UH-60A research helicopter. Tests were conducted in a large moving-base simulator and in flight. The results of the investigation were combined with existing airworthiness criteria to determine quantitative reliability design goals for the control system.

APMS 3.0 Flight Analyst Guide: Aviation Performance Measuring System

NASA Technical Reports Server (NTRS)

Jay, Griff; Prothero, Gary; Romanowski, Timothy; Lynch, Robert; Lawrence, Robert; Rosenthal, Loren

2004-01-01

The Aviation Performance Measuring System (APMS) is a method-embodied in software-that uses mathematical algorithms and related procedures to analyze digital flight data extracted from aircraft flight data recorders. APMS consists of an integrated set of tools used to perform two primary functions: a) Flight Data Importation b) Flight Data Analysis.

Knowledge-based decision support for Space Station assembly sequence planning

NASA Astrophysics Data System (ADS)

1991-04-01

A complete Personal Analysis Assistant (PAA) for Space Station Freedom (SSF) assembly sequence planning consists of three software components: the system infrastructure, intra-flight value added, and inter-flight value added. The system infrastructure is the substrate on which software elements providing inter-flight and intra-flight value-added functionality are built. It provides the capability for building representations of assembly sequence plans and specification of constraints and analysis options. Intra-flight value-added provides functionality that will, given the manifest for each flight, define cargo elements, place them in the National Space Transportation System (NSTS) cargo bay, compute performance measure values, and identify violated constraints. Inter-flight value-added provides functionality that will, given major milestone dates and capability requirements, determine the number and dates of required flights and develop a manifest for each flight. The current project is Phase 1 of a projected two phase program and delivers the system infrastructure. Intra- and inter-flight value-added were to be developed in Phase 2, which has not been funded. Based on experience derived from hundreds of projects conducted over the past seven years, ISX developed an Intelligent Systems Engineering (ISE) methodology that combines the methods of systems engineering and knowledge engineering to meet the special systems development requirements posed by intelligent systems, systems that blend artificial intelligence and other advanced technologies with more conventional computing technologies. The ISE methodology defines a phased program process that begins with an application assessment designed to provide a preliminary determination of the relative technical risks and payoffs associated with a potential application, and then moves through requirements analysis, system design, and development.

Knowledge-based decision support for Space Station assembly sequence planning

NASA Technical Reports Server (NTRS)

1991-01-01

A complete Personal Analysis Assistant (PAA) for Space Station Freedom (SSF) assembly sequence planning consists of three software components: the system infrastructure, intra-flight value added, and inter-flight value added. The system infrastructure is the substrate on which software elements providing inter-flight and intra-flight value-added functionality are built. It provides the capability for building representations of assembly sequence plans and specification of constraints and analysis options. Intra-flight value-added provides functionality that will, given the manifest for each flight, define cargo elements, place them in the National Space Transportation System (NSTS) cargo bay, compute performance measure values, and identify violated constraints. Inter-flight value-added provides functionality that will, given major milestone dates and capability requirements, determine the number and dates of required flights and develop a manifest for each flight. The current project is Phase 1 of a projected two phase program and delivers the system infrastructure. Intra- and inter-flight value-added were to be developed in Phase 2, which has not been funded. Based on experience derived from hundreds of projects conducted over the past seven years, ISX developed an Intelligent Systems Engineering (ISE) methodology that combines the methods of systems engineering and knowledge engineering to meet the special systems development requirements posed by intelligent systems, systems that blend artificial intelligence and other advanced technologies with more conventional computing technologies. The ISE methodology defines a phased program process that begins with an application assessment designed to provide a preliminary determination of the relative technical risks and payoffs associated with a potential application, and then moves through requirements analysis, system design, and development.

Designing for Annual Spacelift Performance

NASA Technical Reports Server (NTRS)

McCleskey, Carey M.; Zapata, Edgar

2017-01-01

This paper presents a methodology for approaching space launch system design from a total architectural point of view. This different approach to conceptual design is contrasted with traditional approaches that focus on a single set of metrics for flight system performance, i.e., payload lift per flight, vehicle mass, specific impulse, etc. The approach presented works with a larger set of metrics, including annual system lift, or "spacelift" performance. Spacelift performance is more inclusive of the flight production capability of the total architecture, i.e., the flight and ground systems working together as a whole to produce flights on a repeated basis. In the proposed methodology, spacelift performance becomes an important design-for-support parameter for flight system concepts and truly advanced spaceport architectures of the future. The paper covers examples of existing system spacelift performance as benchmarks, points out specific attributes of space transportation systems that must be greatly improved over these existing designs, and outlines current activity in this area.

Using wide area differential GPS to improve total system error for precision flight operations

NASA Astrophysics Data System (ADS)

Alter, Keith Warren

Total System Error (TSE) refers to an aircraft's total deviation from the desired flight path. TSE can be divided into Navigational System Error (NSE), the error attributable to the aircraft's navigation system, and Flight Technical Error (FTE), the error attributable to pilot or autopilot control. Improvement in either NSE or FTE reduces TSE and leads to the capability to fly more precise flight trajectories. The Federal Aviation Administration's Wide Area Augmentation System (WAAS) became operational for non-safety critical applications in 2000 and will become operational for safety critical applications in 2002. This navigation service will provide precise 3-D positioning (demonstrated to better than 5 meters horizontal and vertical accuracy) for civil aircraft in the United States. Perhaps more importantly, this navigation system, which provides continuous operation across large regions, enables new flight instrumentation concepts which allow pilots to fly aircraft significantly more precisely, both for straight and curved flight paths. This research investigates the capabilities of some of these new concepts, including the Highway-In-The Sky (HITS) display, which not only improves FTE but also reduces pilot workload when compared to conventional flight instrumentation. Augmentation to the HITS display, including perspective terrain and terrain alerting, improves pilot situational awareness. Flight test results from demonstrations in Juneau, AK, and Lake Tahoe, CA, provide evidence of the overall feasibility of integrated, low-cost flight navigation systems based on these concepts. These systems, requiring no more computational power than current-generation low-end desktop computers, have immediate applicability to general aviation flight from Cessnas to business jets and can support safer and ultimately more economical flight operations. Commercial airlines may also, over time, benefit from these new technologies.

Implementation and flight-test of a multi-mode rotorcraft flight-control system for single-pilot use in poor visibility

NASA Technical Reports Server (NTRS)

Hindson, William S.

1987-01-01

A flight investigation was conducted to evaluate a multi-mode flight control system designed according to the most recent recommendations for handling qualities criteria for new military helicopters. The modes and capabilities that were included in the system are those considered necessary to permit divided-attention (single-pilot) lowspeed and hover operations near the ground in poor visibility conditions. Design features included mode-selection and mode-blending logic, the use of an automatic position-hold mode that employed precision measurements of aircraft position, and a hover display which permitted manually-controlled hover flight tasks in simulated instrument conditions. Pilot evaluations of the system were conducted using a multi-segment evaluation task. Pilot comments concerning the use of the system are provided, and flight-test data are presented to show system performance.

Some special sub-systems for stratospheric balloon flights in India

NASA Astrophysics Data System (ADS)

Damle, S. V.; Gokhale, G. S.; Kundapurkar, R. U.

During last few years several new sub-systems for balloon were developed and are being regularly used in the balloon flights. Some of these sub-systems are i) positive monitor for magnetic ballast release using an opto-electronic device ii) one-way pressure switch to terminate flight for runaway balloon iii) in-flight payload reel down system for atmospheric science experiment. The design, usage and performance of these and other sub-systems will be presented.

Linearized aerodynamic and control law models of the X-29A airplane and comparison with flight data

NASA Technical Reports Server (NTRS)

Bosworth, John T.

1992-01-01

Flight control system design and analysis for aircraft rely on mathematical models of the vehicle dynamics. In addition to a six degree of freedom nonlinear simulation, the X-29A flight controls group developed a set of programs that calculate linear perturbation models throughout the X-29A flight envelope. The models include the aerodynamics as well as flight control system dynamics and were used for stability, controllability, and handling qualities analysis. These linear models were compared to flight test results to help provide a safe flight envelope expansion. A description is given of the linear models at three flight conditions and two flight control system modes. The models are presented with a level of detail that would allow the reader to reproduce the linear results if desired. Comparison between the response of the linear model and flight measured responses are presented to demonstrate the strengths and weaknesses of the linear models' ability to predict flight dynamics.

Flight testing the fixed-wing configuration of the Rotor Systems Research Aircraft (RSRA)

NASA Technical Reports Server (NTRS)

Hall, G. W.; Morris, P. M.

1985-01-01

The Rotor Systems Research Aircraft (RSRA) is a unique research aircraft designed to flight test advanced helicopter rotor system. Its principal flight test configuration is as a compound helicopter. The fixed wing configuration of the RSRA was primarily considered an energy fly-home mode in the event it became necessary to sever an unstable rotor system in flight. While it had always been planned to flight test the fixed wing configuration, the selection of the RSRA as the flight test bed for the X-wing rotor accelerated this schedule. This paper discusses the build-up to, and the test of, the RSRA fixed wing configuration. It is written primarily from the test pilot's perspective.

Preliminary flight test results of a fly-by-throttle emergency flight control system on an F-15 airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Maine, Trindel A.; Fullerton, C. G.; Wells, Edward A.

1993-01-01

A multi-engine aircraft, with some or all of the flight control system inoperative, may use engine thrust for control. NASA Dryden has conducted a study of the capability and techniques for this emergency flight control method for the F-15 airplane. With an augmented control system, engine thrust, along with appropriate feedback parameters, is used to control flightpath and bank angle. Extensive simulation studies have been followed by flight tests. This paper discusses the principles of throttles-only control, the F-15 airplane, the augmented system, and the flight results including landing approaches with throttles-only control to within 10 ft of the ground.

Autonomous Flight Safety System - Phase III

NASA Technical Reports Server (NTRS)

2008-01-01

The Autonomous Flight Safety System (AFSS) is a joint KSC and Wallops Flight Facility project that uses tracking and attitude data from onboard Global Positioning System (GPS) and inertial measurement unit (IMU) sensors and configurable rule-based algorithms to make flight termination decisions. AFSS objectives are to increase launch capabilities by permitting launches from locations without range safety infrastructure, reduce costs by eliminating some downrange tracking and communication assets, and reduce the reaction time for flight termination decisions.

Wireless Instrumentation Systems for Flight Testing at NASA AFRC

NASA Technical Reports Server (NTRS)

Hang, Richard

2017-01-01

NASA Armstrong Flight Research Center is revolutionizing its traditional wired instrumentation systems with wireless technologies. This effort faces many technical challenges, such as spectrum compliance, time synchronization, power distribution and airworthiness. This presentation summarizes NASA AFRC's flight test capabilities with current conventional instrumentation methodology and highlights the technical challenges of wireless systems used for flight test research applications.

Flight test results of the Strapdown hexad Inertial Reference Unit (SIRU). Volume 1: Flight test summary

NASA Technical Reports Server (NTRS)

Hruby, R. J.; Bjorkman, W. S.

1977-01-01

Flight test results of the strapdown inertial reference unit (SIRU) navigation system are presented. The fault-tolerant SIRU navigation system features a redundant inertial sensor unit and dual computers. System software provides for detection and isolation of inertial sensor failures and continued operation in the event of failures. Flight test results include assessments of the system's navigational performance and fault tolerance.

Flight control systems development of highly maneuverable aircraft technology /HiMAT/ vehicle

NASA Technical Reports Server (NTRS)

Petersen, K. L.

1979-01-01

The highly maneuverable aircraft technology (HiMAT) program was conceived to demonstrate advanced technology concepts through scaled-aircraft flight tests using a remotely piloted technique. Closed-loop primary flight control is performed from a ground-based cockpit, utilizing a digital computer and up/down telemetry links. A backup flight control system for emergency operation resides in an onboard computer. The onboard systems are designed to provide fail-operational capabilities and utilize two microcomputers, dual uplink receiver/decoders, and redundant hydraulic actuation and power systems. This paper discusses the design and validation of the primary and backup digital flight control systems as well as the unique pilot and specialized systems interfaces.

Validation of Procedures for Monitoring Crewmember Immune Function SDBI-1900, SMO-015 - Integrated Immune

NASA Technical Reports Server (NTRS)

Crucian, Brian; Stowe, Raymond; Mehta, Satish; Uchakin, Peter; Nehlsen-Cannarella, Sandra; Morukov, Boris; Pierson, Duane; Sams, Clarence

2007-01-01

There is ample evidence to suggest that space flight leads to immune system dysregulation. This may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk from prolonged immune dysregulation during space flight are not yet determined, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. Each of the clinical events resulting from immune dysfunction has the potential to impact mission critical objectives during exploration-class missions. To date, precious little in-flight immune data has been generated to assess this phenomenon. The majority of recent flight immune studies have been post-flight assessments, which may not accurately reflect the in-flight condition. There are no procedures currently in place to monitor immune function or its effect on crew health. The objective of this Supplemental Medical Objective (SMO) is to develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. This SMO will assess the clinical risks resulting from the adverse effects of space flight on the human immune system and will validate a flight-compatible immune monitoring strategy. Characterization of the clinical risk and the development of a monitoring strategy are necessary prerequisite activities prior to validating countermeasures. This study will determine, to the best level allowed by current technology, the in-flight status of crewmembers immune system. Pre-flight, in-flight and post-flight assessments of immune status, immune function, viral reactivation and physiological stress will be performed. The in-flight samples will allow a distinction between legitimate in-flight alterations and the physiological stresses of landing and readaptation which are believed to alter landing day assessments. The overall status of the immune system during flight (activation, deficiency, dysregulation) and the response of the immune system to specific latent virus reactivation (known to occur during space flight) will be thoroughly assessed. Following completion of the SMO the data will be evaluated to determine the optimal set of assays for routine monitoring of crewmember immune system function, should the clinical risk warrant such monitoring.

Modeling pilot interaction with automated digital avionics systems: Guidance and control algorithms for contour and nap-of-the-Earth flight

NASA Technical Reports Server (NTRS)

Hess, Ronald A.

1990-01-01

A collection of technical papers are presented that cover modeling pilot interaction with automated digital avionics systems and guidance and control algorithms for contour and nap-of-the-earth flight. The titles of the papers presented are as follows: (1) Automation effects in a multiloop manual control system; (2) A qualitative model of human interaction with complex dynamic systems; (3) Generalized predictive control of dynamic systems; (4) An application of generalized predictive control to rotorcraft terrain-following flight; (5) Self-tuning generalized predictive control applied to terrain-following flight; and (6) Precise flight path control using a predictive algorithm.

Preparation, characterization and application of Saussurea tridactyla Sch-Bip as green adsorbents for preconcentration of rare earth elements in environmental water samples

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.

Obsessive-compulsive disorder and the risk of subsequent mental disorders: A community study of adolescents and young adults.

PubMed

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.

Tumour necrosis factor-α inhibition with lenalidomide alleviates tissue oxidative injury and apoptosis in ob/ob obese mice.

PubMed

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.

PubMed

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.

Sitophilus granarius L. (Coleoptera) Toxicity and Biological Activities of the Essential Oils of Tanacetum macrophyllum (Waldst. & Kit.) Schultz Bip.

PubMed

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.

Secretagogues differentially activate endoplasmic reticulum stress responses in pancreatic acinar cells.

PubMed

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.

Effects of an energy balance educational intervention and the COPE cognitive behavioral therapy intervention for Division I U.S. Air Force Academy female athletes.

PubMed

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.

Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice.

PubMed

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

Flight Test of a Propulsion-Based Emergency Control System on the MD-11 Airplane with Emphasis on the Lateral Axis

NASA Technical Reports Server (NTRS)

Burken, John J.; Burcham, Frank W., Jr.; Maine, Trindel A.; Feather, John; Goldthorpe, Steven; Kahler, Jeffrey A.

1996-01-01

A large, civilian, multi-engine transport MD-11 airplane control system was recently modified to perform as an emergency backup controller using engine thrust only. The emergency backup system, referred to as the propulsion-controlled aircraft (PCA) system, would be used if a major primary flight control system fails. To allow for longitudinal and lateral-directional control, the PCA system requires at least two engines and is implemented through software modifications. A flight-test program was conducted to evaluate the PCA system high-altitude flying characteristics and to demonstrate its capacity to perform safe landings. The cruise flight conditions, several low approaches and one landing without any aerodynamic flight control surface movement, were demonstrated. This paper presents results that show satisfactory performance of the PCA system in the longitudinal axis. Test results indicate that the lateral-directional axis of the system performed well at high attitude but was sluggish and prone to thermal upsets during landing approaches. Flight-test experiences and test techniques are also discussed with emphasis on the lateral-directional axis because of the difficulties encountered in flight test.

Flight Test Series 3: Flight Test Report

NASA Technical Reports Server (NTRS)

Marston, Mike; Sternberg, Daniel; Valkov, Steffi

2015-01-01

This document is a flight test report from the Operational perspective for Flight Test Series 3, a subpart of the Unmanned Aircraft System (UAS) Integration in the National Airspace System (NAS) project. Flight Test Series 3 testing began on June 15, 2015, and concluded on August 12, 2015. Participants included NASA Ames Research Center, NASA Armstrong Flight Research Center, NASA Glenn Research Center, NASA Langley Research center, General Atomics Aeronautical Systems, Inc., and Honeywell. Key stakeholders analyzed their System Under Test (SUT) in two distinct configurations. Configuration 1, known as Pairwise Encounters, was subdivided into two parts: 1a, involving a low-speed UAS ownship and intruder(s), and 1b, involving a high-speed surrogate ownship and intruder. Configuration 2, known as Full Mission, involved a surrogate ownship, live intruder(s), and integrated virtual traffic. Table 1 is a summary of flights for each configuration, with data collection flights highlighted in green. Section 2 and 3 of this report give an in-depth description of the flight test period, aircraft involved, flight crew, and mission team. Overall, Flight Test 3 gathered excellent data for each SUT. We attribute this successful outcome in large part from the experience that was acquired from the ACAS Xu SS flight test flown in December 2014. Configuration 1 was a tremendous success, thanks to the training, member participation, integration/testing, and in-depth analysis of the flight points. Although Configuration 2 flights were cancelled after 3 data collection flights due to various problems, the lessons learned from this will help the UAS in the NAS project move forward successfully in future flight phases.

Rapid prototyping facility for flight research in artificial-intelligence-based flight systems concepts

NASA Technical Reports Server (NTRS)

Duke, E. L.; Regenie, V. A.; Deets, D. A.

1986-01-01

The Dryden Flight Research Facility of the NASA Ames Research Facility of the NASA Ames Research Center is developing a rapid prototyping facility for flight research in flight systems concepts that are based on artificial intelligence (AI). The facility will include real-time high-fidelity aircraft simulators, conventional and symbolic processors, and a high-performance research aircraft specially modified to accept commands from the ground-based AI computers. This facility is being developed as part of the NASA-DARPA automated wingman program. This document discusses the need for flight research and for a national flight research facility for the rapid prototyping of AI-based avionics systems and the NASA response to those needs.

VIEW OF FLIGHT CREW SYSTEMS, FLIGHT KITS FACILITY, ROOM NO. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

VIEW OF FLIGHT CREW SYSTEMS, FLIGHT KITS FACILITY, ROOM NO. 1N12, FACING NORTH - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

VIEW OF FLIGHT CREW SYSTEMS, FLIGHT KITS FACILITY, ROOM NO. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

VIEW OF FLIGHT CREW SYSTEMS, FLIGHT KITS FACILITY, ROOM NO. 1N12, FACING SOUTH - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

A Unique Software System For Simulation-to-Flight Research

NASA Technical Reports Server (NTRS)

Chung, Victoria I.; Hutchinson, Brian K.

2001-01-01

"Simulation-to-Flight" is a research development concept to reduce costs and increase testing efficiency of future major aeronautical research efforts at NASA. The simulation-to-flight concept is achieved by using common software and hardware, procedures, and processes for both piloted-simulation and flight testing. This concept was applied to the design and development of two full-size transport simulators, a research system installed on a NASA B-757 airplane, and two supporting laboratories. This paper describes the software system that supports the simulation-to-flight facilities. Examples of various simulation-to-flight experimental applications were also provided.

Digital Electronic Engine Control (DEEC) Flight Evaluation in an F-15 Airplane

NASA Technical Reports Server (NTRS)

1984-01-01

Flight evaluation in an F-15 aircraft by digital electronic engine control (DEEC) was investigated. Topics discussed include: system description, F100 engine tests, effects of inlet distortion on static pressure probe, flight tests, digital electronic engine control fault detection and accommodation flight evaluation, flight evaluation of a hydromechanical backup control, augmentor transient capability of an F100 engine, investigation of nozzle instability, real time in flight thrust calculation, and control technology for future aircraft propulsion systems. It is shown that the DEEC system is a powerful and flexible controller for the F100 engine.

A knowledge-based flight status monitor for real-time application in digital avionics systems

NASA Technical Reports Server (NTRS)

Duke, E. L.; Disbrow, J. D.; Butler, G. F.

1989-01-01

The Dryden Flight Research Facility of the National Aeronautics and Space Administration (NASA) Ames Research Center (Ames-Dryden) is the principal NASA facility for the flight testing and evaluation of new and complex avionics systems. To aid in the interpretation of system health and status data, a knowledge-based flight status monitor was designed. The monitor was designed to use fault indicators from the onboard system which are telemetered to the ground and processed by a rule-based model of the aircraft failure management system to give timely advice and recommendations in the mission control room. One of the important constraints on the flight status monitor is the need to operate in real time, and to pursue this aspect, a joint research activity between NASA Ames-Dryden and the Royal Aerospace Establishment (RAE) on real-time knowledge-based systems was established. Under this agreement, the original LISP knowledge base for the flight status monitor was reimplemented using the intelligent knowledge-based system toolkit, MUSE, which was developed under RAE sponsorship. Details of the flight status monitor and the MUSE implementation are presented.

Practical aspects of modeling aircraft dynamics from flight data

NASA Technical Reports Server (NTRS)

Iliff, K. W.; Maine, R. E.

1984-01-01

The purpose of parameter estimation, a subset of system identification, is to estimate the coefficients (such as stability and control derivatives) of the aircraft differential equations of motion from sampled measured dynamic responses. In the past, the primary reason for estimating stability and control derivatives from flight tests was to make comparisons with wind tunnel estimates. As aircraft became more complex, and as flight envelopes were expanded to include flight regimes that were not well understood, new requirements for the derivative estimates evolved. For many years, the flight determined derivatives were used in simulations to aid in flight planning and in pilot training. The simulations were particularly important in research flight test programs in which an envelope expansion into new flight regimes was required. Parameter estimation techniques for estimating stability and control derivatives from flight data became more sophisticated to support the flight test programs. As knowledge of these new flight regimes increased, more complex aircraft were flown. Much of this increased complexity was in sophisticated flight control systems. The design and refinement of the control system required higher fidelity simulations than were previously required.

Collision avoidance in commercial aircraft Free Flight via neural networks and non-linear programming.

PubMed

Christodoulou, Manolis A; Kontogeorgou, Chrysa

2008-10-01

In recent years there has been a great effort to convert the existing Air Traffic Control system into a novel system known as Free Flight. Free Flight is based on the concept that increasing international airspace capacity will grant more freedom to individual pilots during the enroute flight phase, thereby giving them the opportunity to alter flight paths in real time. Under the current system, pilots must request, then receive permission from air traffic controllers to alter flight paths. Understandably the new system allows pilots to gain the upper hand in air traffic. At the same time, however, this freedom increase pilot responsibility. Pilots face a new challenge in avoiding the traffic shares congested air space. In order to ensure safety, an accurate system, able to predict and prevent conflict among aircraft is essential. There are certain flight maneuvers that exist in order to prevent flight disturbances or collision and these are graded in the following categories: vertical, lateral and airspeed. This work focuses on airspeed maneuvers and tries to introduce a new idea for the control of Free Flight, in three dimensions, using neural networks trained with examples prepared through non-linear programming.

An Autonomous Flight Safety System

NASA Technical Reports Server (NTRS)

Bull, James B.; Lanzi, Raymond J.

2007-01-01

The Autonomous Flight Safety System (AFSS) being developed by NASA s Goddard Space Flight Center s Wallops Flight Facility and Kennedy Space Center has completed two successful developmental flights and is preparing for a third. AFSS has been demonstrated to be a viable architecture for implementation of a completely vehicle based system capable of protecting life and property in event of an errant vehicle by terminating the flight or initiating other actions. It is capable of replacing current human-in-the-loop systems or acting in parallel with them. AFSS is configured prior to flight in accordance with a specific rule set agreed upon by the range safety authority and the user to protect the public and assure mission success. This paper discusses the motivation for the project, describes the method of development, and presents an overview of the evolving architecture and the current status.

Flight Projects Office Information Systems Testbed (FIST)

NASA Technical Reports Server (NTRS)

Liggett, Patricia

1991-01-01

Viewgraphs on the Flight Projects Office Information Systems Testbed (FIST) are presented. The goal is to perform technology evaluation and prototyping of information systems to support SFOC and JPL flight projects in order to reduce risk in the development of operational data systems for such projects.

A flight investigation of simulated data-link communications during single-pilot IFR flight. Volume 1: Experimental design and initial test

NASA Technical Reports Server (NTRS)

Parker, J. F., Jr.; Duffy, J. W.; Christensen, D. G.

1981-01-01

A Flight Data Console simulation of a digital communication link to replace the current voice communication system used in air traffic control (ATC) was developed. The study determined how a digital communications system reduces cockpit workload, improve, flight proficiency, and is acceptable to general aviation pilots. It is shown that instrument flight, including approach and landing, can be accomplished by using a digital data link system for ATC communication.

The Human in Space: Lesson from ISS

NASA Technical Reports Server (NTRS)

Sams, Clarence F.

2009-01-01

This viewgraph presentation reviews the lessons learned from manned space flight on the International Space Station. The contents include: 1) Overview of space flight effects on crewmembers; 2) General overview of immune system; 3) How does space flight alter immune system? 4) What factors associated with space flight inteact with crewmember immune function and impact health risks? 5) What is the current understanding of space flight effects on the immune system? and 6) Why should NASA be interested in immunology? Why is it significant?

Advanced fighter technology integration (AFTI)/F-16 Automated Maneuvering Attack System final flight test results

NASA Technical Reports Server (NTRS)

Dowden, Donald J.; Bessette, Denis E.

1987-01-01

The AFTI F-16 Automated Maneuvering Attack System has undergone developmental and demonstration flight testing over a total of 347.3 flying hours in 237 sorties. The emphasis of this phase of the flight test program was on the development of automated guidance and control systems for air-to-air and air-to-ground weapons delivery, using a digital flight control system, dual avionics multiplex buses, an advanced FLIR sensor with laser ranger, integrated flight/fire-control software, advanced cockpit display and controls, and modified core Multinational Stage Improvement Program avionics.

Automation of On-Board Flightpath Management

NASA Technical Reports Server (NTRS)

Erzberger, H.

1981-01-01

The status of concepts and techniques for the design of onboard flight path management systems is reviewed. Such systems are designed to increase flight efficiency and safety by automating the optimization of flight procedures onboard aircraft. After a brief review of the origins and functions of such systems, two complementary methods are described for attacking the key design problem, namely, the synthesis of efficient trajectories. One method optimizes en route, the other optimizes terminal area flight; both methods are rooted in optimal control theory. Simulation and flight test results are reviewed to illustrate the potential of these systems for fuel and cost savings.

Planned flight test of a mercury ion auxiliary propulsion system. 1: Objectives, systems descriptions, and mission operations

NASA Technical Reports Server (NTRS)

Power, J. C.

1978-01-01

A planned flight test of an 8 cm diameter, electron-bombardment mercury ion thruster system is described. The primary objective of the test is to flight qualify the 5 mN (1 mlb.) thruster system for auxiliary propulsion applications. A seven year north-south stationkeeping mission was selected as the basis for the flight test operating profile. The flight test, which will employ two thruster systems, will also generate thruster system space performance data, measure thruster-spacecraft interactions, and demonstrate thruster operation in a number of operating modes. The flight test is designated as SAMSO-601 and will be flown aboard the shuttle-launched Air Force space test program P80-1 satellite in 1981. The spacecraft will be 3- axis stabilized in its final 740 km circular orbit, which will have an inclination of approximately greater than 73 degrees. The spacecraft design lifetime is three years.

Piloted simulator investigation of helicopter control systems effects on handling qualities during instrument flight

NASA Technical Reports Server (NTRS)

Forrest, R. D.; Chen, R. T. N.; Gerdes, R. M.; Alderete, T. S.; Gee, D. R.

1979-01-01

An exploratory piloted simulation was conducted to investigate the effects of the characteristics of helicopter flight control systems on instrument flight handling qualities. This joint FAA/NASA study was motivated by the need to improve instrument flight capability. A near-term objective is to assist in updating the airworthiness criteria for helicopter instrument flight. The experiment consisted of variations of single-rotor helicopter types and levels of stability and control augmentation systems (SCAS). These configurations were evaluated during an omnirange approach task under visual and instrument flight conditions. The levels of SCAS design included a simple rate damping system, collective decoupling plus rate damping, and an attitude command system with collective decoupling. A limited evaluation of stick force versus airspeed stability was accomplished. Some problems were experienced with control system mechanization which had a detrimental effect on longitudinal stability. Pilot ratings, pilot commentary, and performance data related to the task are presented.

Flight Test of an Intelligent Flight-Control System

NASA Technical Reports Server (NTRS)

Davidson, Ron; Bosworth, John T.; Jacobson, Steven R.; Thomson, Michael Pl; Jorgensen, Charles C.

2003-01-01

The F-15 Advanced Controls Technology for Integrated Vehicles (ACTIVE) airplane (see figure) was the test bed for a flight test of an intelligent flight control system (IFCS). This IFCS utilizes a neural network to determine critical stability and control derivatives for a control law, the real-time gains of which are computed by an algorithm that solves the Riccati equation. These derivatives are also used to identify the parameters of a dynamic model of the airplane. The model is used in a model-following portion of the control law, in order to provide specific vehicle handling characteristics. The flight test of the IFCS marks the initiation of the Intelligent Flight Control System Advanced Concept Program (IFCS ACP), which is a collaboration between NASA and Boeing Phantom Works. The goals of the IFCS ACP are to (1) develop the concept of a flight-control system that uses neural-network technology to identify aircraft characteristics to provide optimal aircraft performance, (2) develop a self-training neural network to update estimates of aircraft properties in flight, and (3) demonstrate the aforementioned concepts on the F-15 ACTIVE airplane in flight. The activities of the initial IFCS ACP were divided into three Phases, each devoted to the attainment of a different objective. The objective of Phase I was to develop a pre-trained neural network to store and recall the wind-tunnel-based stability and control derivatives of the vehicle. The objective of Phase II was to develop a neural network that can learn how to adjust the stability and control derivatives to account for failures or modeling deficiencies. The objective of Phase III was to develop a flight control system that uses the neural network outputs as a basis for controlling the aircraft. The flight test of the IFCS was performed in stages. In the first stage, the Phase I version of the pre-trained neural network was flown in a passive mode. The neural network software was running using flight data inputs with the outputs provided to instrumentation only. The IFCS was not used to control the airplane. In another stage of the flight test, the Phase I pre-trained neural network was integrated into a Phase III version of the flight control system. The Phase I pretrained neural network provided realtime stability and control derivatives to a Phase III controller that was based on a stochastic optimal feedforward and feedback technique (SOFFT). This combined Phase I/III system was operated together with the research flight-control system (RFCS) of the F-15 ACTIVE during the flight test. The RFCS enables the pilot to switch quickly from the experimental- research flight mode back to the safe conventional mode. These initial IFCS ACP flight tests were completed in April 1999. The Phase I/III flight test milestone was to demonstrate, across a range of subsonic and supersonic flight conditions, that the pre-trained neural network could be used to supply real-time aerodynamic stability and control derivatives to the closed-loop optimal SOFFT flight controller. Additional objectives attained in the flight test included (1) flight qualification of a neural-network-based control system; (2) the use of a combined neural-network/closed-loop optimal flight-control system to obtain level-one handling qualities; and (3) demonstration, through variation of control gains, that different handling qualities can be achieved by setting new target parameters. In addition, data for the Phase-II (on-line-learning) neural network were collected, during the use of stacked-frequency- sweep excitation, for post-flight analysis. Initial analysis of these data showed the potential for future flight tests that will incorporate the real-time identification and on-line learning aspects of the IFCS.

Intelligent Flight Control System and Aeronautics Research at NASA Dryden

NASA Technical Reports Server (NTRS)

Brown, Nelson A.

2009-01-01

This video presentation reviews the F-15 Intelligent Flight Control System and contains clips of flight tests and aircraft performance in the areas of target tracking, takeoff and differential stabilators. Video of the APG milestone flight 1g formation is included.

Post-Flight Analysis of GPSR Performance During Orion Exploration Flight Test 1

NASA Technical Reports Server (NTRS)

Barker, Lee; Mamich, Harvey; McGregor, John

2016-01-01

On 5 December 2014, the first test flight of the Orion Multi-Purpose Crew Vehicle executed a unique and challenging flight profile including an elevated re-entry velocity and steeper flight path angle to envelope lunar re-entry conditions. A new navigation system including a single frequency (L1) GPS receiver was evaluated for use as part of the redundant navigation system required for human space flight. The single frequency receiver was challenged by a highly dynamic flight environment including flight above low Earth orbit, as well as single frequency operation with ionospheric delay present. This paper presents a brief description of the GPS navigation system, an independent analysis of flight telemetry data, and evaluation of the GPSR performance, including evaluation of the ionospheric model employed to supplement the single frequency receiver. Lessons learned and potential improvements will be discussed.

A flight investigation of simulated data-link communications during single-pilot IFR flight. Volume 2: Flight evaluations

NASA Technical Reports Server (NTRS)

Parker, J. F., Jr.; Duffy, J. W.

1982-01-01

Key problems in single pilot instrument flight operations are in the management of flight data and the processing of cockpit information during conditions of heavy workload. A flight data console was developed to allow simulation of a digital data link to replace the current voice communications stem used in air traffic control. This is a human factors evaluation of a data link communications system to determine how such a system might reduce cockpit workload, improve flight proficiency, and be accepted by general aviation pilots. The need for a voice channel as backup to a digital link is examined. The evaluations cover both airport terminal area operations and full mission instrument flight. Results show that general aviation pilots operate well with a digital data link communications system. The findings indicate that a data link system for pilot/ATC communications, with a backup voice channel, is well accepted by general aviation pilots and is considered to be safer, more efficient, and result in less workload than the current voice system.

Space Shuttle Orbiter Approach and Landing Test Evaluation Report. Captive-Active Flight Test Summary

NASA Technical Reports Server (NTRS)

1977-01-01

Captive-active tests consisted of three mated carrier aircraft/Orbiter flights with an active manned Orbiter. The objectives of this series of flights were to (1) verify the separation profile, (2) verify the integrated structure, aerodynamics, and flight control system, (3) verify Orbiter integrated system operations, and (4) refine and finalize carrier aircraft, Orbiter crew, and ground procedures in preparation for free flight tests. A summary description of the flights is presented with assessments of flight test requirements, and of the performance operations, and of significant flight anomalies is included.

V/STOL Systems Research Aircraft: A Tool for Cockpit Integration

NASA Technical Reports Server (NTRS)

Stortz, Michael W.; ODonoghue, Dennis P.; Tiffany, Geary (Technical Monitor)

1995-01-01

The next generation ASTOVL aircraft will have a complicated propulsion System. The configuration choices include Direct Lift, Lift-Fan and Lift+Lift /Cruise but the aircraft must also have supersonic performance and low-observable characteristics. The propulsion system may have features such as flow blockers, vectoring nozzles and flow transfer schemes. The flight control system will necessarily fully integrate the aerodynamic surfaces and the propulsive elements. With a fully integrated, fly-by-wire flight/propulsion control system, the options for cockpit integration are interesting and varied. It is possible to decouple longitudinal and vertical responses allowing the pilot to close the loop on flight path and flight path acceleration directly. In the hover, the pilot can control the translational rate directly without having to stabilize the inner rate and attitude loops. The benefit of this approach, reduced workload and increased precision. has previously been demonstrated through several motion-based simulations. In order to prove the results in flight, the V/STOL System Research Aircraft (VSRA) was developed at the NASA Ames Research Center. The VSRA is the YAV-8B Prototype modified with a research flight control system using a series-parallel servo configuration in all the longitudinal degrees of freedom (including thrust and thrust vector angle) to provide an integrated flight and propulsion control system in a limited envelope. Development of the system has been completed and flight evaluations of the response types have been performed. In this paper we will discuss the development of the VSRA, the evolution of the flight path command and translational rate command response types and the Guest Pilot evaluations of the system. Pilot evaluation results will be used to draw conclusions regarding the suitability of the system to satisfy V/STOL requirements.

[Review of visual display system in flight simulator].

PubMed

Xie, Guang-hui; Wei, Shao-ning

2003-06-01

Visual display system is the key part and plays a very important role in flight simulators and flight training devices. The developing history of visual display system is recalled and the principle and characters of some visual display systems including collimated display systems and back-projected collimated display systems are described. The future directions of visual display systems are analyzed.

A fault-tolerant control architecture for unmanned aerial vehicles

NASA Astrophysics Data System (ADS)

Drozeski, Graham R.

Research has presented several approaches to achieve varying degrees of fault-tolerance in unmanned aircraft. Approaches in reconfigurable flight control are generally divided into two categories: those which incorporate multiple non-adaptive controllers and switch between them based on the output of a fault detection and identification element, and those that employ a single adaptive controller capable of compensating for a variety of fault modes. Regardless of the approach for reconfigurable flight control, certain fault modes dictate system restructuring in order to prevent a catastrophic failure. System restructuring enables active control of actuation not employed by the nominal system to recover controllability of the aircraft. After system restructuring, continued operation requires the generation of flight paths that adhere to an altered flight envelope. The control architecture developed in this research employs a multi-tiered hierarchy to allow unmanned aircraft to generate and track safe flight paths despite the occurrence of potentially catastrophic faults. The hierarchical architecture increases the level of autonomy of the system by integrating five functionalities with the baseline system: fault detection and identification, active system restructuring, reconfigurable flight control; reconfigurable path planning, and mission adaptation. Fault detection and identification algorithms continually monitor aircraft performance and issue fault declarations. When the severity of a fault exceeds the capability of the baseline flight controller, active system restructuring expands the controllability of the aircraft using unconventional control strategies not exploited by the baseline controller. Each of the reconfigurable flight controllers and the baseline controller employ a proven adaptive neural network control strategy. A reconfigurable path planner employs an adaptive model of the vehicle to re-shape the desired flight path. Generation of the revised flight path is posed as a linear program constrained by the response of the degraded system. Finally, a mission adaptation component estimates limitations on the closed-loop performance of the aircraft and adjusts the aircraft mission accordingly. A combination of simulation and flight test results using two unmanned helicopters validates the utility of the hierarchical architecture.

75 FR 77569 - Special Conditions: Gulfstream Model GVI Airplane; Electronic Flight Control System Mode...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-13

... Unusual Design Features The GVI will have a fly-by-wire electronic flight control system. This system... the design of the flight control system has multiple modes of operation, a means must be provided to... Control System Mode Annunciation AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of...

Crew systems and flight station concepts for a 1995 transport aircraft

NASA Technical Reports Server (NTRS)

Sexton, G. A.

1983-01-01

Aircraft functional systems and crew systems were defined for a 1995 transport aircraft through a process of mission analysis, preliminary design, and evaluation in a soft mockup. This resulted in a revolutionary pilot's desk flight station design featuring an all-electric aircraft, fly-by-wire/light flight and thrust control systems, large electronic color head-down displays, head-up displays, touch panel controls for aircraft functional systems, voice command and response systems, and air traffic control systems projected for the 1990s. The conceptual aircraft, for which crew systems were designed, is a generic twin-engine wide-body, low-wing transport, capable of worldwide operation. The flight control system consists of conventional surfaces (some employed in unique ways) and new surfaces not used on current transports. The design will be incorporated into flight simulation facilities at NASA-Langley, NASA-Ames, and the Lockheed-Georgia Company. When interfaced with advanced air traffic control system models, the facilities will provide full-mission capability for researching issues affecting transport aircraft flight stations and crews of the 1990s.

A Flight Control System Architecture for the NASA AirSTAR Flight Test Infrastructure

NASA Technical Reports Server (NTRS)

Murch, Austin M.

2008-01-01

A flight control system architecture for the NASA AirSTAR infrastructure has been designed to address the challenges associated with safe and efficient flight testing of research control laws in adverse flight conditions. The AirSTAR flight control system provides a flexible framework that enables NASA Aviation Safety Program research objectives, and includes the ability to rapidly integrate and test research control laws, emulate component or sensor failures, inject automated control surface perturbations, and provide a baseline control law for comparison to research control laws and to increase operational efficiency. The current baseline control law uses an angle of attack command augmentation system for the pitch axis and simple stability augmentation for the roll and yaw axes.

14 CFR 415.127 - Flight safety system design and operation data.

Code of Federal Regulations, 2013 CFR

2013-01-01

... system and subsystems design and operational requirements. (c) Flight safety system diagram. An applicant... subsystems. The diagram must include the following subsystems defined in part 417, subpart D of this chapter... data processing, display, and recording system; and flight safety official console. (d) Subsystem...

14 CFR 415.127 - Flight safety system design and operation data.

Code of Federal Regulations, 2011 CFR

2011-01-01

... system and subsystems design and operational requirements. (c) Flight safety system diagram. An applicant... subsystems. The diagram must include the following subsystems defined in part 417, subpart D of this chapter... data processing, display, and recording system; and flight safety official console. (d) Subsystem...

14 CFR 415.127 - Flight safety system design and operation data.

Code of Federal Regulations, 2012 CFR

2012-01-01

... system and subsystems design and operational requirements. (c) Flight safety system diagram. An applicant... subsystems. The diagram must include the following subsystems defined in part 417, subpart D of this chapter... data processing, display, and recording system; and flight safety official console. (d) Subsystem...

14 CFR 415.127 - Flight safety system design and operation data.

Code of Federal Regulations, 2014 CFR

2014-01-01

... system and subsystems design and operational requirements. (c) Flight safety system diagram. An applicant... subsystems. The diagram must include the following subsystems defined in part 417, subpart D of this chapter... data processing, display, and recording system; and flight safety official console. (d) Subsystem...

Ontogeny of flight initiation in the fly Drosophila melanogaster: implications for the giant fibre system.

PubMed

Hammond, Sarah; O'Shea, Michael

2007-11-01

There are two modes of flight initiation in Drosophila melanogaster-escape and voluntary. Although the circuitry underlying escape is accounted for by the Giant fibre (GF) system, the system underlying voluntary flight initiation is unknown. The GF system is functionally complete before the adult fly ecloses, but immature adults initially fail to react to a stimulus known to reliably evoke escape in mature adults. This suggests that escape in early adulthood, approximately 2-h post-eclosion, is not automatically triggered by the hard-wired GF system. Indeed, we reveal that escape behaviour displays a staged emergence during the first hour post-eclosion, suggesting that the GF system is subject to declining levels of suppression. Voluntary flight initiations are not observed at all during the period when the GF system is released from its suppression, nor indeed for some time after. We addressed the question whether voluntary flight initiation requires the GF system by observing take-off in Shak-B ( 2 ) mutant flies, in which the GF system is defunct. While the escape response is severely impaired in these mutants, they displayed normal voluntary flight initiation. Thus, the escape mechanism is subject to developmental modulation following eclosion and the GF system does not underlie voluntary flight.

A Low Cost Simulation System to Demonstrate Pilot Induced Oscillation Phenomenon

NASA Technical Reports Server (NTRS)

Ali, Syed Firasat

1997-01-01

A flight simulation system with graphics and software on Silicon Graphics computer workstations has been installed in the Flight Vehicle Design Laboratory at Tuskegee University. The system has F-15E flight simulation software from NASA Dryden which uses the graphics of SGI flight simulation demos. On the system, thus installed, a study of pilot induced oscillations is planned for future work. Preliminary research is conducted by obtaining two sets of straight level flights with pilot in the loop. In one set of flights no additional delay is used between the stick input and the appearance of airplane response on the computer monitor. In another set of flights, a 500 ms additional delay is used. The flight data is analyzed to find cross correlations between deflections of control surfaces and response of the airplane. The pilot dynamics features depicted from cross correlations of straight level flights are discussed in this report. The correlations presented here will serve as reference material for the corresponding correlations in a future study of pitch attitude tracking tasks involving pilot induced oscillations.

Distributed asynchronous microprocessor architectures in fault tolerant integrated flight systems

NASA Technical Reports Server (NTRS)

Dunn, W. R.

1983-01-01

The paper discusses the implementation of fault tolerant digital flight control and navigation systems for rotorcraft application. It is shown that in implementing fault tolerance at the systems level using advanced LSI/VLSI technology, aircraft physical layout and flight systems requirements tend to define a system architecture of distributed, asynchronous microprocessors in which fault tolerance can be achieved locally through hardware redundancy and/or globally through application of analytical redundancy. The effects of asynchronism on the execution of dynamic flight software is discussed. It is shown that if the asynchronous microprocessors have knowledge of time, these errors can be significantly reduced through appropiate modifications of the flight software. Finally, the papear extends previous work to show that through the combined use of time referencing and stable flight algorithms, individual microprocessors can be configured to autonomously tolerate intermittent faults.

Adaptive control of a millimeter-scale flapping-wing robot.

PubMed

Chirarattananon, Pakpong; Ma, Kevin Y; Wood, Robert J

2014-06-01

Challenges for the controlled flight of a robotic insect are due to the inherent instability of the system, complex fluid-structure interactions, and the general lack of a complete system model. In this paper, we propose theoretical models of the system based on the limited information available from previous work and a comprehensive flight controller. The modular flight controller is derived from Lyapunov function candidates with proven stability over a large region of attraction. Moreover, it comprises adaptive components that are capable of coping with uncertainties in the system that arise from manufacturing imperfections. We have demonstrated that the proposed methods enable the robot to achieve sustained hovering flights with relatively small errors compared to a non-adaptive approach. Simple lateral maneuvers and vertical takeoff and landing flights are also shown to illustrate the fidelity of the flight controller. The analysis suggests that the adaptive scheme is crucial in order to achieve millimeter-scale precision in flight control as observed in natural insect flight.

Practical Application of a Subscale Transport Aircraft for Flight Research in Control Upset and Failure Conditions

NASA Technical Reports Server (NTRS)

Cunningham, Kevin; Foster, John V.; Morelli, Eugene A.; Murch, Austin M.

2008-01-01

Over the past decade, the goal of reducing the fatal accident rate of large transport aircraft has resulted in research aimed at the problem of aircraft loss-of-control. Starting in 1999, the NASA Aviation Safety Program initiated research that included vehicle dynamics modeling, system health monitoring, and reconfigurable control systems focused on flight regimes beyond the normal flight envelope. In recent years, there has been an increased emphasis on adaptive control technologies for recovery from control upsets or failures including damage scenarios. As part of these efforts, NASA has developed the Airborne Subscale Transport Aircraft Research (AirSTAR) flight facility to allow flight research and validation, and system testing for flight regimes that are considered too risky for full-scale manned transport airplane testing. The AirSTAR facility utilizes dynamically-scaled vehicles that enable the application of subscale flight test results to full scale vehicles. This paper describes the modeling and simulation approach used for AirSTAR vehicles that supports the goals of efficient, low-cost and safe flight research in abnormal flight conditions. Modeling of aerodynamics, controls, and propulsion will be discussed as well as the application of simulation to flight control system development, test planning, risk mitigation, and flight research.

Engineering flight and guest pilot evaluation report, phase 2. [DC 8 aircraft

NASA Technical Reports Server (NTRS)

Morrison, J. A.; Anderson, E. B.; Brown, G. W.; Schwind, G. K.

1974-01-01

Prior to the flight evaluation, the two-segment profile capabilities of the DC-8-61 were evaluated and flight procedures were developed in a flight simulator at the UA Flight Training Center in Denver, Colorado. The flight evaluation reported was conducted to determine the validity of the simulation results, further develop the procedures and use of the area navigation system in the terminal area, certify the system for line operation, and obtain evaluations of the system and procedures by a number of pilots from the industry. The full area navigation capabilities of the special equipment installed were developed to provide terminal area guidance for two-segment approaches. The objectives of this evaluation were: (1) perform an engineering flight evaluation sufficient to certify the two-segment system for the six-month in-service evaluation; (2) evaluate the suitability of a modified RNAV system for flying two-segment approaches; and (3) provide evaluation of the two-segment approach by management and line pilots.

Flight control actuation system

NASA Technical Reports Server (NTRS)

Wingett, Paul T. (Inventor); Gaines, Louie T. (Inventor); Evans, Paul S. (Inventor); Kern, James I. (Inventor)

2004-01-01

A flight control actuation system comprises a controller, electromechanical actuator and a pneumatic actuator. During normal operation, only the electromechanical actuator is needed to operate a flight control surface. When the electromechanical actuator load level exceeds 40 amps positive, the controller activates the pneumatic actuator to offset electromechanical actuator loads to assist the manipulation of flight control surfaces. The assistance from the pneumatic load assist actuator enables the use of an electromechanical actuator that is smaller in size and mass, requires less power, needs less cooling processes, achieves high output forces and adapts to electrical current variations. The flight control actuation system is adapted for aircraft, spacecraft, missiles, and other flight vehicles, especially flight vehicles that are large in size and travel at high velocities.

Flight control actuation system

NASA Technical Reports Server (NTRS)

Wingett, Paul T. (Inventor); Gaines, Louie T. (Inventor); Evans, Paul S. (Inventor); Kern, James I. (Inventor)

2006-01-01

A flight control actuation system comprises a controller, electromechanical actuator and a pneumatic actuator. During normal operation, only the electromechanical actuator is needed to operate a flight control surface. When the electromechanical actuator load level exceeds 40 amps positive, the controller activates the pneumatic actuator to offset electromechanical actuator loads to assist the manipulation of flight control surfaces. The assistance from the pneumatic load assist actuator enables the use of an electromechanical actuator that is smaller in size and mass, requires less power, needs less cooling processes, achieves high output forces and adapts to electrical current variations. The flight control actuation system is adapted for aircraft, spacecraft, missiles, and other flight vehicles, especially flight vehicles that are large in size and travel at high velocities.

Advanced transport operating system software upgrade: Flight management/flight controls software description

NASA Technical Reports Server (NTRS)

Clinedinst, Winston C.; Debure, Kelly R.; Dickson, Richard W.; Heaphy, William J.; Parks, Mark A.; Slominski, Christopher J.; Wolverton, David A.

1988-01-01

The Flight Management/Flight Controls (FM/FC) software for the Norden 2 (PDP-11/70M) computer installed on the NASA 737 aircraft is described. The software computes the navigation position estimates, guidance commands, those commands to be issued to the control surfaces to direct the aircraft in flight based on the modes selected on the Advanced Guidance Control System (AGSC) mode panel, and the flight path selected via the Navigation Control/Display Unit (NCDU).

Doppler global velocimetry: Development of a flight research instrumentation system for application to non-intrusive measurements of the flow field

NASA Technical Reports Server (NTRS)

Komine, Hiroshi; Brosnan, Stephen J.; Long, William H.; Stappaerts, Eddy A.

1994-01-01

Doppler Global Velocimetry (DGV) is a new diagnostic tool that offers potential for flow field measurements in flight by acquiring three-component velocity data in near real-time during flight maneuvers. The feasibility of implementation of a flight DGV system aboard NASA's High-Angle-of-Attack Research Vehicle (HARV) was addressed in this work by identifying the essential characteristics of a flight measurement system and by performing calibration and error tests. Results from this work were: an outline that establishes a preliminary basis for system configurations by analyzing measurement errors, installation issues, and operating requirements; measurement of the accuracy of the DGV technique using a laboratory breadboard DGV system based on a frequency-doubled Nd: YAG laser and iodine Absorption Line Filter (ALF), which showed excellent agreement between the DGV data and pilot measurements on a laminar flow jet with velocities of up to 150 m/sec; a survey of DGV system components and technologies that are relevant to the design of a flight measurement system, including a survey of cameras for the next generation DGV receivers; an assessment of the candidate lasers and absorption line filters for the flight system, resulting in a near-term recommendation of Nd: host lasers and an iodine ALF for both flight and wind tunnel applications.

Automation tools for demonstration of goal directed and self-repairing flight control systems

NASA Technical Reports Server (NTRS)

Agarwal, A. K.

1988-01-01

The coupling of expert systems and control design and analysis techniques are documented to provide a realizable self repairing flight control system. Key features of such a flight control system are identified and a limited set of rules for a simple aircraft model are presented.

Validation of Procedures for Monitoring Crewmember Immune Function

NASA Technical Reports Server (NTRS)

Crucian, Brian; Stowe, Raymond; Mehta, Satish; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarence

2008-01-01

There is ample evidence to suggest that space flight leads to immune system dysregulation. This may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk (if any) from prolonged immune dysregulation during exploration-class space flight has not yet been determined, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. Each of the clinical events resulting from immune dysfunction has the potential to impact mission critical objectives during exploration-class missions. To date, precious little in-flight immune data has been generated to assess this phenomenon. The majority of recent flight immune studies have been post-flight assessments, which may not accurately reflect the in-flight status of immunity as it resolves over prolonged flight. There are no procedures currently in place to monitor immune function or its effect on crew health. The objective of this Supplemental Medical Objective (SMO) is to develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. This SMO will assess immunity, latent viral reactivation and physiological stress during both short and long duration flights. Upon completion, it is expected that any clinical risks resulting from the adverse effects of space flight on the human immune system will have been determined. In addition, a flight-compatible immune monitoring strategy will have been developed with which countermeasures validation could be performed. This study will determine, to the best level allowed by current technology, the in-flight status of crewmembers' immune systems. The in-flight samples will allow a distinction between legitimate in-flight alterations and the physiological stresses of landing and readaptation which are believed to alter R+0 assessments. The overall status of the immune system during flight (activation, deficiency, dysregulation) and the response of the immune system to specific latent virus reactivation (known to occur during space flight) will be thoroughly assessed. The first in-flight activity for integrated immunity very recently occurred during the STS-120 Space Shuttle mission. The protocols functioned well from a technical perspective, and accurate in-flight data was obtained from 1 Shuttle and 2 ISS crewmembers. Crew participation rates for the study continue to be robust.

Implementation and Test of the Automatic Flight Dynamics Operations for Geostationary Satellite Mission

NASA Astrophysics Data System (ADS)

Park, Sangwook; Lee, Young-Ran; Hwang, Yoola; Javier Santiago Noguero Galilea

2009-12-01

This paper describes the Flight Dynamics Automation (FDA) system for COMS Flight Dynamics System (FDS) and its test result in terms of the performance of the automation jobs. FDA controls the flight dynamics functions such as orbit determination, orbit prediction, event prediction, and fuel accounting. The designed FDA is independent from the specific characteristics which are defined by spacecraft manufacturer or specific satellite missions. Therefore, FDA could easily links its autonomous job control functions to any satellite mission control system with some interface modification. By adding autonomous system along with flight dynamics system, it decreases the operator’s tedious and repeated jobs but increase the usability and reliability of the system. Therefore, FDA is used to improve the completeness of whole mission control system’s quality. The FDA is applied to the real flight dynamics system of a geostationary satellite, COMS and the experimental test is performed. The experimental result shows the stability and reliability of the mission control operations through the automatic job control.

AGARD Flight Test Techniques Series. Volume 12. The Principles of Flight Test Assessment of Flight-Safety-Critical Systems in Helicopters (Les Principes de l’Evaluation, dans le Cadre des Essais en Vol, des Systemes Indispensables a la Securite de Vol des Helicopteres)

DTIC Science & Technology

1994-08-01

AGARD-AG-300 Vol. 12 04 ADVISORY GROUP FOR AEROSPACE RESEARCH & DEVELOPMENT 7 RUE ANCELLE, 92200 NEUILLY-SUR-SEINE, FRANCE AUG 0195 AGARDograph 300...AGARD Flight Test Techniques Series Volume 12 on The Principles of Flight Test Assessment of Flight-Safety-Critical Systems in Helicopters (Les...and Availability on Back Cover AGARD-AG-300 Vol. 12 ADVISORY GROUP FOR AEROSPACE RESEARCH & DEVELOPMENT 7 RUE ANCELLE, 92200 NEUILLY-SUR-SEINE, FRANCE

Remote radio control of insect flight.

PubMed

Sato, Hirotaka; Berry, Christopher W; Peeri, Yoav; Baghoomian, Emen; Casey, Brendan E; Lavella, Gabriel; Vandenbrooks, John M; Harrison, Jon F; Maharbiz, Michel M

2009-01-01

We demonstrated the remote control of insects in free flight via an implantable radio-equipped miniature neural stimulating system. The pronotum mounted system consisted of neural stimulators, muscular stimulators, a radio transceiver-equipped microcontroller and a microbattery. Flight initiation, cessation and elevation control were accomplished through neural stimulus of the brain which elicited, suppressed or modulated wing oscillation. Turns were triggered through the direct muscular stimulus of either of the basalar muscles. We characterized the response times, success rates, and free-flight trajectories elicited by our neural control systems in remotely controlled beetles. We believe this type of technology will open the door to in-flight perturbation and recording of insect flight responses.

Performance of an Electro-Hydrostatic Actuator on the F-18 Systems Research Aircraft

NASA Technical Reports Server (NTRS)

Navarro, Robert

1997-01-01

An electro-hydrostatic actuator was evaluated at NASA Dryden Flight Research Center, Edwards, California. The primary goal of testing this actuator system was the flight demonstration of power-by-wire technology on a primary flight control surface. The electro-hydrostatic actuator uses an electric motor to drive a hydraulic pump and relies on local hydraulics for force transmission. This actuator replaced the F-18 standard left aileron actuator on the F-18 Systems Research Aircraft and was evaluated throughout the Systems Research Aircraft flight envelope. As of July 24, 1997 the electro-hydrostatic actuator had accumulated 23.5 hours of flight time. This paper presents the electro-hydrostatic actuator system configuration and component description, ground and flight test plans, ground and flight test results, and lessons learned. This actuator performs as well as the standard actuator and has more load capability than required by aileron actuator specifications of McDonnell- Douglas Aircraft, St. Louis, Missouri. The electro-hydrostatic actuator system passed all of its ground tests with the exception of one power-off test during unloaded dynamic cycling.

Designing Flight Deck Procedures

NASA Technical Reports Server (NTRS)

Degani, Asaf; Wiener, Earl

2005-01-01

Three reports address the design of flight-deck procedures and various aspects of human interaction with cockpit systems that have direct impact on flight safety. One report, On the Typography of Flight- Deck Documentation, discusses basic research about typography and the kind of information needed by designers of flight deck documentation. Flight crews reading poorly designed documentation may easily overlook a crucial item on the checklist. The report surveys and summarizes the available literature regarding the design and typographical aspects of printed material. It focuses on typographical factors such as proper typefaces, character height, use of lower- and upper-case characters, line length, and spacing. Graphical aspects such as layout, color coding, fonts, and character contrast are discussed; and several cockpit conditions such as lighting levels and glare are addressed, as well as usage factors such as angular alignment, paper quality, and colors. Most of the insights and recommendations discussed in this report are transferable to paperless cockpit systems of the future and computer-based procedure displays (e.g., "electronic flight bag") in aerospace systems and similar systems that are used in other industries such as medical, nuclear systems, maritime operations, and military systems.

Integrated Neural Flight and Propulsion Control System

NASA Technical Reports Server (NTRS)

Kaneshige, John; Gundy-Burlet, Karen; Norvig, Peter (Technical Monitor)

2001-01-01

This paper describes an integrated neural flight and propulsion control system. which uses a neural network based approach for applying alternate sources of control power in the presence of damage or failures. Under normal operating conditions, the system utilizes conventional flight control surfaces. Neural networks are used to provide consistent handling qualities across flight conditions and for different aircraft configurations. Under damage or failure conditions, the system may utilize unconventional flight control surface allocations, along with integrated propulsion control, when additional control power is necessary for achieving desired flight control performance. In this case, neural networks are used to adapt to changes in aircraft dynamics and control allocation schemes. Of significant importance here is the fact that this system can operate without emergency or backup flight control mode operations. An additional advantage is that this system can utilize, but does not require, fault detection and isolation information or explicit parameter identification. Piloted simulation studies were performed on a commercial transport aircraft simulator. Subjects included both NASA test pilots and commercial airline crews. Results demonstrate the potential for improving handing qualities and significantly increasing survivability rates under various simulated failure conditions.

Digital flight control research

NASA Technical Reports Server (NTRS)

Potter, J. E.; Stern, R. G.; Smith, T. B.; Sinha, P.

1974-01-01

The results of studies which were undertaken to contribute to the design of digital flight control systems, particularly for transport aircraft are presented. In addition to the overall design considerations for a digital flight control system, the following topics are discussed in detail: (1) aircraft attitude reference system design, (2) the digital computer configuration, (3) the design of a typical digital autopilot for transport aircraft, and (4) a hybrid flight simulator.

An overview of the F-117A avionics flight test program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silz, R.

1992-02-01

This paper is an overview of the history of the F-117A avionics flight test program. System design concepts and equipment selections are explored followed by a review of full scale development and full capability development testing. Flight testing the Weapon System Computational Subsystem upgrade and the Offensive Combat Improvement Program are reviewed. Current flight test programs and future system updates are highlighted.

Selected Flight Test Results for Online Learning Neural Network-Based Flight Control System

NASA Technical Reports Server (NTRS)

Williams-Hayes, Peggy S.

2004-01-01

The NASA F-15 Intelligent Flight Control System project team developed a series of flight control concepts designed to demonstrate neural network-based adaptive controller benefits, with the objective to develop and flight-test control systems using neural network technology to optimize aircraft performance under nominal conditions and stabilize the aircraft under failure conditions. This report presents flight-test results for an adaptive controller using stability and control derivative values from an online learning neural network. A dynamic cell structure neural network is used in conjunction with a real-time parameter identification algorithm to estimate aerodynamic stability and control derivative increments to baseline aerodynamic derivatives in flight. This open-loop flight test set was performed in preparation for a future phase in which the learning neural network and parameter identification algorithm output would provide the flight controller with aerodynamic stability and control derivative updates in near real time. Two flight maneuvers are analyzed - pitch frequency sweep and automated flight-test maneuver designed to optimally excite the parameter identification algorithm in all axes. Frequency responses generated from flight data are compared to those obtained from nonlinear simulation runs. Flight data examination shows that addition of flight-identified aerodynamic derivative increments into the simulation improved aircraft pitch handling qualities.

Towards Validation of an Adaptive Flight Control Simulation Using Statistical Emulation

NASA Technical Reports Server (NTRS)

He, Yuning; Lee, Herbert K. H.; Davies, Misty D.

2012-01-01

Traditional validation of flight control systems is based primarily upon empirical testing. Empirical testing is sufficient for simple systems in which a.) the behavior is approximately linear and b.) humans are in-the-loop and responsible for off-nominal flight regimes. A different possible concept of operation is to use adaptive flight control systems with online learning neural networks (OLNNs) in combination with a human pilot for off-nominal flight behavior (such as when a plane has been damaged). Validating these systems is difficult because the controller is changing during the flight in a nonlinear way, and because the pilot and the control system have the potential to co-adapt in adverse ways traditional empirical methods are unlikely to provide any guarantees in this case. Additionally, the time it takes to find unsafe regions within the flight envelope using empirical testing means that the time between adaptive controller design iterations is large. This paper describes a new concept for validating adaptive control systems using methods based on Bayesian statistics. This validation framework allows the analyst to build nonlinear models with modal behavior, and to have an uncertainty estimate for the difference between the behaviors of the model and system under test.

Flight test evaluation of the E-systems Differential GPS category 3 automatic landing system

NASA Technical Reports Server (NTRS)

Kaufmann, David N.; Mcnally, B. David

1995-01-01

Test flights were conducted to evaluate the capability of Differential Global Positioning System (DGPS) to provide the accuracy and integrity required for International Civil Aviation Organization (ICAO) Category (CAT) III precision approach and landings. These test flights were part of a Federal Aviation Administration (FAA) program to evaluate the technical feasibility of using DGPS based technology for CAT III precision approach and landing applications. An IAI Westwind 1124 aircraft (N24RH) was equipped with DGPS receiving equipment and additional computing capability provided by E-Systems. The test flights were conducted at NASA Ames Research Center's Crows Landing Flight Facility, Crows Landing, California. The flight test evaluation was based on completing 100 approaches and landings. The navigation sensor error accuracy requirements were based on ICAO requirements for the Microwave Landing System (MLS). All of the approaches and landings were evaluated against ground truth reference data provided by a laser tracker. Analysis of these approaches and landings shows that the E-Systems DGPS system met the navigation sensor error requirements for a successful approach and landing 98 out of 100 approaches and landings, based on the requirements specified in the FAA CAT III Level 2 Flight Test Plan. In addition, the E-Systems DGPS system met the integrity requirements for a successful approach and landing or stationary trial for all 100 approaches and landings and all ten stationary trials, based on the requirements specified in the FAA CAT III Level 2 Flight Test Plan.

State Estimation of Main Rotor Flap and Lead-Lag Using Accelerometers and Laser Transducers on the RASCAL UH-60 Helicopter

NASA Technical Reports Server (NTRS)

Fletcher, Jay W.; Chen, Robert T. N.; Strasilla, Eric; Aiken, Edwin W. (Technical Monitor)

1995-01-01

Modern rotorcraft flight control system designs which promise to yield high vehicle response bandwidth and good gust rejection can benefit from the use of rotor-state feedbacks. The measurement of main rotor blade motions is also desirable to validate and improve rotorcraft simulation models, to identify high-order linear flight dynamics models, to provide rotor system health monitoring; during flight test, and to provide for correlation with acoustic measurements from wind tunnel and flight tests. However, few attempts have been made to instrument a flight vehicle in this manner, and no previous system has had the robustness and accuracy required for these diverse applications. A rotor blade motion measurement and estimation system has been developed by NASA and the U.S. Army for use on the Rotorcraft Aircrew Systems Concepts Airborne Laboratory (RASCAL) helicopter. RASCAL is a UH-60 Blackhawk which is being modified at Ames Research Center in a phased development program for use in flight dynamics and controls, navigation, airspace management, and rotorcraft human factors research. The aircraft will feature a full-authority, digital, fly-by-wire research flight control system; a coupled ring laser gyro, differential GPS based navigation system; a stereoscopic color wide field of view helmet, mounted display; programmable panel mounted displays; and advanced navigation sensors. The rotor blade motion system is currently installed for data acquisition only, but will be integrated with the research flight control system when it is installed later this year.

Guidance system operations plan for manned CM earth orbital missions using program SKYLARK 1. Section 4: Operational modes

NASA Technical Reports Server (NTRS)

Dunbar, J. C.

1972-01-01

The operational modes for the guidance system operations plan for Program SKYLARK 1 are presented. The procedures control the guidance and navigation system interfaces with the flight crew and the mission control center. The guidance operational concept is designed to comprise a set of manually initiated programs and functions which may be arranged by the flight crew to implement a large class of flight plans. This concept will permit both a late flight plan definition and a capability for real time flight plan changes.

An Overview of NASA's SubsoniC Research Aircraft Testbed (SCRAT)

NASA Technical Reports Server (NTRS)

Baumann, Ethan; Hernandez, Joe; Ruhf, John

2013-01-01

National Aeronautics and Space Administration Dryden Flight Research Center acquired a Gulfstream III (GIII) aircraft to serve as a testbed for aeronautics flight research experiments. The aircraft is referred to as SCRAT, which stands for SubsoniC Research Aircraft Testbed. The aircraft’s mission is to perform aeronautics research; more specifically raising the Technology Readiness Level (TRL) of advanced technologies through flight demonstrations and gathering high-quality research data suitable for verifying the technologies, and validating design and analysis tools. The SCRAT has the ability to conduct a range of flight research experiments throughout a transport class aircraft’s flight envelope. Experiments ranging from flight-testing of a new aircraft system or sensor to those requiring structural and aerodynamic modifications to the aircraft can be accomplished. The aircraft has been modified to include an instrumentation system and sensors necessary to conduct flight research experiments along with a telemetry capability. An instrumentation power distribution system was installed to accommodate the instrumentation system and future experiments. An engineering simulation of the SCRAT has been developed to aid in integrating research experiments. A series of baseline aircraft characterization flights has been flown that gathered flight data to aid in developing and integrating future research experiments. This paper describes the SCRAT’s research systems and capabilities

An Overview of NASA's Subsonic Research Aircraft Testbed (SCRAT)

NASA Technical Reports Server (NTRS)

Baumann, Ethan; Hernandez, Joe; Ruhf, John C.

2013-01-01

National Aeronautics and Space Administration Dryden Flight Research Center acquired a Gulfstream III (GIII) aircraft to serve as a testbed for aeronautics flight research experiments. The aircraft is referred to as SCRAT, which stands for SubsoniC Research Aircraft Testbed. The aircraft's mission is to perform aeronautics research; more specifically raising the Technology Readiness Level (TRL) of advanced technologies through flight demonstrations and gathering high-quality research data suitable for verifying the technologies, and validating design and analysis tools. The SCRAT has the ability to conduct a range of flight research experiments throughout a transport class aircraft's flight envelope. Experiments ranging from flight-testing of a new aircraft system or sensor to those requiring structural and aerodynamic modifications to the aircraft can be accomplished. The aircraft has been modified to include an instrumentation system and sensors necessary to conduct flight research experiments along with a telemetry capability. An instrumentation power distribution system was installed to accommodate the instrumentation system and future experiments. An engineering simulation of the SCRAT has been developed to aid in integrating research experiments. A series of baseline aircraft characterization flights has been flown that gathered flight data to aid in developing and integrating future research experiments. This paper describes the SCRAT's research systems and capabilities.

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.

A Developmentally Regulated Chaperone Complex for the Endoplasmic Reticulum of Male Haploid Germ Cells

PubMed Central

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

Design of a Mission Data Storage and Retrieval System for NASA Dryden Flight Research Center

NASA Technical Reports Server (NTRS)

Lux, Jessica; Downing, Bob; Sheldon, Jack

2007-01-01

The Western Aeronautical Test Range (WATR) at the NASA Dryden Flight Research Center (DFRC) employs the WATR Integrated Next Generation System (WINGS) for the processing and display of aeronautical flight data. This report discusses the post-mission segment of the WINGS architecture. A team designed and implemented a system for the near- and long-term storage and distribution of mission data for flight projects at DFRC, providing the user with intelligent access to data. Discussed are the legacy system, an industry survey, system operational concept, high-level system features, and initial design efforts.

An improved waste collection system for space flight

NASA Technical Reports Server (NTRS)

Thornton, William E.; Lofland, William W., Jr.; Whitmore, Henry

1986-01-01

Waste collection systems are a critical part of manned space flight. Systems to date have had a number of deficiencies. A new system, which uses a simple mechanical piston compactor and disposable pads allows a clean area for defecation and maximum efficiency of waste collection and storage. The concept has been extensively tested. Flight demonstration units are being built, tested, and scheduled for flight. A prototype operational unit is under construction. This system offers several advantages over existing or planned systems in the areas of crew interface and operation, cost, size, weight, and maintenance and power consumption.

F-15 IFCS Intelligent Flight Control System

NASA Technical Reports Server (NTRS)

Bosworth, John T.

2008-01-01

This viewgraph presentation gives a detailed description of the F-15 aircraft, flight tests, aircraft performance and overall advanced neural network based flight control technologies for aerospace systems designs.