Receptor-Mediated and Fluid-Phase Transcytosis of Horseradish Peroxidase across Rat Hepatocytes

PubMed Central

Ellinger, Isabella; Fuchs, Renate

2010-01-01

Horseradish peroxidase (HRP) is often used as a fluid-phase marker to characterize endocytic and transcytotic processes. Likewise, it has been applied to investigate the mechanisms of biliary secretion of fluid in rat liver hepatocytes. However, HRP contains mannose residues and thus binds to mannose receptors (MRs) on liver cells, including hepatocytes. To study the role of MR-mediated endocytosis of HRP transport in hepatocytes, we determined the influence of the oligosaccharid mannan on HRP biliary secretion in the isolated perfused rat liver. A 1-minute pulse of HRP was applied followed by marker-free perfusion. HRP appeared in bile with biphasic kinetics: a first peak at 7 minutes and a second peak at 15 minutes after labeling. Perfusion with 0.8 mg/mL HRP in the presence of a twofold excess of mannan reduced the first peak by 41% without effect on the second one. Together with recently published data on MR expression in rat hepatocytes this demonstrates two different mechanisms for HRP transcytosis: a rapid, receptor-mediated transport and a slower fluid-phase transport. PMID:20168981

Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells

PubMed Central

Kraehling, Jan R.; Chidlow, John H.; Rajagopal, Chitra; Sugiyama, Michael G.; Fowler, Joseph W.; Lee, Monica Y.; Zhang, Xinbo; Ramírez, Cristina M.; Park, Eon Joo; Tao, Bo; Chen, Keyang; Kuruvilla, Leena; Larriveé, Bruno; Folta-Stogniew, Ewa; Ola, Roxana; Rotllan, Noemi; Zhou, Wenping; Nagle, Michael W.; Herz, Joachim; Williams, Kevin Jon; Eichmann, Anne; Lee, Warren L.; Fernández-Hernando, Carlos; Sessa, William C.

2016-01-01

In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL. PMID:27869117

Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells.

PubMed

Kraehling, Jan R; Chidlow, John H; Rajagopal, Chitra; Sugiyama, Michael G; Fowler, Joseph W; Lee, Monica Y; Zhang, Xinbo; Ramírez, Cristina M; Park, Eon Joo; Tao, Bo; Chen, Keyang; Kuruvilla, Leena; Larriveé, Bruno; Folta-Stogniew, Ewa; Ola, Roxana; Rotllan, Noemi; Zhou, Wenping; Nagle, Michael W; Herz, Joachim; Williams, Kevin Jon; Eichmann, Anne; Lee, Warren L; Fernández-Hernando, Carlos; Sessa, William C

2016-11-21

In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL.

Transcytosis-blocking abs elicited by an oligomeric immunogen based on the membrane proximal region of HIV-1 gp41 target non-neutralizing epitopes.

PubMed

Matoba, Nobuyuki; Griffin, Tagan A; Mittman, Michele; Doran, Jeffrey D; Alfsen, Annette; Montefiori, David C; Hanson, Carl V; Bomsel, Morgane; Mor, Tsafrir S

2008-05-01

CTB-MPR(649-684), a translational fusion protein consisting of cholera toxin B subunit (CTB) and residues 649 684 of gp41 membrane proximal region (MPR), is a candidate vaccine aimed at blocking early steps of HIV-1 mucosal transmission. Bacterially produced CTB MPR(649-684) was purified to homogeneity by two affinity chromatography steps. Similar to gp41 and derivatives thereof, the MPR domain can specifically and reversibly self-associate. The affinities of the broadly-neutralizing monoclonal Abs 4E10 and 2F5 to CTB MPR(649-684) were equivalent to their nanomolar affinities toward an MPR peptide. The fusion protein's affinity to GM1 ganglioside was comparable to that of native CTB. Rabbits immunized with CTB-MPR(649-684) raised only a modest level of anti-MPR(649-684) Abs. However, a prime-boost immunization with CTB-MPR(649-684) and a second MPR(649-684)-based immunogen elicited a more productive anti-MPR(649-684) antibody response. These Abs strongly blocked the epithelial transcytosis of a primary subtype B HIV-1 isolate in a human tight epithelial model, expanding our previously reported results using a clade D virus. The Abs recognized epitopes at the N-terminal portion of the MPR peptide, away from the 2F5 and 4E10 epitopes and were not effective in neutralizing infection of CD4+ cells. These results indicate distinct vulnerabilities of two separate interactions of HIV-1 with human cells - Abs against the C-terminal portion of the MPR can neutralize CD4+-dependent infection, while Abs targeting the MPR's N-terminal portion can effectively block galactosyl ceramide dependent transcytosis. We propose that Abs induced by MPR(649-684)-based immunogens may provide broad protective value independent of infection neutralization.

Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin.

PubMed

Nikitas, Georgios; Deschamps, Chantal; Disson, Olivier; Niault, Théodora; Cossart, Pascale; Lecuit, Marc

2011-10-24

Listeria monocytogenes (Lm) is a foodborne pathogen that crosses the intestinal barrier upon interaction between its surface protein InlA and its species-specific host receptor E-cadherin (Ecad). Ecad, the key constituent of adherens junctions, is typically situated below tight junctions and therefore considered inaccessible from the intestinal lumen. In this study, we investigated how Lm specifically targets its receptor on intestinal villi and crosses the intestinal epithelium to disseminate systemically. We demonstrate that Ecad is luminally accessible around mucus-expelling goblet cells (GCs), around extruding enterocytes at the tip and lateral sides of villi, and in villus epithelial folds. We show that upon preferential adherence to accessible Ecad on GCs, Lm is internalized, rapidly transcytosed across the intestinal epithelium, and released in the lamina propria by exocytosis from where it disseminates systemically. Together, these results show that Lm exploits intrinsic tissue heterogeneity to access its receptor and reveal transcytosis as a novel and unanticipated pathway that is hijacked by Lm to breach the intestinal epithelium and cause systemic infection.

Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin

PubMed Central

Nikitas, Georgios; Deschamps, Chantal; Disson, Olivier; Niault, Théodora; Cossart, Pascale

2011-01-01

Listeria monocytogenes (Lm) is a foodborne pathogen that crosses the intestinal barrier upon interaction between its surface protein InlA and its species-specific host receptor E-cadherin (Ecad). Ecad, the key constituent of adherens junctions, is typically situated below tight junctions and therefore considered inaccessible from the intestinal lumen. In this study, we investigated how Lm specifically targets its receptor on intestinal villi and crosses the intestinal epithelium to disseminate systemically. We demonstrate that Ecad is luminally accessible around mucus-expelling goblet cells (GCs), around extruding enterocytes at the tip and lateral sides of villi, and in villus epithelial folds. We show that upon preferential adherence to accessible Ecad on GCs, Lm is internalized, rapidly transcytosed across the intestinal epithelium, and released in the lamina propria by exocytosis from where it disseminates systemically. Together, these results show that Lm exploits intrinsic tissue heterogeneity to access its receptor and reveal transcytosis as a novel and unanticipated pathway that is hijacked by Lm to breach the intestinal epithelium and cause systemic infection. PMID:21967767

Smuggling Drugs into the Brain: An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood-Brain Barrier.

PubMed

Georgieva, Julia V; Hoekstra, Dick; Zuhorn, Inge S

2014-11-17

The blood-brain barrier acts as a physical barrier that prevents free entry of blood-derived substances, including those intended for therapeutic applications. The development of molecular Trojan horses is a promising drug targeting technology that allows for non-invasive delivery of therapeutics into the brain. This concept relies on the application of natural or genetically engineered proteins or small peptides, capable of specifically ferrying a drug-payload that is either directly coupled or encapsulated in an appropriate nanocarrier, across the blood-brain barrier via receptor-mediated transcytosis. Specifically, in this process the nanocarrier-drug system ("Trojan horse complex") is transported transcellularly across the brain endothelium, from the blood to the brain interface, essentially trailed by a native receptor. Naturally, only certain properties would favor a receptor to serve as a transporter for nanocarriers, coated with appropriate ligands. Here we briefly discuss brain microvascular endothelial receptors that have been explored until now, highlighting molecular features that govern the efficiency of nanocarrier-mediated drug delivery into the brain.

Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones.

PubMed

Zensi, Anja; Begley, David; Pontikis, Charles; Legros, Celine; Mihoreanu, Larisa; Wagner, Sylvia; Büchel, Claudia; von Briesen, Hagen; Kreuter, Jörg

2009-07-01

The blood-brain barrier (BBB) represents a considerable obstacle to brain entry of the majority of drugs and thus severely restricts the therapy of many serious CNS diseases including brain tumours, brain HIV, Alzheimer and other neurodegenerative diseases. The use of nanoparticles coated with polysorbate 80 or with attached apolipoprotein E has enabled the delivery of drugs across the BBB. However, the mechanism of this enhanced transport is still not fully understood. In this present study, human serum albumin nanoparticles, with covalently bound apolipoprotein E (Apo E) as a targetor as well as without apolipoprotein E, were manufactured and injected intravenously into SV 129 mice. The animals were sacrificed after 15 and 30 min, and their brains were examined by transmission electron microscopy. Only the nanoparticles with covalently bound apolipoprotein E were detected in brain capillary endothelial cells and neurones, whereas no uptake into the brain was detectable with nanoparticles without apolipoprotein E. We have also demonstrated uptake of the albumin/ApoE nanoparticles into mouse endothelial (b.End3) cells in vitro and their intracellular localisation. These findings indicate that nanoparticles with covalently bound apolipoprotein E are taken up into the cerebral endothelium by an endocytic mechanism followed by transcytosis into brain parenchyma.

Internal benchmarking of a human blood-brain barrier cell model for screening of nanoparticle uptake and transcytosis.

PubMed

Ragnaill, Michelle Nic; Brown, Meredith; Ye, Dong; Bramini, Mattia; Callanan, Sean; Lynch, Iseult; Dawson, Kenneth A

2011-04-01

Transport of drugs across the blood-brain barrier, which protects the brain from harmful agents, is considered the holy grail of targeted delivery, due to the extreme effectiveness of this barrier at preventing passage of non-essential molecules through to the brain. This has caused severe limitations for therapeutics for many brain-associated diseases, such as HIV and neurodegenerative diseases. Nanomaterials, as a result of their small size (in the order of many protein-lipid clusters routinely transported by cells) and their large surface area (which acts as a scaffold for proteins thereby rendering nanoparticles as biological entities) offer great promise for neuro-therapeutics. However, in parallel with developing neuro-therapeutic applications based on nanotechnology, it is essential to ensure their safety and long-term consequences upon reaching the brain. One approach to determining safe application of nanomaterials in biology is to obtain a deep mechanistic understanding of the interactions between nanomaterials and living systems (bionanointeractions). To this end, we report here on the establishment and internal round robin validation of a human cell model of the blood-brain barrier for use as a tool for screening nanoparticles interactions, and assessing the critical nanoscale parameters that determine transcytosis. Copyright © 2011 Elsevier B.V. All rights reserved.

The low molecular weight fraction of commercial human serum albumin induces acetylation of α-tubulin and reduces transcytosis in retinal endothelial cells.

PubMed

Thomas, Gregory W; Rael, Leonard T; Hausburg, Melissa; Frederick, Elizabeth D; Brody, Edward; Bar-Or, David

2016-09-30

It has long been appreciated that the microtubule network plays a critical role in endothelial cell function. Chemical inhibition of tubulin polymerization has been shown to drastically increases endothelial permeability via interactions with the actin cytoskeleton. Conversely, stabilization of microtubules significantly decreases vascular permeability. The purpose of this investigation was to determine if the low molecular weight fraction of commercial 5% human serum albumin (LMWF5A) alters endothelial cell cytoskeletal dynamics and function. To investigate this, human retinal endothelial cells (HREC) were treated with LMWF5A and the acetylation of α-tubulin was determined by immunofluorescent staining and immunoblotting. In addition, permeability assays were performed to evaluate functional changes. We found that HREC treated with LMWF5A exhibit a rapid increase in the amount and distribution of acetylated α-tubulin. This was accompanied by a reduction in macromolecular permeability. Calcium depletion and inhibition of PI3-kinase reduced LMWF5A-induced acetylation while p38 MAPK inhibition potentiated this effect. These findings suggest that LMWF5A mediates changes in the microtubule network and reduces transcytosis in HREC. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Role of M Cells in Human Mucosal Immunity to Mycobacterium tuberculosis

PubMed Central

Nair, Vidhya; Khan, Haaris; Mitchell, Ron; Shiloh, Michael U

2017-01-01

Abstract Background Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a bacterial pathogen that infects roughly one-third of the worldÕs population and causes 1–2 million deaths per year. The current paradigm is that phagocytosis of Mtb by patrolling alveolar macrophages initiates Mtb infection. While this model can account for pulmonary TB, it does not adequately explain the occurrence of extrapulmonary forms of TB that manifest in the absence of obvious lung involvement, such as tuberculous cervical lymphadenitis, also known as scrofula. We hypothesized that specialized epithelial cells called microfold cells (M cells) may be an alternate portal of entry for Mtb. Previously we demonstrated that Mtb is able to transcytose across an epithelial barrier in an M cell dependent manner and that M cell mediated transcytosis is vital for Mtb pathogenesis in a mouse model of tuberculosis. Methods We used an in vitro M-cell mediated translocation assay and a Mtb mutant lacking a key virulence factor, ESAT6. We used biochemistry and genetics to identify a novel receptor for ESAT6. We also developed a novel explanted human adenoid Mtb infection model to study mucosal immunity. Results We now demonstrate that the Mtb virulence factor ESAT6 is necessary and sufficient to mediate binding and transcytosis by M cells in vitro and in vivo, and that uptake of Mtb by M cells requires a unique cell surface ESAT6 receptor. We developed a novel explanted human adenoid model of M cell biology and demonstrate rapid Mtb transcytosis by primary human tissue within 60–120 minutes. Using flow cytometry we find that Mtb is first ingested by M cells and then after transcytosis, by tissue resident antigen-presenting cells. Explanted adenoids from 10 independent donors display a wide range of Mtb uptake. Conclusion We conclude that Mtb ESAT6 is necessary for Mtb uptake by M-cells and that binding and transcytosis require a host receptor. Because explanted

Routes for Drug Translocation Across the Blood-Brain Barrier: Exploiting Peptides as Delivery Vectors.

PubMed

Kristensen, Mie; Brodin, Birger

2017-09-01

A number of potent drugs for the treatment of brain diseases are available. However, in order for them to reach their target site of action, they must pass the blood-brain barrier (BBB). The capillary endothelium comprises the major barrier of the BBB and allows only passive permeation of some small lipophilic molecules. Brain delivery of the larger biopharmaceuticals, which today includes an increasing number of novel drug entities, is therefore restricted, both due to their molecular size and their hydrophilic nature. Thus, the development of novel drug entities intended for the treatment of brain diseases such as neurodegenerative diseases or brain cancers require a delivery strategy for overcoming the BBB before reaching its final target within the brain. Peptide-based delivery vector is an emerging tool as shuttles for drug delivery across the BBB and one may explore receptor-mediated transcytosis, adsorptive-mediated transcytosis, and the paracellular route. The latter, however, being controversial due to the risk of co-delivery of blood-borne potential harmful substances. On the other hand, a number of studies report on drug delivery across the BBB exploiting receptor-mediated transcytosis and adsorptive-mediated transcytosis, indicating that peptides and peptide vectors may be of use in a central nervous system delivery context. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Transduction of rat pancreatic islets with pseudotyped adeno-associated virus vectors

PubMed Central

Craig, Anthony T; Gavrilova, Oksana; Dwyer, Nancy K; Jou, William; Pack, Stephanie; Liu, Eric; Pechhold, Klaus; Schmidt, Michael; McAlister, Victor J; Chiorini, John A; Blanchette-Mackie, E Joan; Harlan, David M; Owens, Roland A

2009-01-01

Background Pancreatic islet transplantation is a promising treatment for type I diabetes mellitus, but current immunosuppressive strategies do not consistently provide long-term survival of transplanted islets. We are therefore investigating the use of adeno-associated viruses (AAVs) as gene therapy vectors to transduce rat islets with immunosuppressive genes prior to transplantation into diabetic mice. Results We compared the transduction efficiency of AAV2 vectors with an AAV2 capsid (AAV2/2) to AAV2 vectors pseudotyped with AAV5 (AAV2/5), AAV8 (AAV2/8) or bovine adeno-associated virus (BAAV) capsids, or an AAV2 capsid with an insertion of the low density lipoprotein receptor ligand from apolipoprotein E (AAV2apoE), on cultured islets, in the presence of helper adenovirus infection to speed expression of a GFP transgene. Confocal microscopy and flow cytometry were used. The AAV2/5 vector was superior to AAV2/2 and AAV2/8 in rat islets. Flow cytometry indicated AAV2/5-mediated gene expression in approximately 9% of rat islet cells and almost 12% of insulin-positive cells. The AAV2/8 vector had a higher dependence on the helper virus multiplicity of infection than the AAV 2/5 vector. In addition, the BAAV and AAV2apoE vectors were superior to AAV2/2 for transducing rat islets. Rat islets (300 per mouse) transduced with an AAV2/5 vector harboring the immunosuppressive transgene, tgfβ1, retain the ability to correct hyperglycemia when transplanted into immune-deficient diabetic mice. Conclusion AAV2/5 vectors may therefore be useful for pre-treating donor islets prior to transplantation. PMID:19450275

Characterization of newly established bovine intestinal epithelial cell line.

PubMed

Miyazawa, Kohtaro; Hondo, Tetsuya; Kanaya, Takashi; Tanaka, Sachi; Takakura, Ikuro; Itani, Wataru; Rose, Michael T; Kitazawa, Haruki; Yamaguchi, Takahiro; Aso, Hisashi

2010-01-01

Membranous epithelial cells (M cells) of the follicle-associated epithelium in Peyer's patches have a high capacity for transcytosis of several viruses and microorganisms. Here, we report that we have successfully established a bovine intestinal epithelial cell line (BIE cells) and developed an in vitro M cell model. BIE cells have a cobblestone morphology and microvilli-like structures, and strongly express cell-to-cell junctional proteins and cytokeratin, which is a specific intermediate filament protein of epithelial cells. After co-culture with murine intestinal lymphocytes or treatment with supernatant from bovine PBMC cultured with IL-2, BIE cells acquired the ability of transcytosis. Therefore, BIE cells have typical characteristics of bovine intestinal epithelial cells and also have the ability to differentiate into an M cell like linage. In addition, our results indicate that contact between immune cells and epithelial cells may not be absolutely required for the differentiation of M cells. We think that BIE cells will be useful for studying the transport mechanisms of various pathogens and also the evaluation of drug delivery via M cells.

Combinatorial Approaches for the Identification of Brain Drug Delivery Targets

PubMed Central

Stutz, Charles C.; Zhang, Xiaobin; Shusta, Eric V.

2018-01-01

The blood-brain barrier (BBB) represents a large obstacle for the treatment of central nervous system diseases. Targeting endogenous nutrient transporters that transcytose the BBB is one promising approach to selectively and noninvasively deliver a drug payload to the brain. The main limitations of the currently employed transcytosing receptors are their ubiquitous expression in the peripheral vasculature and the inherent low levels of transcytosis mediated by such systems. In this review, approaches designed to increase the repertoire of transcytosing receptors which can be targeted for the purpose of drug delivery are discussed. In particular, combinatorial protein libraries can be screened on BBB cells in vitro or in vivo to isolate targeting peptides or antibodies that can trigger transcytosis. Once these targeting reagents are discovered, the cognate BBB transcytosis system can be identified using techniques such as expression cloning or immunoprecipitation coupled with mass spectrometry. Continued technological advances in BBB genomics and proteomics, membrane protein manipulation, and in vitro BBB technology promise to further advance the capability to identify and optimize peptides and antibodies capable of mediating drug transport across the BBB. PMID:23789958

Regulation of podocalyxin trafficking by Rab small GTPases in 2D and 3D epithelial cell cultures

PubMed Central

Mrozowska, Paulina S.

2016-01-01

MDCK II cells, a widely used model of polarized epithelia, develop into different structures depending on culture conditions: two-dimensional (2D) monolayers when grown on synthetic supports or three-dimensional (3D) cysts when surrounded by an extracellular matrix. The establishment of epithelial polarity is accompanied by transcytosis of the apical marker podocalyxin from the outer plasma membrane to the newly formed apical domain, but its exact route and regulation remain poorly understood. Here, through comprehensive colocalization and knockdown screenings, we identified the Rab GTPases mediating podocalyxin transcytosis and showed that different sets of Rabs coordinate its transport during cell polarization in 2D and 3D structures. Moreover, we demonstrated that different Rab35 effectors regulate podocalyxin trafficking in 2D and 3D environments; trafficking is mediated by OCRL in 2D monolayers and ACAP2 in 3D cysts. Our results give substantial insight into regulation of the transcytosis of this apical marker and highlight differences between trafficking mechanisms in 2D and 3D cell cultures. PMID:27138252

Membrane Transport across Polarized Epithelia.

PubMed

Garcia-Castillo, Maria Daniela; Chinnapen, Daniel J-F; Lencer, Wayne I

2017-09-01

Polarized epithelial cells line diverse surfaces throughout the body forming selective barriers between the external environment and the internal milieu. To cross these epithelial barriers, large solutes and other cargoes must undergo transcytosis, an endocytic pathway unique to polarized cell types, and significant for the development of cell polarity, uptake of viral and bacterial pathogens, transepithelial signaling, and immunoglobulin transport. Here, we review recent advances in our knowledge of the transcytotic pathway for proteins and lipids. We also discuss briefly the promise of harnessing the molecules that undergo transcytosis as vehicles for clinical applications in drug delivery. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core.

PubMed

Clark, Andrew J; Davis, Mark E

2015-10-06

Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.

Use of LDL receptor-targeting peptide vectors for in vitro and in vivo cargo transport across the blood-brain barrier.

PubMed

Molino, Yves; David, Marion; Varini, Karine; Jabès, Françoise; Gaudin, Nicolas; Fortoul, Aude; Bakloul, Karima; Masse, Maxime; Bernard, Anne; Drobecq, Lucile; Lécorché, Pascaline; Temsamani, Jamal; Jacquot, Guillaume; Khrestchatisky, Michel

2017-05-01

The blood-brain barrier (BBB) prevents the entry of many drugs into the brain and, thus, is a major obstacle in the treatment of CNS diseases. There is some evidence that the LDL receptor (LDLR) is expressed at the BBB and may participate in the transport of endogenous ligands from blood to brain, a process referred to as receptor-mediated transcytosis. We previously described a family of peptide vectors that were developed to target the LDLR. In the present study, in vitro BBB models that were derived from wild-type and LDLR-knockout animals ( ldlr -/- ) were used to validate the specific LDLR-dependent transcytosis of LDL via a nondegradative route. We next showed that LDLR-targeting peptide vectors, whether in fusion or chemically conjugated to an Ab Fc fragment, promote binding to apical LDLR and transendothelial transfer of the Fc fragment across BBB monolayers via the same route as LDL. Finally, we demonstrated in vivo that LDLR significantly contributes to the brain uptake of vectorized Fc. We thus provide further evidence that LDLR is a relevant receptor for CNS drug delivery via receptor-mediated transcytosis and that the peptide vectors we developed have the potential to transport drugs, including proteins or Ab based, across the BBB.-Molino, Y., David, M., Varini, K., Jabès, F., Gaudin, N., Fortoul, A., Bakloul, K., Masse, M., Bernard, A., Drobecq, L., Lécorché, P., Temsamani, J., Jacquot, G., Khrestchatisky, M. Use of LDL receptor-targeting peptide vectors for in vitro and in vivo cargo transport across the blood-brain barrier. © FASEB.

Effect of threonine on secretory immune system using a chicken intestinal ex vivo model with lipopolysaccharide challenge

USDA-ARS?s Scientific Manuscript database

Secretory IgA (sIgA) and its transcytosis receptor, polymeric immunoglobulin receptor (pIgR), along with mucus, form the first lines of intestinal defense. Threonine (Thr) is a major constituent component of intestinal mucins and IgA, which are highly secreted under lipopolysaccharide (LPS) induced ...

Differentiation of a murine intestinal epithelial cell line (MIE) toward the M cell lineage.

PubMed

Kanaya, Takashi; Miyazawa, Kohtaro; Takakura, Ikuro; Itani, Wataru; Watanabe, Kouichi; Ohwada, Shyuichi; Kitazawa, Haruki; Rose, Michael T; McConochie, Huw R; Okano, Hideyuki; Yamaguchi, Takahiro; Aso, Hisashi

2008-08-01

M cells are a kind of intestinal epithelial cell in the follicle-associated epithelium of Peyer's patches. These cells can transport antigens and microorganisms into underlying lymphoid tissues. Despite the important role of M cells in mucosal immune responses, the origin and mechanisms of differentiation as well as cell death of M cells remain unclear. To clarify the mechanism of M cell differentiation, we established a novel murine intestinal epithelial cell line (MIE) from the C57BL/6 mouse. MIE cells grow rapidly and have a cobblestone morphology, which is a typical feature of intestinal epithelial cells. Additionally, they express cytokeratin, villin, cell-cell junctional proteins, and alkaline phosphatase activity and can form microvilli. Their expression of Musashi-1 antigen indicates that they may be close to intestinal stem cells or transit-amplifying cells. MIE cells are able to differentiate into the M cell lineage following coculture with intestinal lymphocytes, but not with Peyer's patch lymphocytes (PPL). However, PPL costimulated with anti-CD3/CD28 MAbs caused MIE cells to display typical features of M cells, such as transcytosis activity, the disorganization of microvilli, and the expression of M cell markers. This transcytosis activity of MIE cells was not induced by T cells isolated from PPL costimulated with the same MAbs and was reduced by the depletion of the T cell population from PPL. A mixture of T cells treated with MAbs and B cells both from PPL led MIE cells to differentiate into M cells. We report here that MIE cells have the potential ability to differentiate into M cells and that this differentiation required activated T cells and B cells.

Listeria monocytogenes InlP interacts with afadin and facilitates basement membrane crossing.

PubMed

Faralla, Cristina; Bastounis, Effie E; Ortega, Fabian E; Light, Samuel H; Rizzuto, Gabrielle; Nocadello, Salvatorre; Anderson, Wayne F; Robbins, Jennifer R; Theriot, Julie A; Bakardjiev, Anna I

2018-05-30

During pregnancy, the placenta protects the fetus against the maternal immune response, as well as bacterial and viral pathogens. Bacterial pathogens that have evolved specific mechanisms of breaching this barrier, such as Listeria monocytogenes, present a unique opportunity for learning how the placenta carries out its protective function. We previously identified the L. monocytogenes protein Internalin P (InlP) as a secreted virulence factor critical for placental infection. Here, we show that InlP, but not the highly similar L. monocytogenes internalin Lmo2027, binds to human afadin (encoded by AF-6), a protein associated with cell-cell junctions. A crystal structure of InlP reveals several unique features, including an extended leucine-rich repeat (LRR) domain with a distinctive Ca2+-binding site. Despite afadin's involvement in the formation of cell-cell junctions, MDCK epithelial cells expressing InlP displayed a decrease in the magnitude of the traction stresses they could exert on deformable substrates, similar to the decrease in traction exhibited by AF-6 knock-out MDCK cells. L. monocytogenes ΔinlP mutants were deficient in their ability to form actin-rich protrusions from the basal face of polarized epithelial monolayers, a necessary step in the crossing of such monolayers (transcytosis). A similar phenotype was observed for bacteria expressing an internal in-frame deletion in inlP (inlP ΔLRR5) that specifically disrupts its interaction with afadin. However, afadin deletion in the host cells did not rescue the transcytosis defect. We conclude that secreted InlP targets cytosolic afadin to specifically promote L. monocytogenes transcytosis across the basal face of epithelial monolayers, which may contribute to the crossing of the basement membrane during placental infection.

Brain uptake of multivalent and multi-specific DVD-Ig proteins after systemic administration.

PubMed

Karaoglu Hanzatian, Denise; Schwartz, Annette; Gizatullin, Farid; Erickson, Jamie; Deng, Kangwen; Villanueva, Ruth; Stedman, Christopher; Harris, Cristina; Ghayur, Tariq; Goodearl, Andrew

2018-05-17

Therapeutic monoclonal antibodies and endogenous IgG antibodies show limited uptake into the central nervous system (CNS) due to the blood-brain barrier (BBB), which regulates and controls the selective and specific transport of both exogenous and endogenous materials to the brain. The use of natural transport mechanisms, such as receptor-mediated transcytosis (RMT), to deliver antibody therapeutics into the brain have been studied in rodents and monkeys. Recent successful examples include monovalent bispecific antibodies and mono- or bivalent fusion proteins; however, these formats do not have the capability to bind to both the CNS target and the BBB transport receptor in a bivalent fashion as a canonical antibody would. Dual-variable-domain immunoglobulin (DVD-Ig) proteins offer a bispecific format where monoclonal antibody-like bivalency to both the BBB receptor and the therapeutic target is preserved, enabling independent engineering of binding affinity, potency, valency, epitope and conformation, essential for successful generation of clinical candidates for CNS applications with desired drug-like properties. Each of these parameters can affect the binding and transcytosis ability mediated by different receptors on the brain endothelium differentially, allowing exploration of diverse properties. Here, we describe generation and characterization of several different DVD-Ig proteins, specific for four different CNS targets, capable of crossing the BBB through transcytosis mediated by the transferrin receptor 1 (TfR1). After systemic administration of each DVD-Ig, we used two independent methods in parallel to observe specific uptake into the brain. An electrochemiluminescent-based sensitive quantitative assay and a semi-quantitative immunohistochemistry technique were used for brain concentration determination and biodistribution/localization in brain, respectively. Significantly enhanced brain uptake and retention was observed for all TfR1 DVD-Ig proteins

Transcellular transport of cobalamin in aortic endothelial cells.

PubMed

Hannibal, Luciana; Bolisetty, Keerthana; Axhemi, Armend; DiBello, Patricia M; Quadros, Edward V; Fedosov, Sergey; Jacobsen, Donald W

2018-05-09

Cobalamin [Cbl (or B 12 )] deficiency causes megaloblastic anemia and a variety of neuropathies. However, homeostatic mechanisms of cyanocobalamin (CNCbl) and other Cbls by vascular endothelial cells are poorly understood. Herein, we describe our investigation into whether cultured bovine aortic endothelial cells (BAECs) perform transcytosis of B 12 , namely, the complex formed between serum transcobalamin and B 12 , designated as holo-transcobalamin (holo-TC). We show that cultured BAECs endocytose [ 57 Co]-CNCbl-TC (source material) via the CD320 receptor. The bound Cbl is transported across the cell both via exocytosis in its free form, [ 57 Co]-CNCbl, and via transcytosis as [ 57 Co]-CNCbl-TC. Transcellular mobilization of Cbl occurred in a bidirectional manner. A portion of the endocytosed [ 57 Co]-CNCbl was enzymatically processed by methylmalonic aciduria combined with homocystinuria type C (cblC) with subsequent formation of hydroxocobalamin, methylcobalamin, and adenosylcobalamin, which were also transported across the cell in a bidirectional manner. This demonstrates that transport mechanisms for Cbl in vascular endothelial cells do not discriminate between various β-axial ligands of the vitamin. Competition studies with apoprotein- and holo-TC and holo-intrinsic factor showed that only holo-TC was effective at inhibiting transcellular transport of Cbl. Incubation of BAECs with a blocking antibody against the extracellular domain of the CD320 receptor inhibited uptake and transcytosis by ∼40%. This study reveals that endothelial cells recycle uncommitted intracellular Cbl for downstream usage by other cell types and suggests that the endothelium is self-sufficient for the specific acquisition and subsequent distribution of circulating B 12 via the CD320 receptor. We posit that the endothelial lining of the vasculature is an essential component for the maintenance of serum-tissue homeostasis of B 12 .-Hannibal, L., Bolisetty, K., Axhemi, A., DiBello, P

The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA.

PubMed Central

Kaetzel, C S; Robinson, J K; Chintalacharuvu, K R; Vaerman, J P; Lamm, M E

1991-01-01

The polymeric immunoglobulin receptor (pIgR) on mucosal epithelial cells binds dimeric IgA (dIgA) on the basolateral surface and mediates transport of dIgA to the apical surface. Using Madin-Darby canine kidney epithelial cells stably transfected with pIgR cDNA, we found that soluble immune complexes (ICs) of 125I-labeled rat monoclonal antidinitrophenyl (DNP) dIgA (125I-dIgA) and DNP/biotin-bovine serum albumin were transported from the basolateral to the apical surface and then released. Monomeric IgA ICs were not transported, consistent with the specificity of pIgR for polymeric immunoglobulins. Essentially all the 125I-dIgA in apical culture supernatants was streptavidin precipitable, indicating that dIgA remained bound to antigen during transcytosis. While both dIgA and dIgA ICs bound pIgR with equal affinity (Kd approximately 8 nM), the number of high-affinity binding sites per cell was 2- to 3-fold greater for dIgA than for dIgA ICs. The extent of endocytosis of dIgA and dIgA ICs was correlated with the number of high-affinity binding sites. SDS/PAGE analysis of intracellular dIgA and dIgA ICs demonstrated that in both cases IgA remained undegraded during transport. The results suggest that the pathways of epithelial transcytosis of free dIgA and dIgA ICs are the same. Given the high population density of mucosal IgA plasma cells and the enormous surface area of pIgR-expressing mucosal epithelium, it is likely that significant local transcytosis of IgA ICs occurs in vivo. Such a process would allow direct elimination of IgA ICs at the mucosal sites where they are likely to form, thus providing an important defense function for IgA. Images PMID:1924341

Clathrin and AP1 are required for apical sorting of glycosyl phosphatidyl inositol-anchored proteins in biosynthetic and recycling routes in Madin-Darby canine kidney cells.

PubMed

Castillon, Guillaume A; Burriat-Couleru, Patricia; Abegg, Daniel; Criado Santos, Nina; Watanabe, Reika

2018-03-01

Recently, studies in animal models demonstrate potential roles for clathrin and AP1 in apical protein sorting in epithelial tissue. However, the precise functions of these proteins in apical protein transport remain unclear. Here, we reveal mistargeting of endogenous glycosyl phosphatidyl inositol-anchored proteins (GPI-APs) and soluble secretory proteins in Madin-Darby canine kidney (MDCK) cells upon clathrin heavy chain or AP1 subunit knockdown (KD). Using a novel directional endocytosis and recycling assay, we found that these KD cells are not only affected for apical sorting of GPI-APs in biosynthetic pathway but also for their apical recycling and basal-to-apical transcytosis routes. The apical distribution of the t-SNARE syntaxin 3, which is known to be responsible for selective targeting of various apical-destined cargo proteins in both biosynthetic and endocytic routes, is compromised suggesting a molecular explanation for the phenotype in KD cells. Our results demonstrate the importance of biosynthetic and endocytic routes for establishment and maintenance of apical localization of GPI-APs in polarized MDCK cells. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma.

PubMed

Johnsen, Kasper Bendix; Burkhart, Annette; Melander, Fredrik; Kempen, Paul Joseph; Vejlebo, Jonas Bruun; Siupka, Piotr; Nielsen, Morten Schallburg; Andresen, Thomas Lars; Moos, Torben

2017-09-04

Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibility of delivering neuroactive drugs by way of receptors already present on the brain endothelium has been of interest for many years. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does not correlate with increased cargo transcytosis. Furthermore, we show that the transferrin receptor-targeted immunoliposomes accumulate along the microvessels of the brains of rats, but find no evidence for transcytosis of the immunoliposome. Conversely, the increased accumulation correlated both with increased cargo uptake in the brain endothelium and subsequent cargo transport into the brain. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain.

Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung.

PubMed

Oh, Phil; Borgström, Per; Witkiewicz, Halina; Li, Yan; Borgström, Bengt J; Chrastina, Adrian; Iwata, Koji; Zinn, Kurt R; Baldwin, Richard; Testa, Jacqueline E; Schnitzer, Jan E

2007-03-01

How effectively and quickly endothelial caveolae can transcytose in vivo is unknown, yet critical for understanding their function and potential clinical utility. Here we use quantitative proteomics to identify aminopeptidase P (APP) concentrated in caveolae of lung endothelium. Electron microscopy confirms this and shows that APP antibody targets nanoparticles to caveolae. Dynamic intravital fluorescence microscopy reveals that targeted caveolae operate effectively as pumps, moving antibody within seconds from blood across endothelium into lung tissue, even against a concentration gradient. This active transcytosis requires normal caveolin-1 expression. Whole body gamma-scintigraphic imaging shows rapid, specific delivery into lung well beyond that achieved by standard vascular targeting. This caveolar trafficking in vivo may underscore a key physiological mechanism for selective transvascular exchange and may provide an enhanced delivery system for imaging agents, drugs, gene-therapy vectors and nanomedicines. 'In vivo proteomic imaging' as described here integrates organellar proteomics with multiple imaging techniques to identify an accessible target space that includes the transvascular pumping space of the caveola.

Rab17 Regulates Membrane Trafficking through Apical Recycling Endosomes in Polarized Epithelial Cells

PubMed Central

Zacchi, Paola; Stenmark, Harald; Parton, Robert G.; Orioli, Donata; Lim, Filip; Giner, Angelika; Mellman, Ira; Zerial, Marino; Murphy, Carol

1998-01-01

A key feature of polarized epithelial cells is the ability to maintain the specific biochemical composition of the apical and basolateral plasma membrane domains while selectively allowing transport of proteins and lipids from one pole to the opposite by transcytosis. The small GTPase, rab17, a member of the rab family of regulators of intracellular transport, is specifically induced during cell polarization in the developing kidney. We here examined its intracellular distribution and function in both nonpolarized and polarized cells. By confocal immunofluorescence microscopy, rab17 colocalized with internalized transferrin in the perinuclear recycling endosome of BHK-21 cells. In polarized Eph4 cells, rab17 associated with the apical recycling endosome that has been implicated in recycling and transcytosis. The localization of rab17, therefore, strengthens the proposed homology between this compartment and the recycling endosome of nonpolarized cells. Basolateral to apical transport of two membrane-bound markers, the transferrin receptor and the FcLR 5-27 chimeric receptor, was specifically increased in Eph4 cells expressing rab17 mutants defective in either GTP binding or hydrolysis. Furthermore, the mutant proteins stimulated apical recycling of FcLR 5-27. These results support a role for rab17 in regulating traffic through the apical recycling endosome, suggesting a function in polarized sorting in epithelial cells. PMID:9490718

Impaired angiopoietin/Tie2 signaling compromises Schlemm’s canal integrity and induces glaucoma

PubMed Central

Kim, Jaeryung; Park, Dae-Young; Park, Do Young; Kim, Dongkyu; Lee, Choong-kun; Song, Sukhyun; Chung, Tae-Young; Lim, Dong Hui; Hong, Young-Kwon; Augustin, Hellmut G.

2017-01-01

Primary open-angle glaucoma (POAG) is often caused by elevated intraocular pressure (IOP), which arises due to increased resistance to aqueous humor outflow (AHO). Aqueous humor flows through Schlemm’s canal (SC), a lymphatic-like vessel encircling the cornea, and via intercellular spaces of ciliary muscle cells. However, the mechanisms underlying increased AHO resistance are poorly understood. Here, we demonstrate that signaling between angiopoietin (Angpt) and the Angpt receptor Tie2, which is critical for SC formation, is also indispensable for maintaining SC integrity during adulthood. Deletion of Angpt1/Angpt2 or Tie2 in adult mice severely impaired SC integrity and transcytosis, leading to elevated IOP, retinal neuron damage, and impairment of retinal ganglion cell function, all hallmarks of POAG in humans. We found that SC integrity is maintained by interconnected and coordinated functions of Angpt-Tie2 signaling, AHO, and Prox1 activity. These functions diminish in the SC during aging, leading to impaired integrity and transcytosis. Intriguingly, Tie2 reactivation using a Tie2 agonistic antibody rescued the POAG phenotype in Angpt1/Angpt2-deficient mice and rejuvenated the SC in aged mice. These results indicate that the Angpt-Tie2 system is essential for SC integrity. The impairment of this system underlies POAG-associated pathogenesis, supporting the possibility that Tie2 agonists could be a therapeutic option for glaucoma. PMID:28920924

Receptor-mediated transcytosis of cyclophilin B through the blood-brain barrier.

PubMed

Carpentier, M; Descamps, L; Allain, F; Denys, A; Durieux, S; Fenart, L; Kieda, C; Cecchelli, R; Spik, G

1999-07-01

Cyclophilin B (CyPB) is a cyclosporin A (CsA)-binding protein mainly located in intracellular vesicles and secreted in biological fluids. In previous works, we demonstrated that CyPB interacts with T lymphocytes and enhances in vitro cellular incorporation and activity of CsA. In addition to its immunosuppressive activity, CsA is able to promote regeneration of damaged peripheral nerves. However, the crossing of the drug from plasma to neural tissue is restricted by the relative impermeability of the blood-brain barrier. To know whether CyPB might also participate in the delivery of CsA into the brain, we have analyzed the interactions of CyPB with brain capillary endothelial cells. First, we demonstrated that CyPB binds to two types of binding sites present at the surface of capillary endothelial cells from various species of tissues. The first type of binding sites (K(D) = 300 nM; number of sites = 3 x 10(6)) is related to interactions with negatively charged compounds such as proteoglycans. The second type of binding sites, approximately 50,000 per cell, exhibits a higher affinity for CyPB (K(D) = 15 nM) and is involved in an endocytosis process, indicating it might correspond to a functional receptor. Finally, the use of an in vitro model of blood-brain barrier allowed us to demonstrate that CyPB is transcytosed by a receptor-mediated pathway (flux = 16.5 fmol/cm2/h). In these conditions, CyPB did not significantly modify the passage of CsA, indicating that it is unlikely to provide a pathway for CsA brain delivery.

Cross-talk between adipose and gastric leptins for the control of food intake and energy metabolism.

PubMed

Cammisotto, Philippe G; Levy, Emile; Bukowiecki, Ludwik J; Bendayan, Moise

2010-09-01

The understanding of the regulation of food intake has become increasingly complex. More than 20 hormones, both orexigenic and anorexigenic, have been identified. After crossing the blood-brain barrier, they reach their main site of action located in several hypothalamic areas and interact to balance satiety and hunger. One of the most significant advances in this matter has been the discovery of leptin. This hormone plays fundamental roles in the control of appetite and in regulating energy expenditure. In accordance with the lipostatic theory stated by Kennedy in 1953, leptin was originally discovered in white adipose tissue. Its expression by other tissues was later established. Among them, the gastric mucosa has been shown to secrete large amounts of leptin. Both the adipose and the gastric tissues share similar characteristics in the synthesis and storage of leptin in granules, in the formation of a complex with the soluble receptor and a secretion modulated by hormones and energy substrates. However while adipose tissue secretes leptin in a slow constitutive endocrine way, the gastric mucosa releases leptin in a rapid regulated exocrine fashion into the gastric juice. Exocrine-secreted leptin survives the extreme hydrolytic conditions of the gastric juice and reach the duodenal lumen in an intact active form. Scrutiny into transport mechanisms revealed that a significant amount of the exocrine leptin crosses the intestinal wall by active transcytosis. Leptin receptors, expressed on the luminal and basal membrane of intestinal epithelial cells, are involved in the control of nutrient absorption by enterocytes, mucus secretion by goblet cells and motility, among other processes, and this control is indeed different depending upon luminal or basal stimulus. Gastric leptin after transcytosis reaches the central nervous system, to control food intake. Studies using the Caco-2, the human intestinal cell line, in vitro allowed analysis of the mechanisms of leptin

Mechanism of increased clearance of glycated albumin by proximal tubule cells

PubMed Central

Wagner, Mark C.; Myslinski, Jered; Pratap, Shiv; Flores, Brittany; Rhodes, George; Campos-Bilderback, Silvia B.; Sandoval, Ruben M.; Kumar, Sudhanshu; Patel, Monika; Ashish

2016-01-01

Serum albumin is the most abundant plasma protein and has a long half-life due to neonatal Fc receptor (FcRn)-mediated transcytosis by many cell types, including proximal tubule cells of the kidney. Albumin also interacts with, and is modified by, many small and large molecules. Therefore, the focus of the present study was to address the impact of specific known biological albumin modifications on albumin-FcRn binding and cellular handling. Binding at pH 6.0 and 7.4 was performed since FcRn binds albumin strongly at acidic pH and releases it after transcytosis at physiological pH. Equilibrium dissociation constants were measured using microscale thermophoresis. Since studies have shown that glycated albumin is excreted in the urine at a higher rate than unmodified albumin, we studied glucose and methylgloxal modified albumins (21 days). All had reduced affinity to FcRn at pH 6.0, suggesting these albumins would not be returned to the circulation via the transcytotic pathway. To address why modified albumin has reduced affinity, we analyzed the structure of the modified albumins using small-angle X-ray scattering. This analysis showed significant structural changes occurring to albumin with glycation, particularly in the FcRn-binding region, which could explain the reduced affinity to FcRn. These results offer an explanation for enhanced proximal tubule-mediated sorting and clearance of abnormal albumins. PMID:26887834

Identification of collagenase as a critical virulence factor for invasiveness and transmission of pathogenic Leptospira species.

PubMed

Kassegne, Kokouvi; Hu, Weilin; Ojcius, David M; Sun, Dexter; Ge, Yumei; Zhao, Jinfang; Yang, X Frank; Li, Lanjuan; Yan, Jie

2014-04-01

 Leptospirosis is a global zoonotic disease. Transmission of Leptospira from animals to humans occurs through contact with water contaminated with leptospire-containing urine of infected animals. However, the molecular basis for the invasiveness of Leptospira and transmission of leptospirosis remains unknown.  Activity of Leptospira interrogans strain Lai colA gene product (ColA) to hydrolyze different collagenic substrates was determined by spectrophotometry. Expression and secretion of ColA during infection were detected by reverse-transcription quantitative polymerase chain reaction and Western blot assay. The colA gene-deleted (ΔcolA) and colA gene-complemented (CΔcolA) mutants were generated to determine the roles of ColA in transcytosis in vitro and virulence in hamsters.  Recombinant or native ColA hydrolyzed all the tested substrates in which type III collagen was the favorite substrate with 2.16 mg/mL Km and 35.6 h(-)(1) Kcat values. Coincubation of the spirochete with HUVEC or HEK293 cells directly caused the significant elevation of ColA expression and secretion. Compared with wild-type strain, ΔcolA mutant displayed much-attenuated transcytosis through HEK293 and HUVEC monolayers, and less leptospires in blood, lung, liver, kidney and urine and 25-fold-decreased 50% lethal dose and milder histopathological injury in hamsters.  The product of colA gene is a collagenase as a crucial virulence factor in the invasiveness and transmission of L. interrogans.

Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection.

PubMed

Real, Fernando; Sennepin, Alexis; Ganor, Yonatan; Schmitt, Alain; Bomsel, Morgane

2018-05-08

During sexual intercourse, HIV-1 crosses epithelial barriers composing the genital mucosa, a poorly understood feature that requires an HIV-1-infected cell vectoring efficient mucosal HIV-1 entry. Therefore, urethral mucosa comprising a polarized epithelium and a stroma composed of fibroblasts and macrophages were reconstructed in vitro. Using this system, we demonstrate by live imaging that efficient HIV-1 transmission to stromal macrophages depends on cell-mediated transfer of the virus through virological synapses formed between HIV-1-infected CD4 + T cells and the epithelial cell mucosal surface. We visualized HIV-1 translocation through mucosal epithelial cells via transcytosis in regions where virological synapses occurred. In turn, interleukin-13 is secreted and HIV-1 targets macrophages, which develop a latent state of infection reversed by lipopolysaccharide (LPS) activation. The live observation of virological synapse formation reported herein is key in the design of vaccines and antiretroviral therapies aimed at blocking HIV-1 access to cellular reservoirs in genital mucosa. Copyright © 2018. Published by Elsevier Inc.

Cellular interactions of a lipid-based nanocarrier model with human keratinocytes: Unravelling transport mechanisms.

PubMed

Silva, Elisabete; Barreiros, Luísa; Segundo, Marcela A; Costa Lima, Sofia A; Reis, Salette

2017-04-15

Knowledge of delivery system transport through epidermal cell monolayer is vital to improve skin permeation and bioavailability. Recently, nanostructured lipid carriers (NLCs) have gained great attention for transdermal delivery due to their biocompatibility, high drug payload, occlusive properties and skin hydration effect. However, the nanocarriers transport related mechanisms in epidermal epithelial cells are not yet understood. In this research, the internalization and transport pathways of the NLCs across the epidermal epithelial cell monolayer (HaCaT cells) were investigated. The 250nm sized witepsol/miglyol NLCs, prepared by hot homogenization had reduced cytotoxicity and no effect on the integrity of cell membrane in human HaCaT keratinocytes. The internalization was time-, concentration- and energy-dependent, and the uptake of NLCs was a vesicle-mediated process by macropinocytosis and clathrin-mediated pathways. 3% of NLCs were found at the apical membrane side of the HaCaT monolayer through exocytosis mechanism. Additionally, the endoplasmic reticulum, Golgi apparatus and microtubules played crucial roles in the transport of NLCs out of HaCaT cells. NLCs were transported intact across the human keratinocytes monolayer, without disturbing the tight junction's structure. From the transcytosis data only approximately 12% of the internalized NLCs were passed from the apical to the basolateral side. The transcytosis of NLCs throughout the HaCaT cell monolayer towards the basolateral membrane side requires the involvement of the endoplasmic reticulum, Golgi apparatus and microtubules. Our findings may contribute to a systematic understanding of NLCs transport across epidermal epithelial cell monolayers and their optimization for clinical transdermal application. Transdermal drug delivery is a challenging and growing area of clinical application. Lipid nanoparticles such as nanostructured lipid carriers (NLCs) have gained wide interest for transdermal drug

BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.

PubMed

Crispino, Giulia; Di Pasquale, Giovanni; Scimemi, Pietro; Rodriguez, Laura; Galindo Ramirez, Fabian; De Siati, Romolo Daniele; Santarelli, Rosa Maria; Arslan, Edoardo; Bortolozzi, Mario; Chiorini, John A; Mammano, Fabio

2011-01-01

The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26(Sox10Cre) mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10-Cre line. Cx26(Sox10Cre) mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26(Sox10Cre) mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans.

Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier

PubMed Central

Strazielle, Nathalie; Ghersi-Egea, Jean-François

2016-01-01

The blood-brain interfaces restrict the cerebral bioavailability of pharmacological compounds. Various drug delivery strategies have been developed to improve drug penetration into the brain. Most strategies target the microvascular endothelium forming the blood-brain barrier proper. Targeting the blood-cerebrospinal fluid (CSF) barrier formed by the epithelium of the choroid plexuses in addition to the blood-brain barrier may offer added-value for the treatment of central nervous system diseases. For instance, targeting the CSF spaces, adjacent tissue, or the choroid plexuses themselves is of interest for the treatment of neuroinflammatory and infectious diseases, cerebral amyloid angiopathy, selected brain tumors, hydrocephalus or neurohumoral dysregulation. Selected CSF-borne materials seem to reach deep cerebral structures by mechanisms that need to be understood in the context of chronic CSF delivery. Drug delivery through both barriers can reduce CSF sink action towards parenchymal drugs. Finally, targeting the choroid plexus-CSF system can be especially relevant in the context of neonatal and pediatric diseases of the central nervous system. Transcytosis appears the most promising mechanism to target in order to improve drug delivery through brain barriers. The choroid plexus epithelium displays strong vesicular trafficking and secretory activities that deserve to be explored in the context of cerebral drug delivery. Folate transport and exosome release into the CSF, plasma protein transport, and various receptor-mediated endocytosis pathways may prove useful mechanisms to exploit for efficient drug delivery into the CSF. This calls for a clear evaluation of transcytosis mechanisms at the blood-CSF barrier, and a thorough evaluation of CSF drug delivery rates. PMID:27464721

Formation of the long range Dpp morphogen gradient.

PubMed

Schwank, Gerald; Dalessi, Sascha; Yang, Schu-Fee; Yagi, Ryohei; de Lachapelle, Aitana Morton; Affolter, Markus; Bergmann, Sven; Basler, Konrad

2011-07-01

The TGF-β homolog Decapentaplegic (Dpp) acts as a secreted morphogen in the Drosophila wing disc, and spreads through the target tissue in order to form a long range concentration gradient. Despite extensive studies, the mechanism by which the Dpp gradient is formed remains controversial. Two opposing mechanisms have been proposed: receptor-mediated transcytosis (RMT) and restricted extracellular diffusion (RED). In these scenarios the receptor for Dpp plays different roles. In the RMT model it is essential for endocytosis, re-secretion, and thus transport of Dpp, whereas in the RED model it merely modulates Dpp distribution by binding it at the cell surface for internalization and subsequent degradation. Here we analyzed the effect of receptor mutant clones on the Dpp profile in quantitative mathematical models representing transport by either RMT or RED. We then, using novel genetic tools, experimentally monitored the actual Dpp gradient in wing discs containing receptor gain-of-function and loss-of-function clones. Gain-of-function clones reveal that Dpp binds in vivo strongly to the type I receptor Thick veins, but not to the type II receptor Punt. Importantly, results with the loss-of-function clones then refute the RMT model for Dpp gradient formation, while supporting the RED model in which the majority of Dpp is not bound to Thick veins. Together our results show that receptor-mediated transcytosis cannot account for Dpp gradient formation, and support restricted extracellular diffusion as the main mechanism for Dpp dispersal. The properties of this mechanism, in which only a minority of Dpp is receptor-bound, may facilitate long-range distribution.

VPS9a Activates the Rab5 GTPase ARA7 to Confer Distinct Pre- and Postinvasive Plant Innate Immunity[OPEN

PubMed Central

2017-01-01

Plant innate immunity can effectively prevent the proliferation of filamentous pathogens. Papilla formation at the site of attack is essential for preinvasive immunity; in postinvasive immunity, the encasement of pathogen structures inside host cells can hamper disease. Whereas papillae are highly dependent on transcytosis of premade material, little is known about encasement formation. Here, we show that endosome-associated VPS9a, the conserved guanine-nucleotide exchange factor activating Rab5 GTPases, is required for both pre- and postinvasive immunity against a nonadapted powdery mildew fungus (Blumeria graminis f. sp hordei) in Arabidopsis thaliana. Surprisingly, VPS9a acts in addition to two previously well-described innate immunity components and thus represents an additional step in the regulation of how plants resist pathogens. We found VPS9a to be important for delivering membrane material to the encasement and VPS9a also plays a predominant role in postinvasive immunity. GTP-bound Rab5 GTPases accumulate in the encasement, but not the papillae, suggesting that two independent pathways form these defense structures. VPS9a also mediates defense to an adapted powdery mildew fungus, thus regulating a durable type of defense that works in both host and nonhost resistance. We propose that VPS9a plays a conserved role in organizing cellular endomembrane trafficking, required for delivery of defense components in response to powdery mildew fungi. PMID:28808134

Transport Study of Egg-Derived Antihypertensive Peptides (LKP and IQW) Using Caco-2 and HT29 Coculture Monolayers.

PubMed

Xu, Qingbiao; Fan, Hongbing; Yu, Wenlin; Hong, Hui; Wu, Jianping

2017-08-30

The objective of this study was to investigate the mechanisms of the transport of antihypertensive tripeptides LKP (Leu-Lys-Pro) and IQW (Ile-Gln-Trp) derived from egg white using a coculture system of Caco-2 and HT29 cell monolayers. The results revealed that LKP and IQW have no cytotoxicity to the cell viability after 2 h incubation, could be transported intact across coculture monolayers (apparent permeability coefficient: (18.11 ± 1.57) × 10 -8 and (13.21 ± 1.12) × 10 -8 cm/s, respectively), and were resistant to peptidase secreted by enterocytes. In addition, the transports were significantly inhibited by dipeptide Gly-Pro (P < 0.05), a competitive substance of peptide transporter 1 (PepT1). The transports from apical to basolateral side were significantly higher than that of the reverse direction (P < 0.05). These results suggest that PepT1 is involved in LKP and IQW transports. The transports were also significantly decreased by theaflavin-3'-O-gallate (P < 0.05), an enhancer of tight junction (TJ) and increased by cytochalasin D (P < 0.05), a disruptor of TJ but not influenced by wortamanin, a transcytosis inhibitor, suggesting that passive paracellular route via TJs is also involved in LKP and IQW transports but not transcytosis. In addition, siRNA was also used to knockdown the expression of PepT1 and significantly inhibited the transport (P < 0.05), confirming that PepT1 is involved in transport process. Therefore, both passive paracellular route via TJ and active route via PepT1 coexist in the transport of antihypertensive LKP and IQW across Caco-2/HT29 coculture monolayers.

Minimal Effects of VEGF and Anti-VEGF Drugs on the Permeability or Selectivity of RPE Tight Junctions

PubMed Central

Peng, Shaomin; Adelman, Ron A.

2010-01-01

Purpose. Bevacizumab and ranibizumab are currently used to treat age-related macular degeneration by neutralizing vascular endothelial growth factor (VEGF). In this study, the potential side effects on the outer blood–retinal barrier were examined. Methods. Human fetal RPE (hfRPE) cells were used because they are highly differentiated in culture. The claudin composition of RPE tight junctions was determined by RT-PCR, immunoblot analysis, and immunofluorescence. ELISA assays monitored the secretion and trafficking of VEGF and a fluid-phase marker, methylpolyethylene glycol (mPEG). Tight junction functions were assessed by the conductance of K+ and Na+ (derived from the transepithelial electrical resistance, TER) and the flux of NaCl and mPEG. Results. Claudin-3, claudin-10, and claudin-19 were detected in RPE tight junctions. VEGF was secreted in equal amounts across the apical and basolateral membranes, but the apical membrane was more active in endocytosing and degrading VEGF. Exogenous VEGF and mPEG crossed the RPE monolayer by transcytosis, predominantly in the apical-to-basal direction. RPE tight junctions were selective for K+, but did not discriminate between Na+ and Cl−. VEGF, bevacizumab, and ranibizumab had minimal effects on TER, permeation of mPEG, and selectivity for K+, Na+, and Cl−. They had minimal effects on the expression and distribution of the claudins. Conclusions. RPE has mechanisms for maintaining low concentrations of VEGF in the subretinal space that include endocytosis and degradation and fluid-phase transcytosis in the apical-to-basal direction. RPE tight junctions are selective for K+ over Na+ and Cl−. Permeability and selectivity of the junctions are not affected by VEGF, bevacizumab, or ranibizumab. PMID:20042644

Assessing Requirements Quality through Requirements Coverage

NASA Technical Reports Server (NTRS)

Rajan, Ajitha; Heimdahl, Mats; Woodham, Kurt

2008-01-01

In model-based development, the development effort is centered around a formal description of the proposed software system the model. This model is derived from some high-level requirements describing the expected behavior of the software. For validation and verification purposes, this model can then be subjected to various types of analysis, for example, completeness and consistency analysis [6], model checking [3], theorem proving [1], and test-case generation [4, 7]. This development paradigm is making rapid inroads in certain industries, e.g., automotive, avionics, space applications, and medical technology. This shift towards model-based development naturally leads to changes in the verification and validation (V&V) process. The model validation problem determining that the model accurately captures the customer's high-level requirements has received little attention and the sufficiency of the validation activities has been largely determined through ad-hoc methods. Since the model serves as the central artifact, its correctness with respect to the users needs is absolutely crucial. In our investigation, we attempt to answer the following two questions with respect to validation (1) Are the requirements sufficiently defined for the system? and (2) How well does the model implement the behaviors specified by the requirements? The second question can be addressed using formal verification. Nevertheless, the size and complexity of many industrial systems make formal verification infeasible even if we have a formal model and formalized requirements. Thus, presently, there is no objective way of answering these two questions. To this end, we propose an approach based on testing that, when given a set of formal requirements, explores the relationship between requirements-based structural test-adequacy coverage and model-based structural test-adequacy coverage. The proposed technique uses requirements coverage metrics defined in [9] on formal high-level software

The method to divide a sentence of requirement into individual requirements and the development of requirement specification editor which can describe individual requirements.

PubMed

Sato, Kuniya; Ooba, Masahiro; Takagi, Tomohiko; Furukawa, Zengo; Komiya, Seiichi; Yaegashi, Rihito

2013-12-01

Agile software development gains requirements from the direct discussion with customers and the development staff each time, and the customers evaluate the appropriateness of the requirement. If the customers divide the complicated requirement into individual requirements, the engineer who is in charge of software development can understand it easily. This is called division of requirement. However, the customers do not understand how much and how to divide the requirements. This paper proposes the method to divide a complicated requirement into individual requirements. Also, it shows the development of requirement specification editor which can describe individual requirements. The engineer who is in charge of software development can understand requirements easily.

Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer's disease.

PubMed

Agrawal, Mukta; Ajazuddin; Tripathi, Dulal K; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Mourtas, Spyridon; Hammarlund-Udenaes, Margareta; Alexander, Amit

2017-08-28

In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli. This functionally essential structure creates a major hurdle for delivery of any drug into the brain. Still, there are some provisions on BBB which facilitate the entry of useful substances in the brain via specific mechanisms like passive diffusion, receptor-mediated transcytosis, carrier-mediated transcytosis etc. Another important factor for drug transport is the selection of a suitable drug delivery systems like, liposome, which is a novel drug carrier system offering a potential approach to resolving this problem. Its unique phospholipid bilayer structure (similar to physiological membrane) had made it more compatible with the lipoidal layer of BBB and helps the drug to enter the brain. The present review work focused on various surface modifications with functional ligand (like lactoferrin, transferrin etc.) and carrier molecules (such as glutathione, glucose etc.) on the liposomal structure to enhance its brain targeting ability towards the successful treatment of Alzheimer disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficient clearance of Aβ protofibrils in AβPP-transgenic mice treated with a brain-penetrating bifunctional antibody.

PubMed

Syvänen, Stina; Hultqvist, Greta; Gustavsson, Tobias; Gumucio, Astrid; Laudon, Hanna; Söderberg, Linda; Ingelsson, Martin; Lannfelt, Lars; Sehlin, Dag

2018-05-24

Amyloid-β (Aβ) immunotherapy is one of the most promising disease-modifying strategies for Alzheimer's disease (AD). Despite recent progress targeting aggregated forms of Aβ, low antibody brain penetrance remains a challenge. In the present study, we used transferrin receptor (TfR)-mediated transcytosis to facilitate brain uptake of our previously developed Aβ protofibril-selective mAb158, with the aim of increasing the efficacy of immunotherapy directed toward soluble Aβ protofibrils. Aβ protein precursor (AβPP)-transgenic mice (tg-ArcSwe) were given a single dose of mAb158, modified for TfR-mediated transcytosis (RmAb158-scFv8D3), in comparison with an equimolar dose or a tenfold higher dose of unmodified recombinant mAb158 (RmAb158). Soluble Aβ protofibrils and total Aβ in the brain were measured by enzyme-linked immunosorbent assay (ELISA). Brain distribution of radiolabeled antibodies was visualized by positron emission tomography (PET) and ex vivo autoradiography. ELISA analysis of Tris-buffered saline brain extracts demonstrated a 40% reduction of soluble Aβ protofibrils in both RmAb158-scFv8D3- and high-dose RmAb158-treated mice, whereas there was no Aβ protofibril reduction in mice treated with a low dose of RmAb158. Further, ex vivo autoradiography and PET imaging revealed different brain distribution patterns of RmAb158-scFv8D3 and RmAb158, suggesting that these antibodies may affect Aβ levels by different mechanisms. With a combination of biochemical and imaging analyses, this study demonstrates that antibodies engineered to be transported across the blood-brain barrier can be used to increase the efficacy of Aβ immunotherapy. This strategy may allow for decreased antibody doses and thereby reduced side effects and treatment costs.

The Functions of Auxilin and Rab11 in Drosophila Suggest That the Fundamental Role of Ligand Endocytosis in Notch Signaling Cells Is Not Recycling

PubMed Central

Bilder, David; Fischer, Janice A.

2011-01-01

Notch signaling requires ligand internalization by the signal sending cells. Two endocytic proteins, epsin and auxilin, are essential for ligand internalization and signaling. Epsin promotes clathrin-coated vesicle formation, and auxilin uncoats clathrin from newly internalized vesicles. Two hypotheses have been advanced to explain the requirement for ligand endocytosis. One idea is that after ligand/receptor binding, ligand endocytosis leads to receptor activation by pulling on the receptor, which either exposes a cleavage site on the extracellular domain, or dissociates two receptor subunits. Alternatively, ligand internalization prior to receptor binding, followed by trafficking through an endosomal pathway and recycling to the plasma membrane may enable ligand activation. Activation could mean ligand modification or ligand transcytosis to a membrane environment conducive to signaling. A key piece of evidence supporting the recycling model is the requirement in signaling cells for Rab11, which encodes a GTPase critical for endosomal recycling. Here, we use Drosophila Rab11 and auxilin mutants to test the ligand recycling hypothesis. First, we find that Rab11 is dispensable for several Notch signaling events in the eye disc. Second, we find that Drosophila female germline cells, the one cell type known to signal without clathrin, also do not require auxilin to signal. Third, we find that much of the requirement for auxilin in Notch signaling was bypassed by overexpression of both clathrin heavy chain and epsin. Thus, the main role of auxilin in Notch signaling is not to produce uncoated ligand-containing vesicles, but to maintain the pool of free clathrin. Taken together, these results argue strongly that at least in some cell types, the primary function of Notch ligand endocytosis is not for ligand recycling. PMID:21448287

Morphogen transport

PubMed Central

Müller, Patrick; Rogers, Katherine W.; Yu, Shuizi R.; Brand, Michael; Schier, Alexander F.

2013-01-01

The graded distribution of morphogens underlies many of the tissue patterns that form during development. How morphogens disperse from a localized source and how gradients in the target tissue form has been under debate for decades. Recent imaging studies and biophysical measurements have provided evidence for various morphogen transport models ranging from passive mechanisms, such as free or hindered extracellular diffusion, to cell-based dispersal by transcytosis or cytonemes. Here, we analyze these transport models using the morphogens Nodal, fibroblast growth factor and Decapentaplegic as case studies. We propose that most of the available data support the idea that morphogen gradients form by diffusion that is hindered by tortuosity and binding to extracellular molecules. PMID:23533171

VPS9a Activates the Rab5 GTPase ARA7 to Confer Distinct Pre- and Postinvasive Plant Innate Immunity.

PubMed

Nielsen, Mads E; Jürgens, Gerd; Thordal-Christensen, Hans

2017-08-01

Plant innate immunity can effectively prevent the proliferation of filamentous pathogens. Papilla formation at the site of attack is essential for preinvasive immunity; in postinvasive immunity, the encasement of pathogen structures inside host cells can hamper disease. Whereas papillae are highly dependent on transcytosis of premade material, little is known about encasement formation. Here, we show that endosome-associated VPS9a, the conserved guanine-nucleotide exchange factor activating Rab5 GTPases, is required for both pre- and postinvasive immunity against a nonadapted powdery mildew fungus ( Blumeria graminis f. sp hordei ) in Arabidopsis thaliana Surprisingly, VPS9a acts in addition to two previously well-described innate immunity components and thus represents an additional step in the regulation of how plants resist pathogens. We found VPS9a to be important for delivering membrane material to the encasement and VPS9a also plays a predominant role in postinvasive immunity. GTP-bound Rab5 GTPases accumulate in the encasement, but not the papillae, suggesting that two independent pathways form these defense structures. VPS9a also mediates defense to an adapted powdery mildew fungus, thus regulating a durable type of defense that works in both host and nonhost resistance. We propose that VPS9a plays a conserved role in organizing cellular endomembrane trafficking, required for delivery of defense components in response to powdery mildew fungi. © 2017 American Society of Plant Biologists. All rights reserved.

Dendritic cells in oral tolerance in the gut.

PubMed

Rescigno, Maria

2011-09-01

Oral tolerance is a process that allows generation of systemic unresponsiveness to food antigens. Hence if the same antigen is introduced systemically even under immunogenic conditions it does not induce immune responsiveness. Dendritic cells (DCs) have been identified as essential players in this process. DCs in the gut are located in a strategic position as they can interact directly with luminal antigens or indirectly after their transcytosis across epithelial cells. DCs can then migrate to associated lymphoid tissues to induce tolerance. Antigen presenting cells in the gut are specialized in function and have divided their labour so that there are cells capable to migrate to the draining mesenteric lymph node for induction of T regulatory cells, while other subsets are resident and are required to enforce tolerance locally in the gut after food antigen exposure. In this review, I shall summarize the characteristics of antigen presenting cells in the gut and their involvement in oral tolerance induction. In addition, I will also emphasize that tolerance to food allergens may be contributed by plasmacytoid DCs in the liver that participate to the elimination or anergy of allergen-specific CD8 T cells. Hence specialized functions are associated to different subsets of antigen presenting cells and different organs. © 2011 Blackwell Publishing Ltd.

40 CFR 161.101 - Required vs. conditionally required data.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Required vs. conditionally required data. 161.101 Section 161.101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR REGISTRATION OF ANTIMICROBIAL PESTICIDES How To Use Data Tables...

Discovering system requirements

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

Bahill, A.T.; Bentz, B.; Dean, F.F.

1996-07-01

Cost and schedule overruns are often caused by poor requirements that are produced by people who do not understand the requirements process. This report provides a high-level overview of the system requirements process, explaining types, sources, and characteristics of good requirements. System requirements, however, are seldom stated by the customer. Therefore, this report shows ways to help you work with your customer to discover the system requirements. It also explains terminology commonly used in the requirements development field, such as verification, validation, technical performance measures, and the various design reviews.

The Requirements Generation System: A tool for managing mission requirements

NASA Technical Reports Server (NTRS)

Sheppard, Sylvia B.

1994-01-01

Historically, NASA's cost for developing mission requirements has been a significant part of a mission's budget. Large amounts of time have been allocated in mission schedules for the development and review of requirements by the many groups who are associated with a mission. Additionally, tracing requirements from a current document to a parent document has been time-consuming and costly. The Requirements Generation System (RGS) is a computer-supported cooperative-work tool that assists mission developers in the online creation, review, editing, tracing, and approval of mission requirements as well as in the production of requirements documents. This paper describes the RGS and discusses some lessons learned during its development.

An Investigation of Online Homework: Required or Not Required?

ERIC Educational Resources Information Center

Wooten, Tommy; Dillard-Eggers, Jane

2013-01-01

In our research we investigate the use of online homework in principles of accounting classes where some classes required online homework while other classes did not. Users of online homework, compared to nonusers, had a higher grade point average and earned a higher grade in class. On average, both required and not-required users rated the online…

Capturing Requirements for Autonomous Spacecraft with Autonomy Requirements Engineering

NASA Astrophysics Data System (ADS)

Vassev, Emil; Hinchey, Mike

2014-08-01

The Autonomy Requirements Engineering (ARE) approach has been developed by Lero - the Irish Software Engineering Research Center within the mandate of a joint project with ESA, the European Space Agency. The approach is intended to help engineers develop missions for unmanned exploration, often with limited or no human control. Such robotics space missions rely on the most recent advances in automation and robotic technologies where autonomy and autonomic computing principles drive the design and implementation of unmanned spacecraft [1]. To tackle the integration and promotion of autonomy in software-intensive systems, ARE combines generic autonomy requirements (GAR) with goal-oriented requirements engineering (GORE). Using this approach, software engineers can determine what autonomic features to develop for a particular system (e.g., a space mission) as well as what artifacts that process might generate (e.g., goals models, requirements specification, etc.). The inputs required by this approach are the mission goals and the domain-specific GAR reflecting specifics of the mission class (e.g., interplanetary missions).

10 CFR 76.8 - Information collection requirements: OMB approval not required.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Information collection requirements: OMB approval not required. 76.8 Section 76.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS General Provisions § 76.8 Information collection requirements: OMB approval not required...

10 CFR 76.8 - Information collection requirements: OMB approval not required.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Information collection requirements: OMB approval not required. 76.8 Section 76.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS General Provisions § 76.8 Information collection requirements: OMB approval not required...

10 CFR 76.8 - Information collection requirements: OMB approval not required.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Information collection requirements: OMB approval not required. 76.8 Section 76.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS General Provisions § 76.8 Information collection requirements: OMB approval not required...

10 CFR 76.8 - Information collection requirements: OMB approval not required.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Information collection requirements: OMB approval not required. 76.8 Section 76.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS General Provisions § 76.8 Information collection requirements: OMB approval not required...

10 CFR 76.8 - Information collection requirements: OMB approval not required.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Information collection requirements: OMB approval not required. 76.8 Section 76.8 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS General Provisions § 76.8 Information collection requirements: OMB approval not required...

Flight program language requirements. Volume 2: Requirements and evaluations

NASA Technical Reports Server (NTRS)

1972-01-01

The efforts and results are summarized for a study to establish requirements for a flight programming language for future onboard computer applications. Several different languages were available as potential candidates for future NASA flight programming efforts. The study centered around an evaluation of the four most pertinent existing aerospace languages. Evaluation criteria were established, and selected kernels from the current Saturn 5 and Skylab flight programs were used as benchmark problems for sample coding. An independent review of the language specifications incorporated anticipated future programming requirements into the evaluation. A set of detailed language requirements was synthesized from these activities. The details of program language requirements and of the language evaluations are described.

Managing System of Systems Requirements with a Requirements Screening Group

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

Ronald R. Barden

2012-07-01

Figuring out an effective and efficient way to manage not only your Requirement’s Baseline, but also the development of all your individual requirements during a Program’s/Project’s Conceptual and Development Life Cycle Stages can be both daunting and difficult. This is especially so when you are dealing with a complex and large System of Systems (SoS) Program with potentially thousands and thousands of Top Level Requirements as well as an equal number of lower level System, Subsystem and Configuration Item requirements that need to be managed. This task is made even more overwhelming when you have to add in integration withmore » multiple requirements’ development teams (e.g., Integrated Product Development Teams (IPTs)) and/or numerous System/Subsystem Design Teams. One solution for tackling this difficult activity on a recent large System of Systems Program was to develop and make use of a Requirements Screening Group (RSG). This group is essentially a Team made up of co-chairs from the various Stakeholders with an interest in the Program of record that are enabled and accountable for Requirements Development on the Program/Project. The RSG co-chairs, often with the help of individual support team, work together as a Program Board to monitor, make decisions on, and provide guidance on all Requirements Development activities during the Conceptual and Development Life Cycle Stages of a Program/Project. In addition, the RSG can establish and maintain the Requirements Baseline, monitor and enforce requirements traceability across the entire Program, and work with other elements of the Program/Project to ensure integration and coordination.« less

Environmental Requirements Management

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

Cusack, Laura J.; Bramson, Jeffrey E.; Archuleta, Jose A.

2015-01-08

CH2M HILL Plateau Remediation Company (CH2M HILL) is the U.S. Department of Energy (DOE) prime contractor responsible for the environmental cleanup of the Hanford Site Central Plateau. As part of this responsibility, the CH2M HILL is faced with the task of complying with thousands of environmental requirements which originate from over 200 federal, state, and local laws and regulations, DOE Orders, waste management and effluent discharge permits, Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) response and Resource Conservation and Recovery Act (RCRA) corrective action documents, and official regulatory agency correspondence. The challenge is to manage this vast number ofmore » requirements to ensure they are appropriately and effectively integrated into CH2M HILL operations. Ensuring compliance with a large number of environmental requirements relies on an organization’s ability to identify, evaluate, communicate, and verify those requirements. To ensure that compliance is maintained, all changes need to be tracked. The CH2M HILL identified that the existing system used to manage environmental requirements was difficult to maintain and that improvements should be made to increase functionality. CH2M HILL established an environmental requirements management procedure and tools to assure that all environmental requirements are effectively and efficiently managed. Having a complete and accurate set of environmental requirements applicable to CH2M HILL operations will promote a more efficient approach to: • Communicating requirements • Planning work • Maintaining work controls • Maintaining compliance« less

The modA10 phasevarion of nontypeable Haemophilus influenzae R2866 regulates multiple virulence-associated traits.

PubMed

VanWagoner, Timothy M; Atack, John M; Nelson, Kevin L; Smith, Hannah K; Fox, Kate L; Jennings, Michael P; Stull, Terrence L; Smith, Arnold L

2016-03-01

Non-typeable Haemophilus influenzae (NTHi) is a human restricted commensal and pathogen that elicits inflammation by adhering to and invading airway epithelia cells: transcytosis across these cells can result in systemic infection. NTHi strain R2866 was isolated from the blood of a normal 30-month old infant with meningitis, and is unusual for NTHi in that it is able to cause systemic infection. Strain R2866 is able to replicate in normal human serum due to expression of lgtC which mimics human blood group p(k). R2866 contains a phase-variable DNA methyltransferase, modA10 which switches ON and OFF randomly and reversibly due to polymerase slippage over a long tetrameric repeat tract located in its open reading frame. Random gain or loss of repeats during replication can results in expressed (ON), or not expressed (OFF) states, the latter due to a frameshift or transcriptional termination at a premature stop codon. We sought to determine if the unusual virulence of R2866 was modified by modA10 phase-variation. A modA10 knockout mutant was found to have increased adherence to, and invasion of, human ear and airway monolayers in culture, and increased invasion and transcytosis of polarized human bronchial epithelial cells. Intriguingly, the rate of bacteremia was lower in the infant rat model of infection than a wild-type R2866 strain, but the fatality rate was greater. Transcriptional analysis comparing the modA10 knockout to the R2866 wild-type parent strain showed increased expression of genes in the modA10 knockout whose products mediate cellular adherence. We conclude that loss of ModA10 function in strain R2866 enhances colonization and invasion by increasing expression of genes that allow for increased adherence, which can contribute to the increased virulence of this strain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Testing, Requirements, and Metrics

NASA Technical Reports Server (NTRS)

Rosenberg, Linda; Hyatt, Larry; Hammer, Theodore F.; Huffman, Lenore; Wilson, William

1998-01-01

The criticality of correct, complete, testable requirements is a fundamental tenet of software engineering. Also critical is complete requirements based testing of the final product. Modern tools for managing requirements allow new metrics to be used in support of both of these critical processes. Using these tools, potential problems with the quality of the requirements and the test plan can be identified early in the life cycle. Some of these quality factors include: ambiguous or incomplete requirements, poorly designed requirements databases, excessive or insufficient test cases, and incomplete linkage of tests to requirements. This paper discusses how metrics can be used to evaluate the quality of the requirements and test to avoid problems later. Requirements management and requirements based testing have always been critical in the implementation of high quality software systems. Recently, automated tools have become available to support requirements management. At NASA's Goddard Space Flight Center (GSFC), automated requirements management tools are being used on several large projects. The use of these tools opens the door to innovative uses of metrics in characterizing test plan quality and assessing overall testing risks. In support of these projects, the Software Assurance Technology Center (SATC) is working to develop and apply a metrics program that utilizes the information now available through the application of requirements management tools. Metrics based on this information provides real-time insight into the testing of requirements and these metrics assist the Project Quality Office in its testing oversight role. This paper discusses three facets of the SATC's efforts to evaluate the quality of the requirements and test plan early in the life cycle, thus preventing costly errors and time delays later.

76 FR 41138 - Insurer Reporting Requirements; List of Insurers Required To File Reports

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-13

... Leasing Companies (Including Licensees and Franchisees) Subject to the Reporting Requirements of Part 544... [Docket No.: NHTSA-2011-0016] RIN 2127-AK90 Insurer Reporting Requirements; List of Insurers Required To... Requirements. This Part specifies the requirements for annual insurer reports and lists in appendices those...

75 FR 54041 - Insurer Reporting Requirements; List of Insurers Required To File Reports

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

... and Franchisees) Subject to the Reporting Requirements of Part 544 Cendant Car Rental Dollar Thrifty... [Docket No. NHTSA-2010-0017] RIN 2127-AK69 Insurer Reporting Requirements; List of Insurers Required To... Reporting Requirements. The regulations specify the requirements for annual insurer reports and lists in...

Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease

PubMed Central

Sehlin, Dag; Fang, Xiaotian T.; Cato, Linda; Antoni, Gunnar; Lannfelt, Lars; Syvänen, Stina

2016-01-01

Owing to their specificity and high-affinity binding, monoclonal antibodies have potential as positron emission tomography (PET) radioligands and are currently used to image various targets in peripheral organs. However, in the central nervous system, antibody uptake is limited by the blood–brain barrier (BBB). Here we present a PET ligand to be used for diagnosis and evaluation of treatment effects in Alzheimer's disease. The amyloid β (Aβ) antibody mAb158 is radiolabelled and conjugated to a transferrin receptor antibody to enable receptor-mediated transcytosis across the BBB. PET imaging of two different mouse models with Aβ pathology clearly visualize Aβ in the brain. The PET signal increases with age and correlates closely with brain Aβ levels. Thus, we demonstrate that antibody-based PET ligands can be successfully used for brain imaging. PMID:26892305

The Role of Caveolin 1 in HIV Infection and Pathogenesis.

PubMed

Mergia, Ayalew

2017-05-26

Caveolin 1 (Cav-1) is a major component of the caveolae structure and is expressed in a variety of cell types including macrophages, which are susceptible to human immunodeficiency virus (HIV) infection. Caveolae structures are present in abundance in mechanically stressed cells such as endothelial cells and adipocytes. HIV infection induces dysfunction of these cells and promotes pathogenesis. Cav-1 and the caveolae structure are believed to be involved in multiple cellular processes that include signal transduction, lipid regulation, endocytosis, transcytosis, and mechanoprotection. Such a broad biological role of Cav-1/caveolae is bound to have functional cross relationships with several molecular pathways including HIV replication and viral-induced pathogenesis. The current review covers the relationship of Cav-1 and HIV in respect to viral replication, persistence, and the potential role in pathogenesis.

Functional architecture of the retromer cargo-recognition complex

PubMed Central

Hierro, Aitor; Rojas, Adriana L.; Rojas, Raul; Murthy, Namita; Effantin, Grégory; Kajava, Andrey V.; Steven, Alasdair C.; Bonifacino, Juan S.; Hurley, James H.

2008-01-01

The retromer complex 1, 2 is required for the sorting of acid hydrolases to lysosomes 3-7, transcytosis of the polymeric Ig receptor 8, Wnt gradient formation 9, 10, iron transporter recycling 11, and processing of the amyloid precursor protein 12. Human retromer consists of two smaller complexes, the cargo recognition Vps26:Vps29:Vps35 heterotrimer, and a membrane-targeting heterodimer or homodimer of SNX1 and/or SNX2 13. The crystal structure of a Vps29:Vps35 subcomplex shows how the metallophosphoesterase-fold subunit Vps29 14, 15 acts as a scaffold for the C-terminal half of Vps35. Vps35 forms a horseshoe-shaped right-handed α-helical solenoid whose concave face completely covers the metal-binding site of Vps29 and whose convex face exposes a series of hydrophobic interhelical grooves. Electron microscopy shows that the intact Vps26:Vps29:Vps35 complex is a stick-shaped, somewhat flexible, structure, ∼ 21 nm long. A hybrid structural model derived from crystal structures, electron microscopy, interaction studies, and bioinformatics shows that the α-solenoid fold extends the full length of Vps35, and that Vps26 is bound at the opposite end from Vps29. This extended structure presents multiple binding sites for the SNX complex and receptor cargo, and appears capable of flexing to conform to curved vesicular membranes. PMID:17891154

Enhanced Delivery and Effects of Acid Sphingomyelinase by ICAM-1-Targeted Nanocarriers in Type B Niemann-Pick Disease Mice.

PubMed

Garnacho, Carmen; Dhami, Rajwinder; Solomon, Melani; Schuchman, Edward H; Muro, Silvia

2017-07-05

Acid sphingomyelinase deficiency in type B Niemann-Pick disease leads to lysosomal sphingomyelin storage, principally affecting lungs, liver, and spleen. Infused recombinant enzyme is beneficial, yet its delivery to the lungs is limited and requires higher dosing than liver and spleen, leading to potentially adverse reactions. Previous studies showed increased enzyme pulmonary uptake by nanocarriers targeted to ICAM-1, a protein overexpressed during inflammation. Here, using polystyrene and poly(lactic-co-glycolic acid) nanocarriers, we optimized lung delivery by varying enzyme dose and nanocarrier concentration, verified endocytosis and lysosomal trafficking in vivo, and evaluated delivered activity and effects. Raising the enzyme load of nanocarriers progressively increased absolute enzyme delivery to all lung, liver, and spleen, over the naked enzyme. Varying nanocarrier concentration inversely impacted lung versus liver and spleen uptake. Mouse intravital and postmortem examination verified endocytosis, transcytosis, and lysosomal trafficking using nanocarriers. Compared to naked enzyme, nanocarriers increased enzyme activity in organs and reduced lung sphingomyelin storage and macrophage infiltration. Although old mice with advanced disease showed reactivity (pulmonary leukocyte infiltration) to injections, including buffer without carriers, antibody, or enzyme, younger mice with mild disease did not. We conclude that anti-ICAM nanocarriers may result in effective lung enzyme therapy using low enzyme doses. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Traffic Jam at the Blood Brain Barrier Promotes Greater Accumulation of Alzheimer’s Disease Amyloid-β Proteins in the Cerebral Vasculature

PubMed Central

Agyare, Edward K.; Leonard, Sarah R.; Curran, Geoffry L.; Yu, Caroline C.; Lowe, Val J.; Paravastu, Anant K.; Poduslo, Joseph F.; Kandimalla, Karunya K.

2013-01-01

Amyloid-β (Aβ) deposition in the brain vasculature results in cerebral amyloid angiopathy (CAA), which occurs in about 80% of Alzheimer’s disease (AD) patients. While Aβ42 predominates parenchymal amyloid plaques in AD brain, Aβ40 is prevalent in the cerebrovascular amyloid. Dutch mutation of Aβ40 (E22Q) promotes aggressive cerebrovascular accumulation and leads to severe CAA in the mutation carriers; knowledge of how DutchAβ40 drives this process more efficiently than Aβ40 could reveal various pathophysiological events that promote CAA. In this study we have demonstrated that DutchAβ40 show preferential accumulation in the blood-brain-barrier (BBB) endothelial cells due to its inefficient blood-to-brain transcytosis. Consequently, DutchAβ40 establishes a permeation barrier in the BBB endothelium, prevents its own clearance from the brain and promotes the formation of amyloid deposits in the cerebral microvessels. The BBB endothelial accumulation of native Aβ40 is not robust enough to exercise such a significant impact on its brain clearance. Hence, the cerebrovascular accumulation of Aβ40 is slow and may require other co-pathologies to precipitate into CAA. In conclusion, the magnitude of Aβ accumulation in the BBB endothelial cells is a critical factor that promotes CAA; hence, clearing vascular endothelium of Aβ proteins may halt or even reverse CAA. PMID:23249146

75 FR 1548 - Insurer Reporting Requirements; List of Insurers Required To File Reports

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-12

... Franchisees) Subject to the Reporting Requirements of Part 544 Cendant Car Rental Dollar Thrifty Automotive... [Docket No.: NHTSA-2009-0050] RIN 2127-AK46 Insurer Reporting Requirements; List of Insurers Required To... Transportation (DOT). ACTION: Final rule. SUMMARY: This final rule amends the Insurer Reporting Requirements. The...

40 CFR 600.010-08 - Vehicle test requirements and minimum data requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... data requirements. 600.010-08 Section 600.010-08 Protection of Environment ENVIRONMENTAL PROTECTION... requirements and minimum data requirements. (a) Unless otherwise exempted from specific emission compliance... applicable): (1) The manufacturer shall generate FTP fuel economy data by testing according to the applicable...

12 CFR 722.3 - Appraisals required; transactions requiring a State certified or licensed appraiser.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Appraisals required; transactions requiring a... ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS APPRAISALS § 722.3 Appraisals required; transactions requiring... certified or licensed appraiser is required for all real estate-related financial transactions except those...

40 CFR 600.010-08 - Vehicle test requirements and minimum data requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., US06, SC03 and Cold temperature FTP data from each subconfiguration included within the model type. (2... data requirements. 600.010-08 Section 600.010-08 Protection of Environment ENVIRONMENTAL PROTECTION... Provisions § 600.010-08 Vehicle test requirements and minimum data requirements. (a) Unless otherwise...

40 CFR 600.010-86 - Vehicle test requirements and minimum data requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... additional model types established under § 600.207(a)(2), data from each subconfiguration included within the... data requirements. 600.010-86 Section 600.010-86 Protection of Environment ENVIRONMENTAL PROTECTION... requirements and minimum data requirements. (a) For each certification vehicle defined in this part, and for...

Requirements Specification Document

DOT National Transportation Integrated Search

1996-04-26

The System Definition Document identifies the top level processes, data flows, : and system controls for the Gary-Chicago-Milwaukee (GCM) Corridor Transportation Information Center (C-TIC). This Requirements Specification establishes the requirements...

Oil Discharge Reporting Requirements

EPA Pesticide Factsheets

If a facility or vessel discharges oil to navigable waters or adjoining shorelines, the owner/operator is required to follow certain federal reporting requirements. This fact sheet outlines those reporting requirements.

40 CFR 600.010-86 - Vehicle test requirements and minimum data requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... base level, and (iii) For additional model types established under § 600.207(a)(2), data from each... data requirements. 600.010-86 Section 600.010-86 Protection of Environment ENVIRONMENTAL PROTECTION... Provisions § 600.010-86 Vehicle test requirements and minimum data requirements. (a) For each certification...

An Engineering Method of Civil Jet Requirements Validation Based on Requirements Project Principle

NASA Astrophysics Data System (ADS)

Wang, Yue; Gao, Dan; Mao, Xuming

2018-03-01

A method of requirements validation is developed and defined to meet the needs of civil jet requirements validation in product development. Based on requirements project principle, this method will not affect the conventional design elements, and can effectively connect the requirements with design. It realizes the modern civil jet development concept, which is “requirement is the origin, design is the basis”. So far, the method has been successfully applied in civil jet aircraft development in China. Taking takeoff field length as an example, the validation process and the validation method of the requirements are detailed introduced in the study, with the hope of providing the experiences to other civil jet product design.

LANL surveillance requirements management and surveillance requirements from NA-12 tasking memo

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

Hills, Charles R

2011-01-25

Surveillance briefing to NNSA to support a tasking memo from NA-12 on Surveillance requirements. This talk presents the process for developing surveillance requirements, discusses the LANL requirements that were issued as part of that tasking memo, and presents recommendations on Component Evaluation and Planning Committee activities for FY11.

Advanced technology requirements for large space structures. Part 5: Atlas program requirements

NASA Technical Reports Server (NTRS)

Katz, E.; Lillenas, A. N.; Broddy, J. A.

1977-01-01

The results of a special study which identifies and assigns priorities to technology requirements needed to accomplish a particular scenario of future large area space systems are described. Proposed future systems analyzed for technology requirements included large Electronic Mail, Microwave Radiometer, and Radar Surveillance Satellites. Twenty technology areas were identified as requirements to develop the proposed space systems.

STEP Experiment Requirements

NASA Technical Reports Server (NTRS)

Brumfield, M. L. (Compiler)

1984-01-01

A plan to develop a space technology experiments platform (STEP) was examined. NASA Langley Research Center held a STEP Experiment Requirements Workshop on June 29 and 30 and July 1, 1983, at which experiment proposers were invited to present more detailed information on their experiment concept and requirements. A feasibility and preliminary definition study was conducted and the preliminary definition of STEP capabilities and experiment concepts and expected requirements for support services are presented. The preliminary definition of STEP capabilities based on detailed review of potential experiment requirements is investigated. Topics discussed include: Shuttle on-orbit dynamics; effects of the space environment on damping materials; erectable beam experiment; technology for development of very large solar array deployers; thermal energy management process experiment; photovoltaic concentrater pointing dynamics and plasma interactions; vibration isolation technology; flight tests of a synthetic aperture radar antenna with use of STEP.

[Function of the CLC chloride channels and their implication in human pathology].

PubMed

Vandewalle, A

2002-01-01

To date, nine chloride channels belonging to the family of CLC chloride channels have been identified. They are localized either in plasma membranes or in intracellular vesicles (endosomes or lysosomes) and can have an ubiquitus or a more restrained tissue distribution. Recent studies on ClC-K1, ClC-2, ClC-3, ClC-5 and ClC-7 knockout mice and the identification of human inherited diseases caused by mutations of some of these chloride channels (myotonia congenita for ClC-1, Bartter disease for ClC-Kb, Dent's disease for ClC-5 and osteopetrose for ClC-7) have provided lines of direct evidence of the physiological relevance and importance of these chloride channels in the transport of chloride and in the endocytosis and transcytosis of proteins in specialized cells from the kidney and other tissues.

E-ELT requirements management

NASA Astrophysics Data System (ADS)

Schneller, D.

2014-08-01

The E-ELT has completed its design phase and is now entering construction. ESO is acting as prime contractor and usually procures subsystems, including their design, from industry. This, in turn, leads to a large number of requirements, whose validity, consistency and conformity with user needs requires extensive management. Therefore E-ELT Systems Engineering has chosen to follow a systematic approach, based on a reasoned requirement architecture that follows the product breakdown structure of the observatory. The challenge ahead is the controlled flow-down of science user needs into engineering requirements, requirement specifications and system design documents. This paper shows how the E-ELT project manages this. The project has adopted IBM DOORTM as a supporting requirements management tool. This paper deals with emerging problems and pictures potential solutions. It shows trade-offs made to reach a proper balance between the effort put in this activity and potential overheads, and the benefit for the project.

12 CFR 34.43 - Appraisals required; transactions requiring a State certified or licensed appraiser.

Code of Federal Regulations, 2010 CFR

2010-01-01

... advancement of new monies, other than funds necessary to cover reasonable closing costs; (8) The transaction... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Appraisals required; transactions requiring a...; transactions requiring a State certified or licensed appraiser. (a) Appraisals required. An appraisal performed...

12 CFR 564.3 - Appraisals required; transactions requiring a State certified or licensed appraiser.

Code of Federal Regulations, 2010 CFR

2010-01-01

... than funds necessary to cover reasonable closing costs; (8) The transaction involves the purchase, sale... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Appraisals required; transactions requiring a... SUPERVISION, DEPARTMENT OF THE TREASURY APPRAISALS § 564.3 Appraisals required; transactions requiring a State...

Requirement Assurance: A Verification Process

NASA Technical Reports Server (NTRS)

Alexander, Michael G.

2011-01-01

Requirement Assurance is an act of requirement verification which assures the stakeholder or customer that a product requirement has produced its "as realized product" and has been verified with conclusive evidence. Product requirement verification answers the question, "did the product meet the stated specification, performance, or design documentation?". In order to ensure the system was built correctly, the practicing system engineer must verify each product requirement using verification methods of inspection, analysis, demonstration, or test. The products of these methods are the "verification artifacts" or "closure artifacts" which are the objective evidence needed to prove the product requirements meet the verification success criteria. Institutional direction is given to the System Engineer in NPR 7123.1A NASA Systems Engineering Processes and Requirements with regards to the requirement verification process. In response, the verification methodology offered in this report meets both the institutional process and requirement verification best practices.

Advanced EVA system design requirements study: EVAS/space station system interface requirements

NASA Technical Reports Server (NTRS)

Woods, T. G.

1985-01-01

The definition of the Extravehicular Activity (EVA) systems interface requirements and accomodations for effective integration of a production EVA capability into the space station are contained. A description of the EVA systems for which the space station must provide the various interfaces and accomodations are provided. The discussion and analyses of the various space station areas in which the EVA interfaces are required and/or from which implications for EVA system design requirements are derived, are included. The rationale is provided for all EVAS mechanical, fluid, electrical, communications, and data system interfaces as well as exterior and interior requirements necessary to facilitate EVA operations. Results of the studies supporting these discussions are presented in the appendix.

40 CFR 600.010 - Vehicle test requirements and minimum data requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Vehicle test requirements and minimum data requirements. 600.010 Section 600.010 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND GREENHOUSE GAS EXHAUST EMISSIONS OF MOTOR VEHICLES General...

40 CFR 600.010 - Vehicle test requirements and minimum data requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Vehicle test requirements and minimum data requirements. 600.010 Section 600.010 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND GREENHOUSE GAS EXHAUST EMISSIONS OF MOTOR VEHICLES General...

40 CFR 600.010 - Vehicle test requirements and minimum data requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 30 2014-07-01 2014-07-01 false Vehicle test requirements and minimum data requirements. 600.010 Section 600.010 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND GREENHOUSE GAS EXHAUST EMISSIONS OF MOTOR VEHICLES General...

E-ELT requirements flow down

NASA Astrophysics Data System (ADS)

Gonzalez, J. C.; Kurlandczyk, H.; Schmid, C.; Schneller, D.

2016-08-01

One of the critical activities in the systems engineering scope of work is managing requirements. In line with this, E-ELT devotes a significant effort to this activity, which follows a well-established process. This involves optimally deriving requirements from the user (Top-Level Requirements) through the system Level 1 Requirements and from here down to subsystems procurement specifications. This paper describes the process, which is illustrated with some practical examples, including in particular the role of technical budgets to derive requirements on subsystems. Also, the provisions taken for the requirements verification are discussed.

Requirements based system risk modeling

NASA Technical Reports Server (NTRS)

Meshkat, Leila; Cornford, Steven; Feather, Martin

2004-01-01

The problem that we address in this paper is assessing the expected degree of success of the system or mission based on the degree to which each requirement is satisfied and the relative weight of the requirements. We assume a complete list of the requirements, the relevant risk elements and their probability of occurrence and the quantified effect of the risk elements on the requirements. In order to assess the degree to which each requirement is satisfied, we need to determine the effect of the various risk elements on the requirement.

48 CFR 3023.1004 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Requirements. 3023.1004...-Know Laws and Pollution Requirements 3023.1004 Requirements. DHS Directive 023-02 Environmental... contain appropriate sustainable practices requirements, provisions and clauses. Contractors shall support...

48 CFR 3023.1004 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Requirements. 3023.1004...-Know Laws and Pollution Requirements 3023.1004 Requirements. DHS Directive 023-02 Environmental... contain appropriate sustainable practices requirements, provisions and clauses. Contractors shall support...

48 CFR 3023.1004 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Requirements. 3023.1004...-Know Laws and Pollution Requirements 3023.1004 Requirements. DHS Directive 023-02 Environmental... contain appropriate sustainable practices requirements, provisions and clauses. Contractors shall support...

48 CFR 2906.501 - Requirement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Requirement. 2906.501... COMPETITION REQUIREMENTS Competition Advocate 2906.501 Requirement. The Assistant Secretary for Administration... be predicated on an understanding of the competition requirements in the FAR, and particularly small...

48 CFR 2906.501 - Requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Requirement. 2906.501... COMPETITION REQUIREMENTS Competition Advocate 2906.501 Requirement. The Assistant Secretary for Administration... be predicated on an understanding of the competition requirements in the FAR, and particularly small...

48 CFR 2906.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Requirement. 2906.501... COMPETITION REQUIREMENTS Competition Advocate 2906.501 Requirement. The Assistant Secretary for Administration... be predicated on an understanding of the competition requirements in the FAR, and particularly small...

48 CFR 2906.501 - Requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Requirement. 2906.501... COMPETITION REQUIREMENTS Competition Advocate 2906.501 Requirement. The Assistant Secretary for Administration... be predicated on an understanding of the competition requirements in the FAR, and particularly small...

48 CFR 6.501 - Requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Requirement. 6.501 Section 6.501 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 6.501 Requirement. As required by section 20 of the Office of...

48 CFR 6.501 - Requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Requirement. 6.501 Section 6.501 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 6.501 Requirement. As required by section 20 of the Office of...

48 CFR 6.501 - Requirement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Requirement. 6.501 Section 6.501 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 6.501 Requirement. As required by section 20 of the Office of...

48 CFR 6.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Requirement. 6.501 Section 6.501 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING COMPETITION REQUIREMENTS Advocates for Competition 6.501 Requirement. As required by 41 U.S.C. 1705, the head...

Basic Hitchhiker Payload Requirements

NASA Technical Reports Server (NTRS)

Horan, Stephen

1999-01-01

This document lists the requirements for the NMSU Hitchhiker experiment payload that were developed as part of the EE 498/499 Capstone Design class during the 1999-2000 academic year. This document is used to describe the system needs as described in the mission document. The requirements listed here are those primarily used to generate the basic electronic and data processing requirements developed in the class design document. The needs of the experiment components are more fully described in the draft NASA hitchhiker customer requirements document. Many of the details for the overall payload are given in full detail in the NASA hitchhiker documentation.

Science, Technology & Requirements Forum

DTIC Science & Technology

2012-10-01

Science, Technology & Requirements Forum COL Barry K. Williams Assistant Commandant US Army Engineer School Engineer Warriors leading to...2012 4. TITLE AND SUBTITLE Science, Technology & Requirements Forum 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...unlimited 13. SUPPLEMENTARY NOTES Presented at the 2012 Science, Technology & Requirements Forum held 17-18 October in Fort Leonard Wood, MO. 14

16 CFR 1204.3 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Requirements. 1204.3 Section 1204.3... STANDARD FOR OMNIDIRECTIONAL CITIZENS BAND BASE STATION ANTENNAS The Standard § 1204.3 Requirements. All omnidirectional CB base station antennas are required to comply with the following requirements. (a) Field joints...

Customer requirements process

NASA Technical Reports Server (NTRS)

Russell, Yvonne; Falsetti, Christine M.

1991-01-01

Customer requirements are presented through three viewgraphs. One graph presents the range of services, which include requirements management, network engineering, operations, and applications support. Another viewgraph presents the project planning process. The third viewgraph presents the programs and/or projects actively supported including life sciences, earth science and applications, solar system exploration, shuttle flight engineering, microgravity science, space physics, and astrophysics.

40 CFR 63.982 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 10 2011-07-01 2011-07-01 false Requirements. 63.982 Section 63.982... Process § 63.982 Requirements. (a) General compliance requirements for storage vessels, process vents... routing to a fuel gas system or process shall comply with the applicable requirements of paragraphs (a)(1...

18 CFR 807.1 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 2 2014-04-01 2014-04-01 false Requirement. 807.1... WITHDRAWAL REGISTRATION § 807.1 Requirement. In addition to any other requirements of Commission regulations, and subject to the consent of the affected member state to this requirement, any person withdrawing or...

18 CFR 807.1 - Requirement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Requirement. 807.1... WITHDRAWAL REGISTRATION § 807.1 Requirement. In addition to any other requirements of Commission regulations, and subject to the consent of the affected member state to this requirement, any person withdrawing or...

18 CFR 807.1 - Requirement.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Requirement. 807.1... WITHDRAWAL REGISTRATION § 807.1 Requirement. In addition to any other requirements of Commission regulations, and subject to the consent of the affected member state to this requirement, any person withdrawing or...

24 CFR 966.52 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Requirements. 966.52 Section 966.52... HOUSING LEASE AND GRIEVANCE PROCEDURE Grievance Procedures and Requirements § 966.52 Requirements. (a... grievance as defined in § 966.53 in accordance with the requirements, standards, and criteria contained in...

24 CFR 966.52 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Requirements. 966.52 Section 966.52... HOUSING LEASE AND GRIEVANCE PROCEDURE Grievance Procedures and Requirements § 966.52 Requirements. (a... grievance as defined in § 966.53 in accordance with the requirements, standards, and criteria contained in...

40 CFR 63.982 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 11 2014-07-01 2014-07-01 false Requirements. 63.982 Section 63.982... Process § 63.982 Requirements. (a) General compliance requirements for storage vessels, process vents... routing to a fuel gas system or process shall comply with the applicable requirements of paragraphs (a)(1...

16 CFR 1513.3 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Requirements. 1513.3 Section 1513.3... REQUIREMENTS FOR BUNK BEDS § 1513.3 Requirements. (a) Guardrails. (1) Any bunk bed shall provide at least two... bed. This requirement does not prohibit a wall-side guardrail that terminates in a quarter-circle bend...

16 CFR 1513.3 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Requirements. 1513.3 Section 1513.3... REQUIREMENTS FOR BUNK BEDS § 1513.3 Requirements. (a) Guardrails. (1) Any bunk bed shall provide at least two... bed. This requirement does not prohibit a wall-side guardrail that terminates in a quarter-circle bend...

16 CFR 1510.3 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Requirements. 1510.3 Section 1510.3... REQUIREMENTS FOR RATTLES § 1510.3 Requirements. No portion of a rattle, when tested in accordance with the... shall meet this requirement both before and after performing the use and abuse tests of § 1500.51 of...

Proteomic identification of dysferlin-interacting protein complexes in human vascular endothelium

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

Leung, Cleo; Utokaparch, Soraya; Sharma, Arpeeta

2011-11-18

Highlights: Black-Right-Pointing-Pointer Bi-directional (inward and outward) movement of GFP-dysferlin in COS-7 cells. Black-Right-Pointing-Pointer Dysferlin interacts with key signaling proteins for transcytosis in EC. Black-Right-Pointing-Pointer Dysferlin mediates trafficking of vesicles carrying protein cargos in EC. -- Abstract: Dysferlin is a membrane-anchored protein known to facilitate membrane repair in skeletal muscles following mechanical injury. Mutations of dysferlin gene impair sarcolemma integrity, a hallmark of certain forms of muscular dystrophy in patients. Dysferlin contains seven calcium-dependent C2 binding domains, which are required to promote fusion of intracellular membrane vesicles. Emerging evidence reveal the unexpected expression of dysferlin in non-muscle, non-mechanically active tissues, suchmore » as endothelial cells, which cast doubts over the belief that ferlin proteins act exclusively as membrane repair proteins. We and others have shown that deficient trafficking of membrane bound proteins in dysferlin-deficient cells, suggesting that dysferlin might mediate trafficking of client proteins. Herein, we describe the intracellular trafficking and movement of GFP-dysferlin positive vesicles in unfixed reconstituted cells using live microscopy. By performing GST pull-down assays followed by mass spectrometry, we identified dysferlin binding protein complexes in human vascular endothelial cells. Together, our data further support the claims that dysferlin not only mediates membrane repair but also trafficking of client proteins, ultimately, help bridging dysferlinopathies to aberrant membrane signaling.« less

Mechanism and developmental changes in iron transport across the blood-brain barrier.

PubMed

Morgan, Evan H; Moos, Torben

2002-01-01

Transferrin and iron uptake by the brain were measured using [(59)Fe-(125)I]transferrin injected intravenously in rats aged from 15 days to 22 weeks. The values for both decreased with age. In rats aged 18 and 70 days the uptake was measured at short time intervals after the injection. When expressed as the volume of distribution (Vd), which represents the volume of plasma from which the transferrin and iron were derived, the results for iron were greater than those of transferrin as early as 7 min after injection and the difference increased rapidly with time, especially in the younger animals. A very similar time course was found for uptake by bone marrow (femurs) where iron uptake involves receptor-mediated endocytosis of Fe-transferrin, release of iron in the cell and recycling of apo-transferrin to the blood. It is concluded that, during transport of transferrin-bound plasma iron into the brain, a similar process occurs in brain capillary endothelial cells (BCECs) and that transcytosis of transferrin into the brain interstitium is only a minor pathway. Also, the high rate of iron transport into the brain in young animals, when iron requirements are high due to rapid growth of the brain, is a consequence of the level of expression and rate of recycling of transferrin receptors on BCECs. As the animal and brain mature both decrease. Copyright 2002 S. Karger AG, Basel

Anthropometric Requirements for Constellation

NASA Technical Reports Server (NTRS)

Raulu, Sudhakar; Margerum, Sarah; Dory, Jonathan; Rochlis, Jennifer

2009-01-01

This slide presentation reviews the requirement from an Anthropometric standpoint for the development of the Constellation's programs hardware, specifically the Orion crew exploration vehicle. The NASA JSC Anthropometry and Biomechanics Facility (ABF) provides anthropometry, strength, mobility, and mass properties requirements; gathers, interprets, manages and maintains the flight crew anthropometry database; and participates and provides input during crew selection. This is used to assist in requirements for vehicle and space suit design and for crew selection.

14 CFR 91.5 - Pilot in command of aircraft requiring more than one required pilot.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Pilot in command of aircraft requiring more... RULES General § 91.5 Pilot in command of aircraft requiring more than one required pilot. No person may... the pilot in command meets the requirements of § 61.58 of this chapter. ...

14 CFR 91.5 - Pilot in command of aircraft requiring more than one required pilot.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Pilot in command of aircraft requiring more... RULES General § 91.5 Pilot in command of aircraft requiring more than one required pilot. No person may... the pilot in command meets the requirements of § 61.58 of this chapter. ...

14 CFR 91.5 - Pilot in command of aircraft requiring more than one required pilot.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Pilot in command of aircraft requiring more... RULES General § 91.5 Pilot in command of aircraft requiring more than one required pilot. No person may... the pilot in command meets the requirements of § 61.58 of this chapter. ...

14 CFR 91.5 - Pilot in command of aircraft requiring more than one required pilot.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Pilot in command of aircraft requiring more... RULES General § 91.5 Pilot in command of aircraft requiring more than one required pilot. No person may... the pilot in command meets the requirements of § 61.58 of this chapter. ...

14 CFR 91.5 - Pilot in command of aircraft requiring more than one required pilot.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Pilot in command of aircraft requiring more... RULES General § 91.5 Pilot in command of aircraft requiring more than one required pilot. No person may... the pilot in command meets the requirements of § 61.58 of this chapter. ...

12 CFR 323.3 - Appraisals required; transactions requiring a State certified or licensed appraiser.

Code of Federal Regulations, 2010 CFR

2010-01-01

... advancement of new monies, other than funds necessary to cover reasonable closing costs; (8) The transaction... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Appraisals required; transactions requiring a... CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY APPRAISALS § 323.3 Appraisals required; transactions...

Role of maternal elimination diets and human milk IgA in development of cow’s milk allergy in the infants

PubMed Central

Järvinen, Kirsi M.; Westfall, Jennifer E.; Seppo, Max S.; James, Aisha K.; Tsuang, Angela J.; Feustel, Paul J.; Sampson, Hugh A.; Berin, Cecilia

2014-01-01

Background The role of maternal avoidance diets in the prevention of food allergies is currently under debate. Little is known regarding the effects of such diets on human milk (HM) composition or induction of infant humoral responses. Objective To assess the association of maternal cow’s milk (CM) avoidance during breastfeeding with specific IgA levels in HM and development of cow’s milk allergy (CMA) in infants. Methods We utilized HM and infant serum samples from a prospective birth cohort of 145 dyads. Maternal serum and HM samples were assessed for casein and beta-lactoglobulin (BLG)-specific IgA and IgG by ELISA; 21 mothers prophylactically initiated a strict maternal CM avoidance diet due to a sibling’s history of food allergy and 16 due to atopic eczema or regurgitation/vomiting seen in their infants within the first 3 months of life. Infants’ sera were assessed for casein and BLG-specific IgG, IgA and IgE; CMA was confirmed by an oral food challenge. The impact of HM on BLG uptake was assessed in transcytosis assays utilizing Caco-2 intestinal epithelial cell line. Results Mothers avoiding CM had lower casein- and BLG-specific IgA in HM than mothers with no CM restriction (p=0.019 and p=0.047). Their infants had lower serum casein- and BLG-specific IgG1 (p=0.025 and p<0.001) and BLG-specific IgG4 levels (p=0.037) and their casein- and BLG-specific IgA levels were less often detectable than those with no CM elimination diet (p=0.003 and p=0.007). Lower CM-specific IgG4 and IgA levels in turn were associated with infant CMA. Transcytosis of BLG was impaired by HM with high, but not low levels of specific IgA. Conclusions Maternal CM avoidance was associated with lower levels of mucosal specific IgA levels and development of CMA in infants. Clinical relevance HM IgA may play a role in preventing excessive, uncontrolled food antigen uptake in the gut lumen and thereby in the prevention of CMA. PMID:24164317

Role of maternal elimination diets and human milk IgA in the development of cow's milk allergy in the infants.

PubMed

Järvinen, K M; Westfall, J E; Seppo, M S; James, A K; Tsuang, A J; Feustel, P J; Sampson, H A; Berin, C

2014-01-01

The role of maternal avoidance diets in the prevention of food allergies is currently under debate. Little is known regarding the effects of such diets on human milk (HM) composition or induction of infant humoral responses. To assess the association of maternal cow's milk (CM) avoidance during breastfeeding with specific IgA levels in HM and development of cow's milk allergy (CMA) in infants. We utilized HM and infant serum samples from a prospective birth cohort of 145 dyads. Maternal serum and HM samples were assessed for casein and beta-lactoglobulin (BLG)-specific IgA and IgG by ELISA; 21 mothers prophylactically initiated a strict maternal CM avoidance diet due to a sibling's history of food allergy and 16 due to atopic eczema or regurgitation/vomiting seen in their infants within the first 3 months of life. Infants' sera were assessed for casein and BLG-specific IgG, IgA and IgE; CMA was confirmed by an oral food challenge. The impact of HM on BLG uptake was assessed in transcytosis assays utilizing Caco-2 intestinal epithelial cell line. Mothers avoiding CM had lower casein- and BLG-specific IgA in HM than mothers with no CM restriction (P = 0.019 and P = 0.047). Their infants had lower serum casein- and BLG-specific IgG(1) (P = 0.025 and P < 0.001) and BLG-specific IgG(4) levels (P = 0.037), and their casein- and BLG-specific IgA levels were less often detectable than those with no CM elimination diet (P = 0.003 and P = 0.007). Lower CM-specific IgG4 and IgA levels in turn were associated with infant CMA. Transcytosis of BLG was impaired by HM with high, but not low levels of specific IgA. Maternal CM avoidance was associated with lower levels of mucosal-specific IgA levels and the development of CMA in infants. HM IgA may play a role in preventing excessive, uncontrolled food antigen uptake in the gut lumen and thereby in the prevention of CMA. © 2013 John Wiley & Sons Ltd.

Requirements controlled design: A method for discovery of discontinuous system boundaries in the requirements hyperspace

NASA Astrophysics Data System (ADS)

Hollingsworth, Peter Michael

The drive toward robust systems design, especially with respect to system affordability throughout the system life-cycle, has led to the development of several advanced design methods. While these methods have been extremely successful in satisfying the needs for which they have been developed, they inherently leave a critical area unaddressed. None of them fully considers the effect of requirements on the selection of solution systems. The goal of all of current modern design methodologies is to bring knowledge forward in the design process to the regions where more design freedom is available and design changes cost less. Therefore, it seems reasonable to consider the point in the design process where the greatest restrictions are placed on the final design, the point in which the system level requirements are set. Historically the requirements have been treated as something handed down from above. However, neither the customer nor the solution provider completely understood all of the options that are available in the broader requirements space. If a method were developed that provided the ability to understand the full scope of the requirements space, it would allow for a better comparison of potential solution systems with respect to both the current and potential future requirements. The key to a requirements conscious method is to treat requirements differently from the traditional approach. The method proposed herein is known as Requirements Controlled Design (RCD). By treating the requirements as a set of variables that control the behavior of the system, instead of variables that only define the response of the system, it is possible to determine a-priori what portions of the requirements space that any given system is capable of satisfying. Additionally, it should be possible to identify which systems can satisfy a given set of requirements and the locations where a small change in one or more requirements poses a significant risk to a design program

43 CFR 3815.8 - Notation required in application for patent; conditions required in patent.

Code of Federal Regulations, 2012 CFR

2012-10-01

... patent; conditions required in patent. 3815.8 Section 3815.8 Public Lands: Interior Regulations Relating... Notation required in application for patent; conditions required in patent. (a) Every application for patent for any minerals located subject to this Act must bear on its face, before being executed by the...

43 CFR 3815.8 - Notation required in application for patent; conditions required in patent.

Code of Federal Regulations, 2011 CFR

2011-10-01

... patent; conditions required in patent. 3815.8 Section 3815.8 Public Lands: Interior Regulations Relating... Notation required in application for patent; conditions required in patent. (a) Every application for patent for any minerals located subject to this Act must bear on its face, before being executed by the...

43 CFR 3815.8 - Notation required in application for patent; conditions required in patent.

Code of Federal Regulations, 2014 CFR

2014-10-01

... patent; conditions required in patent. 3815.8 Section 3815.8 Public Lands: Interior Regulations Relating... Notation required in application for patent; conditions required in patent. (a) Every application for patent for any minerals located subject to this Act must bear on its face, before being executed by the...

43 CFR 3815.8 - Notation required in application for patent; conditions required in patent.

Code of Federal Regulations, 2013 CFR

2013-10-01

... patent; conditions required in patent. 3815.8 Section 3815.8 Public Lands: Interior Regulations Relating... Notation required in application for patent; conditions required in patent. (a) Every application for patent for any minerals located subject to this Act must bear on its face, before being executed by the...

14 CFR 121.317 - Passenger information requirements, smoking prohibitions, and additional seat belt requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Passenger information requirements, smoking... OPERATIONS Instrument and Equipment Requirements § 121.317 Passenger information requirements, smoking... command. (c) No person may operate an airplane on a flight on which smoking is prohibited by part 252 of...

14 CFR 121.317 - Passenger information requirements, smoking prohibitions, and additional seat belt requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Passenger information requirements, smoking... OPERATIONS Instrument and Equipment Requirements § 121.317 Passenger information requirements, smoking... command. (c) No person may operate an airplane on a flight on which smoking is prohibited by part 252 of...

14 CFR 121.317 - Passenger information requirements, smoking prohibitions, and additional seat belt requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Passenger information requirements, smoking... OPERATIONS Instrument and Equipment Requirements § 121.317 Passenger information requirements, smoking... command. (c) No person may operate an airplane on a flight on which smoking is prohibited by part 252 of...

14 CFR 121.317 - Passenger information requirements, smoking prohibitions, and additional seat belt requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Passenger information requirements, smoking... OPERATIONS Instrument and Equipment Requirements § 121.317 Passenger information requirements, smoking... command. (c) No person may operate an airplane on a flight on which smoking is prohibited by part 252 of...

14 CFR 121.317 - Passenger information requirements, smoking prohibitions, and additional seat belt requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Passenger information requirements, smoking... OPERATIONS Instrument and Equipment Requirements § 121.317 Passenger information requirements, smoking... command. (c) No person may operate an airplane on a flight on which smoking is prohibited by part 252 of...

75 FR 34966 - Insurer Reporting Requirements; List of Insurers Required To File Reports

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-21

... meet the reporting requirements. Each of the remaining five companies (including franchisees and... and Franchisees) Subject to the Reporting Requirements of Part 544 Cendant Car Rental Dollar Thrifty...

Autonomous Real Time Requirements Tracing

NASA Technical Reports Server (NTRS)

Plattsmier, George I.; Stetson, Howard K.

2014-01-01

One of the more challenging aspects of software development is the ability to verify and validate the functional software requirements dictated by the Software Requirements Specification (SRS) and the Software Detail Design (SDD). Insuring the software has achieved the intended requirements is the responsibility of the Software Quality team and the Software Test team. The utilization of Timeliner-TLX(sup TM) Auto-Procedures for relocating ground operations positions to ISS automated on-board operations has begun the transition that would be required for manned deep space missions with minimal crew requirements. This transition also moves the auto-procedures from the procedure realm into the flight software arena and as such the operational requirements and testing will be more structured and rigorous. The autoprocedures would be required to meet NASA software standards as specified in the Software Safety Standard (NASASTD- 8719), the Software Engineering Requirements (NPR 7150), the Software Assurance Standard (NASA-STD-8739) and also the Human Rating Requirements (NPR-8705). The Autonomous Fluid Transfer System (AFTS) test-bed utilizes the Timeliner-TLX(sup TM) Language for development of autonomous command and control software. The Timeliner- TLX(sup TM) system has the unique feature of providing the current line of the statement in execution during real-time execution of the software. The feature of execution line number internal reporting unlocks the capability of monitoring the execution autonomously by use of a companion Timeliner-TLX(sup TM) sequence as the line number reporting is embedded inside the Timeliner-TLX(sup TM) execution engine. This negates I/O processing of this type data as the line number status of executing sequences is built-in as a function reference. This paper will outline the design and capabilities of the AFTS Autonomous Requirements Tracker, which traces and logs SRS requirements as they are being met during real-time execution of the

Autonomous Real Time Requirements Tracing

NASA Technical Reports Server (NTRS)

Plattsmier, George; Stetson, Howard

2014-01-01

One of the more challenging aspects of software development is the ability to verify and validate the functional software requirements dictated by the Software Requirements Specification (SRS) and the Software Detail Design (SDD). Insuring the software has achieved the intended requirements is the responsibility of the Software Quality team and the Software Test team. The utilization of Timeliner-TLX(sup TM) Auto- Procedures for relocating ground operations positions to ISS automated on-board operations has begun the transition that would be required for manned deep space missions with minimal crew requirements. This transition also moves the auto-procedures from the procedure realm into the flight software arena and as such the operational requirements and testing will be more structured and rigorous. The autoprocedures would be required to meet NASA software standards as specified in the Software Safety Standard (NASASTD- 8719), the Software Engineering Requirements (NPR 7150), the Software Assurance Standard (NASA-STD-8739) and also the Human Rating Requirements (NPR-8705). The Autonomous Fluid Transfer System (AFTS) test-bed utilizes the Timeliner-TLX(sup TM) Language for development of autonomous command and control software. The Timeliner-TLX(sup TM) system has the unique feature of providing the current line of the statement in execution during real-time execution of the software. The feature of execution line number internal reporting unlocks the capability of monitoring the execution autonomously by use of a companion Timeliner-TLX(sup TM) sequence as the line number reporting is embedded inside the Timeliner-TLX(sup TM) execution engine. This negates I/O processing of this type data as the line number status of executing sequences is built-in as a function reference. This paper will outline the design and capabilities of the AFTS Autonomous Requirements Tracker, which traces and logs SRS requirements as they are being met during real-time execution of the

BRD usability requirements

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

Deshpande, Alina

2015-03-12

This document describes the usability requirements for the Biosurveillance resource directory (BRD); that is, who will be using the tool and what tasks they will be using it for. It does not include information on technical implementation (e.g., whether specific information is contained in the database or pulled on demand from other sources). It also avoids specific design ideas (such as widget descriptions) unless they are necessary to illustrate a requirement.

Anti-transferrin receptor-modified amphotericin B-loaded PLA-PEG nanoparticles cure Candidal meningitis and reduce drug toxicity.

PubMed

Tang, Xiaolong; Liang, Yong; Zhu, Yongqiang; Xie, Chunmei; Yao, Aixia; Chen, Li; Jiang, Qinglin; Liu, Tingting; Wang, Xiaoyu; Qian, Yunyun; Wei, Jia; Ni, Wenxuan; Dai, Jingjing; Jiang, Zhenyou; Hou, Wei

2015-01-01

Fatal fungal infections in central nervous system (CNS) can occur through hematogenous spread or direct extension. At present, hydrophobic amphotericin B (AMB) is the most effective antifungal drug in clinical trials. However, AMB is hydrophobic and therefore penetrates poorly into the CNS, and therapeutic levels of AMB are hard to achieve. The transferrin receptor (TfR/CD71) located at the blood-brain barrier mediates transferrin transcytosis. In order to enhance the receptor-mediated delivery of AMB into CNS with therapeutic level, an anti-TfR antibody (OX26)-modified AMB-loaded PLA (poly[lactic acid])-PEG (polyethylene glycol)-based micellar drug delivery system was constructed. The prepared OX26-modified AMB-loaded nanoparticles (OX26-AMB-NPs) showed significant reduction of CNS fungal burden and an increase of mouse survival time. In conclusion, OX26-AMB-NPs represent a promising novel drug delivery system for intracerebral fungal infection.

Carrier of Wingless (Cow), a Secreted Heparan Sulfate Proteoglycan, Promotes Extracellular Transport of Wingless

PubMed Central

Chang, Yung-Heng; Sun, Yi Henry

2014-01-01

Morphogens are signaling molecules that regulate growth and patterning during development by forming a gradient and activating different target genes at different concentrations. The extracellular distribution of morphogens is tightly regulated, with the Drosophila morphogen Wingless (Wg) relying on Dally-like (Dlp) and transcytosis for its distribution. However, in the absence of Dlp or endocytic activity, Wg can still move across cells along the apical (Ap) surface. We identified a novel secreted heparan sulfate proteoglycan (HSPG) that binds to Wg and promotes its extracellular distribution by increasing Wg mobility, which was thus named Carrier of Wg (Cow). Cow promotes the Ap transport of Wg, independent of Dlp and endocytosis, and this function addresses a previous gap in the understanding of Wg movement. This is the first example of a diffusible HSPG acting as a carrier to promote the extracellular movement of a morphogen. PMID:25360738

Albumin as a "Trojan Horse" for polymeric nanoconjugate transendothelial transport across tumor vasculatures for improved cancer targeting.

PubMed

Yin, Qian; Tang, Li; Cai, Kaimin; Yang, Xujuan; Yin, Lichen; Zhang, Yanfeng; Dobrucki, Lawrence W; Helferich, William G; Fan, Timothy M; Cheng, Jianjun

2018-05-01

Although polymeric nanoconjugates (NCs) hold great promise for the treatment of cancer patients, their clinical utility has been hindered by the lack of efficient delivery of therapeutics to targeted tumor sites. Here, we describe an albumin-functionalized polymeric NC (Alb-NC) capable of crossing the endothelium barrier through a caveolae-mediated transcytosis pathway to better target cancer. The Alb-NC is prepared by nanoprecipitation of doxorubicin (Doxo) conjugates of poly(phenyl O-carboxyanhydrides) bearing aromatic albumin-binding domains followed by subsequent surface decoration of albumin. The administration of Alb-NCs into mice bearing MCF-7 human breast cancer xenografts with limited tumor vascular permeability resulted in markedly increased tumor accumulation and anti-tumor efficacy compared to their conventional counterpart PEGylated NCs (PEG-NCs). The Alb-NC provides a simple, low-cost and broadly applicable strategy to improve the cancer targeting efficiency and therapeutic effectiveness of polymeric nanomedicine.

Requirements for Medical Modeling Languages

PubMed Central

van der Maas, Arnoud A.F.; Ter Hofstede, Arthur H.M.; Ten Hoopen, A. Johannes

2001-01-01

Objective: The development of tailor-made domain-specific modeling languages is sometimes desirable in medical informatics. Naturally, the development of such languages should be guided. The purpose of this article is to introduce a set of requirements for such languages and show their application in analyzing and comparing existing modeling languages. Design: The requirements arise from the practical experience of the authors and others in the development of modeling languages in both general informatics and medical informatics. The requirements initially emerged from the analysis of information modeling techniques. The requirements are designed to be orthogonal, i.e., one requirement can be violated without violation of the others. Results: The proposed requirements for any modeling language are that it be “formal” with regard to syntax and semantics, “conceptual,” “expressive,” “comprehensible,” “suitable,” and “executable.” The requirements are illustrated using both the medical logic modules of the Arden Syntax as a running example and selected examples from other modeling languages. Conclusion: Activity diagrams of the Unified Modeling Language, task structures for work flows, and Petri nets are discussed with regard to the list of requirements, and various tradeoffs are thus made explicit. It is concluded that this set of requirements has the potential to play a vital role in both the evaluation of existing domain-specific languages and the development of new ones. PMID:11230383

Capturing security requirements for software systems.

PubMed

El-Hadary, Hassan; El-Kassas, Sherif

2014-07-01

Security is often an afterthought during software development. Realizing security early, especially in the requirement phase, is important so that security problems can be tackled early enough before going further in the process and avoid rework. A more effective approach for security requirement engineering is needed to provide a more systematic way for eliciting adequate security requirements. This paper proposes a methodology for security requirement elicitation based on problem frames. The methodology aims at early integration of security with software development. The main goal of the methodology is to assist developers elicit adequate security requirements in a more systematic way during the requirement engineering process. A security catalog, based on the problem frames, is constructed in order to help identifying security requirements with the aid of previous security knowledge. Abuse frames are used to model threats while security problem frames are used to model security requirements. We have made use of evaluation criteria to evaluate the resulting security requirements concentrating on conflicts identification among requirements. We have shown that more complete security requirements can be elicited by such methodology in addition to the assistance offered to developers to elicit security requirements in a more systematic way.

Capturing security requirements for software systems

PubMed Central

El-Hadary, Hassan; El-Kassas, Sherif

2014-01-01

Security is often an afterthought during software development. Realizing security early, especially in the requirement phase, is important so that security problems can be tackled early enough before going further in the process and avoid rework. A more effective approach for security requirement engineering is needed to provide a more systematic way for eliciting adequate security requirements. This paper proposes a methodology for security requirement elicitation based on problem frames. The methodology aims at early integration of security with software development. The main goal of the methodology is to assist developers elicit adequate security requirements in a more systematic way during the requirement engineering process. A security catalog, based on the problem frames, is constructed in order to help identifying security requirements with the aid of previous security knowledge. Abuse frames are used to model threats while security problem frames are used to model security requirements. We have made use of evaluation criteria to evaluate the resulting security requirements concentrating on conflicts identification among requirements. We have shown that more complete security requirements can be elicited by such methodology in addition to the assistance offered to developers to elicit security requirements in a more systematic way. PMID:25685514

48 CFR 806.501 - Requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Requirement. 806.501 Section 806.501 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 806.501 Requirement. (a) The Associate...

48 CFR 2406.501 - Requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Requirement. 2406.501 Section 2406.501 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 2406.501 Requirement. The...

48 CFR 606.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Requirement. 606.501 Section 606.501 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 606.501 Requirement. (a) The Procurement Executive...

48 CFR 606.501 - Requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Requirement. 606.501 Section 606.501 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 606.501 Requirement. (a) The Procurement Executive...

48 CFR 906.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Requirement. 906.501 Section 906.501 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 906.501 Requirement. The Secretary of Energy and...

48 CFR 2406.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Requirement. 2406.501 Section 2406.501 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 2406.501 Requirement. The...

48 CFR 406.501 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Requirements. 406.501 Section 406.501 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 406.501 Requirements. (a) The Chief...

48 CFR 1306.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Requirement. 1306.501 Section 1306.501 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 1306.501 Requirement. The designee authorized to...

48 CFR 1206.501 - Requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Requirement. 1206.501 Section 1206.501 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 1206.501 Requirement. The DOT Senior Competition Advocate (SCA...

48 CFR 31.703 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Requirements. 31.703 Section 31.703 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Nonprofit Organizations 31.703 Requirements...

48 CFR 606.501 - Requirement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Requirement. 606.501 Section 606.501 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 606.501 Requirement. (a) The Procurement Executive...

48 CFR 1206.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Requirement. 1206.501 Section 1206.501 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 1206.501 Requirement. The DOT Senior Competition Advocate (SCA...

48 CFR 3406.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Requirement. 3406.501 Section 3406.501 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 3406.501 Requirement. The...

48 CFR 31.703 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Requirements. 31.703 Section 31.703 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Nonprofit Organizations 31.703 Requirements...

48 CFR 1306.501 - Requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Requirement. 1306.501 Section 1306.501 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 1306.501 Requirement. The designee authorized to...

48 CFR 806.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Requirement. 806.501 Section 806.501 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 806.501 Requirement. (a) The Associate...

48 CFR 406.501 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Requirements. 406.501 Section 406.501 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 406.501 Requirements. (a) The Chief...

48 CFR 906.501 - Requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Requirement. 906.501 Section 906.501 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 906.501 Requirement. The Secretary of Energy has...

48 CFR 406.501 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Requirements. 406.501 Section 406.501 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 406.501 Requirements. (a) The Chief...

48 CFR 3406.501 - Requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Requirement. 3406.501 Section 3406.501 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 3406.501 Requirement. The...

48 CFR 406.501 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Requirements. 406.501 Section 406.501 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 406.501 Requirements. (a) The Chief...

48 CFR 1406.501 - Requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Requirement. 1406.501 Section 1406.501 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 1406.501 Requirement. (a) The competition...

48 CFR 606.501 - Requirement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Requirement. 606.501 Section 606.501 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 606.501 Requirement. (a) The Procurement Executive...

48 CFR 31.703 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Requirements. 31.703 Section 31.703 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Nonprofit Organizations 31.703 Requirements...

48 CFR 406.501 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Requirements. 406.501 Section 406.501 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 406.501 Requirements. (a) The Chief...

48 CFR 2406.501 - Requirement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Requirement. 2406.501 Section 2406.501 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 2406.501 Requirement. The...

48 CFR 1406.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Requirement. 1406.501 Section 1406.501 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 1406.501 Requirement. (a) The competition...

48 CFR 31.703 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Requirements. 31.703 Section 31.703 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Nonprofit Organizations 31.703 Requirements...

48 CFR 2406.501 - Requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Requirement. 2406.501 Section 2406.501 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 2406.501 Requirement. The...

48 CFR 3406.501 - Requirement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Requirement. 3406.501 Section 3406.501 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 3406.501 Requirement. The...

48 CFR 606.501 - Requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Requirement. 606.501 Section 606.501 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 606.501 Requirement. (a) The Procurement Executive...

48 CFR 306.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Requirement. 306.501 Section 306.501 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 306.501 Requirement. The HHS CA is the...

48 CFR 306.501 - Requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Requirement. 306.501 Section 306.501 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 306.501 Requirement. The HHS CA is the...

48 CFR 3006.501 - Requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Requirement. 3006.501... ACQUISITION REGULATION (HSAR) ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 3006.501 Requirement. The DHS Senior Competition Advocate (SCA) is located in the Office of the Chief Procurement...

48 CFR 3006.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Requirement. 3006.501... ACQUISITION REGULATION (HSAR) ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 3006.501 Requirement. The DHS Senior Competition Advocate (SCA) is located in the Office of the Chief Procurement...

48 CFR 2806.501 - Requirement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Requirement. 2806.501 Section 2806.501 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 2806.501 Requirement. In accordance with FAR 6.501...

48 CFR 3003.1003 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Requirements. 3003.1003 Section 3003.1003 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... INTEREST Contractor Code of Business Ethics and Conduct 3003.1003 Requirements. (a) Contractor requirements...

48 CFR 2806.501 - Requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Requirement. 2806.501 Section 2806.501 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 2806.501 Requirement. In accordance with FAR 6.501...

48 CFR 306.501 - Requirement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Requirement. 306.501 Section 306.501 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 306.501 Requirement. The HHS CA is the...

48 CFR 3006.501 - Requirement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Requirement. 3006.501... ACQUISITION REGULATION (HSAR) ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 3006.501 Requirement. The DHS Senior Competition Advocate (SCA) is located in the Office of the Chief Procurement...

48 CFR 231.303 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Requirements. 231.303... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Educational Institutions 231.303 Requirements. (1) Pursuant to section 841 of the National Defense...

48 CFR 3003.1003 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Requirements. 3003.1003 Section 3003.1003 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... INTEREST Contractor Code of Business Ethics and Conduct 3003.1003 Requirements. (a) Contractor requirements...

48 CFR 2806.501 - Requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Requirement. 2806.501 Section 2806.501 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 2806.501 Requirement. In accordance with FAR 6.501...

48 CFR 3003.1003 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Requirements. 3003.1003 Section 3003.1003 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... INTEREST Contractor Code of Business Ethics and Conduct 3003.1003 Requirements. (a) Contractor requirements...

48 CFR 231.303 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Requirements. 231.303... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Educational Institutions 231.303 Requirements. (1) Pursuant to section 841 of the National Defense...

48 CFR 231.303 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Requirements. 231.303... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Educational Institutions 231.303 Requirements. (1) Pursuant to section 841 of the National Defense...

48 CFR 3006.501 - Requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Requirement. 3006.501... ACQUISITION REGULATION (HSAR) ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 3006.501 Requirement. The DHS Senior Competition Advocate (SCA) is located in the Office of the Chief Procurement...

Requirement Development Process and Tools

NASA Technical Reports Server (NTRS)

Bayt, Robert

2017-01-01

Requirements capture the system-level capabilities in a set of complete, necessary, clear, attainable, traceable, and verifiable statements of need. Requirements should not be unduly restrictive, but should set limits that eliminate items outside the boundaries drawn, encourage competition (or alternatives), and capture source and reason of requirement. If it is not needed by the customer, it is not a requirement. They establish the verification methods that will lead to product acceptance. These must be reproducible assessment methods.

Writing testable software requirements

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

Knirk, D.

1997-11-01

This tutorial identifies common problems in analyzing requirements in the problem and constructing a written specification of what the software is to do. It deals with two main problem areas: identifying and describing problem requirements, and analyzing and describing behavior specifications.

48 CFR 31.303 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Requirements. 31.303... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Educational Institutions 31.303 Requirements. (a) Contracts that refer to this subpart 31.3 for determining allowable costs under contracts...

48 CFR 231.603 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Requirements. 231.603... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With State, Local, and Federally Recognized Indian Tribal Governments 231.603 Requirements. Under 10 U.S.C...

48 CFR 31.303 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Requirements. 31.303... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Educational Institutions 31.303 Requirements. (a) Contracts that refer to this subpart 31.3 for determining allowable costs under contracts...

48 CFR 231.603 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Requirements. 231.603... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With State, Local, and Federally Recognized Indian Tribal Governments 231.603 Requirements. Under 10 U.S.C...

48 CFR 41.301 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Requirements. 41.301... CONTRACTING ACQUISITION OF UTILITY SERVICES Requests for Assistance 41.301 Requirements. (a) Requests for... utility service requirements, the agency shall furnish the information in paragraph (a) of this section...

48 CFR 41.301 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Requirements. 41.301... CONTRACTING ACQUISITION OF UTILITY SERVICES Requests for Assistance 41.301 Requirements. (a) Requests for... utility service requirements, the agency shall furnish the information in paragraph (a) of this section...

48 CFR 31.303 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Requirements. 31.303... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Educational Institutions 31.303 Requirements. (a) Contracts that refer to this subpart 31.3 for determining allowable costs under contracts...

48 CFR 31.303 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Requirements. 31.303... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Educational Institutions 31.303 Requirements. (a) Contracts that refer to this subpart 31.3 for determining allowable costs under contracts...

48 CFR 231.603 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Requirements. 231.603... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With State, Local, and Federally Recognized Indian Tribal Governments 231.603 Requirements. Under 10 U.S.C...

48 CFR 231.603 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Requirements. 231.603... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With State, Local, and Federally Recognized Indian Tribal Governments 231.603 Requirements. Under 10 U.S.C...

30 CFR 75.1100 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Requirements. 75.1100 Section 75.1100 Mineral... SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection § 75.1100 Requirements. [Statutory Provision... conditions of the mine. The Secretary shall establish minimum requirements of the type, quality, and quantity...

30 CFR 75.1100 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Requirements. 75.1100 Section 75.1100 Mineral... SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection § 75.1100 Requirements. [Statutory Provision... conditions of the mine. The Secretary shall establish minimum requirements of the type, quality, and quantity...

30 CFR 75.1100 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Requirements. 75.1100 Section 75.1100 Mineral... SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection § 75.1100 Requirements. [Statutory Provision... conditions of the mine. The Secretary shall establish minimum requirements of the type, quality, and quantity...

24 CFR 200.620 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Requirements. 200.620 Section 200... Requirements. With respect to all FHA subsidized or unsubsidized programs in which the applicant hereafter... of these regulations), the applicant shall meet the following requirements or, if he contracts...

24 CFR 200.620 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Requirements. 200.620 Section 200... Requirements. With respect to all FHA subsidized or unsubsidized programs in which the applicant hereafter... of these regulations), the applicant shall meet the following requirements or, if he contracts...

30 CFR 75.1100 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Requirements. 75.1100 Section 75.1100 Mineral... SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection § 75.1100 Requirements. [Statutory Provision... conditions of the mine. The Secretary shall establish minimum requirements of the type, quality, and quantity...

Physician Requirements-1990. For Cardiology.

ERIC Educational Resources Information Center

Tracy, Octavious; Birchette-Pierce, Cheryl

Professional requirements for physicians specializing in cardiology were estimated to assist policymakers in developing guidelines for graduate medical education. The determination of physician requirements was based on an adjusted needs rather than a demand or utilization model. For each illness, manpower requirements were modified by the…

Navigating the Requirements Jungle

NASA Astrophysics Data System (ADS)

Langer, Boris; Tautschnig, Michael

Research on validation and verification of requirements specifications has thus far focused on functional properties. Yet, in embedded systems, functional requirements constitute only a small fraction of the properties that must hold to guarantee proper and safe operation of the system under design.

Closed Loop Requirements and Analysis Management

NASA Technical Reports Server (NTRS)

Lamoreaux, Michael; Verhoef, Brett

2015-01-01

Effective systems engineering involves the use of analysis in the derivation of requirements and verification of designs against those requirements. The initial development of requirements often depends on analysis for the technical definition of specific aspects of a product. Following the allocation of system-level requirements to a product's components, the closure of those requirements often involves analytical approaches to verify that the requirement criteria have been satisfied. Meanwhile, changes that occur in between these two processes need to be managed in order to achieve a closed-loop requirement derivation/verification process. Herein are presented concepts for employing emerging Team center capabilities to jointly manage requirements and analysis data such that analytical techniques are utilized to effectively derive and allocate requirements, analyses are consulted and updated during the change evaluation processes, and analyses are leveraged during the design verification process. Recommendations on concept validation case studies are also discussed.

48 CFR 370.503 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Requirements. 370.503... SPECIAL PROGRAMS AFFECTING ACQUISITION Acquisitions Under the Buy Indian Act 370.503 Requirements. (a.... Contracts awarded under the Buy Indian Act are subject to the requirements of section 7(b) of the Indian...

23 CFR 500.105 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 23 Highways 1 2012-04-01 2012-04-01 false Requirements. 500.105 Section 500.105 Highways FEDERAL... AND MONITORING SYSTEMS Management Systems § 500.105 Requirements. (a) The metropolitan transportation... requirements of § 500.109 of this regulation. (b) States shall develop, establish, and implement a TMS that...

49 CFR 569.7 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 6 2012-10-01 2012-10-01 false Requirements. 569.7 Section 569.7 Transportation..., DEPARTMENT OF TRANSPORTATION REGROOVED TIRES § 569.7 Requirements. (a) Regrooved tires. (1) Except as... requirements: (i) The tire being regrooved shall be a regroovable tire; (ii) After regrooving, cord material...

30 CFR 40.2 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Requirements. 40.2 Section 40.2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR FILING AND OTHER ADMINISTRATIVE REQUIREMENTS REPRESENTATIVE OF MINERS § 40.2 Requirements. (a) A representative of miners shall file with the...

48 CFR 231.703 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Requirements. 231.703... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Nonprofit Organizations 231.703 Requirements. Under 10 U.S.C. 2249, the costs cited in 231.205-22(a) are...

30 CFR 40.2 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Requirements. 40.2 Section 40.2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR FILING AND OTHER ADMINISTRATIVE REQUIREMENTS REPRESENTATIVE OF MINERS § 40.2 Requirements. (a) A representative of miners shall file with the...

48 CFR 231.703 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Requirements. 231.703... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Nonprofit Organizations 231.703 Requirements. Under 10 U.S.C. 2249, the costs cited in 231.205-22(a) are...

48 CFR 231.703 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Requirements. 231.703... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Nonprofit Organizations 231.703 Requirements. Under 10 U.S.C. 2249, the costs cited in 231.205-22(a) are...

30 CFR 40.2 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Requirements. 40.2 Section 40.2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR FILING AND OTHER ADMINISTRATIVE REQUIREMENTS REPRESENTATIVE OF MINERS § 40.2 Requirements. (a) A representative of miners shall file with the...

49 CFR 569.7 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 6 2014-10-01 2014-10-01 false Requirements. 569.7 Section 569.7 Transportation..., DEPARTMENT OF TRANSPORTATION REGROOVED TIRES § 569.7 Requirements. (a) Regrooved tires. (1) Except as... requirements: (i) The tire being regrooved shall be a regroovable tire; (ii) After regrooving, cord material...

23 CFR 500.105 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Requirements. 500.105 Section 500.105 Highways FEDERAL... AND MONITORING SYSTEMS Management Systems § 500.105 Requirements. (a) The metropolitan transportation... requirements of § 500.109 of this regulation. (b) States shall develop, establish, and implement a TMS that...

30 CFR 40.2 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Requirements. 40.2 Section 40.2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR FILING AND OTHER ADMINISTRATIVE REQUIREMENTS REPRESENTATIVE OF MINERS § 40.2 Requirements. (a) A representative of miners shall file with the...

48 CFR 370.503 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Requirements. 370.503... SPECIAL PROGRAMS AFFECTING ACQUISITION Acquisitions Under the Buy Indian Act 370.503 Requirements. (a.... Contracts awarded under the Buy Indian Act are subject to the requirements of section 7(b) of the Indian...

48 CFR 370.503 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Requirements. 370.503... SPECIAL PROGRAMS AFFECTING ACQUISITION Acquisitions Under the Buy Indian Act 370.503 Requirements. (a.... Contracts awarded under the Buy Indian Act are subject to the requirements of section 7(b) of the Indian...

49 CFR 569.7 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 6 2011-10-01 2011-10-01 false Requirements. 569.7 Section 569.7 Transportation..., DEPARTMENT OF TRANSPORTATION REGROOVED TIRES § 569.7 Requirements. (a) Regrooved tires. (1) Except as... requirements: (i) The tire being regrooved shall be a regroovable tire; (ii) After regrooving, cord material...

48 CFR 370.503 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Requirements. 370.503... SPECIAL PROGRAMS AFFECTING ACQUISITION Acquisitions Under the Buy Indian Act 370.503 Requirements. (a.... Contracts awarded under the Buy Indian Act are subject to the requirements of section 7(b) of the Indian...

48 CFR 370.503 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Requirements. 370.503... SPECIAL PROGRAMS AFFECTING ACQUISITION Acquisitions Under the Buy Indian Act 370.503 Requirements. (a.... Contracts awarded under the Buy Indian Act are subject to the requirements of section 7(b) of the Indian...

48 CFR 231.703 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Requirements. 231.703... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Nonprofit Organizations 231.703 Requirements. Under 10 U.S.C. 2249, the costs cited in 231.205-22(a) are...

Requirements for soldered electrical connections

NASA Technical Reports Server (NTRS)

1992-01-01

This publication is applicable to NASA programs involving solder connections for flight hardware, mission essential support equipment, and elements thereof. This publication sets forth hand and wave soldering requirements for reliable electrical connections. The prime consideration is the physical integrity of solder connections. Special requirements may exist which are not in conformance with the requirements of this publication. Design documentation contains the detail for these requirements, and they take precedence over conflicting portions of this publication when they are approved in writing by the procuring NASA installation.

Managing Information On Technical Requirements

NASA Technical Reports Server (NTRS)

Mauldin, Lemuel E., III; Hammond, Dana P.

1993-01-01

Technical Requirements Analysis and Control Systems/Initial Operating Capability (TRACS/IOC) computer program provides supplemental software tools for analysis, control, and interchange of project requirements so qualified project members have access to pertinent project information, even if in different locations. Enables users to analyze and control requirements, serves as focal point for project requirements, and integrates system supporting efficient and consistent operations. TRACS/IOC is HyperCard stack for use on Macintosh computers running HyperCard 1.2 or later and Oracle 1.2 or later.

Range Flight Safety Requirements

NASA Technical Reports Server (NTRS)

Loftin, Charles E.; Hudson, Sandra M.

2018-01-01

The purpose of this NASA Technical Standard is to provide the technical requirements for the NPR 8715.5, Range Flight Safety Program, in regards to protection of the public, the NASA workforce, and property as it pertains to risk analysis, Flight Safety Systems (FSS), and range flight operations. This standard is approved for use by NASA Headquarters and NASA Centers, including Component Facilities and Technical and Service Support Centers, and may be cited in contract, program, and other Agency documents as a technical requirement. This standard may also apply to the Jet Propulsion Laboratory or to other contractors, grant recipients, or parties to agreements to the extent specified or referenced in their contracts, grants, or agreements, when these organizations conduct or participate in missions that involve range flight operations as defined by NPR 8715.5.1.2.2 In this standard, all mandatory actions (i.e., requirements) are denoted by statements containing the term “shall.”1.3 TailoringTailoring of this standard for application to a specific program or project shall be formally documented as part of program or project requirements and approved by the responsible Technical Authority in accordance with NPR 8715.3, NASA General Safety Program Requirements.

45 CFR 1000.3 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Requirements. 1000.3 Section 1000.3 Public Welfare... ESTABLISHED PURSUANT TO GRANTS FOR ASSETS FOR INDEPENDENCE § 1000.3 Requirements. (a) A qualified entity... and Human Services' uniform administrative requirements under 45 CFR part 74. (b) Any reserve fund...

45 CFR 1000.3 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 3 2012-10-01 2012-10-01 false Requirements. 1000.3 Section 1000.3 Public Welfare... ESTABLISHED PURSUANT TO GRANTS FOR ASSETS FOR INDEPENDENCE § 1000.3 Requirements. (a) A qualified entity... and Human Services' uniform administrative requirements under 45 CFR part 74. (b) Any reserve fund...

45 CFR 1000.3 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Requirements. 1000.3 Section 1000.3 Public Welfare... ESTABLISHED PURSUANT TO GRANTS FOR ASSETS FOR INDEPENDENCE § 1000.3 Requirements. (a) A qualified entity... and Human Services' uniform administrative requirements under 45 CFR part 74. (b) Any reserve fund...

45 CFR 1000.3 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Requirements. 1000.3 Section 1000.3 Public Welfare... ESTABLISHED PURSUANT TO GRANTS FOR ASSETS FOR INDEPENDENCE § 1000.3 Requirements. (a) A qualified entity... and Human Services' uniform administrative requirements under 45 CFR part 74. (b) Any reserve fund...

50 CFR 15.12 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 1 2012-10-01 2012-10-01 false Requirements. 15.12 Section 15.12 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR TAKING, POSSESSION... CONSERVATION ACT Prohibitions and Requirements § 15.12 Requirements. (a) No person shall import into the United...

50 CFR 15.12 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 1 2013-10-01 2013-10-01 false Requirements. 15.12 Section 15.12 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR TAKING, POSSESSION... CONSERVATION ACT Prohibitions and Requirements § 15.12 Requirements. (a) No person shall import into the United...

36 CFR 254.3 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 2 2013-07-01 2013-07-01 false Requirements. 254.3 Section... ADJUSTMENTS Land Exchanges § 254.3 Requirements. (a) Discretionary nature of exchanges. The Secretary is not... requirements for notices established in 40 CFR part 373. Unless the non-Federal party is a potentially...

45 CFR 1000.3 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 3 2014-10-01 2014-10-01 false Requirements. 1000.3 Section 1000.3 Public Welfare... ESTABLISHED PURSUANT TO GRANTS FOR ASSETS FOR INDEPENDENCE § 1000.3 Requirements. (a) A qualified entity... and Human Services' uniform administrative requirements under 45 CFR part 74. (b) Any reserve fund...

50 CFR 15.12 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 1 2011-10-01 2011-10-01 false Requirements. 15.12 Section 15.12 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR TAKING, POSSESSION... CONSERVATION ACT Prohibitions and Requirements § 15.12 Requirements. (a) No person shall import into the United...

16 CFR 1204.3 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... omnidirectional CB base station antennas are required to comply with the following requirements. (a) Field joints. Parts or accessories intended to protect a field joint so that it will meet any other requirement of... of the cable shall be supplied by the manufacturer with the antenna system. (c) Electrical protection...

16 CFR 1204.3 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... omnidirectional CB base station antennas are required to comply with the following requirements. (a) Field joints. Parts or accessories intended to protect a field joint so that it will meet any other requirement of... of the cable shall be supplied by the manufacturer with the antenna system. (c) Electrical protection...

Historical and projected power requirements

NASA Technical Reports Server (NTRS)

Wolfe, M. G.

1978-01-01

Policy planning for projected space power requirements is discussed. Topics of discussion cover: (1) historical space power trends (prime power requirements and power system costs); and (2) two approaches to future space power requirements (mission/traffic model approach and advanced system scenario approach). Graphs, tables, and flow charts are presented.

32 CFR 101.5 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false Requirements. 101.5 Section 101.5 National... PARTICIPATION IN RESERVE TRAINING PROGRAMS § 101.5 Requirements. (a) Reserve participation—(1) Training requirements under 10 U.S.C. 270(a). (i) Each individual inducted, enlisted, or appointed in the U.S. Armed...

32 CFR 101.5 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Requirements. 101.5 Section 101.5 National... PARTICIPATION IN RESERVE TRAINING PROGRAMS § 101.5 Requirements. (a) Reserve participation—(1) Training requirements under 10 U.S.C. 270(a). (i) Each individual inducted, enlisted, or appointed in the U.S. Armed...

29 CFR 548.200 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 3 2014-07-01 2014-07-01 false Requirements. 548.200 Section 548.200 Labor Regulations... ESTABLISHED BASIC RATES FOR COMPUTING OVERTIME PAY Interpretations Requirements for A Basic Rate § 548.200 Requirements. The following conditions must be satisfied if a “basic” rate is to be considered proper under...

29 CFR 548.200 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 3 2013-07-01 2013-07-01 false Requirements. 548.200 Section 548.200 Labor Regulations... ESTABLISHED BASIC RATES FOR COMPUTING OVERTIME PAY Interpretations Requirements for A Basic Rate § 548.200 Requirements. The following conditions must be satisfied if a “basic” rate is to be considered proper under...

29 CFR 548.200 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 3 2012-07-01 2012-07-01 false Requirements. 548.200 Section 548.200 Labor Regulations... ESTABLISHED BASIC RATES FOR COMPUTING OVERTIME PAY Interpretations Requirements for A Basic Rate § 548.200 Requirements. The following conditions must be satisfied if a “basic” rate is to be considered proper under...

16 CFR 1213.3 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Requirements. 1213.3 Section 1213.3... STANDARD FOR ENTRAPMENT HAZARDS IN BUNK BEDS § 1213.3 Requirements. (a) Guardrails. (1) Any bunk bed shall... instructions is on the bed. This requirement does not prohibit a wall-side guardrail that terminates in a...

32 CFR 101.5 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false Requirements. 101.5 Section 101.5 National... PARTICIPATION IN RESERVE TRAINING PROGRAMS § 101.5 Requirements. (a) Reserve participation—(1) Training requirements under 10 U.S.C. 270(a). (i) Each individual inducted, enlisted, or appointed in the U.S. Armed...

16 CFR 1213.3 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Requirements. 1213.3 Section 1213.3... STANDARD FOR ENTRAPMENT HAZARDS IN BUNK BEDS § 1213.3 Requirements. (a) Guardrails. (1) Any bunk bed shall... instructions is on the bed. This requirement does not prohibit a wall-side guardrail that terminates in a...

Requirements for an Advanced Ocean Radiometer

NASA Technical Reports Server (NTRS)

Meister, Gerhard; McClain, Charles R.; Ahmad, Ziauddin; Bailey, Sean W.; Barnes, Robert A.; Brown, Steven; Eplee, Robert E.; Franz, Bryan; Holmes, Alan; Monosmith, W. Bryan;

49 CFR 585.45 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Fuel System Integrity Phase-In Reporting Requirements § 585.45 Reporting requirements. (a) General reporting requirements... manufactured during the current production year. (2) Production. Each manufacturer shall report for the...

49 CFR 585.45 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Fuel System Integrity Phase-In Reporting Requirements § 585.45 Reporting requirements. (a) General reporting requirements... manufactured during the current production year. (2) Production. Each manufacturer shall report for the...

42 CFR 66.205 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Requirements. 66.205 Section 66.205 Public Health... NATIONAL RESEARCH SERVICE AWARDS Institutional Grants § 66.205 Requirements. (a) No Award shall be made to... the form and manner the Secretary may prescribe, that he or she will satisfy the requirements of § 66...

48 CFR 242.7302 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Requirements. 242.7302.../Pension Review 242.7302 Requirements. (a)(1) An in-depth CIPR as described at DFARS 242.7301(a)(1) shall... requirements in paragraph (a) of this section) when any of the following circumstances exists, but only if the...

42 CFR 66.205 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Requirements. 66.205 Section 66.205 Public Health... NATIONAL RESEARCH SERVICE AWARDS Institutional Grants § 66.205 Requirements. (a) No Award shall be made to... the form and manner the Secretary may prescribe, that he or she will satisfy the requirements of § 66...

48 CFR 242.7302 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Requirements. 242.7302.../Pension Review 242.7302 Requirements. (a)(1) An in-depth CIPR as described at DFARS 242.7301(a)(1) shall... requirements in paragraph (a) of this section) when any of the following circumstances exists, but only if the...

49 CFR 585.116 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Roof Crush Resistance Phase-in Reporting Requirements § 585.116 Reporting requirements. (a) General reporting requirements... years, or, at the manufacturer's option, for the current production year. A new manufacturer that has...

49 CFR 585.116 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Roof Crush Resistance Phase-in Reporting Requirements § 585.116 Reporting requirements. (a) General reporting requirements... years, or, at the manufacturer's option, for the current production year. A new manufacturer that has...

48 CFR 630.201 - Contract requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Contract requirements. 630.201 Section 630.201 Federal Acquisition Regulations System DEPARTMENT OF STATE GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 630.201 Contract requirements. ...

48 CFR 330.201 - Contract requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Contract requirements. 330.201 Section 330.201 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS CAS Program Requirements 330.201 Contract requirements. ...

Information System Requirements Determination: Factors Impeding Stakeholders from Reaching Common Understandings and Agreements on Requirements

ERIC Educational Resources Information Center

Gissel, Richard L.

2010-01-01

Information system implementations require developers to first know what they must create and then determine how best to create it. The requirements determination phase of the system development life cycle typically determines what functions a system must perform and how well it must accomplish required functions. Implementation success depends on…

48 CFR 806.570 - Planning requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Planning requirements. 806... AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Competition Advocates 806.570 Planning requirements... planning that is required. (3) A description of how to integrate the Competition Plan into advance...

46 CFR 67.220 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Requirements. 67.220 Section 67.220 Shipping COAST GUARD... Filing and Recording of Instruments-Bills of Sale and Related Instruments § 67.220 Requirements. An instrument in the nature of a bill of sale or a deed of gift must: (a) Meet all of the requirements of...

40 CFR 82.84 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Requirements. 82.84 Section 82.84... STRATOSPHERIC OZONE Federal Procurement § 82.84 Requirements. (a) No later than October 24, 1994, each... requirements and policies of title VI of the Clean Air Act, 42 U.S.C. 7671-7671g. Each such regulation shall...

40 CFR 82.84 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Requirements. 82.84 Section 82.84... STRATOSPHERIC OZONE Federal Procurement § 82.84 Requirements. (a) No later than October 24, 1994, each... requirements and policies of title VI of the Clean Air Act, 42 U.S.C. 7671-7671g. Each such regulation shall...

40 CFR 82.84 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 18 2013-07-01 2013-07-01 false Requirements. 82.84 Section 82.84... STRATOSPHERIC OZONE Federal Procurement § 82.84 Requirements. (a) No later than October 24, 1994, each... requirements and policies of title VI of the Clean Air Act, 42 U.S.C. 7671-7671g. Each such regulation shall...

40 CFR 82.84 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 17 2011-07-01 2011-07-01 false Requirements. 82.84 Section 82.84... STRATOSPHERIC OZONE Federal Procurement § 82.84 Requirements. (a) No later than October 24, 1994, each... requirements and policies of title VI of the Clean Air Act, 42 U.S.C. 7671-7671g. Each such regulation shall...

40 CFR 82.84 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 18 2012-07-01 2012-07-01 false Requirements. 82.84 Section 82.84... STRATOSPHERIC OZONE Federal Procurement § 82.84 Requirements. (a) No later than October 24, 1994, each... requirements and policies of title VI of the Clean Air Act, 42 U.S.C. 7671-7671g. Each such regulation shall...

46 CFR 67.220 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Requirements. 67.220 Section 67.220 Shipping COAST GUARD... Filing and Recording of Instruments-Bills of Sale and Related Instruments § 67.220 Requirements. An instrument in the nature of a bill of sale or a deed of gift must: (a) Meet all of the requirements of...

46 CFR 67.220 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Requirements. 67.220 Section 67.220 Shipping COAST GUARD... Filing and Recording of Instruments-Bills of Sale and Related Instruments § 67.220 Requirements. An instrument in the nature of a bill of sale or a deed of gift must: (a) Meet all of the requirements of...

49 CFR 585.15 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting Requirements § 585.15 Reporting requirements. (a) Advanced credit phase-in reporting... any of those production years as complying with phase one of the advanced air bag requirements of...

49 CFR 585.15 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Advanced Air Bag Phase-in Reporting Requirements § 585.15 Reporting requirements. (a) Advanced credit phase-in reporting... any of those production years as complying with phase one of the advanced air bag requirements of...

47 CFR 101.1325 - Construction requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Construction requirements. 101.1325 Section 101... FIXED MICROWAVE SERVICES Multiple Address Systems System Requirements § 101.1325 Construction requirements. (a) Incumbent and site-based licenses are subject to the construction requirements set forth in...

47 CFR 101.1325 - Construction requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Construction requirements. 101.1325 Section 101... FIXED MICROWAVE SERVICES Multiple Address Systems System Requirements § 101.1325 Construction requirements. (a) Incumbent and site-based licenses are subject to the construction requirements set forth in...

7 CFR 3565.255 - Environmental requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 15 2011-01-01 2011-01-01 false Environmental requirements. 3565.255 Section 3565.255... AGRICULTURE GUARANTEED RURAL RENTAL HOUSING PROGRAM Property Requirements § 3565.255 Environmental requirements. Under the National Environmental Policy Act, the Agency is required to assess the potential...

49 CFR 565.15 - Content requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 6 2012-10-01 2012-10-01 false Content requirements. 565.15 Section 565.15 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VEHICLE IDENTIFICATION NUMBER (VIN) REQUIREMENTS VIN Requirements § 565.15 Content requirements. (a) The...

49 CFR 565.15 - Content requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 6 2014-10-01 2014-10-01 false Content requirements. 565.15 Section 565.15 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VEHICLE IDENTIFICATION NUMBER (VIN) REQUIREMENTS VIN Requirements § 565.15 Content requirements. (a) The...

49 CFR 565.15 - Content requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 6 2013-10-01 2013-10-01 false Content requirements. 565.15 Section 565.15 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VEHICLE IDENTIFICATION NUMBER (VIN) REQUIREMENTS VIN Requirements § 565.15 Content requirements. (a) The...

49 CFR 383.111 - Required knowledge.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 false Required knowledge. 383.111 Section 383.111... STANDARDS; REQUIREMENTS AND PENALTIES Required Knowledge and Skills § 383.111 Required knowledge. (a) All CMV operators must have knowledge of the following 20 general areas: (1) Safe operations regulations...

49 CFR 383.111 - Required knowledge.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Required knowledge. 383.111 Section 383.111... STANDARDS; REQUIREMENTS AND PENALTIES Required Knowledge and Skills § 383.111 Required knowledge. All commercial motor vehicle operators must have knowledge of the following general areas: (a) Safe operations...

49 CFR 585.105 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Ejection Mitigation Phase-in Reporting Requirements § 585.105 Reporting requirements. (a) Advanced credit phase-in reporting... paragraph (c) of this section and in § 585.2 of this part. (b) Phase-in reporting requirements. Within 60...

49 CFR 585.76 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Side Impact Protection Phase-in Reporting Requirements § 585.76 Reporting requirements. (a) Advanced credit phase-in reporting... and in § 585.2 of this part. (2) [Reserved] (b) Phase-in reporting requirements. Within 60 days after...

40 CFR 141.70 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) NATIONAL PRIMARY DRINKING WATER REGULATIONS Filtration and Disinfection § 141.70 General requirements. (a) The requirements of this subpart H constitute national primary drinking water regulations. These... filtration requirements in § 141.73 and the disinfection requirements in § 141.72(b). (c) Each public water...

48 CFR 306.303-1 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Requirements. 306.303-1... ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 306.303-1 Requirements. (b... written in a manner to permit an individual without technical knowledge of the requirement to understand...

48 CFR 6.303-1 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Requirements. 6.303-1... COMPETITION REQUIREMENTS Other Than Full and Open Competition 6.303-1 Requirements. (a) A contracting officer... are made public after award in accordance with 6.305. (c) Technical and requirements personnel are...

40 CFR 240.210-1 - Requirement.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Requirement. 240.210-1 Section 240.210... THE THERMAL PROCESSING OF SOLID WASTES Requirements and Recommended Procedures § 240.210-1 Requirement... the design requirements. An operations manual describing the various tasks to be performed, operating...

48 CFR 306.303-1 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Requirements. 306.303-1... ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 306.303-1 Requirements. (b... written in a manner to permit an individual without technical knowledge of the requirement to understand...

48 CFR 306.303-1 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Requirements. 306.303-1... ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 306.303-1 Requirements. (b... written in a manner to permit an individual without technical knowledge of the requirement to understand...

40 CFR 240.210-1 - Requirement.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Requirement. 240.210-1 Section 240.210... THE THERMAL PROCESSING OF SOLID WASTES Requirements and Recommended Procedures § 240.210-1 Requirement... the design requirements. An operations manual describing the various tasks to be performed, operating...

48 CFR 306.303-1 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Requirements. 306.303-1... ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 306.303-1 Requirements. (b... written in a manner to permit an individual without technical knowledge of the requirement to understand...

40 CFR 240.210-1 - Requirement.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Requirement. 240.210-1 Section 240.210... THE THERMAL PROCESSING OF SOLID WASTES Requirements and Recommended Procedures § 240.210-1 Requirement... the design requirements. An operations manual describing the various tasks to be performed, operating...

48 CFR 306.303-1 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Requirements. 306.303-1... ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 306.303-1 Requirements. (b... written in a manner to permit an individual without technical knowledge of the requirement to understand...

49 CFR 585.24 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Rear Inboard Lap/Shoulder Belt Phase-In Reporting Requirements § 585.24 Reporting requirements. (a) Advanced credit phase-in... paragraph (c) of this section and in § 585.2 of this part. (b) Phase-in reporting requirements. Within 60...

49 CFR 585.24 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Rear Inboard Lap/Shoulder Belt Phase-In Reporting Requirements § 585.24 Reporting requirements. (a) Advanced credit phase-in... paragraph (c) of this section and in § 585.2 of this part. (b) Phase-in reporting requirements. Within 60...

20 CFR 655.152 - Advertising requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Advertising requirements. 655.152 Section 655... Employment in the United States (H-2A Workers) Post-Acceptance Requirements § 655.152 Advertising requirements. All advertising conducted to satisfy the required recruitment activities under § 655.151 must...

20 CFR 655.152 - Advertising requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Advertising requirements. 655.152 Section 655... Employment in the United States (H-2A Workers) Post-Acceptance Requirements § 655.152 Advertising requirements. All advertising conducted to satisfy the required recruitment activities under § 655.151 must...

20 CFR 655.152 - Advertising requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Advertising requirements. 655.152 Section 655... Employment in the United States (H-2A Workers) Post-Acceptance Requirements § 655.152 Advertising requirements. All advertising conducted to satisfy the required recruitment activities under § 655.151 must...

20 CFR 655.152 - Advertising requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Advertising requirements. 655.152 Section 655... Employment in the United States (H-2A Workers) Post-Acceptance Requirements § 655.152 Advertising requirements. All advertising conducted to satisfy the required recruitment activities under § 655.151 must...

20 CFR 655.152 - Advertising requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Advertising requirements. 655.152 Section 655... Employment in the United States (H-2A Workers) Post-Acceptance Requirements § 655.152 Advertising requirements. All advertising conducted to satisfy the required recruitment activities under § 655.151 must...

Data Crosscutting Requirements Review

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

Kleese van Dam, Kerstin; Shoshani, Arie; Plata, Charity

2013-04-01

In April 2013, a diverse group of researchers from the U.S. Department of Energy (DOE) scientific community assembled to assess data requirements associated with DOE-sponsored scientific facilities and large-scale experiments. Participants in the review included facilities staff, program managers, and scientific experts from the offices of Basic Energy Sciences, Biological and Environmental Research, High Energy Physics, and Advanced Scientific Computing Research. As part of the meeting, review participants discussed key issues associated with three distinct aspects of the data challenge: 1) processing, 2) management, and 3) analysis. These discussions identified commonalities and differences among the needs of varied scientific communities.more » They also helped to articulate gaps between current approaches and future needs, as well as the research advances that will be required to close these gaps. Moreover, the review provided a rare opportunity for experts from across the Office of Science to learn about their collective expertise, challenges, and opportunities. The "Data Crosscutting Requirements Review" generated specific findings and recommendations for addressing large-scale data crosscutting requirements.« less

48 CFR 252.237-7003 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Requirements. 252.237-7003... Clauses 252.237-7003 Requirements. As prescribed in 237.7003(b), use the following clause: Requirements... from the Contractor all of its requirements in the area of performance for the supplies and services...

48 CFR 52.216-21 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Requirements. 52.216-21... Requirements. As prescribed in 16.506(d), insert the following clause: Requirements (OCT 1995) (a) This is a requirements contract for the supplies or services specified, and effective for the period stated, in the...

48 CFR 52.216-21 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Requirements. 52.216-21... Requirements. As prescribed in 16.506(d), insert the following clause: Requirements (OCT 1995) (a) This is a requirements contract for the supplies or services specified, and effective for the period stated, in the...

48 CFR 252.237-7003 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Requirements. 252.237-7003... Clauses 252.237-7003 Requirements. As prescribed in 237.7003(b), use the following clause: Requirements... from the Contractor all of its requirements in the area of performance for the supplies and services...

48 CFR 52.216-21 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Requirements. 52.216-21... Requirements. As prescribed in 16.506(d), insert the following clause: Requirements (OCT 1995) (a) This is a requirements contract for the supplies or services specified, and effective for the period stated, in the...

48 CFR 52.216-21 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Requirements. 52.216-21... Requirements. As prescribed in 16.506(d), insert the following clause: Requirements (OCT 1995) (a) This is a requirements contract for the supplies or services specified, and effective for the period stated, in the...

48 CFR 252.237-7003 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Requirements. 252.237-7003... Clauses 252.237-7003 Requirements. As prescribed in 237.7003(b), use the following clause: Requirements... from the Contractor all of its requirements in the area of performance for the supplies and services...

48 CFR 252.237-7003 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Requirements. 252.237-7003... Clauses 252.237-7003 Requirements. As prescribed in 237.7003(b), use the following clause: Requirements... from the Contractor all of its requirements in the area of performance for the supplies and services...

46 CFR 11.707 - Examination requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Examination requirements. 11.707 Section 11.707 Shipping... OFFICER ENDORSEMENTS Professional Requirements for Pilots § 11.707 Examination requirements. (a) An... required to pass the examination described in subpart I of this part. (b) An applicant for an extension of...

14 CFR 298.33 - Security requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Security requirements. 298.33 Section 298... on Exemptions and Operations § 298.33 Security requirements. In conducting operations under this part, an air taxi operator or a commuter air carrier is required to adhere to all security requirements...

14 CFR 298.33 - Security requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Security requirements. 298.33 Section 298... on Exemptions and Operations § 298.33 Security requirements. In conducting operations under this part, an air taxi operator or a commuter air carrier is required to adhere to all security requirements...

14 CFR 298.33 - Security requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Security requirements. 298.33 Section 298... on Exemptions and Operations § 298.33 Security requirements. In conducting operations under this part, an air taxi operator or a commuter air carrier is required to adhere to all security requirements...

14 CFR 298.33 - Security requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Security requirements. 298.33 Section 298... on Exemptions and Operations § 298.33 Security requirements. In conducting operations under this part, an air taxi operator or a commuter air carrier is required to adhere to all security requirements...

Teleoperator system man-machine interface requirements for satellite retrieval and satellite servicing. Volume 1: Requirements

NASA Technical Reports Server (NTRS)

Malone, T. B.

1972-01-01

Requirements were determined analytically for the man machine interface for a teleoperator system performing on-orbit satellite retrieval and servicing. Requirements are basically of two types; mission/system requirements, and design requirements or design criteria. Two types of teleoperator systems were considered: a free flying vehicle, and a shuttle attached manipulator. No attempt was made to evaluate the relative effectiveness or efficiency of the two system concepts. The methodology used entailed an application of the Essex Man-Systems analysis technique as well as a complete familiarization with relevant work being performed at government agencies and by private industry.

Non-functional Avionics Requirements

NASA Astrophysics Data System (ADS)

Paulitsch, Michael; Ruess, Harald; Sorea, Maria

Embedded systems in aerospace become more and more integrated in order to reduce weight, volume/size, and power of hardware for more fuel-effi ciency. Such integration tendencies change architectural approaches of system ar chi tec tures, which subsequently change non-functional requirements for plat forms. This paper provides some insight into state-of-the-practice of non-func tional requirements for developing ultra-critical embedded systems in the aero space industry, including recent changes and trends. In particular, formal requi re ment capture and formal analysis of non-functional requirements of avionic systems - including hard-real time, fault-tolerance, reliability, and per for mance - are exemplified by means of recent developments in SAL and HiLiTE.

14 CFR 1214.608 - Safety requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Safety requirements. 1214.608 Section 1214... Space Shuttle Flights § 1214.608 Safety requirements. The contents of OFK's and PPK's must meet the requirements set forth in NASA Handbook 1700.7, “Safety Policy and Requirements for Payloads Using the Space...

14 CFR 1214.608 - Safety requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Safety requirements. 1214.608 Section 1214... Space Shuttle Flights § 1214.608 Safety requirements. The contents of OFK's and PPK's must meet the requirements set forth in NASA Handbook 1700.7, “Safety Policy and Requirements for Payloads Using the Space...

40 CFR 141.70 - General requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) NATIONAL PRIMARY DRINKING WATER REGULATIONS Filtration and Disinfection § 141.70 General requirements. (a... avoiding filtration in § 141.71 and the disinfection requirements in § 141.72(a); or (2) It meets the filtration requirements in § 141.73 and the disinfection requirements in § 141.72(b). (c) Each public water...

40 CFR 141.70 - General requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) NATIONAL PRIMARY DRINKING WATER REGULATIONS Filtration and Disinfection § 141.70 General requirements. (a... avoiding filtration in § 141.71 and the disinfection requirements in § 141.72(a); or (2) It meets the filtration requirements in § 141.73 and the disinfection requirements in § 141.72(b). (c) Each public water...

40 CFR 141.70 - General requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) NATIONAL PRIMARY DRINKING WATER REGULATIONS Filtration and Disinfection § 141.70 General requirements. (a... avoiding filtration in § 141.71 and the disinfection requirements in § 141.72(a); or (2) It meets the filtration requirements in § 141.73 and the disinfection requirements in § 141.72(b). (c) Each public water...

40 CFR 141.70 - General requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) NATIONAL PRIMARY DRINKING WATER REGULATIONS Filtration and Disinfection § 141.70 General requirements. (a... avoiding filtration in § 141.71 and the disinfection requirements in § 141.72(a); or (2) It meets the filtration requirements in § 141.73 and the disinfection requirements in § 141.72(b). (c) Each public water...

Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of airway allergic inflammation

USDA-ARS?s Scientific Manuscript database

The epithelium lining the airway tract and allergen-specific IgE are considered essential controllers of inflammatory responses to allergens. The human IgE receptor, CD23 (Fc'RII), is capable of transporting IgE or IgE-allergen complexes across the polarized human airway epithelial cell (AEC) monola...

Selective binding and transcytosis of Ulex europaeus 1 lectin by mouse Peyer's patch M-cells in vivo.

PubMed

Clark, M A; Jepson, M A; Simmons, N L; Hirst, B H

1995-12-01

The in vivo interaction of the lectin Ulex europaeus agglutinin 1 with mouse Peyer's patch follicle-associated epithelial cells was studied in the mouse Peyer's patch gut loop model by immunofluorescence and electron microscopy. The lectin targets to mouse Peyer's patch M-cells and is rapidly endocytosed and transcytosed. These processes are accompanied by morphological changes in the M-cell microvilli and by redistribution of polymerised actin. The demonstration of selective binding and uptake of a lectin by intestinal M-cells in vivo suggests that M-cell-specific surface glycoconjugates might act as receptors for the selective adhesion/uptake of microorganisms.

Utilization requirements. A southern California Gas Company project SAGE report: Utilization requirements

NASA Technical Reports Server (NTRS)

Barbieri, R. H.; Schoen, R.; Hirshberg, A. S.

1978-01-01

Utilization requirements are given and comparisons made of two phase III SAGE (solar assisted gas energy) installations in California: (1) a retrofit installation in an existing apartment building in El Toro, and (2) an installation in a new apartment building in Upland. Such testing in the field revealed the requirements to be met if SAGE-type installations are to become commercially practical on a widespread basis in electric and gas energy usage.

Sustainable Land Imaging User Requirements

NASA Astrophysics Data System (ADS)

Wu, Z.; Snyder, G.; Vadnais, C. M.

2017-12-01

The US Geological Survey (USGS) Land Remote Sensing Program (LRSP) has collected user requirements from a range of applications to help formulate the Landsat 9 follow-on mission (Landsat 10) through the Requirements, Capabilities and Analysis (RCA) activity. The USGS is working with NASA to develop Landsat 10, which is scheduled to launch in the 2027 timeframe as part of the Sustainable Land Imaging program. User requirements collected through RCA will help inform future Landsat 10 sensor designs and mission characteristics. Current Federal civil community users have provided hundreds of requirements through systematic, in-depth interviews. Academic, State, local, industry, and international Landsat user community input was also incorporated in the process. Emphasis was placed on spatial resolution, temporal revisit, and spectral characteristics, as well as other aspects such as accuracy, continuity, sampling condition, data access and format. We will provide an overview of the Landsat 10 user requirements collection process and summary results of user needs from the broad land imagining community.

National Land Imaging Requirements (NLIR) Pilot Project summary report: summary of moderate resolution imaging user requirements

USGS Publications Warehouse

Vadnais, Carolyn; Stensaas, Gregory

2014-01-01

Under the National Land Imaging Requirements (NLIR) Project, the U.S. Geological Survey (USGS) is developing a functional capability to obtain, characterize, manage, maintain and prioritize all Earth observing (EO) land remote sensing user requirements. The goal is a better understanding of community needs that can be supported with land remote sensing resources, and a means to match needs with appropriate solutions in an effective and efficient way. The NLIR Project is composed of two components. The first component is focused on the development of the Earth Observation Requirements Evaluation System (EORES) to capture, store and analyze user requirements, whereas, the second component is the mechanism and processes to elicit and document the user requirements that will populate the EORES. To develop the second component, the requirements elicitation methodology was exercised and refined through a pilot project conducted from June to September 2013. The pilot project focused specifically on applications and user requirements for moderate resolution imagery (5–120 meter resolution) as the test case for requirements development. The purpose of this summary report is to provide a high-level overview of the requirements elicitation process that was exercised through the pilot project and an early analysis of the moderate resolution imaging user requirements acquired to date to support ongoing USGS sustainable land imaging study needs. The pilot project engaged a limited set of Federal Government users from the operational and research communities and therefore the information captured represents only a subset of all land imaging user requirements. However, based on a comparison of results, trends, and analysis, the pilot captured a strong baseline of typical applications areas and user needs for moderate resolution imagery. Because these results are preliminary and represent only a sample of users and application areas, the information from this report should only

21 CFR 118.11 - Registration requirements for shell egg producers covered by the requirements of this part.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Registration requirements for shell egg producers..., STORAGE, AND TRANSPORTATION OF SHELL EGGS § 118.11 Registration requirements for shell egg producers covered by the requirements of this part. (a) Shell egg producers covered under § 118.1(a) are required to...

24 CFR 241.1 - Eligibility requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SUPPLEMENTARY FINANCING FOR INSURED PROJECT MORTGAGES Eligibility Requirements § 241.1 Eligibility requirements. The requirements set forth in 24 CFR part 200, subpart A, apply to multifamily project mortgages...

UTM TCL2 Software Requirements

NASA Technical Reports Server (NTRS)

Smith, Irene S.; Rios, Joseph L.; McGuirk, Patrick O.; Mulfinger, Daniel G.; Venkatesan, Priya; Smith, David R.; Baskaran, Vijayakumar; Wang, Leo

2017-01-01

The Unmanned Aircraft Systems (UAS) Traffic Management (UTM) Technical Capability Level (TCL) 2 software implements the UTM TCL 2 software requirements described herein. These software requirements are linked to the higher level UTM TCL 2 System Requirements. Each successive TCL implements additional UTM functionality, enabling additional use cases. TCL 2 demonstrated how to enable expanded multiple operations by implementing automation for beyond visual line-of-sight, tracking operations, and operations flying over sparsely populated areas.

Requirements for company-wide management

NASA Technical Reports Server (NTRS)

Southall, J. W.

1980-01-01

Computing system requirements were developed for company-wide management of information and computer programs in an engineering data processing environment. The requirements are essential to the successful implementation of a computer-based engineering data management system; they exceed the capabilities provided by the commercially available data base management systems. These requirements were derived from a study entitled The Design Process, which was prepared by design engineers experienced in development of aerospace products.

Advanced Scientific Computing Research Network Requirements: ASCR Network Requirements Review Final Report

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

Bacon, Charles; Bell, Greg; Canon, Shane

The Energy Sciences Network (ESnet) is the primary provider of network connectivity for the U.S. Department of Energy (DOE) Office of Science (SC), the single largest supporter of basic research in the physical sciences in the United States. In support of SC programs, ESnet regularly updates and refreshes its understanding of the networking requirements of the instruments, facilities, scientists, and science programs that it serves. This focus has helped ESnet to be a highly successful enabler of scientific discovery for over 25 years. In October 2012, ESnet and the Office of Advanced Scientific Computing Research (ASCR) of the DOE SCmore » organized a review to characterize the networking requirements of the programs funded by the ASCR program office. The requirements identified at the review are summarized in the Findings section, and are described in more detail in the body of the report.« less

19 CFR 11.3 - Package and notice requirements for cigars and cigarettes; package requirements for cigarette...

Code of Federal Regulations, 2013 CFR

2013-04-01

... cigarettes; package requirements for cigarette papers and tubes. 11.3 Section 11.3 Customs Duties U.S... STAMPING; MARKING Packing and Stamping § 11.3 Package and notice requirements for cigars and cigarettes; package requirements for cigarette papers and tubes. Exemptions from tax on cigars, cigarettes, and...

19 CFR 11.3 - Package and notice requirements for cigars and cigarettes; package requirements for cigarette...

Code of Federal Regulations, 2011 CFR

2011-04-01

... cigarettes; package requirements for cigarette papers and tubes. 11.3 Section 11.3 Customs Duties U.S... STAMPING; MARKING Packing and Stamping § 11.3 Package and notice requirements for cigars and cigarettes; package requirements for cigarette papers and tubes. Exemptions from tax on cigars, cigarettes, and...

19 CFR 11.3 - Package and notice requirements for cigars and cigarettes; package requirements for cigarette...

Code of Federal Regulations, 2014 CFR

2014-04-01

... cigarettes; package requirements for cigarette papers and tubes. 11.3 Section 11.3 Customs Duties U.S... STAMPING; MARKING Packing and Stamping § 11.3 Package and notice requirements for cigars and cigarettes; package requirements for cigarette papers and tubes. Exemptions from tax on cigars, cigarettes, and...

19 CFR 11.3 - Package and notice requirements for cigars and cigarettes; package requirements for cigarette...

Code of Federal Regulations, 2010 CFR

2010-04-01

... cigarettes; package requirements for cigarette papers and tubes. 11.3 Section 11.3 Customs Duties U.S... STAMPING; MARKING Packing and Stamping § 11.3 Package and notice requirements for cigars and cigarettes; package requirements for cigarette papers and tubes. Exemptions from tax on cigars, cigarettes, and...

19 CFR 11.3 - Package and notice requirements for cigars and cigarettes; package requirements for cigarette...

Code of Federal Regulations, 2012 CFR

2012-04-01

... cigarettes; package requirements for cigarette papers and tubes. 11.3 Section 11.3 Customs Duties U.S... STAMPING; MARKING Packing and Stamping § 11.3 Package and notice requirements for cigars and cigarettes; package requirements for cigarette papers and tubes. Exemptions from tax on cigars, cigarettes, and...

Requirements for color technology

NASA Astrophysics Data System (ADS)

Campbell, Ronald B., Jr.

1993-06-01

The requirements for color technology in the general office are reviewed. The two most salient factors driving the requirements for color are the information explosion and the virtually negligible growth in white collar productivity in the recent past. Accordingly, the business requirement upon color technology is that it be utilized in an effective and efficient manner to increase office productivity. Recent research on productivity and growth has moved beyond the classical two factor productivity model of labor and capital to explicitly include knowledge as a third and vital factor. Documents are agents of knowledge in the general office. Documents articulate, express, disseminate, and communicate knowledge. The central question addressed here is how can color, in conjunction with other techniques such as graphics and document design, improve the growth of knowledge? The central thesis is that the effective use of color to convert information into knowledge is one of the most powerful ways to increase office productivity. Material on the value of color is reviewed. This material is related to the role of documents. Document services are the way in which users access and utilize color technology. The requirements for color technology are then defined against the services taxonomy.

Lipid- and sugar-modified endomorphins: novel targets for the treatment of neuropathic pain

PubMed Central

Varamini, Pegah; Toth, Istvan

2013-01-01

Endomorphins are endogenous opioid peptides that cause potent antinociception in rodent models of acute and neuropathic pain with less undesirable side effects than opioid alkaloids. However, endomorphins are poorly suited to clinical applications because of low membrane permeability and a susceptibility to enzymatic degradation. Glycosylation and lipidation have proven to be two of the most robust approaches for the generation of new therapeutic endomorphin derivatives. Conjugation with lipoamino acids (LAA) confers an amphipathic character to the peptide, which improved interaction between the peptide and the lipid bilayer of the cell membranes, increasing permeability. Glycosylation can also improve peptide stability and blood brain barrier (BBB) transport. It is believed that an endocytotic mechanism (transcytosis) is responsible for the systemic delivery of water-soluble glycopeptides. This review discusses the application of glycosylation and lipidation strategies to improve the drug-like properties of endomorphins. Pharmacologically active endomorphin analogs with less adverse effects are also discussed. PMID:24379782

Lactobacillus rhamnosus GG Suppresses Meningitic E. coli K1 Penetration across Human Intestinal Epithelial Cells In Vitro and Protects Neonatal Rats against Experimental Hematogenous Meningitis

PubMed Central

Huang, Sheng-He; He, Lina; Zhou, Yanhong; Wu, Chun-Hua; Jong, Ambrose

2009-01-01

The purpose of this study was to examine prophylactic efficacy of probiotics in neonatal sepsis and meningitis caused by E. coli K1. The potential inhibitory effect of Lactobacillus rhamnosus GG (LGG) on meningitic E. coli K1 infection was examined by using (i) in vitro inhibition assays with E44 (a CSF isolate from a newborn baby with E. coli meningitis), and (ii) the neonatal rat model of E. coli sepsis and meningitis. The in vitro studies demonstrated that LGG blocked E44 adhesion, invasion, and transcytosis in a dose-dependent manner. A significant reduction in the levels of pathogen colonization, E. coli bacteremia, and meningitis was observed in the LGG-treated neonatal rats, as assessed by viable cultures, compared to the levels in the control group. In conclusion, probiotic LGG strongly suppresses meningitic E. coli pathogens in vitro and in vivo. The results support the use of probiotic strains such as LGG for prophylaxis of neonatal sepsis and meningitis. PMID:20016677

Interneuronal Transfer and Distal Action of Tetanus Toxin and Botulinum Neurotoxins A and D in Central Neurons.

PubMed

Bomba-Warczak, Ewa; Vevea, Jason D; Brittain, Joel M; Figueroa-Bernier, Annette; Tepp, William H; Johnson, Eric A; Yeh, Felix L; Chapman, Edwin R

2016-08-16

Recent reports suggest that botulinum neurotoxin (BoNT) A, which is widely used clinically to inhibit neurotransmission, can spread within networks of neurons to have distal effects, but this remains controversial. Moreover, it is not known whether other members of this toxin family are transferred between neurons. Here, we investigate the potential distal effects of BoNT/A, BoNT/D, and tetanus toxin (TeNT), using central neurons grown in microfluidic devices. Toxins acted upon the neurons that mediated initial entry, but all three toxins were also taken up, via an alternative pathway, into non-acidified organelles that mediated retrograde transport to the somato-dendritic compartment. Toxins were then released into the media, where they entered and exerted their effects upon upstream neurons. These findings directly demonstrate that these agents undergo transcytosis and interneuronal transfer in an active form, resulting in long-distance effects. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents.

PubMed

Cho, Choi-Fong; Wolfe, Justin M; Fadzen, Colin M; Calligaris, David; Hornburg, Kalvis; Chiocca, E Antonio; Agar, Nathalie Y R; Pentelute, Bradley L; Lawler, Sean E

2017-06-06

Culture-based blood-brain barrier (BBB) models are crucial tools to enable rapid screening of brain-penetrating drugs. However, reproducibility of in vitro barrier properties and permeability remain as major challenges. Here, we report that self-assembling multicellular BBB spheroids display reproducible BBB features and functions. The spheroid core is comprised mainly of astrocytes, while brain endothelial cells and pericytes encase the surface, acting as a barrier that regulates transport of molecules. The spheroid surface exhibits high expression of tight junction proteins, VEGF-dependent permeability, efflux pump activity and receptor-mediated transcytosis of angiopep-2. In contrast, the transwell co-culture system displays comparatively low levels of BBB regulatory proteins, and is unable to discriminate between the transport of angiopep-2 and a control peptide. Finally, we have utilized the BBB spheroids to screen and identify BBB-penetrant cell-penetrating peptides (CPPs). This robust in vitro BBB model could serve as a valuable next-generation platform for expediting the development of CNS therapeutics.

RhoB-dependent modulation of postendocytic traffic in polarized Madin-Darby canine kidney cells.

PubMed

Rondanino, Christine; Rojas, Raul; Ruiz, Wily G; Wang, Exing; Hughey, Rebecca P; Dunn, Kenneth W; Apodaca, Gerard

2007-07-01

The Rho family of GTPases is implicated in the control of endocytic and biosynthetic traffic of many cell types; however, the cellular distribution of RhoB remains controversial and its function is not well understood. Using confocal microscopy, we found that endogenous RhoB and green fluorescent protein-tagged wild-type RhoB were localized to early endosomes, and to a much lesser extent to recycling endosomes, late endosomes or Golgi complex of fixed or live polarized Madin-Darby canine kidney cells. Consistent with RhoB localization to early endosomes, we observed that expression of dominant-negative RhoBN19 or dominant-active RhoBV14 altered postendocytic traffic of ligand-receptor complexes that undergo recycling, degradation or transcytosis. In vitro assays established that RhoB modulated the basolateral-to-apical transcytotic pathway by regulating cargo exit from basolateral early endosomes. Our results indicate that RhoB is localized, in part, to early endosomes where it regulates receptor egress through the early endocytic system.

Regulation of podocalyxin trafficking by Rab small GTPases in epithelial cells

PubMed Central

Mrozowska, Paulina S.; Fukuda, Mitsunori

2016-01-01

ABSTRACT The characteristic feature of polarity establishment in MDCK II cells is transcytosis of apical glycoprotein podocalyxin (PCX) from the outer plasma membrane to the newly formed apical domain. This transcytotic event consists of multiple steps, including internalization from the plasma membrane, transport through early endosomes and Rab11-positive recycling endosomes, and delivery to the apical membrane. These steps are known to be tightly coordinated by Rab small GTPases, which act as molecular switches cycling between active GTP-bound and inactive GDP-bound states. However, our knowledge regarding which sets of Rabs regulate particular steps of PCX trafficking was rather limited. Recently, we have performed a comprehensive analysis of Rab GTPase engagement in the transcytotic pathway of PCX during polarity establishment in 2-dimensional (2D) and 3-dimensional (3D) MDCK II cell cultures. In this Commentary we summarize our findings and set them in the context of previous reports. PMID:27463697

Teratogenicity induced by targeting a placental immunoglobulin transporter

PubMed Central

Kolonin, Mikhail G.; Pasqualini, Renata; Arap, Wadih

2002-01-01

Approximately 3% of children in developed countries are born with nongenetic birth defects. However, the nature and mechanisms of teratogenesis are poorly understood. We investigated mechanisms of teratogen-mediated blockade of maternofetal transport by screening a combinatorial library for peptides that bind nonendothelial placental vasculature in pregnant mice. Here, we identified a peptide motif, TPKTSVT, that homes to the yolk sac, induces placental necrosis, and disrupts embryo development. We show that TPKTSVT promotes transcytosis of phage into the embryo and blocks the transplacental transport of immunoglobulins. Based on these data, we propose a model in which TPKTSVT targets a placental Fc receptor. Absence of TPKTSVT placental homing in mice lacking β2-microglobulin (β2m) suggests FcRn/β2m as a target for the TPKTSVT, which is unexpected, given the normal development of FcRn/β2m-deficient progeny. High-throughput screening for embryotoxins that target placental receptors could be developed to systematically identify and avoid exposure to teratogenic drugs. PMID:12242328

Pleural liquid and its exchanges.

PubMed

Agostoni, Emilio; Zocchi, Luciano

2007-12-15

After an account on morphological features of visceral and parietal pleura, mechanical coupling between lung and chest wall is outlined. Volume of pleural liquid is considered along with its thickness in various regions, and its composition. Pleural liquid pressure (P(liq)) and pressure exerted by lung recoil in various species and postures are then compared, and the vertical gradient of P(liq) considered. Implications of lower P(liq) in the lung zone than in the costo-phrenic sinus at iso-height are pointed out. Mesothelial permeability to H(2)O, Cl(-), Na(+), mannitol, sucrose, inulin, albumin, and various size dextrans is provided, along with paracellular "pore" radius of mesothelium. Pleural liquid is produced by filtration from parietal pleura capillaries according to Starling forces. It is removed by absorption in visceral pleura capillaries according to Starling forces (at least in some species), lymphatic drainage through stomata of parietal mesothelium (essential to remove cells, particles, and large macromolecules), solute-coupled liquid absorption, and transcytosis through mesothelium.

Lactobacillus rhamnosus GG Suppresses Meningitic E. coli K1 Penetration across Human Intestinal Epithelial Cells In Vitro and Protects Neonatal Rats against Experimental Hematogenous Meningitis.

PubMed

Huang, Sheng-He; He, Lina; Zhou, Yanhong; Wu, Chun-Hua; Jong, Ambrose

2009-01-01

The purpose of this study was to examine prophylactic efficacy of probiotics in neonatal sepsis and meningitis caused by E. coli K1. The potential inhibitory effect of Lactobacillus rhamnosus GG (LGG) on meningitic E. coli K1 infection was examined by using (i) in vitro inhibition assays with E44 (a CSF isolate from a newborn baby with E. coli meningitis), and (ii) the neonatal rat model of E. coli sepsis and meningitis. The in vitro studies demonstrated that LGG blocked E44 adhesion, invasion, and transcytosis in a dose-dependent manner. A significant reduction in the levels of pathogen colonization, E. coli bacteremia, and meningitis was observed in the LGG-treated neonatal rats, as assessed by viable cultures, compared to the levels in the control group. In conclusion, probiotic LGG strongly suppresses meningitic E. coli pathogens in vitro and in vivo. The results support the use of probiotic strains such as LGG for prophylaxis of neonatal sepsis and meningitis.

Report of the 2014 Cent Gardes HIV Vaccine Conference-Part 2: Cell-mediated immunity, mucosal protection, and clinical trials: Fondation Mérieux Conference Center, Veyrier du Lac, France, 5-7 October, 2014.

PubMed

Girard, Marc P; Picot, Valentina; Longuet, Christophe; Nabel, Gary J

2015-08-07

The 2014 Cent Gardes Conference took place on October 5-7, 2014, at the Fondation Mérieux Conference Center, on the shores of the Annecy Lake and aimed to review the progress and promise of HIV vaccines. The elicitation of broadly neutralizing antibodies (bNAbs), their use in passive immunization, as well as their genetic delivery (vector immunoprophylaxis) by a recombinant Adenovirus-associated virus (AAV) vector were reviewed in a preceding article [1]. Approaches to the elicitation of long-lasting T cell or mucosal immunity were also discussed and are now reviewed here. The possibility of eliciting mucosal IgAs was discussed, since it was demonstrated that transcytosis-blocking IgAs can protect monkeys against repeated vaginal challenge with a pathogenic chimeric simian and human immunodeficiency virus (SHIV). The possibility of purging the HIV reservoirs from HIV-infected persons and developing a cure of the disease was also discussed. Copyright © 2015. Published by Elsevier Ltd.. All rights reserved.

LRP-1-mediated intracellular antibody delivery to the Central Nervous System

NASA Astrophysics Data System (ADS)

Tian, Xiaohe; Nyberg, Sophie; S. Sharp, Paul; Madsen, Jeppe; Daneshpour, Nooshin; Armes, Steven P.; Berwick, Jason; Azzouz, Mimoun; Shaw, Pamela; Abbott, N. Joan; Battaglia, Giuseppe

2015-07-01

The blood-brain barrier (BBB) is by far the most important target in developing new approaches to improve delivery of drugs and diagnostic tools into the Central Nervous System (CNS). Here we report the engineering of pH- sensitive polymersomes (synthetic vesicles formed by amphiphilic copolymers) that exploit endogenous transport mechanisms to traverse the BBB, enabling delivery of large macromolecules into both the CNS parenchyma and CNS cells. We achieve this by targeting the Low Density Lipoprotein Receptor-Related Protein 1 (LRP-1) receptor. We show that LRP-1 is associated with endothelial transcytosis that does not involve acidification of cargo in membrane-trafficking organelles. By contrast, this receptor is also associated with traditional endocytosis in CNS cells, thus aiding the delivery of relevant cargo within their cytosol. We prove this using IgG as a model cargo, thus demonstrating that the combination of appropriate targeting combined with pH-sensitive polymersomes enables the efficient delivery of macromolecules into CNS cells.

SE Requirements Development Tool User Guide

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

Benson, Faith Ann

2016-05-13

The LANL Systems Engineering Requirements Development Tool (SERDT) is a data collection tool created in InfoPath for use with the Los Alamos National Laboratory’s (LANL) SharePoint sites. Projects can fail if a clear definition of the final product requirements is not performed. For projects to be successful requirements must be defined early in the project and those requirements must be tracked during execution of the project to ensure the goals of the project are met. Therefore, the focus of this tool is requirements definition. The content of this form is based on International Council on Systems Engineering (INCOSE) and Departmentmore » of Defense (DoD) process standards and allows for single or collaborative input. The “Scoping” section is where project information is entered by the project team prior to requirements development, and includes definitions and examples to assist the user in completing the forms. The data entered will be used to define the requirements and once the form is filled out, a “Requirements List” is automatically generated and a Word document is created and saved to a SharePoint document library. SharePoint also includes the ability to download the requirements data defined in the InfoPath from into an Excel spreadsheet. This User Guide will assist you in navigating through the data entry process.« less

40 CFR 57.701 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... of the requirements within the NSO as expeditiously as practicable but in no case later than the... extent to which any required reports or studies have already been completed. Requirements for smelters to...

46 CFR 170.170 - Calculations required.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REQUIREMENTS FOR ALL INSPECTED VESSELS Weather Criteria § 170.170 Calculations required. (a) Each vessel must... weather deck or abnormal sheer. (c) When doing the calculations required by paragraph (a) of this section...

Requirements for Space Settlement Design

NASA Astrophysics Data System (ADS)

Gale, Anita E.; Edwards, Richard P.

2004-02-01

When large space settlements are finally built, inevitably the customers who pay for them will start the process by specifying requirements with a Request for Proposal (RFP). Although we are decades away from seeing the first of these documents, some of their contents can be anticipated now, and provide insight into the variety of elements that must be researched and developed before space settlements can happen. Space Settlement Design Competitions for High School students present design challenges in the form of RFPs, which predict basic requirements for space settlement attributes in the future, including structural features, infrastructure, living conveniences, computers, business areas, and safety. These requirements are generically summarized, and unique requirements are noted for specific space settlement locations and applications.

Requirements Modeling with the Aspect-oriented User Requirements Notation (AoURN): A Case Study

NASA Astrophysics Data System (ADS)

Mussbacher, Gunter; Amyot, Daniel; Araújo, João; Moreira, Ana

The User Requirements Notation (URN) is a recent ITU-T standard that supports requirements engineering activities. The Aspect-oriented URN (AoURN) adds aspect-oriented concepts to URN, creating a unified framework that allows for scenario-based, goal-oriented, and aspect-oriented modeling. AoURN is applied to the car crash crisis management system (CCCMS), modeling its functional and non-functional requirements (NFRs). AoURN generally models all use cases, NFRs, and stakeholders as individual concerns and provides general guidelines for concern identification. AoURN handles interactions between concerns, capturing their dependencies and conflicts as well as the resolutions. We present a qualitative comparison of aspect-oriented techniques for scenario-based and goal-oriented requirements engineering. An evaluation carried out based on the metrics adapted from literature and a task-based evaluation suggest that AoURN models are more scalable than URN models and exhibit better modularity, reusability, and maintainability.

7 CFR 4284.18 - Audit requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Grant Programs § 4284.18 Audit requirements. Grantees must comply with the audit requirements of 7 CFR part 3052. The audit requirements apply to the years in which grant funds are received and years in...

14 CFR 1214.608 - Safety requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Space Shuttle Flights § 1214.608 Safety requirements. The contents of OFK's and PPK's must meet the requirements set forth in NASA Handbook 1700.7, “Safety Policy and Requirements for Payloads Using the Space...

14 CFR 1214.608 - Safety requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Space Shuttle Flights § 1214.608 Safety requirements. The contents of OFK's and PPK's must meet the requirements set forth in NASA Handbook 1700.7, “Safety Policy and Requirements for Payloads Using the Space...

The JPL functional requirements tool

NASA Technical Reports Server (NTRS)

Giffin, Geoff; Skinner, Judith; Stoller, Richard

1987-01-01

Planetary spacecraft are complex vehicles which are built according to many thousands of requirements. Problems encountered in documenting and maintaining these requirements led to the current attempt to reduce or eliminate these problems by a computer automated data base Functional Requirements Tool. The tool developed at JPL and in use on several JPL Projects is described. The organization and functionality of the Tool, together with an explanation of the data base inputs, their relationships, and use are presented. Methods of interfacing with external documents, representation of tables and figures, and methods of approval and change processing are discussed. The options available for disseminating information from the Tool are identified. The implementation of the Requirements Tool is outlined, and the operation is summarized. The conclusions drawn from this work is that the Requirements Tool represents a useful addition to the System Engineer's Tool kit, it is not currently available elsewhere, and a clear development path exists to expand the capabilities of the Tool to serve larger and more complex projects.

Next Generation Microbiology Requirements

NASA Technical Reports Server (NTRS)

Ott, C. M.; Oubre, C. M.; Elliott, T. F.; Castro, V. A.; Pierson, D. L.

2012-01-01

As humans continue to explore deep into space, microorganisms will travel with them. The primary means to mitigate the risk of infectious disease are a combination of prudent spacecraft design and rigorous operational controls. The effectiveness of these methods are evaluated by microbiological monitoring of spacecraft, food, water, and the crew that is performed preflight, in-flight, and post-flight. Current NASA requirements associated with microbiological monitoring are based on culture-based methodology where microorganisms are grown on a semi-solid growth medium and enumerated. Subsequent identification of the organisms requires specialized labor and large equipment, which historically has been performed on Earth. Requirements that rely strictly on culture-based units limit the use of non-culture based monitoring technology. Specifically, the culture-based "measurement criteria" are Colony Forming Units (CFU, representing the growth of one microorganism at a single location on the agar medium) per a given volume, area, or sample size. As the CFU unit by definition is culture-based, these requirements limit alternative technologies for spaceflight applications. As spaceflight missions such as those to Mars extend further into space, culture-based technology will become difficult to implement due to the (a) limited shelf life of the culture media, (b) mass/volume necessary to carry these consumables, and (c) problems associated with the production of biohazardous material in the habitable volume of the spacecraft. In addition, an extensive amount of new knowledge has been obtained during the Space Shuttle, NASA-Mir, and International Space Station Programs, which gave direction for new or modified microbial control requirements for vehicle design and mission operations. The goal of this task is to develop and recommend a new set of requirements for vehicle design and mission operations, including microbiological monitoring, based upon "lessons learned" and new

Crewed Space Vehicle Battery Safety Requirements

NASA Technical Reports Server (NTRS)

Jeevarajan, Judith A.; Darcy, Eric C.

2014-01-01

This requirements document is applicable to all batteries on crewed spacecraft, including vehicle, payload, and crew equipment batteries. It defines the specific provisions required to design a battery that is safe for ground personnel and crew members to handle and/or operate during all applicable phases of crewed missions, safe for use in the enclosed environment of a crewed space vehicle, and safe for use in launch vehicles, as well as in unpressurized spaces adjacent to the habitable portion of a space vehicle. The required provisions encompass hazard controls, design evaluation, and verification. The extent of the hazard controls and verification required depends on the applicability and credibility of the hazard to the specific battery design and applicable missions under review. Evaluation of the design and verification program results shall be completed prior to certification for flight and ground operations. This requirements document is geared toward the designers of battery systems to be used in crewed vehicles, crew equipment, crew suits, or batteries to be used in crewed vehicle systems and payloads (or experiments). This requirements document also applies to ground handling and testing of flight batteries. Specific design and verification requirements for a battery are dependent upon the battery chemistry, capacity, complexity, charging, environment, and application. The variety of battery chemistries available, combined with the variety of battery-powered applications, results in each battery application having specific, unique requirements pertinent to the specific battery application. However, there are basic requirements for all battery designs and applications, which are listed in section 4. Section 5 includes a description of hazards and controls and also includes requirements.

Maintainability Program Requirements for Space Systems

NASA Technical Reports Server (NTRS)

1987-01-01

This document is established to provide common general requirements for all NASA programs to: design maintainability into all systems where maintenance is a factor in system operation and mission success; and ensure that maintainability characteristics are developed through the systems engineering process. These requirements are not new. Design for ease of maintenance and minimization of repair time have always been fundamental requirements of the systems engineering process. However, new or reusable orbital manned and in-flight maintainable unmanned space systems demand special emphasis on maintainability, and this document has been prepared to meet that need. Maintainability requirements on many NASA programs differ in phasing and task emphasis from requirements promulgated by other Government agencies. This difference is due to the research and development nature of NASA programs where quantities produced are generally small; therefore, the depth of logistics support typical of many programs is generally not warranted. The cost of excessive maintenance is very high due to the logistics problems associated with the space environment. The ability to provide timely maintenance often involves safety considerations for manned space flight applications. This document represents a basic set of requirements that will achieve a design for maintenance. These requirements are directed primarily at manned and unmanned orbital space systems. To be effective, maintainability requirements should be tailored to meet specific NASA program and project needs and constraints. NASA activities shall invoke the requirements of this document consistent with program planning in procurements or on inhouse development efforts.

40 CFR 141.132 - Monitoring requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Disinfectant Residuals, Disinfection Byproducts, and Disinfection Byproduct Precursors § 141.132 Monitoring requirements. (a) General requirements. (1) Systems must... this subpart to qualify for reduced monitoring. (b) Monitoring requirements for disinfection byproducts...

40 CFR 141.132 - Monitoring requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Disinfectant Residuals, Disinfection Byproducts, and Disinfection Byproduct Precursors § 141.132 Monitoring requirements. (a) General requirements. (1) Systems must... this subpart to qualify for reduced monitoring. (b) Monitoring requirements for disinfection byproducts...

40 CFR 141.132 - Monitoring requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Disinfectant Residuals, Disinfection Byproducts, and Disinfection Byproduct Precursors § 141.132 Monitoring requirements. (a) General requirements. (1) Systems must... this subpart to qualify for reduced monitoring. (b) Monitoring requirements for disinfection byproducts...

Human Research Program Requirements Document

NASA Technical Reports Server (NTRS)

Rieger, Gabe

2007-01-01

The purpose of this document is to define, document, and allocate the Human Research Program (HRP) requirements to the HRP Program elements. It establishes the flow-down of requirements from Exploration Systems Mission Directorate (ESMD) and Office of the Chief Health and Medical Officer (OCHMO) to the various Program Elements of the HRP to ensure that human research and technology countermeasure investments are made to insure the delivery of countermeasures and technologies that satisfy ESMD s and OCHMO's exploration mission requirements.

SIENA Customer Problem Statement and Requirements

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

L. Sauer; R. Clay; C. Adams

2000-08-01

This document describes the problem domain and functional requirements of the SIENA framework. The software requirements and system architecture of SIENA are specified in separate documents (called SIENA Software Requirement Specification and SIENA Software Architecture, respectively). While currently this version of the document describes the problems and captures the requirements within the Analysis domain (concentrating on finite element models), it is our intention to subsequent y expand this document to describe problems and capture requirements from the Design and Manufacturing domains. In addition, SIENA is designed to be extendible to support and integrate elements from the other domains (see SIENAmore » Software Architecture document).« less

48 CFR 9903.202 - Disclosure requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Program Requirements 9903.202 Disclosure requirements. ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Disclosure requirements. 9903.202 Section 9903.202 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

76 FR 26802 - Application Filing Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-09

... DEPARTMENT OF THE TREASURY Office of Thrift Supervision Application Filing Requirements AGENCY... concerning the following information collection. Title of Proposal: Application Filing Requirements. OMB Number: 1550-0056. Form Number: N/A. Description: OTS regulations require that applications, notices, or...

76 FR 41331 - Application Filing Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-13

... DEPARTMENT OF THE TREASURY Office of Thrift Supervision Application Filing Requirements AGENCY... following information collection. Title of Proposal: Application Filing Requirements. OMB Number: 1550-0056. Form Number: N/A. Description: OTS regulations require that applications, notices, or other filings...

Software Requirements

DTIC Science & Technology

1990-01-01

Real-Time Systems Specifications 11 Convenient Auto Rental System Marea82 12 Systems Architecture Marca , D. A., and C. L. McGowan. "Static and...Requirements Marca88 Structured Analysis. Orr’s work is worthy of study Marca , D. A., and C. L. McGowan. SADT: Struc- by the instructor, since it enjoys

Airspace Operations Demo Functional Requirements Matrix

NASA Technical Reports Server (NTRS)

2005-01-01

The Flight IPT assessed the reasonableness of demonstrating each of the Access 5 Step 1 functional requirements. The functional requirements listed in this matrix are from the September 2005 release of the Access 5 Functional Requirements Document. The demonstration mission considered was a notional Western US mission (WUS). The conclusion of the assessment is that 90% of the Access 5 Step 1 functional requirements can be demonstrated using the notional Western US mission.

Deaf mobile application accessibility requirements

NASA Astrophysics Data System (ADS)

Nathan, Shelena Soosay; Hussain, Azham; Hashim, Nor Laily

2016-08-01

Requirement for deaf mobile applications need to be analysed to ensure the disabilities need are instilled into the mobile applications developed for them. Universal design is understandable to comply every user needs, however specific disability is argued by the authors to have different need and requirements. These differences are among the reasons for these applications being developed to target for a specific group of people, however they are less usable and later abandoned. This study focuses on deriving requirements that are needed by the deaf in their mobile applications that are meant specifically for them. Studies on previous literature was conducted it can be concluded that graphic, text, multimedia and sign language interpreter are among mostly required features to be included in their mobile application to ensure the applications are usable for this community.

LH2 airport requirements study

NASA Technical Reports Server (NTRS)

Brewer, G. D. (Editor)

1976-01-01

A preliminary assessment of the facilities and equipment which will be required at a representative airport is provided so liquid hydrogen LH2 can be used as fuel in long range transport aircraft in 1995-2000. A complete facility was conceptually designed, sized to meet the projected air traffic requirement. The facility includes the liquefaction plant, LH2, storage capability, and LH2 fuel handling system. The requirements for ground support and maintenance for the LH2 fueled aircraft were analyzed. An estimate was made of capital and operating costs which might be expected for the facility. Recommendations were made for design modifications to the reference aircraft, reflecting results of the analysis of airport fuel handling requirements, and for a program of additional technology development for air terminal related items.

49 CFR 585.86 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Electronic Stability Control System Phase-In Reporting Requirements § 585.86 Reporting requirements. (a) General reporting..., or, at the manufacturer's option, for the current production year. A new manufacturer that has not...

49 CFR 585.86 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PHASE-IN REPORTING REQUIREMENTS Electronic Stability Control System Phase-In Reporting Requirements § 585.86 Reporting requirements. (a) General reporting..., or, at the manufacturer's option, for the current production year. A new manufacturer that has not...

48 CFR 1330.202 - Disclosure requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Disclosure requirements. 1330.202 Section 1330.202 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 1330.202 Disclosure...

48 CFR 1430.202 - Disclosure requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Disclosure requirements. 1430.202 Section 1430.202 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 1430.202 Disclosure...

48 CFR 30.202 - Disclosure requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Disclosure requirements. 30.202 Section 30.202 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.202 Disclosure...

48 CFR 430.202 - Disclosure requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Disclosure requirements. 430.202 Section 430.202 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 430.202 Disclosure...

40 CFR 141.130 - General requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Disinfectant Residuals, Disinfection Byproducts, and Disinfection Byproduct Precursors § 141.130 General requirements. (a) The requirements of this subpart L... treatment technique requirements for disinfection byproduct precursors in § 141.135. (2) The regulations in...

40 CFR 141.130 - General requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Disinfectant Residuals, Disinfection Byproducts, and Disinfection Byproduct Precursors § 141.130 General requirements. (a) The requirements of this subpart L... treatment technique requirements for disinfection byproduct precursors in § 141.135. (2) The regulations in...

Organizing Performance Requirements For Dynamical Systems

NASA Technical Reports Server (NTRS)

Malchow, Harvey L.; Croopnick, Steven R.

1990-01-01

Paper describes methodology for establishing performance requirements for complicated dynamical systems. Uses top-down approach. In series of steps, makes connections between high-level mission requirements and lower-level functional performance requirements. Provides systematic delineation of elements accommodating design compromises.

48 CFR 30.202 - Disclosure requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Disclosure requirements. 30.202 Section 30.202 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.202 Disclosure...

48 CFR 1330.202 - Disclosure requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Disclosure requirements. 1330.202 Section 1330.202 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 1330.202 Disclosure...

48 CFR 1430.201 - Contract requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract requirements. 1430.201 Section 1430.201 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 1430.201 Contract...

48 CFR 1430.202 - Disclosure requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Disclosure requirements. 1430.202 Section 1430.202 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 1430.202 Disclosure...

48 CFR 430.201 - Contract requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Contract requirements. 430.201 Section 430.201 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 430.201 Contract...

48 CFR 430.202 - Disclosure requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Disclosure requirements. 430.202 Section 430.202 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 430.202 Disclosure...

48 CFR 30.201 - Contract requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Contract requirements. 30.201 Section 30.201 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 30.201 Contract...

48 CFR 1330.201 - Contract requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract requirements. 1330.201 Section 1330.201 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 1330.201 Contract...

14 CFR 125.265 - Flight engineer requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Flight engineer requirements. 125.265... Requirements § 125.265 Flight engineer requirements. (a) No person may operate an airplane for which a flight engineer is required by the type certification requirements without a flight crewmember holding a current...

14 CFR 125.265 - Flight engineer requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Flight engineer requirements. 125.265... Requirements § 125.265 Flight engineer requirements. (a) No person may operate an airplane for which a flight engineer is required by the type certification requirements without a flight crewmember holding a current...

14 CFR 125.265 - Flight engineer requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Flight engineer requirements. 125.265... Requirements § 125.265 Flight engineer requirements. (a) No person may operate an airplane for which a flight engineer is required by the type certification requirements without a flight crewmember holding a current...

14 CFR 125.265 - Flight engineer requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Flight engineer requirements. 125.265... Requirements § 125.265 Flight engineer requirements. (a) No person may operate an airplane for which a flight engineer is required by the type certification requirements without a flight crewmember holding a current...

14 CFR 125.265 - Flight engineer requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Flight engineer requirements. 125.265... Requirements § 125.265 Flight engineer requirements. (a) No person may operate an airplane for which a flight engineer is required by the type certification requirements without a flight crewmember holding a current...

Aggregate complexes of HIV-1 induced by multimeric antibodies.

PubMed

Stieh, Daniel J; King, Deborah F; Klein, Katja; Liu, Pinghuang; Shen, Xiaoying; Hwang, Kwan Ki; Ferrari, Guido; Montefiori, David C; Haynes, Barton; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Michael, Nelson L; Robb, Merlin L; Kim, Jerome H; Denny, Thomas N; Tomaras, Georgia D; Shattock, Robin J

2014-10-02

Antibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible mucosal CD4 T cells and dendritic cells. These functions may work together to provide effective immune exclusion of virus from mucosal tissue; however little is known about the antibody characteristics required to induce HIV aggregation. Such knowledge may be critical to the design of successful immunization strategies to facilitate viral immune exclusion at the mucosal portals of entry. The potential of neutralizing and non-neutralizing IgG and IgA monoclonals (mAbs) to induce HIV-1 aggregation was assessed by Dynamic light scattering (DLS). Although neutralizing and non-neutralizing IgG mAbs and polyclonal HIV-Ig efficiently aggregated soluble Env trimers, they were not capable of forming viral aggregates. In contrast, dimeric (but not monomeric) IgA mAbs induced stable viral aggregate populations that could be separated from uncomplexed virions. Epitope specificity influenced both the degree of aggregation and formation of higher order complexes by dIgA. IgA purified from serum of uninfected RV144 vaccine trial responders were able to efficiently opsonize viral particles in the absence of significant aggregation, reflective of monomeric IgA. These results collectively demonstrate that dIgA is capable of forming stable viral aggregates providing a plausible basis for testing the effectiveness of aggregation as a potential protection mechanism at the mucosal portals of viral entry.

Current concepts on Escherichia coli K1 translocation of the blood-brain barrier.

PubMed

Xie, Yi; Kim, Kee Jun; Kim, Kwang Sik

2004-11-01

The mortality and morbidity associated with neonatal gram-negative meningitis have remained significant despite advances in antimicrobial chemotherapy. Escherichia coli K1 is the most common gram-negative organism causing neonatal meningitis. Our incomplete knowledge of the pathogenesis of this disease is one of the main reasons for this high mortality and morbidity. We have previously established both in vitro and in vivo models of the blood-brain barrier (BBB) using human brain microvascular endothelial cells (HBMEC) and hematogenous meningitis in neonatal rats, respectively. With these in vitro and in vivo models, we have shown that successful crossing of the BBB by circulating E. coli requires a high-degree of bacteremia, E. coli binding to and invasion of HBMEC, and E. coli traversal of the BBB as live bacteria. Our previous studies using TnphoA, signature-tagged mutagenesis and differential fluorescence induction identified several E. coli K1 determinants such as OmpA, Ibe proteins, AslA, TraJ and CNF1 contributing to invasion of HBMEC in vitro and traversal of the blood-brain barrier in vivo. We have shown that some of these determinants interact with specific receptors on HBMEC, suggesting E. coli translocation of the BBB is the result of specific pathogen-host cell interactions. Recent studies using functional genomics techniques have identified additional E. coli K1 factors that contribute to the high degree of bacteremia and HBMEC binding/invasion/transcytosis. In this review, we summarize the current knowledge on the mechanisms underlying the successful E. coli translocation of the BBB.

The GTP-bound and Sumoylated Form of the rab17 Small Molecular Weight GTPase Selectively Binds Syntaxin 2 in Polarized Hepatic WIF-B Cells*

PubMed Central

Striz, Anneliese C.; Tuma, Pamela L.

2016-01-01

A major focus for our laboratory is identifying the molecules and mechanisms that regulate polarized apical protein sorting in hepatocytes, the major epithelial cells of the liver. These trafficking pathways are regulated, in part, by small molecular weight rab GTPases. We chose to investigate rab17, whose expression is restricted to polarized epithelial cells, is enriched in liver, and has been implicated in regulating basolateral to apical transcytosis. To initiate our studies, we generated three recombinant adenoviruses expressing wild type, constitutively active (GTP bound), or dominant-negative (GDP bound) rab17. Immunoblotting revealed rab17 immunoreactive species at 25 kDa (the predicted rab17 molecular mass) and 40 kDa. We determined that mono-sumoylation of the 25-kDa rab17 is responsible for the shift in molecular mass, and that rab17 prenylation is required for sumoylation. We further determined that sumoylation selectively promotes interactions with syntaxin 2 (but not syntaxins 3 or 4) and that these interactions are nucleotide dependent. Furthermore, a K68R-mutated rab17 led to the redistribution of syntaxin 2 and 5′ nucleotidase from the apical membrane to subapical puncta, whereas multidrug resistance protein 2 distributions were not changed. Together these data are consistent with the proposed role of rab17 in vesicle fusion with the apical plasma membrane and further implicate sumoylation as an important mediator of protein-protein interactions. The selectivity in syntaxin binding and apical protein redistribution further suggests that rab17 and syntaxin 2 mediate fusion of transcytotic vesicles at the apical surface. PMID:26957544

48 CFR 8.1103 - Contract requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract requirements. 8.1103 Section 8.1103 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING REQUIRED SOURCES OF SUPPLIES AND SERVICES Leasing of Motor Vehicles 8.1103 Contract requirements...

49 CFR 172.704 - Training requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Training requirements. 172.704 Section 172.704... PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Training § 172.704 Training requirements. (a) Hazmat employee training must include the...

7 CFR 3575.9 - Environmental requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 15 2011-01-01 2011-01-01 false Environmental requirements. 3575.9 Section 3575.9 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE GENERAL Community Programs Guaranteed Loans § 3575.9 Environmental requirements. Requirements for...

7 CFR 3575.9 - Environmental requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 15 2012-01-01 2012-01-01 false Environmental requirements. 3575.9 Section 3575.9 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE GENERAL Community Programs Guaranteed Loans § 3575.9 Environmental requirements. Requirements for...

7 CFR 3575.9 - Environmental requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Environmental requirements. 3575.9 Section 3575.9 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE GENERAL Community Programs Guaranteed Loans § 3575.9 Environmental requirements. Requirements for...

7 CFR 3575.9 - Environmental requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 15 2013-01-01 2013-01-01 false Environmental requirements. 3575.9 Section 3575.9 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE GENERAL Community Programs Guaranteed Loans § 3575.9 Environmental requirements. Requirements for...

7 CFR 3575.9 - Environmental requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 15 2014-01-01 2014-01-01 false Environmental requirements. 3575.9 Section 3575.9 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE GENERAL Community Programs Guaranteed Loans § 3575.9 Environmental requirements. Requirements for...

47 CFR 24.103 - Construction requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Construction requirements. 24.103 Section 24... COMMUNICATIONS SERVICES Narrowband PCS § 24.103 Construction requirements. (a) Nationwide narrowband PCS... compliance with the construction requirements set forth in this section, licensees must base their...

47 CFR 24.103 - Construction requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 2 2012-10-01 2012-10-01 false Construction requirements. 24.103 Section 24... COMMUNICATIONS SERVICES Narrowband PCS § 24.103 Construction requirements. (a) Nationwide narrowband PCS... compliance with the construction requirements set forth in this section, licensees must base their...

47 CFR 24.103 - Construction requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Construction requirements. 24.103 Section 24... COMMUNICATIONS SERVICES Narrowband PCS § 24.103 Construction requirements. (a) Nationwide narrowband PCS... compliance with the construction requirements set forth in this section, licensees must base their...

47 CFR 24.103 - Construction requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Construction requirements. 24.103 Section 24... COMMUNICATIONS SERVICES Narrowband PCS § 24.103 Construction requirements. (a) Nationwide narrowband PCS... compliance with the construction requirements set forth in this section, licensees must base their...

5 CFR 339.203 - Physical requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Physical requirements. 339.203 Section... QUALIFICATION DETERMINATIONS Physical and Medical Qualifications § 339.203 Physical requirements. Agencies are authorized to establish physical requirements for individual positions without OPM approval when such...

5 CFR 339.203 - Physical requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Physical requirements. 339.203 Section... QUALIFICATION DETERMINATIONS Physical and Medical Qualifications § 339.203 Physical requirements. Agencies are authorized to establish physical requirements for individual positions without OPM approval when such...

5 CFR 339.203 - Physical requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Physical requirements. 339.203 Section... QUALIFICATION DETERMINATIONS Physical and Medical Qualifications § 339.203 Physical requirements. Agencies are authorized to establish physical requirements for individual positions without OPM approval when such...

5 CFR 339.203 - Physical requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Physical requirements. 339.203 Section... QUALIFICATION DETERMINATIONS Physical and Medical Qualifications § 339.203 Physical requirements. Agencies are authorized to establish physical requirements for individual positions without OPM approval when such...

5 CFR 339.203 - Physical requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Physical requirements. 339.203 Section... QUALIFICATION DETERMINATIONS Physical and Medical Qualifications § 339.203 Physical requirements. Agencies are authorized to establish physical requirements for individual positions without OPM approval when such...

14 CFR 171.27 - Performance requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Performance requirements. 171.27 Section 171.27 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Performance requirements. (a) The facility must meet the performance requirements set forth in the...

14 CFR 171.27 - Performance requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Performance requirements. 171.27 Section 171.27 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Performance requirements. (a) The facility must meet the performance requirements set forth in the...

14 CFR 171.27 - Performance requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Performance requirements. 171.27 Section 171.27 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Performance requirements. (a) The facility must meet the performance requirements set forth in the...

14 CFR 171.27 - Performance requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Performance requirements. 171.27 Section 171.27 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Performance requirements. (a) The facility must meet the performance requirements set forth in the...

49 CFR 661.5 - General requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false General requirements. 661.5 Section 661.5 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BUY AMERICA REQUIREMENTS § 661.5 General requirements. (a) Except as provided in...

49 CFR 661.5 - General requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false General requirements. 661.5 Section 661.5 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BUY AMERICA REQUIREMENTS § 661.5 General requirements. (a) Except as provided in...

49 CFR 661.5 - General requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false General requirements. 661.5 Section 661.5 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BUY AMERICA REQUIREMENTS § 661.5 General requirements. (a) Except as provided in...

49 CFR 661.5 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false General requirements. 661.5 Section 661.5 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BUY AMERICA REQUIREMENTS § 661.5 General requirements. (a) Except as provided in...

49 CFR 661.5 - General requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false General requirements. 661.5 Section 661.5 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BUY AMERICA REQUIREMENTS § 661.5 General requirements. (a) Except as provided in...

Managing Legal Texts in Requirements Engineering

NASA Astrophysics Data System (ADS)

Otto, Paul N.; Antón, Annie I.

Laws and regulations are playing an increasingly important role in requirements engineering and systems development. Monitoring systems for requirements and policy compliance has been recognized in the requirements engineering community as a key area for research. Similarly, legal compliance is critical in systems development, especially given that non-compliance can result in both financial and criminal penalties. Working with legal texts can be very challenging, however, because they contain numerous ambiguities, cross-references, domain-specific definitions, and acronyms, and are frequently amended via new statutes, regulations, and case law. Requirements engineers and compliance auditors must be able to identify relevant legal texts, extract requirements and other key concepts, and monitor compliance. This chapter surveys research efforts over the past 50 years in handling legal texts for systems development. This survey can aid requirements engineers and auditors to better specify, test, and monitor systems for compliance.

An airline study of advanced technology requirements for advanced high speed commercial engines. 3: Propulsion system requirements

NASA Technical Reports Server (NTRS)

Sallee, G. P.

1973-01-01

The advanced technology requirements for an advanced high speed commercial transport engine are presented. The results of the phase 3 effort cover the requirements and objectives for future aircraft propulsion systems. These requirements reflect the results of the Task 1 and 2 efforts and serve as a baseline for future evaluations, specification development efforts, contract/purchase agreements, and operational plans for future subsonic commercial engines. This report is divided into five major sections: (1) management objectives for commercial propulsion systems, (2) performance requirements for commercial transport propulsion systems, (3) design criteria for future transport engines, (4) design requirements for powerplant packages, and (5) testing.

Physical requirements in Olympic sailing.

PubMed

Bojsen-Møller, J; Larsson, B; Aagaard, P

2015-01-01

Physical fitness and muscular strength are important performance parameters in Olympic sailing although their relative importance changes between classes. The Olympic format consists of eight yacht types combined into 10 so-called events with total 15 sailors (male and female) in a complete national Olympic delegation. The yachts have different requirements with respect to handling, and moreover, each sailor plays a specific role when sailing. Therefore physical demands remain heterogeneous for Olympic sailors. Previous studies have mainly examined sailors where 'hiking' (the task of leaning over the side of the yacht to increase righting moment) is the primary requirement. Other than the ability to sustain prolonged quasi-isometric contractions, hiking seems to require significant maximal muscle strength especially in knee extensors, hip flexors and abdominal and lower back muscles. Another group of studies has investigated boardsailing and provided evidence to show that windsurfing requires very high aerobic and anaerobic capacity. Although data exist on other types of sailors, the information is limited, and moreover the profile of the Olympic events has changed markedly over the last few years to involve more agile, fast and spectacular yachts. The change of events in Olympic sailing has likely added to physical requirements; however, data on sailors in the modern-type yachts are scarce. The present paper describes the recent developments in Olympic sailing with respect to yacht types, and reviews the existing knowledge on physical requirements in modern Olympic sailing. Finally, recommendations for future research in sailing are given.

47 CFR 10.500 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false General requirements. 10.500 Section 10.500 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL MOBILE ALERT SYSTEM Equipment Requirements § 10.500 General requirements. CMAS mobile device functionality is dependent on the capabilities of a...

48 CFR 2806.303-1 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Requirements. 2806.303-1 Section 2806.303-1 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 2806.303-1 Requirements...

40 CFR 246.202-1 - Requirement.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Requirement. 246.202-1 Section 246.202-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.202-1 Requirement...

40 CFR 246.200-1 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Requirements. 246.200-1 Section 246.200-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.200-1 Requirements...

40 CFR 246.201-1 - Requirement.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Requirement. 246.201-1 Section 246.201-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.201-1 Requirement...

40 CFR 246.202-1 - Requirement.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Requirement. 246.202-1 Section 246.202-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.202-1 Requirement...

48 CFR 706.303-1 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Requirements. 706.303-1 Section 706.303-1 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 706.303-1 Requirements. (a)-(c...

48 CFR 606.303-1 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Requirements. 606.303-1 Section 606.303-1 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 606.303-1 Requirements...

40 CFR 246.201-1 - Requirement.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Requirement. 246.201-1 Section 246.201-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.201-1 Requirement...

48 CFR 606.303-1 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Requirements. 606.303-1 Section 606.303-1 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 606.303-1 Requirements...

48 CFR 706.303-1 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Requirements. 706.303-1 Section 706.303-1 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 706.303-1 Requirements. (a)-(c...

40 CFR 246.202-1 - Requirement.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Requirement. 246.202-1 Section 246.202-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.202-1 Requirement...

48 CFR 2806.303-1 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Requirements. 2806.303-1 Section 2806.303-1 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 2806.303-1 Requirements...

40 CFR 246.200-1 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Requirements. 246.200-1 Section 246.200-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.200-1 Requirements...

40 CFR 246.200-1 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Requirements. 246.200-1 Section 246.200-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.200-1 Requirements...

48 CFR 606.303-1 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Requirements. 606.303-1 Section 606.303-1 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 606.303-1 Requirements...

48 CFR 2806.303-1 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Requirements. 2806.303-1 Section 2806.303-1 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE Competition and Acquisition Planning COMPETITION REQUIREMENTS Other Than Full and Open Competition 2806.303-1 Requirements...

48 CFR 606.303-1 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Requirements. 606.303-1 Section 606.303-1 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 606.303-1 Requirements...

40 CFR 246.201-1 - Requirement.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Requirement. 246.201-1 Section 246.201-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.201-1 Requirement...

48 CFR 606.303-1 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Requirements. 606.303-1 Section 606.303-1 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 606.303-1 Requirements...

48 CFR 2806.303-1 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Requirements. 2806.303-1 Section 2806.303-1 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE COMPETITION AND ACQUISITION PLANNING COMPETITION REQUIREMENTS Other Than Full and Open Competition 2806.303-1 Requirements...

45 CFR 164.105 - Organizational requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Organizational requirements. 164.105 Section 164.105 Public Welfare Department of Health and Human Services ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS SECURITY AND PRIVACY General Provisions § 164.105 Organizational requirements. (a)(1) Standard...

49 CFR 565.25 - Content requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 6 2012-10-01 2012-10-01 false Content requirements. 565.25 Section 565.25 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VEHICLE IDENTIFICATION NUMBER (VIN) REQUIREMENTS Alternative VIN Requirements In Effect for Limited Period...

49 CFR 565.25 - Content requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 6 2014-10-01 2014-10-01 false Content requirements. 565.25 Section 565.25 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VEHICLE IDENTIFICATION NUMBER (VIN) REQUIREMENTS Alternative VIN Requirements In Effect for Limited Period...

49 CFR 565.25 - Content requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 6 2013-10-01 2013-10-01 false Content requirements. 565.25 Section 565.25 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VEHICLE IDENTIFICATION NUMBER (VIN) REQUIREMENTS Alternative VIN Requirements In Effect for Limited Period...

36 CFR 801.7 - Information requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Information requirements. 801... HISTORIC PRESERVATION REQUIREMENTS OF THE URBAN DEVELOPMENT ACTION GRANT PROGRAM § 801.7 Information requirements. (a) Information To Be Retained by Applicants Determining No Effect. (1) Recommended Documentation...

14 CFR 137.19 - Certification requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Certification requirements. 137.19 Section 137.19 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... economic poisons, that applicant is not required to demonstrate the knowledge required in paragraphs (e)(1...

45 CFR 164.105 - Organizational requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Organizational requirements. 164.105 Section 164.105 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS SECURITY AND PRIVACY General Provisions § 164.105 Organizational requirements. (a)(1) Standard...

45 CFR 164.105 - Organizational requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Organizational requirements. 164.105 Section 164.105 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS SECURITY AND PRIVACY General Provisions § 164.105 Organizational requirements. (a)(1) Standard...

25 CFR 531.1 - Required provisions.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) years if the Chairman is satisfied that the capital investment required, and the income projections, for... satisfied that the capital investment required and income projections for the gaming operation require the... the gaming facility; (2) Providing operating capital; (3) Establishing operating days and hours; (4...

7 CFR 1944.672 - Environmental requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 13 2011-01-01 2009-01-01 true Environmental requirements. 1944.672 Section 1944.672...) PROGRAM REGULATIONS (CONTINUED) HOUSING Housing Preservation Grants § 1944.672 Environmental requirements. Subpart G of part 1940 of this chapter will be followed regarding environmental requirements. The...

13 CFR 107.505 - Facsimile requirement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Facsimile requirement. 107.505 Section 107.505 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES Managing the Operations of a Licensee General Requirements § 107.505 Facsimile requirement. You...

33 CFR 151.2060 - Reporting requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Reporting requirements. 151.2060 Section 151.2060 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... § 151.2060 Reporting requirements. (a) Ballast water reporting requirements exist for each vessel...

33 CFR 151.2060 - Reporting requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Reporting requirements. 151.2060 Section 151.2060 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... § 151.2060 Reporting requirements. (a) Ballast water reporting requirements exist for each vessel...

33 CFR 151.2060 - Reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Reporting requirements. 151.2060 Section 151.2060 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... § 151.2060 Reporting requirements. (a) Ballast water reporting requirements exist for each vessel...

76 FR 50881 - Required Scale Tests

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-17

... RIN 0580-AB10 Required Scale Tests AGENCY: Grain Inspection, Packers and Stockyards Administration... required scale tests. Those documents defined ``limited seasonal basis'' incorrectly. This document... 20, 2011 (76 FR 3485) and on April 4, 2011 (76 FR 18348), concerning required scale tests. Those...

49 CFR 229.206 - Design requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Design requirements. 229.206 Section 229.206..., DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Locomotive Crashworthiness Design Requirements § 229.206 Design requirements. Each locomotive used in occupied service must meet the minimum anti...

10 CFR 20.2302 - Additional requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Additional requirements. 20.2302 Section 20.2302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Exemptions and Additional Requirements § 20.2302 Additional requirements. The Commission may, by rule, regulation, or order, impose...

10 CFR 20.2302 - Additional requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Additional requirements. 20.2302 Section 20.2302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Exemptions and Additional Requirements § 20.2302 Additional requirements. The Commission may, by rule, regulation, or order, impose...

10 CFR 20.2302 - Additional requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Additional requirements. 20.2302 Section 20.2302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Exemptions and Additional Requirements § 20.2302 Additional requirements. The Commission may, by rule, regulation, or order, impose...

5 CFR 1315.9 - Required documentation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Required documentation. 1315.9 Section 1315.9 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES PROMPT PAYMENT § 1315.9 Required documentation. Agencies are required to ensure the following payment documentation is established...

49 CFR 172.304 - Marking requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Marking requirements. 172.304 Section 172.304 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SECURITY PLANS Marking § 172.304 Marking requirements. (a) The marking required in this subpart— (1) Must...

7 CFR 1770.13 - Accounting requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Accounting requirements. 1770.13 Section 1770.13... AGRICULTURE (CONTINUED) ACCOUNTING REQUIREMENTS FOR RUS TELECOMMUNICATIONS BORROWERS Uniform System of Accounts § 1770.13 Accounting requirements. (a) Each borrower shall maintain its books of accounts on the...

14 CFR 135.229 - Airport requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Airport requirements. 135.229 Section 135.229 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Operating Limitations and Weather Requirements § 135.229 Airport requirements. (a) No certificate holder may...