Executive Overview of SEI MOSAIC: Managing for Success Using a Risk-Based Approach

DTIC Science & Technology

2007-03-01

and pro - vides the lens through which all potential outcomes are viewed and interpreted. Defining the con - text is thus an essential first step when...Success Analysis and Improvement Crite- ria (SEI MOSAIC)—a suite of advanced analysis methods for assessing complex, distributed pro - grams, processes...achieve that set of objectives, four ac- tivities must be executed in the order shown, while also adhering to any cost and schedule con - straints. Process

Structure-Based Design and Synthesis of a Small Molecule that Exhibits Anti-inflammatory Activity by Inhibition of MyD88-mediated Signaling to Bacterial Toxin Exposure.

PubMed

Alam, Shahabuddin; Javor, Sacha; Degardin, Melissa; Ajami, Dariush; Rebek, Mitra; Kissner, Teri L; Waag, David M; Rebek, Julius; Saikh, Kamal U

2015-08-01

Both Gram-positive and Gram-negative pathogens or pathogen-derived components, such as staphylococcal enterotoxins (SEs) and endotoxin (LPS) exposure, activate MyD88-mediated pro-inflammatory cellular immunity for host defense. However, dysregulated MyD88-mediated signaling triggers exaggerated immune response that often leads to toxic shock and death. Previously, we reported a small molecule compound 1 mimicking BB-loop structure of MyD88 was capable of inhibiting pro-inflammatory response to SEB exposure in mice. In this study, we designed a dimeric structure compound 4210 covalently linked with compound 1 by a non-polar cyclohexane linker which strongly inhibited the production of pro-inflammatory cytokines in human primary cells to SEB (IC50 1-50 μm) or LPS extracted from Francisella tularensis, Escherichia coli, or Burkholderia mallei (IC50 10-200 μm). Consistent with cytokine inhibition, in a ligand-induced cell-based reporter assay, compound 4210 inhibited Burkholderia mallei or LPS-induced MyD88-mediated NF-kB-dependent expression of reporter activity (IC50 10-30 μm). Furthermore, results from a newly expressed MyD88 revealed that 4210 inhibited MyD88 dimer formation which is critical for pro-inflammatory signaling. Importantly, a single administration of compound 4210 in mice showed complete protection from lethal toxin challenge. Collectively, these results demonstrated that compound 4210 inhibits toxin-induced inflated pro-inflammatory immune signaling, thus displays a potential bacterial toxin therapeutic. © 2014 John Wiley & Sons A/S.

Crosstalk: The Journal of Defense Software Engineering. Volume 22, Number 1, January 2009

DTIC Science & Technology

2009-01-01

con - tract project. They manage the pro - ject plan and its execution and ask: How do we get all of this accom- plished? • The marketing manager...struggle with the pros and cons of technological toys at home, with the cell phone probably being the most divisive. It’s great to keep our kids in...their technology behind? These concerns present us practitioners with many challenges. We must build trust with pro - gram managers, proving over and

Preschool-Based Programs for Externalizing Problems

ERIC Educational Resources Information Center

Arnold, David H.; Brown, Sharice A.; Meagher, Susan; Baker, Courtney N.; Dobbs, Jennifer; Doctoroff, Greta L.

2006-01-01

Few mental health initiatives for young children have used classroom programs. Preschool-based efforts targeting externalizing behavior could help prevent conduct disorders. Additional benefits may include improved academic achievement and reduced risk for other mental health difficulties. Pro-grams that target multiple developmental domains are…

Bacteroides fragilis Lipopolysaccharide and Inflammatory Signaling in Alzheimer’s Disease

PubMed Central

Lukiw, Walter J.

2016-01-01

The human microbiome consists of ~3.8 × 1013 symbiotic microorganisms that form a highly complex and dynamic ecosystem: the gastrointestinal (GI) tract constitutes the largest repository of the human microbiome by far, and its impact on human neurological health and disease is becoming increasingly appreciated. Bacteroidetes, the largest phylum of Gram-negative bacteria in the GI tract microbiome, while generally beneficial to the host when confined to the GI tract, have potential to secrete a remarkably complex array of pro-inflammatory neurotoxins that include surface lipopolysaccharides (LPSs) and toxic proteolytic peptides. The deleterious effects of these bacterial exudates appear to become more important as GI tract and blood-brain barriers alter or increase their permeability with aging and disease. For example, presence of the unique LPSs of the abundant Bacteroidetes species Bacteroides fragilis (BF-LPS) in the serum represents a major contributing factor to systemic inflammation. BF-LPS is further recognized by TLR2, TLR4, and/or CD14 microglial cell receptors as are the pro-inflammatory 42 amino acid amyloid-beta (Aβ42) peptides that characterize Alzheimer’s disease (AD) brain. Here we provide the first evidence that BF-LPS exposure to human primary brain cells is an exceptionally potent inducer of the pro-inflammatory transcription factor NF-kB (p50/p65) complex, a known trigger in the expression of pathogenic pathways involved in inflammatory neurodegeneration. This ‘Perspectives communication’ will in addition highlight work from recent studies that advance novel and emerging concepts on the potential contribution of microbiome-generated factors, such as BF-LPS, in driving pro-inflammatory degenerative neuropathology in the AD brain. PMID:27725817

Hardware Algorithm Implementation for Mission Specific Processing

DTIC Science & Technology

2008-03-01

knowledge about the VLSI technology and understands VHDL, scripting, and intergrating the script in Cadencersoftware pro- gram or Modelsimr. The main...possible to have a trade off between parallel and serial logic design for the circuit. Power can be saved by using parallization, pipelining, or a

A Type System For Certified Runtime Type Analysis

DTIC Science & Technology

2002-12-01

1999 ACM SIGPLAN International Conf. on Functional Pro- gramming (ICFP’99), pages 183–196. ACM Press, September 1999. [Min97] Yasuhiko Minamide. Full...lifting of type parameters. Technical report, RIMS, Kyoto University, 1997. [MMH96] Yasuhiko Minamide, Greg Morrisett, and Robert Harper. Typed

Intellectual Property Protection for Software

DTIC Science & Technology

1989-07-01

regulations. This book is useful for its practical, nical Data. New York: Government Contracts Pro- in-depth coverage of copyright licensing. gram, George ...quence and ordering of input formats could give rise Taylor to copyright liability. Synercom had developed a Taylor Instrument Cos. v. Fawley- Brost Co

U.S. Department of Energy’s Industrial Technology Program and Its Impacts

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

Weakley, Steven A.; Roop, Joseph M.

The U.S. Department of Energy’s Industrial Technologies Program (ITP) has been working with industry since 1976 to encourage the development and adoption of new, energy-efficient technologies. ITP has helped industry not only use energy and materials more efficiently but also improve environ-mental performance, product quality, and productivity. To help ITP determine the impacts of its pro-grams, Pacific Northwest National Laboratory (PNNL) periodically reviews and analyzes ITP pro-gram benefits. PNNL contacts vendors and users of ITP-sponsored technologies that have been commer-cialized, estimates the number of units that have penetrated the market, conducts engineering analyses to estimate energy savings from the newmore » technolo¬gies, and estimates air pollution and carbon emission reductions. This paper discusses the results of PNNL’s most recent review (conducted in 2009). From 1976-2008, the commercialized technologies from ITP’s research and development programs and other activities have cumulatively saved 9.27 quadrillion Btu, with a net cost savings of $63.91 billion.« less

U.S. Department of Energy’s Industrial Technologies Program and Its Impacts

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

Weakley, Steven A.; Brown, Scott A.

The U.S. Department of Energy’s Industrial Technologies Program (ITP) has been working with industry since 1976 to encourage the development and adoption of new, energy-efficient technologies. ITP has helped industry not only use energy and materials more efficiently but also improve environ-mental performance, product quality, and productivity. To help ITP determine the impacts of its pro-grams, Pacific Northwest National Laboratory (PNNL) periodically reviews and analyzes ITP pro-gram benefits. PNNL contacts vendors and users of ITP-sponsored technologies that have been commer-cialized, estimates the number of units that have penetrated the market, conducts engineering analyses to estimate energy savings from the newmore » technolo-gies, and estimates air pollution and carbon emission reductions. This paper discusses the results of PNNL’s most recent review (conducted in 2010). From 1976-2009, the commercialized technologies from ITP’s research and development programs and other activities have cumulatively saved 10.0 quadrillion Btu, with a net cost savings of $61.82 billion.« less

U.S. Department of Energy’s Industrial Technology Program and Its Impacts

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

Weakley, Steven A.; Roop, Joseph M.

The U.S. Department of Energy’s Industrial Technologies Program (ITP) has been working with industry since 1976 to encourage the development and adoption of new, energy-efficient technologies. ITP has helped industry not only use energy and materials more efficiently but also improve environ-mental performance, product quality, and productivity. To help ITP determine the impacts of its pro-grams, Pacific Northwest National Laboratory (PNNL) periodically reviews and analyzes ITP pro-gram benefits. PNNL contacts vendors and users of ITP-sponsored technologies that have been commer-cialized, estimates the number of units that have penetrated the market, conducts engineering analyses to estimate energy savings from the newmore » technolo¬gies, and estimates air pollution and carbon emission reductions. This paper discusses the results of PNNL’s most recent review (conducted in 2008). From 1976-2007, the commercialized technologies from ITP’s research and development programs and other activities have cumulatively saved 6.17 quadrillion Btu, with a net cost savings of $63.0 billion.« less

Antagonistic Properties of Some Halophilic Thermoactinomycetes Isolated from Superficial Sediment of a Solar Saltern and Production of Cyclic Antimicrobial Peptides by the Novel Isolate Paludifilum halophilum

PubMed Central

Frikha Dammak, Donyez; Zarai, Ziad; Najah, Soumaya; Abdennabi, Rayed; Belbahri, Lassaad; Rateb, Mostafa E.; Mejdoub, Hafedh

2017-01-01

This study has focused on the isolation of twenty-three halophilic actinomycetes from two ponds of different salinity and the evaluation of their ability to exert an antimicrobial activity against both their competitors and several other pathogens. From the 23 isolates, 18 strains showed antagonistic activity, while 19 showed activities against one or more of the seven pathogen strains tested. Six strains exhibited consistent antibacterial activity against Gram-negative and Gram-positive pathogens characterized at the physiological and molecular levels. These strains shared only 94-95% 16S rRNA sequence identity with the closely related species of the Thermoactinomycetaceae family. Among them, the potent strain SMBg3 was further characterized and assigned to a new genus in the family for which the name Paludifilum halophilum (DSM 102817T) is proposed. Sequential extraction of the antimicrobial compounds with ethyl acetate revealed that the crude extract from SMBg3 strain had inhibitory effect on the growth of the plant pathogen Agrobacterium tumefaciens and the human pathogens Staphylococcus aureus, Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa. Based on the HRESI-MS spectral data, the cyclic lipopeptide Gramicidin S and four cyclic dipeptides (CDPs) named cyclo(L-4-OH-Pro-L-Leu), cyclo(L-Tyr-L-Pro), cyclo(L-Phe-L-Pro), and cyclo(L-Leu-L-Pro) were detected in the fermentation broth of Paludifilum halophilum. To our knowledge, this is the first report on the isolation of these compounds from members of the Thermoactinomycetaceae family. PMID:28819625

LAND USE CHANGE DUE TO URBANIZATION FOR THE MID-ATLANTIC INTEGRATED ASSESSMENT REGION OF THE EASTERN UNITED STATES

EPA Science Inventory

The U.S. Environmental Protection Agency's (EPA) Regional Vulnerability Assessment Pro- gram (REVA) is designed to develop and demonstrate approaches to identify the ecosystems at the greatest risk from regional population growth and economic activity (Smith, 1999). A region is a...

Nurses’ Assessment and Teaching Behaviors Regarding Breast Self-Examination with Reasons for Actions.

DTIC Science & Technology

1984-01-01

between patients and physicians because their training is more oriented toward illness and rehabilitation. No matter who provides the education it...client education based on 55 this assessment. Continuing education and inservice pro- grams could be provided oa BSE and how to complete more thorough

Iraq Reconstruction: Lessons from Auditing U.S.-funded Stabilization and Reconstruction Activities

DTIC Science & Technology

2012-10-01

Emergency Response Program: Hotel Construction Successfully Completed, but Project Management Issues Remain 09-025 7/26/2009 Commander’s Emergency...Emergency Response Pro- gram: Hotel Construction Completed, but Project Management Issues Remain,” 7/26/2009. 47. SIGIR Audit 11-003, “Iraqi Security Forces

Linear- and Repetitive Feature Detection Within Remotely Sensed Imagery

DTIC Science & Technology

2017-04-01

applicable to Python or other pro- gramming languages with image- processing capabilities. 4.1 Classification machine learning The first methodology uses...remotely sensed images that are in panchromatic or true-color formats. Image- processing techniques, in- cluding Hough transforms, machine learning, and...data fusion .................................................................................................... 44 6.3 Context-based processing

A new C-type lectin (FcLec5) from the Chinese white shrimp Fenneropenaeus chinensis.

PubMed

Xu, Wen-Teng; Wang, Xian-Wei; Zhang, Xiao-Wen; Zhao, Xiao-Fan; Yu, Xiao-Qiang; Wang, Jin-Xing

2010-11-01

C-type lectins are one family of pattern recognition receptors (PRRs) that play important roles in innate immunity. In this work, cDNA and genomic sequences for a new C-type lectin (FcLec5) were obtained from the Chinese white shrimp Fenneropenaeus chinensis. FcLec5 cDNA contains an open reading frame of 1,008 bp and its genomic sequence is 1,137 bp with 4 exons and 3 introns. The predicted FcLec5 protein contains a signal peptide and two carbohydrate recognition domains (CRDs). The N-terminal CRD of FcLec5 has a predicted carbohydrate recognition motif of Gln-Pro-Asp (QPD), while the C-terminal CRD contains a motif of Glu-Pro-Gln (EPQ). Northern blot analysis showed that FcLec5 mRNA was specifically expressed in hepatopancreas. FcLec5 protein was expressed in hepatopancreas and secreted into hemolymph. Real-time PCR showed that FcLec5 transcript exhibited different expression profiles after immune-challenged with Vibrio anguillarum or White Spot Syndrome Virus (WSSV). Recombinant FcLec5 and its two individual CRDs could agglutinate most bacteria tested, and the agglutinating activity was Ca2+-dependent. Besides, the agglutinating activity to gram-negative bacteria is higher than that to gram-positive bacteria. Direct binding assay showed that recombinant FcLec5 could bind to all microorganisms tested (five gram-positive and four gram-negative bacteria, as well as yeast) in a Ca2+-independent manner. Recombinant FcLec5 also directly bound to bacterial peptidoglycan, lipopolysaccharide and lipoteichoic acids. These results suggest that FcLec5 may act as a PRR for bacteria via binding to bacterial cell wall polysaccharides in Chinese white shrimp.

Seismic classification through sparse filter dictionaries

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

Hickmann, Kyle Scott; Srinivasan, Gowri

We tackle a multi-label classi cation problem involving the relation between acoustic- pro le features and the measured seismogram. To isolate components of the seismo- grams unique to each class of acoustic pro le we build dictionaries of convolutional lters. The convolutional- lter dictionaries for the individual classes are then combined into a large dictionary for the entire seismogram set. A given seismogram is classi ed by computing its representation in the large dictionary and then comparing reconstruction accuracy with this representation using each of the sub-dictionaries. The sub-dictionary with the minimal reconstruction error identi es the seismogram class.

Lipoproteins/peptides are sepsis-inducing toxins from bacteria that can be neutralized by synthetic anti-endotoxin peptides

PubMed Central

de Tejada, Guillermo Martinez; Heinbockel, Lena; Ferrer-Espada, Raquel; Heine, Holger; Alexander, Christian; Bárcena-Varela, Sergio; Goldmann, Torsten; Correa, Wilmar; Wiesmüller, Karl-Heinz; Gisch, Nicolas; Sánchez-Gómez, Susana; Fukuoka, Satoshi; Schürholz, Tobias; Gutsmann, Thomas; Brandenburg, Klaus

2015-01-01

Sepsis, a life-threatening syndrome with increasing incidence worldwide, is triggered by an overwhelming inflammation induced by microbial toxins released into the bloodstream during infection. A well-known sepsis-inducing factor is the membrane constituent of Gram-negative bacteria, lipopolysaccharide (LPS), signalling via Toll-like receptor-4. Although sepsis is caused in more than 50% cases by Gram-positive and mycoplasma cells, the causative compounds are still poorly described. In contradicting investigations lipoproteins/-peptides (LP), lipoteichoic acids (LTA), and peptidoglycans (PGN), were made responsible for eliciting this pathology. Here, we used human mononuclear cells from healthy donors to determine the cytokine-inducing activity of various LPs from different bacterial origin, synthetic and natural, and compared their activity with that of natural LTA and PGN. We demonstrate that LP are the most potent non-LPS pro-inflammatory toxins of the bacterial cell walls, signalling via Toll-like receptor-2, not only in vitro, but also when inoculated into mice: A synthetic LP caused sepsis-related pathological symptoms in a dose-response manner. Additionally, these mice produced pro-inflammatory cytokines characteristic of a septic reaction. Importantly, the recently designed polypeptide Aspidasept® which has been proven to efficiently neutralize LPS in vivo, inhibited cytokines induced by the various non-LPS compounds protecting animals from the pro-inflammatory activity of synthetic LP. PMID:26390973

Evidence for ProTα-TLR4/MD-2 binding: molecular dynamics and gravimetric assay studies.

PubMed

Omotuyi, Olaposi; Matsunaga, Hayato; Ueda, Hiroshi

2015-01-01

During preconditioning, lipopolysaccharide (LPS) selectively activates TLR4/MD-2/Toll/IL-1 receptor-domain-containing adaptor inducing IFN-β (TRIF) pathway instead of pro-inflammatory myeloid differentiation protein-88 (MyD88)/MyD88-adaptor-like protein (MAL) pathway. Extracellular prothymosin alpha (ProTα) is also known to selectively activate the TLR4/MD2/TRIF-IRF3 pathway in certain diseased conditions. In the current study, biophysical evidence for ProTα/TLR4/MD-2 complex formation and its interaction dynamics have been studied. Gravimetric assay was used to investigate ProTα/TLR4/MD-2 complex formation while molecular dynamics (MD) simulation was used to study its interaction dynamics. Through electrostatic interaction, full-length ProTα (F-ProTα) C-terminal peptide (aa 91 - 111) superficially interacts with similar TLR4/MD-2 (KD = 273.36 nm vs 16.07 μg/ml [LPS]) conformation with LPS at an overlapping three-dimensional space while F-ProTα is hinged to the TLR4 scaffold by one-amino acid shift-Mosoian domain (aa-51 - 90). Comparatively, F-ProTα better stabilizes MD-2 metastable states transition and mediates higher TLR4/MD-2 interaction than LPS. ProTα via its C-terminal peptide (aa 91 - 111) exhibits in vitro biophysical contact with TLR4/MD-2 complex conformation recognized by LPS at overlapping LPS-binding positions.

Quantification and Formalization of Security

DTIC Science & Technology

2010-02-01

Quantification of Information Flow . . . . . . . . . . . . . . . . . . 30 2.4 Language Semantics . . . . . . . . . . . . . . . . . . . . . . . . . . 46...system behavior observed by users holding low clearances. This policy, or a variant of it, is enforced by many pro- gramming language -based mechanisms...illustrates with a particular programming language (while-programs plus probabilistic choice). The model is extended in §2.5 to programs in which

Primal Barrier Methods for Linear Programming

DTIC Science & Technology

1989-06-01

A Theoretical Bound Concerning the difficulties introduced by an ill-conditioned H- 1, Dikin [Dik67] and Stewart [Stew87] show for a full-rank A...Dik67] I. I. Dikin (1967). Iterative solution of problems of linear and quadratic pro- gramming, Doklady Akademii Nauk SSSR, Tom 174, No. 4. [Fia79] A. V

Barriers and Solutions to Recruitment Strategies of Students into Post-Secondary Agricultural Education Programs: A Focus Group Approach

ERIC Educational Resources Information Center

Calvin, Jennifer; Pense, Seburn L.

2013-01-01

This qualitative study utilized focus group interviews of secondary Illinois agricultural education teachers to investigate the continuing problem of student recruitment into teacher preparation pro-grams of agricultural education. Using signal theory, image theory and person-organization fit theory, the researchers identified five themes relating…

Understanding the Cost and Quality of Military-Related Education Benefit Programs

DTIC Science & Technology

2013-01-01

2002; Stanley, 2003). Evidence also suggests that a similar pro- gram in Canada led to large increases in college attainment ( Lemieux and Card, 2001...U.S. Government Accountability Office, GAO-10-948T, 2010. Lemieux , Thomas, and David Card, “Education, Earnings, and the Canadian GI Bill,” The

U. S. Department of Energy (DOE) Industrial Programs and Their Impacts

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

Weakley, Steven A.; Roop, Joseph M.

The U.S. Department of Energy’s Industrial Technologies Program (ITP) has been working with industry since 1976 to encourage the development and adoption of new, energy-efficient technologies. ITP has helped industry not only use energy and materials more efficiently but also improve environ¬mental performance, product quality, and productivity. To help ITP determine the impacts of its pro¬grams, Pacific Northwest National Laboratory (PNNL) periodically reviews and analyzes ITP pro¬gram benefits. PNNL contacts vendors and users of ITP-sponsored technologies that have been commer¬cialized, estimates the number of units that have penetrated the market, conducts engineering analyses to estimate energy savings from the newmore » technolo¬gies, and estimates air pollution and carbon emission reductions. This paper discusses the results of the most recent PNNL review (conducted in 2007). From 1976-2006, the commercialized technologies from ITP’s research and development (R&D) programs and other activities have cumulatively saved 5.65 quadrillion Btu, with a net cost savings of $37.8 billion.« less

U.S. Department of Energy (DOE) Industrial Programs and Their Impacts

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

Weakley, Steven A.; Roop, Joseph M.

The U.S. Department of Energy’s Industrial Technologies Program (ITP) has been working with industry since 1976 to encourage the development and adoption of new, energy-efficient technologies. ITP has helped industry not only use energy and materials more efficiently but also improve environ¬mental performance, product quality, and productivity. To help ITP determine the impacts of its pro¬grams, Pacific Northwest National Laboratory (PNNL) periodically reviews and analyzes ITP pro¬gram benefits. PNNL contacts vendors and users of ITP-sponsored technologies that have been commer¬cialized, estimates the number of units that have penetrated the market, conducts engineering analyses to estimate energy savings from the newmore » technolo¬gies, and estimates air pollution and carbon emission reductions. This paper discusses the results of the most recent PNNL review (conducted in 2006). From 1976-2005, the commercialized technologies from ITP’s research and development (R&D) programs and other activities have cumulatively saved 5.13 quadrillion Btu, with a net cost savings of $29.3 billion.« less

Shrimp serine proteinase homologues PmMasSPH-1 and -2 play a role in the activation of the prophenoloxidase system.

PubMed

Jearaphunt, Miti; Amparyup, Piti; Sangsuriya, Pakkakul; Charoensapsri, Walaiporn; Senapin, Saengchan; Tassanakajon, Anchalee

2015-01-01

Melanization mediated by the prophenoloxidase (proPO) activating system is a rapid immune response used by invertebrates against intruding pathogens. Several masquerade-like and serine proteinase homologues (SPHs) have been demonstrated to play an essential role in proPO activation in insects and crustaceans. In a previous study, we characterized the masquerade-like SPH, PmMasSPH1, in the black tiger shrimp Penaeus monodon as a multifunctional immune protein based on its recognition and antimicrobial activity against the Gram-negative bacteria Vibrio harveyi. In the present study, we identify a novel SPH, known as PmMasSPH2, composed of an N-terminal clip domain and a C-terminal SP-like domain that share high similarity to those of other insect and crustacean SPHs. We demonstrate that gene silencing of PmMasSPH1 and PmMasSPH2 significantly reduces PO activity, resulting in a high number of V. harveyi in the hemolymph. Interestingly, knockdown of PmMasSPH1 suppressed not only its gene transcript but also other immune-related genes in the proPO system (e.g., PmPPAE2) and antimicrobial peptides (e.g., PenmonPEN3, PenmonPEN5, crustinPm1 and Crus-likePm). The PmMasSPH1 and PmMasSPH2 also show binding activity to peptidoglycan (PGN) of Gram-positive bacteria. Using a yeast two-hybrid analysis and co-immunoprecipitation, we demonstrate that PmMasSPH1 specifically interacted with the final proteinase of the proPO cascade, PmPPAE2. Furthermore, the presence of both PmMasSPH1 and PmPPAE2 enhances PGN-induced PO activity in vitro. Taken together, these results suggest the importance of PmMasSPHs in the activation of the shrimp proPO system.

Shrimp Serine Proteinase Homologues PmMasSPH-1 and -2 Play a Role in the Activation of the Prophenoloxidase System

PubMed Central

Jearaphunt, Miti; Amparyup, Piti; Sangsuriya, Pakkakul; Charoensapsri, Walaiporn; Senapin, Saengchan; Tassanakajon, Anchalee

2015-01-01

Melanization mediated by the prophenoloxidase (proPO) activating system is a rapid immune response used by invertebrates against intruding pathogens. Several masquerade-like and serine proteinase homologues (SPHs) have been demonstrated to play an essential role in proPO activation in insects and crustaceans. In a previous study, we characterized the masquerade-like SPH, PmMasSPH1, in the black tiger shrimp Penaeus monodon as a multifunctional immune protein based on its recognition and antimicrobial activity against the Gram-negative bacteria Vibrio harveyi. In the present study, we identify a novel SPH, known as PmMasSPH2, composed of an N-terminal clip domain and a C-terminal SP-like domain that share high similarity to those of other insect and crustacean SPHs. We demonstrate that gene silencing of PmMasSPH1 and PmMasSPH2 significantly reduces PO activity, resulting in a high number of V. harveyi in the hemolymph. Interestingly, knockdown of PmMasSPH1 suppressed not only its gene transcript but also other immune-related genes in the proPO system (e.g., PmPPAE2) and antimicrobial peptides (e.g., PenmonPEN3, PenmonPEN5, crustinPm1 and Crus-likePm). The PmMasSPH1 and PmMasSPH2 also show binding activity to peptidoglycan (PGN) of Gram-positive bacteria. Using a yeast two-hybrid analysis and co-immunoprecipitation, we demonstrate that PmMasSPH1 specifically interacted with the final proteinase of the proPO cascade, PmPPAE2. Furthermore, the presence of both PmMasSPH1 and PmPPAE2 enhances PGN-induced PO activity in vitro. Taken together, these results suggest the importance of PmMasSPHs in the activation of the shrimp proPO system. PMID:25803442

Emerging Insights into Noncanonical Inflammasome Recognition of Microbes.

PubMed

Russo, Ashley J; Behl, Bharat; Banerjee, Ishita; Rathinam, Vijay A K

2018-01-19

Inflammasomes are cytosolic multi-molecular complexes that sense intracellular microbial danger signals and metabolic perturbations. Inflammasome activation leads to the activation of caspase-1 and the release of pro-inflammatory cytokines IL-1β and IL-18 accompanied by cell death. An inflammasome-based surveillance machinery for Gram-negative bacterial infections has been recently discovered. This noncanonical inflammasome relies on sensing the cytosolic presence of lipopolysaccharide of Gram-negative bacteria via inflammatory caspases such as caspase-4, -5, and -11. This review discusses the recent findings related to the mechanism of activation of the noncanonical inflammasome and its biological functions. Copyright © 2017. Published by Elsevier Ltd.

'Biologic memory' in response to acute kidney injury: cytoresistance, toll-like receptor hyper-responsiveness and the onset of progressive renal disease.

PubMed

Zager, Richard A

2013-08-01

Following the induction of ischemic or toxin-mediated acute kidney injury (AKI), cellular adaptations occur that 're-program' how the kidney responds to future superimposed insults. This re-programming is not simply a short-lived phenomenon; rather it can persist for many weeks, implying that a state of 'biologic memory' has emerged. These changes can be both adaptive and maladaptive in nature and they can co-exist in time. A beneficial adaptation is the emergence of acquired cytoresistance, whereby a number of physiologic responses develop that serve to protect the kidney against further ischemic or nephrotoxic attack. Conversely, some changes are maladaptive, such as a predisposition to Gram-negative or Gram-positive bacteremia due to a renal tubular up-regulation of toll-like receptor responses. This latter change culminates in exaggerated cytokine production, and with efflux into the systemic circulation, extra-renal tissue injury can result (so-called 'organ cross talk'). Another maladaptive response is a persistent up-regulation of pro-inflammatory, pro-fibrotic and vasoconstrictive genes, culminating in progressive renal injury and ultimately end-stage renal failure. The mechanisms by which this biologic re-programming, or biologic memory, is imparted remain subjects for considerable debate. However, injury-induced, and stable, epigenetic remodeling at pro-inflammatory/pro-fibrotic genes seems likely to be involved. The goal of this editorial is to highlight that the so-called 'maintenance phase' of acute renal failure is not a static one, somewhere between injury induction and the onset of repair. Rather, this period is one in which the induction of 'biologic memory' can ultimately impact renal functional recovery, extra-renal injury and the possible transition of AKI into chronic, progressive renal disease.

Curling dynamics of naturally curved ribbons from high to low Reynolds numbers

NASA Astrophysics Data System (ADS)

Albarran Arriagada, Octavio; Massiera, Gladys; Abkarian, Manouk

2012-11-01

Curling deformation of thin elastic sheets appears in numerous structures in nature, such as membranes of red blood cells, epithelial tissues or green algae colonies to cite just a few examples. However, despite its ubiquity, the dynamics of curling propagation in a naturally curved material remains still poorly investigated. Here, we present a coupled experimental and theoretical study of the dynamical curling deformation of naturally curved ribbons. Using thermoplastic and metallic ribbons molded on cylinders of different radii, we tune separately the natural curvature and the geometry to study curling dynamics in air, water and in viscous oils, thus spanning a wide range of Reynolds numbers. Our theoretical and experimental approaches separate the role of elasticity, gravity and hydrodynamic dissipation from inertia and emphasize the fundamental differences between the curling of a naturally curved ribbon and a rod described by the classical Elastica. Our work shows evidence for the propagation of a single instability front, selected by a local buckling condition. We show that depending on gravity, and both the Reynolds and the Cauchy numbers, the curling speed and shape are modified by the large scale drag and the local lubrication forces. This work was supported by the French Ministry of Research, the CNRS Physics-Chemistry-Biology Interdisciplinary Pro- gram, the University Montpellier 2 Interdisciplinary Program and the Region Languedoc-Roussillon.

Dynamic Analysis of Hammer Mechanism "Twin Hammer" of Impact Wrench

NASA Astrophysics Data System (ADS)

Konečný, M.; Slavík, J.

This paper describes function of the hammer mechanism "Twin hammer" the impact wrench, calculation of dynamic forces exerted on the mechanism and determining the contact pressures between the parts of the mechanism. The modelling of parts was performed in system Pro ENGINEER—standard. The simulation and finding dynamic forces was performed in advanced module Pro ENGINEER—mechanism design and finding contacts pressures in modul Pro ENGENEER—mechanica.

Evol and ProDy for bridging protein sequence evolution and structural dynamics

PubMed Central

Mao, Wenzhi; Liu, Ying; Chennubhotla, Chakra; Lezon, Timothy R.; Bahar, Ivet

2014-01-01

Correlations between sequence evolution and structural dynamics are of utmost importance in understanding the molecular mechanisms of function and their evolution. We have integrated Evol, a new package for fast and efficient comparative analysis of evolutionary patterns and conformational dynamics, into ProDy, a computational toolbox designed for inferring protein dynamics from experimental and theoretical data. Using information-theoretic approaches, Evol coanalyzes conservation and coevolution profiles extracted from multiple sequence alignments of protein families with their inferred dynamics. Availability and implementation: ProDy and Evol are open-source and freely available under MIT License from http://prody.csb.pitt.edu/. Contact: bahar@pitt.edu PMID:24849577

Processing of the mother-cell sigma factor, sigma K, may depend on events occurring in the forespore during Bacillus subtilis development.

PubMed Central

Lu, S; Halberg, R; Kroos, L

1990-01-01

During sporulation of the Gram-positive bacterium Bacillus subtilis, transcription of genes encoding spore coat proteins in the mother-cell compartment of the sporangium is controlled by RNA polymerase containing the sigma subunit called sigma K. Based on comparison of the N-terminal amino acid sequence of sigma K with the nucleotide sequence of the gene encoding sigma K (sigK), the primary product of sigK was inferred to be a pro-protein (pro-sigma K) with 20 extra amino acids at the N terminus. Using antibodies generated against pro-sigma K, we have detected pro-sigma K beginning at the third hour of sporulation and sigma K beginning about 1 hr later. Even when pro-sigma K is expressed artificially during growth and throughout sporulation, sigma K appears at the normal time and expression of a sigma K-controlled gene occurs normally. These results suggest that pro-sigma K is an inactive precursor that is proteolytically processed to active sigma K in a developmentally regulated fashion. Mutations that block forespore gene expression block accumulation of sigma K but not accumulation of pro-sigma K, suggesting that pro-sigma K processing is a regulatory device that couples the programs of gene expression in the two compartments of the sporangium. We propose that this regulatory device ensures completion of forespore morphogenesis prior to the synthesis in the mother-cell of spore coat proteins that will encase the forespore. Images PMID:2124700

Laser Optics/Combustion Diagnostics.

DTIC Science & Technology

1986-07-01

of Blackbody at Various Temperatures (K). . . 153 21 Transmission Attenuation of Quartz Fiber ... ............ .. 155 22 Schematic Diagram of Receiver...transfer pro- time-multiplexed via different lengths of fiber -optic cable to gram (machine code) of the TN- 1710 controls the handshak- a single...linewidths depend upon temperature, pressure, and , composition of the medium as well as the J value of the line. Collisional effects, as demonstrated for

Networked Workstations and Parallel Processing Utilizing Functional Languages

DTIC Science & Technology

1993-03-01

program . This frees the programmer to concentrate on what the program is to do, not how the program is...traditional ’von Neumann’ architecture uses a timer based (e.g., the program counter), sequentially pro- grammed, single processor approach to problem...traditional ’von Neumann’ architecture uses a timer based (e.g., the program counter), sequentially programmed , single processor approach to

A Computational Procedure for the Protection of Industrial Power Systems.

DTIC Science & Technology

1981-11-01

Sumary ................................. ... 79 9 . CONCLUSIONS ....... ..................... ... 80 Recomnendations for Further Work ... ........... ... 81...34- - : "’< ’"’-......................"..-..-..--......-..... 9 Fuses. Two types of fuses are used in the coordination pro- gram. These are current-limiting and...NUMONICS Electronic Graphics Calculator [ 9 ]. The NUMONICS EGC then provided a convenient way to enter X-Y coordinate data representing any curve onto disk

A Focus Group Assessment to Determine Motivations, Barriers and Effectiveness of a University-Based Worksite Wellness Program

PubMed Central

Hill-Mey, Patricia E.; Merrill, Ray M.; Kumpfer, Karol L.; Reel, Justine; Hyatt-Neville, Beverly

2013-01-01

Background: This study explores university employee perceptions and under­standing about its Worksite Health Promotion Program (WHPP). The WHPP included a Health Risk Appraisal (HRA), biometric screening, publicity for on-campus health programs and facilities, and health coaching. Methods: A qualitative design was used based on a grounded theory ap­proach. Four 90 minutes focus groups with 6-8 participants in each were conducted within a two 2 week period among employees, representing fac­ulty/participants, fac­ulty/nonparticipants, staff/participants, and staff/nonparticipants. Responses to questions about motivations, barriers, and perceived health benefits that impacted participation in the WHPP were digi­tally recorded, transcribed and coded for themes. Results: Incentives effectively motivated participation. Biometric screening had the largest impact on behavior change, followed by the information learned from the HRA. However, despite two-thirds of the employees partici­pating in the pro­gram, lack of a full understanding of WHPP benefits and services lowered partici­pation in follow-up services and supplemental pro­grams. Conclusions: Biometric screening and HRAs effectively motivate program par­ticipation. Communication of benefits and services are important when providing WHPPs. PMID:24688965

Antibacterial and anti-inflammatory activity of a temporin B peptide analogue on an in vitro model of cystic fibrosis.

PubMed

Bezzerri, Valentino; Avitabile, Concetta; Dechecchi, Maria Cristina; Lampronti, Ilaria; Borgatti, Monica; Montagner, Giulia; Cabrini, Giulio; Gambari, Roberto; Romanelli, Alessandra

2014-10-01

Natural peptides with antimicrobial properties are deeply investigated as tools to fight bacteria resistant to common antibiotics. Small peptides, as those belonging to the temporin family, are very attractive because their activity can easily be tuned after small modification to their primary sequence. Structure-activity studies previously reported by us allowed the identification of one peptide, analogue of temporin B, TB_KKG6A, showing, unlike temporin B, antimicrobial activity against both Gram-positive and Gram-negative bacteria. In this paper, we investigated the antimicrobial and anti-inflammatory activity of the peptide TB_KKG6A against Pseudomonas aeruginosa. Interestingly, we found that the peptide exhibits antimicrobial activity at low concentrations, being able to downregulate the pro-inflammatory chemokines and cytokines interleukin (IL)-8, IL-1β, IL-6 and tumor necrosis factor-α produced downstream infected human bronchial epithelial cells. Experiments were carried out also with temporin B, which was found to show pro-inflammatory activity. Details on the interaction between TB_KKG6A and the P. aeruginosa LPS were obtained by circular dichroism and fluorescence studies. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

What are the critical steps in processing blood cultures? A prospective audit evaluating current practice of reporting blood cultures in a centralised laboratory serving secondary care hospitals.

PubMed

Meda, Manjula; Clayton, James; Varghese, Reela; Rangaiah, Jayakeerthi; Grundy, Clive; Dashti, Farnaz; Garner, David; Groves, Katherine; Fitzmaurice, Karen; Hutley, E

2017-04-01

To assess current procedures of processing positive blood cultures against national standards with an aim to evaluate its clinical impact and to determine the utility of currently available rapid identification and susceptibility tests in processing of blood cultures. Blood cultures from three secondary care hospitals, processed at a centralised laboratory, were prospectively audited. Data regarding processing times, communication with prescribers, changes to patient management and mortality within 30 days of a significant blood culture were collected in a preplanned pro forma for a 4-week period. Of 2206 blood cultures, 211 positive blood cultures flagged positive. Sixty-nine (3.1%) of all cultures were considered to be contaminated. Fifty per cent of blood cultures that flagged positive had a Gram stain reported within 2 hours. Two (0.99%) patients with a significant bacteraemia had escalation of antimicrobial treatment at the point of reporting the Gram stain that was subsequently deemed necessary once sensitivity results were known. Most common intervention was de-escalation of therapy for Gram-positive organisms at the point of availability of pathogen identification (25.6% in Gram positive vs 10% in Gram negative; p=0.012). For Gram-negative organisms, the most common intervention was de-escalation of therapy at the point of availability of sensitivity results (43% in Gram negatives vs 17.9% in Gram positive; p=0.0097). Overall mortality within 30 days of a positive blood culture was 10.9% (23/211). Antibiotic resistance may have contributed to mortality in four of these patients (three Gram negative and one Gram positive). Gram stain result had the least impact on antibiotic treatment interventions (escalation or de-escalation). Tests that improve identification time for Gram-positive pathogens and sensitivity time for Gram-negative pathogens had the greatest impact in making significant changes to antimicrobial treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Dynamic detection of N-terminal pro-B-type natriuretic peptide helps to predict the outcome of patients with major trauma.

PubMed

Qian, A; Zhang, M; Zhao, G

2015-02-01

NT-proBNP and BNP have been demonstrated to be prognostic markers in cardiac disease and sepsis. However, the prognostic value and the dynamic changes of BNP or NT-proBNP in trauma patients remain unclear. The present study was conducted to investigate the dynamic changes of NT-proBNP in patients with major trauma (injury severity score ≥16), determine whether NT-proBNP could be used as a simple index to predict mortality in major trauma patients. This prospective observational study included 60 patients with major trauma. Serum NT-proBNP levels were measured on the 1st, 3rd and 7th day after injury The NT-proBNP levels in survivors were compared with those in non-survivors. The efficacy of NT-proBNP to predict survival was analyzed using receiver operating characteristic curves. An analysis of correlations between NT-proBNP and various factors, including injury severity score, Glasgow coma score, acute physiology and chronic health evaluation II, central venous pressure, creatine kinase-MB, cardiac troponin I and procalcitonin (PCT) was performed. NT-proBNP levels in patients with traumatic brain injury were compared with those in patients without traumatic brain injury. A comparison of NT-proBNP levels between patients with and without sepsis was also performed at each time point. NT-proBNP levels in non-survivors were significantly higher than those in survivors at all the indicated time points. In the group of non-survivors, NT-proBNP levels on the 7th day were markedly higher than those on the 1st day. In contrast, NT-proBNP levels in survivors showed a reduction over time. The efficacy of NT-proBNP to predict survival was analyzed using ROC curves, and there was no difference in the area under the ROC between NT-proBNP and APACHE II/ISS at the three time points. A significant correlation was found between NT-proBNP and ISS on the 1st day, NT-proBNP and CK-MB, Tn-I and APACHE II on the 3rd day, NT-proBNP and PCT on the 7th day. There were no significant differences in NT-proBNP levels between patients with or without brain trauma at all the indicated time points. NT-proBNP levels in patients with sepsis were significantly higher than those in patients without sepsis at all the indicated time points. These findings suggest that dynamic detection of serum NT-proBNP might help to predict death in patients with major trauma. A high level of NT-proBNP at admission or maintained for several days after trauma indicates poor survival.

Molecular dynamics simulations of cis-trans isomerization for a proline-containing tripeptide in solution

NASA Astrophysics Data System (ADS)

Wan, Shun Zhou; Wang, Cun Xin; Xu, Ying Wu; Shi, Yun Yu

1996-11-01

The cis-trans isomerization of X-Pro (X is Pro or any other residue) often plays a rate-limiting role in protein folding. In order to study the dynamic properties of X-Pro in water, we have analyzed the trajectory data obtained from constrained molecular dynamics (MD) simulations of a tripeptide Phe-Pro-Ala in solution. Via calculation of autocorrelation functions and their corresponding spectral densities, we have found that the structural fluctuations of the solute are affected by the motions of various degrees of freedom, and the solvent dynamic behavior is bimodal rather than exponential or Gaussian. In addition, according to the energy and torque analysis, we suggest that both the anti/endo and the syn/endo could be the possible transition state for the cis-trans isomerization of the tripeptide.

Evol and ProDy for bridging protein sequence evolution and structural dynamics.

PubMed

Bakan, Ahmet; Dutta, Anindita; Mao, Wenzhi; Liu, Ying; Chennubhotla, Chakra; Lezon, Timothy R; Bahar, Ivet

2014-09-15

Correlations between sequence evolution and structural dynamics are of utmost importance in understanding the molecular mechanisms of function and their evolution. We have integrated Evol, a new package for fast and efficient comparative analysis of evolutionary patterns and conformational dynamics, into ProDy, a computational toolbox designed for inferring protein dynamics from experimental and theoretical data. Using information-theoretic approaches, Evol coanalyzes conservation and coevolution profiles extracted from multiple sequence alignments of protein families with their inferred dynamics. ProDy and Evol are open-source and freely available under MIT License from http://prody.csb.pitt.edu/. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Simulation Program with Latency Exploitation and Node Tearing.

DTIC Science & Technology

1985-02-01

translation table JUNODE is constructed to give the relation between the user-defined node set and the node set used in the pro- gram. The ground node...90, 0, 45 and 80, then, user’s node renumbered node JUNODE table 0(ground) 1 nodplc(IUNODE+1)=O 10 2 ( +2)=10 45 3 ( +3)=45 80 4 ( +4)=80 90 5 ( +5

User Language Specification

DTIC Science & Technology

1977-06-30

Digital System Design based on Structural and Function Modeling. Computer Science Dept., UCLA, (UCLA-ENG-7488), 1975. [7] Hamlet, R. G. High-level...of libaries of pro- grams where each library represents a coherent set of data types and parameterized nodes which operate on those types. * Allow...following form: an optional minus sign, concatenated with an optional sequence of digits the first of which is nonzero, concatenated with a single

Language and System Support for Concurrent Programming

DTIC Science & Technology

1990-04-01

language. We give suggestions on how to avoid polling programs , and suggest changes to the rendezvous facilities to eliminate the polling bias. The...concerned with support for concurrent pro- Capsule gramming provided to the application programmer by operating Description systems and programming ...of concurrent programming has widened Philosophy from "pure" operating system applications to a multitude of real-time and distributed programs . Since

Please Reduce Cycle Time

DTIC Science & Technology

2014-12-01

observed an ERP system implementation that encountered this exact model. The modified COTS software worked and passed the acceptance tests but never... software -intensive program. We decided to create a very detailed master sched- ule with multiple supporting subschedules that linked and Implementing ...processes in place as part of the COTS implementation . For hardware , COTS can also present some risks. Many pro- grams use COTS computers and servers

Team Software Process (TSP) Coach Mentoring Program Guidebook

DTIC Science & Technology

2009-08-01

SEI TSP Initiative Team. • All training was conducted in English only, and observations were limited to English- speaking coaches and teams. The...Certified TSP Mentor Coach programs also enable the expansion of TSP implementation to non-English- speaking teams and organizations. This pro- gram also...Communication Needs Significant Improvement Could Benefit from Development Capable and Effective Role Model 1. I listen before speaking . 2. I

Modeling, Simulation, and Analysis for State and Local Emergency Planning and Response. Operational Requirements Document

DTIC Science & Technology

2009-01-01

pro- gram requirements, and administering local and federal funding. Emergency services—organizations that provide for public safety by the...chemicals Nerve agent Chlorine tank explosion Major earthquake Major hurricane Radiological dispersal device Improvised explosive device Food ...state Locally Developed Software 1 city 1 county 1 city 1 county 3 states Lotus Notes Suite 1 NGO MABAS.ORG 1 county

Coal-seismic, desktop computer programs in BASIC; Part 7, Display and compute shear-pair seismograms

USGS Publications Warehouse

Hasbrouck, W.P.

1983-01-01

Processing of geophysical data taken with the U.S. Geological Survey's coal-seismic system is done with a desk-top, stand-alone computer. Programs for this computer are written in the extended BASIC language utilized by the Tektronix 4051 Graphic System. This report discusses and presents five computer pro grams used to display and compute shear-pair seismograms.

The United States Air Force Academy: A Bibliography: 1968 - 1972

DTIC Science & Technology

1972-09-01

Hist - Aerospace Historian Aero Med - Aerospace Medicine Air Reservist Airman America Armed Forces Compt - Armed Forces Comptroller Armed Forces J...center for aviary medicine . Airman 15:48, May 1971. 235 Jeans, Kit. Children learn at Academy school--CHAP pro- gram. AF Times 30:26, 29 Apr...Indoctrination 10355 Merit lists 10356 Organization 10330 Wing strength 10354 Marihuana incidents 10912 Marriage of cadet 10326

Role of coupled dynamics in the catalytic activity of prokaryotic-like prolyl-tRNA synthetases.

PubMed

Sanford, Brianne; Cao, Bach; Johnson, James M; Zimmerman, Kurt; Strom, Alexander M; Mueller, Robyn M; Bhattacharyya, Sudeep; Musier-Forsyth, Karin; Hati, Sanchita

2012-03-13

Prolyl-tRNA synthetases (ProRSs) have been shown to activate both cognate and some noncognate amino acids and attach them to specific tRNA(Pro) substrates. For example, alanine, which is smaller than cognate proline, is misactivated by Escherichia coli ProRS. Mischarged Ala-tRNA(Pro) is hydrolyzed by an editing domain (INS) that is distinct from the activation domain. It was previously shown that deletion of the INS greatly reduced cognate proline activation efficiency. In this study, experimental and computational approaches were used to test the hypothesis that deletion of the INS alters the internal protein dynamics leading to reduced catalytic function. Kinetic studies with two ProRS variants, G217A and E218A, revealed decreased amino acid activation efficiency. Molecular dynamics studies showed motional coupling between the INS and protein segments containing the catalytically important proline-binding loop (PBL, residues 199-206). In particular, the complete deletion of INS, as well as mutation of G217 or E218 to alanine, exhibited significant effects on the motion of the PBL. The presence of coupled dynamics between neighboring protein segments was also observed through in silico mutations and essential dynamics analysis. Altogether, this study demonstrates that structural elements at the editing domain-activation domain interface participate in coupled motions that facilitate amino acid binding and catalysis by bacterial ProRSs, which may explain why truncated or defunct editing domains have been maintained in some systems, despite the lack of catalytic activity.

Molecular dynamics simulation of the enterostatin APGPR and VPDPR peptides in water

NASA Astrophysics Data System (ADS)

Trucco, Gabriella; Fornili, Sandro L.

2007-09-01

We report on structural and dynamic properties in water of all the isomers of both peptides related to the trans and cis conformations of the peptide bonds preceding the proline (Pro) residues. Free-energy calculations indicate that the isomers having the Pro closer to the N-terminus (Pro1) in trans and the Pro2 in cis conformations are the most populated. Furthermore, the backbone is more flexible for APGPR than for VPDPR, and its conformation is more stable in the hydrophilic C-terminal moiety than in the hydrophobic N-terminal region.

Highly dynamic biodegradable micelles capable of lysing Gram-positive and Gram-negative bacterial membrane.

PubMed

Qiao, Yuan; Yang, Chuan; Coady, Daniel J; Ong, Zhan Yuin; Hedrick, James L; Yang, Yi-Yan

2012-02-01

The development of biodegradable antimicrobial polymers adds to the toolbox of attractive antimicrobial agents against antibiotic-resistant microbes. To this end, the potential of polycarbonate polymers as such materials were explored. A series of random polycarbonate polymers consisting of monomers MTC-OEt and MTC-CH(2)CH(3)Cl were designed and synthesized using metal-free organocatalytic ring-opening polymerization. Random polycarbonate polymers self-assembled in solution but appeared highly dynamic; such behaviors are desirable as ready disassembly of polymers at the microbial membrane facilitates membrane disruption. Their activities against clinically relevant Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (E.coli and Pseudomonas aeruginosa) revealed that the hydrophobic-hydrophilic composition balance in polymers are important to render antimicrobial potency. Scanning electron microscopy (SEM) studies indicated microbial cell surface damage after treatment with polymers, and confocal microscopy studies also showed entry of FITC-dextran dye in Escherichia coli as a result of membrane disruption. On the other hand, the polymers exhibited minimal toxicity against red blood cells in hemolysis tests. Therefore, these random polycarbonate polymers are promising antimicrobial agents against both Gram-positive and Gram-negative bacteria for various biomedical applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

Building Great (Coalition) Engineers

DTIC Science & Technology

2011-04-01

36 Engineer May-August 201038 Engineer January-April 1 G’day from the Royal Australian Engineers (RAE) School of Military Engineering (SME) at Steele...Barracks, Moorebank, New South Wales, Austra- lia. Like more than 20 United States Army engineer ma- jors before me, I am the military personnel...exchange pro- gram officer assigned to the United States Army Engineer School, attached to United States Army Pacific, and further attached to SME. By

A Novel Anti-Beta2-Microglobulin Antibody Inhibition of Androgen Receptor Expression, Survival, and Progression in Prostate Cancer Cells

DTIC Science & Technology

2010-05-01

Uro -Oncology Research Pro- gram, Dept. of Medicine, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, CA 90048. Tel.: 310...ORGANIZATION: Cedars-Sinai Medical Center Los Angeles, California 90048 REPORT DATE: May...Cedars-Sinai Medical Center Los Angeles, California 90048 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM

Natural Hazards Observer. Volume 32, Number 2, November 2007

DTIC Science & Technology

2007-11-01

global warming plan that proposed an obligatory, market -based, cap-and-trade pro- gram that would reverse the worst-case effects of climate change by... market penetration for flood insurance, building Report (under Goal 4: "Lofty Targets"). and elevation requirements, hazard mitigation grants, The Report...reinsurance markets in subsequent years. With an unbiased perspective of all catastrophe model- 8th Pacific Conference on Earthquake Engineering-Sin- ing

European Science Notes. Volume 39, Number 10.

DTIC Science & Technology

1985-10-01

A.T. Hubbard (Santa Barbara, US), Electro- MODULEF--A MODULAR FINITE ELEMENT PRO- sorption at Well-Defined Surfaces; D.H. GRAM PACKAGE Kolb (Berlin...was described as having one sorption . of the highest theoretical energy densi- Finally, Despi6 described engineer- ties, about 2600 Wh/kg--a value 150...organic compounds , can be varied by compound these transport agents into changing the high temperature treatment organic solutions exhibiting high

A Decision Support Methodology for Space Technology Advocacy.

DTIC Science & Technology

1984-12-01

determine their parameters. Program control is usually exercised by level of effort funding. 63xx is the designator for advanced development pro- grams... designing systems or models that successfully aid the decision-maker. One remedy for this deficiency in the techniques is to increase the...methodology for use by the Air Force Space Technology Advocate is designed to provide the following features [l11:146-1471: meaningful reduction of available

Efficient Adaptive FIR and IIR Filters.

DTIC Science & Technology

1979-12-01

Squared) algorithm. -An analysis of the simplified gradient approach is presented and confirmed experimentally for the specific example of an adaptive line...APPENDIX A - SIMULATION 130 A.1 - THE SIMULATION METHOD 130 A.2 - FIR SIMULATION PRO)GRAM 133 A.3 - IIR SIMULATION PROGRAM 136 APPENDIX B - RANDOM...surface. The generation of the reference signal is a key consi- deration in adaptive filter implementation. There are various practical methods as

Defense AT&L. Volume 37, Number 4, July-August 2008

DTIC Science & Technology

2008-08-01

allowed the Greek philosopher to share some tidbits of wisdom regarding pro- gram management and changing the way we view chaos and order. 21...on your team. Virtual teaming is chang- ing the way we develop and work with team members. 37 Project Manager and Program Manager : What’s the...Difference? Jeffrey Peisach and Timothy S. Kroecker Identifying the roles and responsibilities of project managers and program managers will

On Nonconvex Decentralized Gradient Descent

DTIC Science & Technology

2016-08-01

and J. Bolte, On the convergence of the proximal algorithm for nonsmooth functions involving analytic features, Math . Program., 116: 5-16, 2009. [2] H...splitting, and regularized Gauss-Seidel methods, Math . Pro- gram., Ser. A, 137: 91-129, 2013. [3] P. Bianchi and J. Jakubowicz, Convergence of a multi-agent...subgradient method under random communication topologies , IEEE J. Sel. Top. Signal Process., 5:754-771, 2011. [11] A. Nedic and A. Ozdaglar, Distributed

Naval Ship Procurement Process Study

DTIC Science & Technology

1978-07-01

was to drdw from the troublesome experiences of the past, compelling lessons which the Navy and the shipbuilding industry would be strongly motivated...These interviews provided a number of insights into the process of planning for the acquisition of Navy ships as well as the legal and business...strategies on recent pro- grams. Prospective shipbuilders have participated in the preparation of the con- tract design package, and it is planned on

The Changing Nature of Warfare, the Factors Mediating Future Conflict, and Implications for SOF

DTIC Science & Technology

2006-04-01

most commonly used vernacular today, one is describing the person’s sexual orientation.13 The English language is replete with other words that have...countries and those that are technologically more advanced, primarily due to labor cost differentials. Globaliza- tion has transmuted economics from a...fascination with forensic sci- ences, ala the acclaimed television pro- gram CSI, has transmuted from civilian criminal proceedings to microscopic

Quality of Life Parity Analysis for POM-82

DTIC Science & Technology

1980-06-01

effectively manage the DOD Family Housing ’Program, and also to provide input for the Five Year Defense Program (FYDP). (U) The requirements resulting from...Program is a centrally managed social services assistance pro- gram. The Navy Family Program is a centrally coordinated support program. The Air Force has...Welfare and Recreation; U Family Housing; Unaccompanied Personnel Housing; 0ff-Duty Education; Familly Support; Alcohol and Drug Abuse 30. AISITRACT

A Day in the Life of JUSMMAT

DTIC Science & Technology

1985-01-01

jurisdiction over all U.S. DOD personnel and their dependents in Turkey. Security Assistance The U.S. Security Assistance Program in Turkey consists of a...variety of related activities. a. The Foreign Military Sales (FMS) and Military Assistance Pro- gram (MAP). These programs are designed to help...training. The FY85 IMET program for Turkey is about $3.1 million. [An expanded discussion of these security assistance activities is provided in the

Minority Representation. Efforts of the Alcohol, Drug Abuse, and Mental Health Administration.

DTIC Science & Technology

1988-05-01

agencies, such as HHS, are required by law, executive order, and regulation to design and implement affirmative action programs. EEOC directed HHS to...outside ADAMHA from both the private and public sectors); and -. . . ., ’According to Equal Employment Opportunity Commission ( EEOC ) guidance...year 1988, we contacted an official in the Office of Federal Sector Pro- grams in EEOC and reviewed pertinent directives issued to federal agen- cies

Preliminary Observations on the Changing Roles of Malaria Vectors in Southern Belize

DTIC Science & Technology

1993-01-01

darlingi (Diptera: Cu- licidae) de la Ceiba, Atlantida, Honduras. Thesis. Maestria en Entomologia. Universidad de Panama, Panama City, Panama. 456...Brown and C. Cordon-Rosales. 1992. Potential malaria vectors in northern Guatemala (Vectores potenciales de ma- laria in la region norte de Guatemala...Serra de Aqua in June 1946 (Linthicum 1988). We initiated a malaria vector research pro- gram in Belize in 1990 and conducted extensive larval

The U.S. Department of Defense Millennium Cohort Study: Career Span and Beyond Longitudinal Follow-Up

DTIC Science & Technology

2009-10-01

PHQ*) Caffeine and fast food intake (2 questions) Strength and duration of physical activity (1 question with 3 items; NHIS *) Daily physical activity...Complementary and Alternative Medicine; NHIS , National Health Interview Survey; NHANES, National Health and Nutrition Examination Survey; SF36-V, Short...USAMRMC) Military Operational Medicine Research Pro- gram (MOMRP). The Millennium Cohort Study requires considerable financial and logistical support that

Double-stranded helical twisted beta-sheet channels in crystals of gramicidin S grown in the presence of trifluoroacetic and hydrochloric acids.

PubMed

Llamas-Saiz, Antonio L; Grotenbreg, Gijsbert M; Overhand, Mark; van Raaij, Mark J

2007-03-01

Gramicidin S is a nonribosomally synthesized cyclic decapeptide antibiotic with twofold symmetry (Val-Orn-Leu-D-Phe-Pro)(2); a natural source is Bacillus brevis. Gramicidin S is active against Gram-positive and some Gram-negative bacteria. However, its haemolytic toxicity in humans limits its use as an antibiotic to certain topical applications. Synthetically obtained gramicidin S was crystallized from a solution containing water, methanol, trifluoroacetic acid and hydrochloric acid. The structure was solved and refined at 0.95 A resolution. The asymmetric unit contains 1.5 molecules of gramicidin S, two trifluoroacetic acid molecules and ten water molecules located and refined in 14 positions. One gramicidin S molecule has an exact twofold-symmetrical conformation; the other deviates from the molecular twofold symmetry. The cyclic peptide adopts an antiparallel beta-sheet secondary structure with two type II' beta-turns. These turns have the residues D-Phe and Pro at positions i + 1 and i + 2, respectively. In the crystals, the gramicidin S molecules line up into double-stranded helical channels that differ from those observed previously. The implications of the supramolecular structure for several models of gramicidin S conformation and assembly in the membrane are discussed.

Identification of a crustacean β-1,3-glucanase related protein as a pattern recognition protein in antibacterial response.

PubMed

Chai, Lian-Qin; Meng, Jing-Hui; Gao, Jie; Xu, Yi-Hui; Wang, Xian-Wei

2018-06-02

Prophenoloxidase (proPO) activating system is an important immune response for arthropods. β-1, 3-glucanase related protein (previously named as lipopolysaccharide and β-1, 3-glucan binding protein (LGBP) in crustaceans) is a typical pattern recognition receptor family involved in the proPO activation by recognizing the invading microbes. In this study, we pay special attention to a bacteria-induced β-1,3-glucanase related protein from red swamp crayfish Procambarus clarkii, an important aquaculture specie in China. This protein, designated PcBGRP, was found a typical member of crustacean BGRP family with the glucanase-related domain and the characteristic motifs. PcBGRP was expressed in hemcoyes and hepatopancreas, and its expression could be induced by the carbohydrate and bacteria stimulants. The induction by lipopolysaccharide (LPS) and β-1,3-glucan (βG) was more significant than by peptidoglycan (PG). The response of PcBGRP to the native Gram-negative bacterial pathogen Aeromonas hydrophila was more obvious than to Gram-positive bacteria. Using RNA interference and recombinant protein, PcBGRP was found to protect crayfish from A. hydrophila infection revealed by the survival test and morphological analysis. A mechanism study found PcBGRP could bind LPS and βG in a dose-dependent manner, and the LPS recognizing ability determined the Gram-negative bacterium binding activity of PcBGRP. PcBGRP was found to enhance the PO activation both in vitro and in vivo, and the protective role was related to the PO activating ability of PcBGRP. This study emphasized the role of BGRP family in crustacean immune response, and provided new insight to the immunity of red swamp crayfish which suffered serious disease during the aquaculture in China. Copyright © 2018 Elsevier Ltd. All rights reserved.

FFTF Passive Safety Test Data for Benchmarks for New LMR Designs

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

Wootan, David W.; Casella, Andrew M.

Liquid Metal Reactors (LMRs) continue to be considered as an attractive concept for advanced reactor design. Software packages such as SASSYS are being used to im-prove new LMR designs and operating characteristics. Significant cost and safety im-provements can be realized in advanced liquid metal reactor designs by emphasizing inherent or passive safety through crediting the beneficial reactivity feedbacks associ-ated with core and structural movement. This passive safety approach was adopted for the Fast Flux Test Facility (FFTF), and an experimental program was conducted to characterize the structural reactivity feedback. The FFTF passive safety testing pro-gram was developed to examine howmore » specific design elements influenced dynamic re-activity feedback in response to a reactivity input and to demonstrate the scalability of reactivity feedback results to reactors of current interest. The U.S. Department of En-ergy, Office of Nuclear Energy Advanced Reactor Technology program is in the pro-cess of preserving, protecting, securing, and placing in electronic format information and data from the FFTF, including the core configurations and data collected during the passive safety tests. Benchmarks based on empirical data gathered during operation of the Fast Flux Test Facility (FFTF) as well as design documents and post-irradiation examination will aid in the validation of these software packages and the models and calculations they produce. Evaluation of these actual test data could provide insight to improve analytical methods which may be used to support future licensing applications for LMRs« less

In-Space Transportation with Tethers

NASA Technical Reports Server (NTRS)

Lorenzini, Enrico; Estes, Robert D.; Cosmo, Mario L.

1998-01-01

The annual report covers the research conducted on the following topics related to the use of spaceborne tethers for in-space transportation: ProSEDS tether modeling (current collection analyses, influence of a varying tether temperature); proSEDS mission analysis and system dynamics (tether thermal model, thermo-electro-dynamics integrated simulations); proSEDS-tether development and testing (tether requirements, deployment test plan, tether properties testing, deployment tests); and tethers for reboosting the space-based laser (mission analysis, tether system preliminary design, evaluation of attitude constraints).

America Makes: The National Additive Manufacturing Innovation Institute (NAMII) Status Report and Future Opportunities (Postprint)

DTIC Science & Technology

2014-09-01

manufacturing, direct part manufacturing, manufacturing institute, public- private partnership, rapid manufacturing, 3D printing 16. SECURITY CLASSIFICATION...Manufacturing Science and Technology Pro- gram and selected Additive Manufacturing (or more popularly known as 3D printing ) as the technical subject. Working...operations, America Makes is starting to hit its stride in developing technology for 3D printing and in leading the way in how the United States should

A Computer Based Educational Aid for the Instruction of Combat Modeling

DTIC Science & Technology

1992-02-27

representation (36:363-370), and, as Knuth put it, "An algorithm must be seen to be believed" (23:4). Graphics not only aid in achieving instructional...consisted primarily of research, identification and use of existing combat model computer algorithms , interviews, and use of operation research...to-air combat models’ operating manuals provided valuable insight into pro- gram structure and algorithms used to represent the combat. From these

Men and Arms in the Middle East: The Human Factor in Military Modernization

DTIC Science & Technology

1979-06-01

countries under study supports their abilities to wield military power effectively, their large- scale reliance on importation of military technologies...statistics, and on quality from area experts. In many cases , we were unable to arrive at numerical estimates of the sources of supply. . Likely future...government agencies); on -the-job training (as in the case of counterpart pro- grams); and thle direct importation of both military and civilian labor

The Visible Signature Modelling and Evaluation ToolBox

DTIC Science & Technology

2008-12-01

Technology Organisation DSTO–TR–2212 ABSTRACT A new software suite, the Visible Signature ToolBox ( VST ), has been developed to model and evaluate the...visible signatures of maritime platforms. The VST is a collection of commercial, off-the-shelf software and DSTO developed pro- grams and procedures. The...suite. The VST can be utilised to model and assess visible signatures of maritime platforms. A number of examples are presented to demonstrate the

A Cache Design to Exploit Structural Locality

DTIC Science & Technology

1991-12-01

memory and secondary storage. Main memory was used to store the instructions and data of an executing pro- gram, while secondary storage held programs ...efficiency of the CPU and faster turnaround of executing programs . In addition to the well known spatial and temporal aspects of locality, Hobart has...identified a third aspect, which he has called structural locality (9). This type of locality is defined as the tendency of an executing program to

High Frontier: The Journal for Space and Cyberspace Professionals. Volume 7, Number 2

DTIC Science & Technology

2011-02-01

result of data provided by the SSA Data Sharing Pro - gram, satellite owners and operators worldwide maneuvered 51 times in 2009 to avoid... increased beyond the point where the US can expect to control it. Even without counterproductive export legislation, the US would have sustainability... timely delivery of integrated SSA information and national intelligence in order to support the command and control of US space forces. It

Survivable Software

DTIC Science & Technology

2013-04-01

machine transitions. 2. We developed the TraceContract API for trace analysis in the Scala programming language. TraceContract combines a high-level...DATE (DD-MM-YYYY) 2. REPORT TYPE 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...awarded within the Software and Systems program . The original Pro- gram Manager was David Luginbuhl. Bob Bonneau took over as PM in March 2011. The award

Report of the Defense Science Board Task Group on Independent Research and Development

DTIC Science & Technology

1967-02-01

been in existence for several years, was apparently rejuvenated . Shortly thereafter, the Minuteman pro- gram came into being. Let us, with a ten-year...the vehicle skin into the boun- dary layer: transpiration cooling. Here there were problems of injection control, to assure proper distribution of...13526QSection 3.5 Date: MAR 8 2011 The interaction of electromagnetic vave vith plasmas, labelled EM propagation, has seen a renewed emphasis in

Computer Program for Vibration Prediction of Fighter Aircraft Equipments

DTIC Science & Technology

1977-11-01

scribing a useful variety of flight vibration phases . Notice that identical variations can be reflected into the high frequency rolloff curve (equation 13...flight attitudes ranging from straight and level states to a variety of significant flight maneuvers and phases . Pro- gram outputs, digital and...R (f) adjusted value of R(f) due to c (g 2/Hz) SBT (f) special function for the buffet turn flight phase PBT (f) pressure spectral density speqtrum

China’s Foreign Aid and Government-Sponsored Investment Activities: Scale, Content, Destinations, and Implications

DTIC Science & Technology

2013-01-01

Ecuador , Brazil, Chile, and Venezuela. Before 2005, many of the regional programs focused on infrastructure, including power plants...prior academic work on China’s pro- grams have focused on Africa and include Davies et al. and Brautigam. Both these provide detailed case studies...Chinese engage- ment there is concentrated on four resource-rich countries: Venezuela, Brazil, Argentina, and Ecuador . 26 China’s Foreign Aid and

The Future of Air Force Motion Imagery Exploitation: Lessons from the Commercial World

DTIC Science & Technology

2012-01-01

works during the filming of the show, the primary exception 14 Although not the first of its kind, the breakthrough program for this genre on U.S...recent genre of popular television pro- gramming that relies on the unscripted performances of people who are not professional actors (the cast...reality television production crews; such moments, from which the genre derives its name, are often prominently featured in reality television

Cyclic fatigue resistance of ProTaper Universal instruments when subjected to static and dynamic tests.

PubMed

Lopes, Hélio P; Britto, Izabelle M O; Elias, Carlos N; Machado de Oliveira, Julio C; Neves, Mônica A S; Moreira, Edson J L; Siqueira, José F

2010-09-01

This study evaluated the number of cycles to fracture of ProTaper Universal S2 instruments when subjected to static and dynamic cyclic fatigue tests. ProTaper Universal S2 instruments were used until fracture in an artificial curved canal under rotational speed of 300 rpm in either a static or a dynamic test model. Afterward, the length of the fractured segments was measured and fractured surfaces and helical shafts analyzed by scanning electron microscopy (SEM). The number of cycles to fracture was significantly increased when instruments were tested in the dynamic model (P<.001). Instrument separation occurred at the point of maximum flexure within the artificial canals, i.e., the midpoint of the curved canal segment. SEM analysis revealed that fractured surfaces exhibited characteristics of the ductile mode. Plastic deformation was not observed in the helical shaft of fractured instruments. The number of cycles to fracture ProTaper Universal S2 instruments significantly increased with the use of instruments in a dynamic cyclic fatigue test compared with a static model. These findings reinforce the need for performing continuous pecking motions during rotary instrumentation of curved root canals. Copyright (c) 2010 Mosby, Inc. All rights reserved.

The cost and management of different types of clinical mastitis in dairy cows estimated by dynamic programming.

PubMed

Cha, E; Bar, D; Hertl, J A; Tauer, L W; Bennett, G; González, R N; Schukken, Y H; Welcome, F L; Gröhn, Y T

2011-09-01

The objective of this study was to estimate the cost of 3 different types of clinical mastitis (CM) (caused by gram-positive bacteria, gram-negative bacteria, and other organisms) at the individual cow level and thereby identify the economically optimal management decision for each type of mastitis. We made modifications to an existing dynamic optimization and simulation model, studying the effects of various factors (incidence of CM, milk loss, pregnancy rate, and treatment cost) on the cost of different types of CM. The average costs per case (US$) of gram-positive, gram-negative, and other CM were $133.73, $211.03, and $95.31, respectively. This model provided a more informed decision-making process in CM management for optimal economic profitability and determined that 93.1% of gram-positive CM cases, 93.1% of gram-negative CM cases, and 94.6% of other CM cases should be treated. The main contributor to the total cost per case was treatment cost for gram-positive CM (51.5% of the total cost per case), milk loss for gram-negative CM (72.4%), and treatment cost for other CM (49.2%). The model affords versatility as it allows for parameters such as production costs, economic values, and disease frequencies to be altered. Therefore, cost estimates are the direct outcome of the farm-specific parameters entered into the model. Thus, this model can provide farmers economically optimal guidelines specific to their individual cows suffering from different types of CM. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Scalable Static and Dynamic Community Detection Using Grappolo

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

Halappanavar, Mahantesh; Lu, Hao; Kalyanaraman, Anantharaman

Graph clustering, popularly known as community detection, is a fundamental kernel for several applications of relevance to the Defense Advanced Research Projects Agency’s (DARPA) Hierarchical Identify Verify Exploit (HIVE) Pro- gram. Clusters or communities represent natural divisions within a network that are densely connected within a cluster and sparsely connected to the rest of the network. The need to compute clustering on large scale data necessitates the development of efficient algorithms that can exploit modern architectures that are fundamentally parallel in nature. How- ever, due to their irregular and inherently sequential nature, many of the current algorithms for community detectionmore » are challenging to parallelize. In response to the HIVE Graph Challenge, we present several parallelization heuristics for fast community detection using the Louvain method as the serial template. We implement all the heuristics in a software library called Grappolo. Using the inputs from the HIVE Challenge, we demonstrate superior performance and high quality solutions based on four parallelization heuristics. We use Grappolo on static graphs as the first step towards community detection on streaming graphs.« less

Exploiting Vector and Multicore Parallelsim for Recursive, Data- and Task-Parallel Programs

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

Ren, Bin; Krishnamoorthy, Sriram; Agrawal, Kunal

Modern hardware contains parallel execution resources that are well-suited for data-parallelism-vector units-and task parallelism-multicores. However, most work on parallel scheduling focuses on one type of hardware or the other. In this work, we present a scheduling framework that allows for a unified treatment of task- and data-parallelism. Our key insight is an abstraction, task blocks, that uniformly handles data-parallel iterations and task-parallel tasks, allowing them to be scheduled on vector units or executed independently as multicores. Our framework allows us to define schedulers that can dynamically select between executing task- blocks on vector units or multicores. We show that thesemore » schedulers are asymptotically optimal, and deliver the maximum amount of parallelism available in computation trees. To evaluate our schedulers, we develop program transformations that can convert mixed data- and task-parallel pro- grams into task block-based programs. Using a prototype instantiation of our scheduling framework, we show that, on an 8-core system, we can simultaneously exploit vector and multicore parallelism to achieve 14×-108× speedup over sequential baselines.« less

Learning Enterprise Malware Triage from Automatic Dynamic Analysis

DTIC Science & Technology

2013-03-01

Kolter and Maloof n-gram method, Dube’s malware target recognition (MaTR) static method performs significantly more accurately at the 95% confidence...from the static method as in Kolter and Maloof. The MIST approach with behavior sequences 9 allows researchers to tailor the level of analysis to the...citations, none publish work that implements it. Only Kolter and Maloof use nearly as long gram structures, although that research uses static grams rather

Causality-Preserving Timestamps in Distributed Programs

DTIC Science & Technology

1993-06-01

monitoring,deh!bigging. tac-hvon,catisaIi tvý Abstract A tachyon is an improperly ordered event in a distributed program. Tachvonis are most often...that tachyons do in fact. occur commonly in distributed pro- grams on our Ethernet at Carnegie Mellon University. and we disc’ss some ways of...before it is sent) is called a tach yon. (’learly it is very disconcerting to try to debug a parallel program that contains tachyons . Of course, in "real

Understanding of Materials State and its Degradation using Non-Linear Ultrasound (NLU) Approaches - Phase 3

DTIC Science & Technology

2013-05-31

j] (11) A MATLAB code was written for finding the displacement at each node for all time steps. Material selected for the study was steel with 1 m...some of the dislocations are annihilated or rearranged. Various stages in the recovery are, entanglement of dislocations, cell formation, annihilation...frequency domain using an in-house pro- gram written in MATLAB . A time-domain signal obtained from nonlinear measurement and its corresponding fast

Initial Effects of Heavy Vehicle Trafficking on Vegetated Soils

DTIC Science & Technology

2012-08-01

ER D C/ CR R EL T R -1 2 -6 Optimal Allocation of Land for Training and Non-training Uses ( OPAL ) Initial Effects of Heavy Vehicle...the outdoor loam test section. Optimal Allocation of Land for Training and Non-training Uses ( OPAL ) ERDC/CRREL TR-12-6 August 2012 Initial...mal Allocation of Land for Training and Non-Training Uses ( OPAL ) Pro- gram. The work was conducted by Nicole Buck and Sally Shoop of the Force

An Analysis of Factors Influencing the Turnover of United States Air Force Pilots in the Six to Eleven Year Group

DTIC Science & Technology

1980-06-01

1979. 16. Donnelly, James H., Jr., James L. Gibson, and JohnM. Ivancevich . Organizations--Structure, Processes, Behavior. Dallas TX: Business...Publications, Inc., 1973. 17. Ivancevich , John M., Andrew D. Szilagyi, Jr., and Marc J. Wallace, Jr. Organizational Behavior and Performance. Santa Monica CA...215. 102 Lyons , Colonel Billy S., USAF, and Colonel KZjnald L. Marks, USAF. "An Alternate Pilot Management Pro- gram for Future Strategic Weapon

The Even-Rho and Even-Epsilon Algorithms for Accelerating Convergence of a Numerical Sequence

DTIC Science & Technology

1981-12-01

equal, leading to zero or very small divisors. Computer programs implementing these algorithms are given along with sample output. An appreciable amount...calculation of the array of Shank’s transforms or, -A equivalently, of the related Padd Table. The :other, the even-rho algorithm, is closely related...leading to zero or very small divisors. Computer pro- grams implementing these algorithms are given along with sample output. An appreciable amount or

An Update of Engine System Research at the Army Propulsion Directorate

DTIC Science & Technology

1990-01-01

6.1) pro- grams. Brush seals , illustrated in figure 14, offer great potential for reduc- ing secondary flow leakages and are inherently self...incorporate brush seals into the build of one of our workhorse engines in the early 1990’s as a replacement for shaft carbon seals , inner air labyrinth seals ...to steam and increasing its cooling capacity (ref. 12). The idea was conceived in-house and, following feasibility studies and fundamental heat

A Program Office Guide to Technology Transfer

DTIC Science & Technology

1988-11-01

Requirements 2-4 2.4.1 Equipment Complexity 2-5 2.4.2 Industrial Capabilities 2-5 2.4.3 Logistics Requirements/Configuration Control 2-5 2.4.4 Schedule...accomplishment of these milestones re- with the leverage of the FSD and production pro- sults in second source full production capability , grams. For more...MANUFACTURING PROCESSES BUILD UP COMPETITIVE PRODUCTION RATE CAPABILITY DURING LOT III Table 1.2-1 AMRAAM Technology Transfer The leader-follower approach is

Analysis of: A Military Leadership Assessment Development Program

DTIC Science & Technology

1990-05-01

assessment pro:’gram. Reliance, however, on these to the enclusion of other research methods such as direct observation, would engender criticism. (15:238...XE A~ICOLLEGE RESEARCH REPORT AD-A241 082 I~I~lhII 111IIJ ldII~l I "~ANALYSIS OF: A MILITARY LEADERSHIP ASSESSMENT DEVELOPMENT PROGRAM COMMANDER...SUBMITTED TO THE FACULTY IN FULFILLMENT OF THE RESEARCH REQU I REMENT Research Advisor: Col. Bryan Strickland MAXWELL AIR FORCE BASE, ALABAMA MAY, 1990

Equilibrium folding of pro-HlyA from Escherichia coli reveals a stable calcium ion dependent folding intermediate.

PubMed

Thomas, Sabrina; Bakkes, Patrick J; Smits, Sander H J; Schmitt, Lutz

2014-09-01

HlyA from Escherichia coli is a member of the repeats in toxin (RTX) protein family, produced by a wide range of Gram-negative bacteria and secreted by a dedicated Type 1 Secretion System (T1SS). RTX proteins are thought to be secreted in an unfolded conformation and to fold upon secretion by Ca(2+) binding. However, the exact mechanism of secretion, ion binding and folding to the correct native state remains largely unknown. In this study we provide an easy protocol for high-level pro-HlyA purification from E. coli. Equilibrium folding studies, using intrinsic tryptophan fluorescence, revealed the well-known fact that Ca(2+) is essential for stability as well as correct folding of the whole protein. In the absence of Ca(2+), pro-HlyA adopts a non-native conformation. Such molecules could however be rescued by Ca(2+) addition, indicating that these are not dead-end species and that Ca(2+) drives pro-HlyA folding. More importantly, pro-HlyA unfolded via a two-state mechanism, whereas folding was a three-state process. The latter is indicative of the presence of a stable folding intermediate. Analysis of deletion and Trp mutants revealed that the first folding transition, at 6-7M urea, relates to Ca(2+) dependent structural changes at the extreme C-terminus of pro-HlyA, sensed exclusively by Trp914. Since all Trp residues of HlyA are located outside the RTX domain, our results demonstrate that Ca(2+) induced folding is not restricted to the RTX domain. Taken together, Ca(2+) binding to the pro-HlyA RTX domain is required to drive the folding of the entire protein to its native conformation. Copyright © 2014 Elsevier B.V. All rights reserved.

The dynamics of behavior in modified dictator games

PubMed Central

2017-01-01

We investigate the dynamics of individual pro-social behavior over time. The dynamics are tested by running the same experiment with the same subjects at several points in time. To exclude learning and reputation building, we employ non-strategic decision tasks and a sequential prisoners-dilemma as a control treatment. In the first wave, pro-social concerns explain a high share of individual decisions. Pro-social decisions decrease over time, however. In the final wave, most decisions can be accounted for by assuming pure selfishness. Stable behavior in the sense that subjects stick to their decisions over time is observed predominantly for purely selfish subjects. We offer two explanation for our results: diminishing experimenter demand effects and moral self-licensing. PMID:28448506

Molecular dynamics study of biodegradation of azo dyes via their interactions with AzrC azoreductase.

PubMed

Haghshenas, Hamed; Kay, Maryam; Dehghanian, Fariba; Tavakol, Hossein

2016-01-01

Azo dyes are one of the most important class of dyes, which have been widely used in industries. Because of the environmental pollution of azo dyes, many studies have been performed to study their biodegradation using bacterial systems. In present work, the AzrC of mesophilic gram-positive Bacillus sp. B29 has been considered to study its interaction with five common azo dyes (orange G, acid red 88, Sudan I, orange I, and methyl red). The molecular dynamics simulations have been employed to study the interaction between AzrC and azo dyes. The trajectory was confirmed using root mean square deviation and the root mean square fluctuation analyses. Then, the hydrogen bond and alanine scanning analyses were performed to reveal active site residues. Phe105 (A), Phe125 (B), Phe172 (B), and Pro132 (B) have been found as the most important hydrophobic residues whereas Asn104 (A), Tyr127 (B), and Asn187 (A) have key role in making hydrogen bond. The results of molecular mechanics Poisson-Boltzmann surface area and molecular mechanics generalized Born surface area calculations proved that the hydrophobic azo dyes like Acid red 88 binds more tightly to the AzrC protein. The calculated data suggested MR A 121 (B) I as a potential candidate for improving the AzrC-MR interactions.

Program Manager: The Journal of the Defense Systems Management College, Volume 15, Number 2, March-April 1986.

DTIC Science & Technology

1986-04-01

benefits to the user, and economic benefits to the host country. Figure 2 shows the develop- ment of the NATO Infrastructure Pro- grams since 1951. FH...generalized benefits of stream- classified programs work with less dollar expenditures based solely on the lined specialized management include: than one-third...for contractors to demon- significant cost and schedule benefits on-site visits by the SPO are strate their management integrity, and new improvements

The Department of Defense Statement on the Science and Technology Program by Mr. H. Mark Grove, Assistant Deputy Under Secretary of Defense for Research and Advanced Technology Before the Defense Subcommittee of the Committee on Appropriations of the United States House of Representatives, 97th Congress, Second Session,

DTIC Science & Technology

1982-06-16

Technology Intergration (AFTI) Pro- gram, (2) a nonmetallic composite helicopter fuselage, and (3) a new initiative to develop Short Take-Off and...range of passive sonobuoys is being extended and the performance of a high gain extended life deployed horizontal line array is being investigated

A Structural Weight Estimation Program (SWEEP) for Aircraft. Volume 4 - Material Properties, Structure Temperature, Flutter and Fatigue

DTIC Science & Technology

1974-06-01

NAME AND ADDRESS Deputy for Development Planning Air Force Systems Command Wright-Patterson Air Force Base, Ohio READ INSTRUCTIONS BEFORE...6600 computer. Two stand-alone pro- grams operating within 100,000 octal units were also developed to provide optional data sources for SWEEP...JAMES H. HALL, Colonel, USAF Deputy for Development Planning ll jgaajaaMteaäiiaaBiiMiffliiäffliiteMä hi*^*Mi*^^*^&äitküli^ riMMiniiiMfWitii

Forward Aeromedical Evacuation: A Brief History, Lessons Learned from the Global War on Terror, and the Way Forward for US Policy

DTIC Science & Technology

2013-01-01

DUSTOFF and PEDRO units increased throughout the conflict and were con - sidered an unqualified success during the war; the DUSTOFF units alone would...direction was provided in most cases by general medical officers ( GMO ) serving with aviation units. These GMOs generally completed internships and were...awaiting placement into residency pro - grams. Their primary job was to provide routine medical care to the aviators in that unit. No standardized

Airport Delay and Improvement Study, John F. Kennedy International Airport and LaGuardia Airport.

DTIC Science & Technology

1981-10-01

assumed aircraft tntv. These capacities are shtsn in lIgure 1. - I hie airfiteld stmiulat ion model used the out put ot the capacii modejl it, pros...atissi sputa D I VI-I OP LA iMAt WAKE VORTEX AVOIDANCE PRO- liuns durintg fle peak 6-liuur usprattng perisd ust the das - GRAM BY 1987: Future Savings...depending si tire as arlartnl of lie u ltimat e Wake Vortex Asoidance System. Withisut rile Wkake Vsortex .Asssdattcc System. an increased annual

Navy Budget: Potential Reductions for Research, Development, Test, and Evaluation

DTIC Science & Technology

1990-11-01

available for use in future Navy programs, including the MK-50 tor- pedo and Vertical Launch Antisubmarine Rocket. A total of $49.9 million of fiscal...346 Travel 03 07 + 04 Support 224 225 + 01 Total Requested $122.61 $122.61 -0- In addition, the Navy plans to acquire six Acoustic Video Processor...units at $2.4 million in fiscal year 1991. The Acoustic Video Processor pro- gram is experiencing development problems, and the full-scale develop- ment

European Science Notes Information Bulletin. Reports on Current European and Middle Eastern Science

DTIC Science & Technology

1993-04-01

beamwidth of 2 degrees . Hie had interesting data wideband backscatter in the 2-50 kHz band and on profiles, including hydrothermal plumes ob- forward...civil aviation. Academician P. Naza- gravity in casting Al-Pb alloys. This process renko is rector of the institut’. and Professor N . produces a...pro- east -west sections across 36’ N from Gibraltar to grams such as WOCE (World Ocean Circulation Bermuda and northwest across the Gulf Stream

Improving the Cost Estimation of Space Systems. Past Lessons and Future Recommendations

DTIC Science & Technology

2008-01-01

a reasonable gauge for the relative propor- tions of cost growth attributable to errors, decisions, and other causes in any MDAP. Analysis of the...program. The program offices visited were the Defense Metrological Satellite Pro- gram (DMSP), Evolved Expendable Launch Vehicle (EELV), Advanced...3 years 1.8 0.9 3–8 years 1.8 0.9 8+ years 3.7 1.8 Staffing Requirement 7.4 3.7 areas represent earned value and budget drills ; the tan area on top

Historical Record of the U.S. Army Finance School for the Period 1 January 1963 - 31 December 1963

DTIC Science & Technology

1963-12-31

Canada 1 1 China Ghana - - Indonesia - Iran 4 1 1 1 6 1 1 2 3 Japan - - - - 2 2 Korea - 2 1 3 Peru - - - - - - - - 1 1 2...Finance Center, U S Army 28 Mr Eugene Newnam, Department of May Applied Mathematics and Sta- 63 tistics, Army Management En - gineer Training Agency...Management En - gineer Training Agency, Rock Island, Illinois 3 Maj Gen William B Bunker, Comp- Jun troller and Director of Pro- 63 grams, U S Army

Space WARC 1985 - Legal Issues and Implications.

DTIC Science & Technology

1984-01-01

public releoa.I |_Distribution Unlimited DISTRIBUTION STATEMENT ACCESSION FOR NTIS GRAM! DTIC TAB UNANNOUNCED E] JUSTIFICATION 3LC r DISTRIBUTIOND...EXHAUSTED. -7 77 7-7 77 .1- *~AD-A 150 972 "A INSTRUCTIONS____ 1.RGOVT AC(,.iN~.~j~ RECIPIENT’S CATALOG NUMBER * ~AFIT/CI/NR 85-9T IO EOT&PRO OEE r ...reere ide if neceeeesy anid identiy by bock numbas,) 20. ABSTRACT (Continue orn revere. sid. If nocep--ty end idetify by bla~ck r --mbsr) ATTACHED FORM

Rapid Human-Computer Interactive Conceptual Design of Mobile and Manipulative Robot Systems

DTIC Science & Technology

2015-05-19

algorithm based on Age-Fitness Pareto Optimization (AFPO) ([9]) with an additional user prefer- ence objective and a neural network-based user model, we...greater than 40, which is about 5 times further than any robot traveled in our experiments. 6 3.3 Methods The algorithm uses a client -server computational...architecture. The client here is an interactive pro- gram which takes a pair of controllers as input, simulates4 two copies of the robot with

Risk Factors for Colostomy in Military Colorectal Trauma: A Review of 867 Patients

DTIC Science & Technology

2014-06-01

tion with ostomy rate (43% for >12 U compared with 35% for #12 U; P = .06). Presenting base deficit did not differ between the 2 groups (2.82 colostomy...outcomes data to include postoperative morbidity, ostomy reversal rates, and complication rates, as well as overall quality-of-life outcomes requires...Health Pro- gram 6.7 grant ‘‘Quality of Life and Obstacles to Care in Injured Personnel with Ostomies ,’’ Primary Investigator: Sean C. Glasgow, MD

Sequence inversion and phenylalanine surrogates at the beta-turn enhance the antibiotic activity of gramicidin S.

PubMed

Solanas, Concepción; de la Torre, Beatriz G; Fernández-Reyes, María; Santiveri, Clara M; Jiménez, M Angeles; Rivas, Luis; Jiménez, Ana I; Andreu, David; Cativiela, Carlos

2010-05-27

A series of gramicidin S (GS) analogues have been synthesized where the Phe (i + 1) and Pro (i + 2) residues of the beta-turn have been swapped while the respective chiralities (D-, L-) at each position are preserved, and Phe is replaced by surrogates with aromatic side chains of diverse size, orientation, and flexibility. Although most analogues preserve the beta-sheet structure, as assessed by NMR, their antibiotic activities turn out to be highly dependent on the bulkiness and spatial arrangement of the aromatic side chain. Significant increases in microbicidal potency against both Gram-positive and Gram-negative pathogens are observed for several analogues, resulting in improved therapeutic profiles. Data indicate that seemingly minor replacements at the GS beta-turn can have significant impact on antibiotic activity, highlighting this region as a hot spot for modulating GS plasticity and activity.

Sequence inversion and phenylalanine surrogates at the β-turn enhance the antibiotic activity of gramicidin S

PubMed Central

Solanas, Concepción; de la Torre, Beatriz G.; Fernández-Reyes, María; Santiveri, Clara M.; Jiménez, M. Ángeles; Rivas, Luis; Jiménez, Ana I.; Andreu, David; Cativiela, Carlos

2010-01-01

A series of gramicidin S (GS) analogs have been synthesized where the Phe (i+1) and Pro (i+2) residues of the β-turn have been swapped while the respective chiralities (D-, L-) at each position are preserved, and Phe is replaced by surrogates with aromatic side chains of diverse size, orientation and flexibility. Although most analogs preserve the β-sheet structure, as assessed by NMR, their antibiotic activities turn out to be highly dependent on the bulkiness and spatial arrangement of the aromatic side chain. Significant increases in microbicidal potency against both Gram-positive and Gram-negative pathogens are observed for several analogs, resulting in improved therapeutic profiles. Data indicate that seemingly minor replacements at the GS β-turn can have significant impact on antibiotic activity, highlighting this region as a hot spot for modulating GS plasticity and activity. PMID:20411945

Conformational and chemical selection by a trans-acting editing domain

PubMed Central

Danhart, Eric M.; Bakhtina, Marina; Cantara, William A.; Kuzmishin, Alexandra B.; Ma, Xiao; Sanford, Brianne L.; Vargas-Rodriguez, Oscar; Košutić, Marija; Goto, Yuki; Suga, Hiroaki; Nakanishi, Kotaro; Micura, Ronald; Musier-Forsyth, Karin

2017-01-01

Molecular sieves ensure proper pairing of tRNAs and amino acids during aminoacyl-tRNA biosynthesis, thereby avoiding detrimental effects of mistranslation on cell growth and viability. Mischarging errors are often corrected through the activity of specialized editing domains present in some aminoacyl-tRNA synthetases or via single-domain trans-editing proteins. ProXp-ala is a ubiquitous trans-editing enzyme that edits Ala-tRNAPro, the product of Ala mischarging by prolyl-tRNA synthetase, although the structural basis for discrimination between correctly charged Pro-tRNAPro and mischarged Ala-tRNAAla is unclear. Deacylation assays using substrate analogs reveal that size discrimination is only one component of selectivity. We used NMR spectroscopy and sequence conservation to guide extensive site-directed mutagenesis of Caulobacter crescentus ProXp-ala, along with binding and deacylation assays to map specificity determinants. Chemical shift perturbations induced by an uncharged tRNAPro acceptor stem mimic, microhelixPro, or a nonhydrolyzable mischarged Ala-microhelixPro substrate analog identified residues important for binding and deacylation. Backbone 15N NMR relaxation experiments revealed dynamics for a helix flanking the substrate binding site in free ProXp-ala, likely reflecting sampling of open and closed conformations. Dynamics persist on binding to the uncharged microhelix, but are attenuated when the stably mischarged analog is bound. Computational docking and molecular dynamics simulations provide structural context for these findings and predict a role for the substrate primary α-amine group in substrate recognition. Overall, our results illuminate strategies used by a trans-editing domain to ensure acceptance of only mischarged Ala-tRNAPro, including conformational selection by a dynamic helix, size-based exclusion, and optimal positioning of substrate chemical groups. PMID:28768811

Microbial population dynamics in the sediments of a eutrophic lake (Aydat, France) and characterization of some heterotrophic bacterial isolates.

PubMed

Mallet, C; Basset, M; Fonty, G; Desvilettes, C; Bourdier, G; Debroas, D

2004-07-01

The bacterial populations of anoxic sediments in a eutrophic lake (Aydat, Puy-de-Dôme-France) were studied by phospholipid fatty acid analysis (PLFA) and also by culturing heterotrophic bacteria under strictly anaerobic conditions. The mean PLFA concentrations of prokaryotes and microeukaryotes were 5.7 +/- 2.9 mgC g(-1) DS and 9.6 +/- 6.7 mgC g(-1) DS, respectively. The analysis of bacterial PLFA markers was used to determine the dynamics of the Gram-positive and Gram-negative species of anaerobic bacteria, Clostridiae, and sulfate-reducing bacteria. Throughout the sampling period the concentrations of i15:0 (from 20 nmol g(-1) DS to 130 nmol g(-1) DS), markers of Gram-positive bacteria, were higher than those for Gram-negative bacteria. The dynamics of Clostridiae (Cy15:0) paralleled those of sulfate-reducing bacteria that were marked by i17:1omega7. Partial 16S rDNA sequencing and the physiological study of the various fermenting strains, whose abundance in the superficial sediment layer was 1.1 +/- 0.4 x 10(6) cells mL(-1), showed that all the isolates belonged to the Clostridiae and related taxa ( Lactosphaera pasteurii, Clostridium vincentii, C. butyricum, C. algidixylanolyticum, C. puniceum, C. lituseburense, and C. gasigenes). All the isolates were capable of metabolizing a wide range of organic substrates.

Rise and fall of NT-proBNP in aortic valve intervention.

PubMed

Hultkvist, Henrik; Holm, Jonas; Svedjeholm, Rolf; Vánky, Farkas

2018-01-01

To describe the dynamics of N-terminal pro-B-type natriuretic peptide (NT-proBNP) from preoperative evaluation to 6-month follow-up in patients undergoing aortic valve intervention, and to evaluate NT-proBNP with regard to 1-year mortality. At preoperative evaluation, we prospectively included 462 patients accepted for aortic valve intervention. The median time to surgical aortic valve replacement (SAVR; n=336) or transcatheter aortic valve implantation (TAVI; n=126) was 4 months. NT-proBNP was measured at enrolment for preoperative evaluation, on the day of surgery, postoperatively on day 1, day 3 and at the 6-month follow-up. Subgroups of patients undergoing SAVR with aortic regurgitation and aortic stenosis with and without coronary artery bypass were also analysed. NT-proBNP remained stable in all subgroups during the preoperative waiting period, but displayed a substantial transient early postoperative increase with a peak on day 3 except in the TAVI group, which peaked on day 1. At the 6-month follow-up, NT-proBNP had decreased to or below the preoperative level in all groups. In the SAVR group, NT-proBNP preoperatively and on postoperative days 1 and 3 revealed significant discriminatory power with regard to 1-year mortality (area under the curve (AUC)=0.79, P=0.0001; AUC=0.71, P=0.03; and AUC=0.79, P=0.002, respectively). This was not found in the TAVI group, which had higher levels of NT-proBNP both preoperatively and at the 6-month follow-up compared with the SAVR group. The dynamic profile of NT-proBNP differed between patients undergoing TAVI and SAVR. NT-proBNP in the perioperative course was associated with increased risk of 1-year mortality in SAVR but not in TAVI.

Dynamics of Gram-negative bacteria population density in a soil in the course of the succession initiated by chitin and cellulose

NASA Astrophysics Data System (ADS)

Konstantin, Ivanov; Lubov, Polyanskaya

2014-05-01

The functions of actinomycetes in polymer destruction in soil traditionally considered as the dominant, compare to another groups of bacteria. Gram-positive bacteria also have ecological functions in destruction of soil organic matter. The role of Gram-negative bacteria has been researched in the microbial succession in terms of polymers destruction, which are widely spreads in soils: chitin and cellulose. The method with nalidixic acid as an inhibitor of DNA division of Gram-negative bacteria was modified. By modified method microbial succession of Gram-negative bacteria in the different horizons of a chernozem under aerobic and anaerobic conditions was researched. Chitin and cellulose as the source of nutrients with moistening was used in experiments. The introduction of chitin had no positive effect on the population density of Gram-negative bacteria in a chernozem, but it advanced the date of their appearance in microbial succession: the maximum of Gram-negative bacteria population density was registered on the 3rd- 7th day of the experiment with adding chitin. Compare to the control, which one was without any nutrient adding this dynamics registered much earlier. Consequently, the introduction of chitin as an additional source of nutrition promoted revealing of the Gram-negative bacteria in soil already at the early stages of the succession. In the course of the succession, when the fungal mycelium begins to die off, the actinomycetic mycelium increases in length, i.e., Gram-negative bacteria are replaced at this stage with Gram-positive ones, the leading role among which belongs to actinomycetes. The growth rate of Gram-negative bacteria is higher than that of actinomycetes, so they start chitin utilization at the early stages of the succession, whereas actinomycetes dominate at the late stages. The population density of Gram-negative bacteria was lower under the anaerobic conditions as compared with that in the aerobic ones. The population density of Gram-negative bacteria in the lower layer of the A horizon of the chernozem and in the B horizon was slightly higher only in the case of the chitin introduction. When cellulose was introduced into the soil under aerobic conditions, the population density of Gram-negative bacteria in all the layers of the A horizon of the chernozem was maximal from the 14th to the 22nd day of the experiment. Simultaneously, an increase in the length of the actinomycetal mycelium was observed, as these organisms also perform cellulose hydrolysis in soils. The Gram-negative bacteria began to develop at the stage of the fungal mycelium destruction, which indirectly confirmed the chitinolytic activity of these bacteria.

Identification of antimicrobial compound, diketopiperazines, from a Bacillus sp. N strain associated with a rhabditid entomopathogenic nematode against major plant pathogenic fungi.

PubMed

Nishanth Kumar, S; Mohandas, C; Siji, J V; Rajasekharan, K N; Nambisan, Bala

2012-10-01

To purify and characterize antimicrobial compounds from Bacillus sp. strain N associated with rhabditid entomopathogenic nematode (EPN). The cell-free culture filtrate of a bacterium associated with an EPN, Rhabditis (Oscheius) sp., exhibited strong antimicrobial activity. The ethyl acetate extract of the bacterial culture filtrate was purified by silica gel column chromatography to obtain three diketopiperazines (DKPs). The structure and absolute stereochemistry of this compound were determined based on extensive spectroscopic analyses (FABMS, (1) H NMR, (13) C NMR, (1) H-(1) H COSY, (1) H-(13) C HMBC) and Marfey's method. The compounds were identified as cyclo(l-Pro-l-Leu), cyclo(d-Pro-l-Leu) and cyclo(d-Pro-l-Tyr), respectively. Three DKPs were active against all the five fungi tested (Aspergillus flavus, Candida albicans, Fusarium oxysporum, Rhizoctonia solani and Penicillium expansum) and are more effective than the standard fungicide bavistin. The highest activity of 4 μg ml(-1) by cyclo(l-Pro-l-Leu) and cyclo(d-Pro-l-Tyr) was recorded against P. expansum, a plant pathogen responsible for causing postharvest decay of stored apples and oranges. Cyclo(d-Pro-l-Leu) recorded good antibacterial activity against all the four bacteria tested (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa), and cyclo(l-Pro-l-Leu) and cyclo(d-Pro-l-Tyr) recorded good activity only against Gram-positive bacteria. To our knowledge, this is the first report of antifungal activity of the DKPs against the plant pathogenic fungi F. oxysporum, R. solani and P. expansum. The production of cyclo(l-Pro-l-Leu), cyclo(d-Pro-l-Leu) and cyclo-(d-Pro-l-Tyr) by a bacterium associated with EPN is also reported here for the first time. Isolated DKPs demonstrated high antimicrobial activity against bacteria and fungi, especially against plant pathogenic fungi. We conclude that the bacterium associated with EPN is a promising source of natural bioactive secondary metabolites which may receive great benefit in the field of agriculture. This study is a significant contribution to the knowledge of compounds unique from EPN bacteria as potential sources of new drugs in the agricultural and pharmacological industry. © 2012 The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

Optimization of Shipboard Manning Levels Using Imprint Pro Forces Module

DTIC Science & Technology

2015-09-01

NPS-OR-15-008 NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA OPTIMIZATION OF SHIPBOARD MANNING LEVELS USING IMPRINT PRO...Optimization of Shipboard Manning Levels Using IMPRINT Pro Forces Module 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...ABSTRACT The Improved Performance Research Integration Tool ( IMPRINT ) is a dynamic, stochastic, discrete-event modeling tool used to develop a model

Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis.

PubMed

Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Mörgelin, Matthias; van der Plas, Mariena J A; Rydengård, Victoria; Malmsten, Martin; Albiger, Barbara; Schmidtchen, Artur

2012-01-01

Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin in vitro and in vivo. Furthermore, they interfere with coagulation by modulating contact activation and tissue factor-mediated clotting in vitro, leading to normalization of coagulation responses in vivo, a previously unknown function of host defense peptides. In a mouse model of Pseudomonas aeruginosa sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate bacterial levels, pro-inflammatory responses, and coagulation, renders them attractive therapeutic candidates for the treatment of invasive infections and sepsis.

A Comparative Study on the Amount of Extruded Material from the Apical Foramen with NiTi Rotary and Stainless Steel Hand Instruments

PubMed Central

Nazari, Shahrzad; MirMotalebi, Farshid

2006-01-01

INTRODUCTION: The purpose of the present study was to quantify and compare the amount of extruded debris from apical foramen after instrumentation of the root canal system with hand and rotary instruments. MATERIALS AND METHODS: Root canals of forty five fresh extracted single rooted human teeth with mature apexes and less than 15 degree of root curvature were instrumented in group A with stainless steel K-Type files, in group B with rotary NiTi Flex Master files, and in group C with rotary NiTi ProTaper files and followed weighting the extruded debris by a digital scale to within 0.0001 gram accuracy. RESULTS: In all groups, the mean weight of extruded debris was not more than 5 mg (P=0.0l) and was ranked as: Group A>Group B>Group C. There were statistically significant differences among three groups (p=0.0l). The mean value of extruded debris in the ProTaper and Flex Master groups were 0.652 and 0.788 mg, respectively. CONCLUSION: The study revealed that the amount of extruded debris from the apical foramen was minimal when ProTaper files were used. PMID:24470804

Role of Coupled-Dynamics in the Catalytic Activity of Prokaryotic-like Prolyl-tRNA Synthetases

PubMed Central

Sanford, Brianne; Cao, Bach; Johnson, James M.; Zimmerman, Kurt; Strom, Alexander M.; Mueller, Robyn M.; Bhattacharyya, Sudeep; Musier-Forsyth, Karin; Hati, Sanchita

2012-01-01

Prolyl-tRNA synthetases (ProRSs) have been shown to activate both cognate and some noncognate amino acids and attach them to specific tRNAPro substrates. For example, alanine, which is smaller than cognate proline, is misactivated by Escherichia coli ProRS. Mischarged Ala-tRNAPro is hydrolyzed by an editing domain (INS) that is distinct from the activation domain. It was previously shown that deletion of the INS greatly reduced cognate proline activation efficiency. In the present study, experimental and computational approaches were used to test the hypothesis that INS deletion alters the internal protein dynamics leading to reduce catalytic function. Kinetic studies with two ProRS variants, G217A and E218A, revealed decreased amino acid activation efficiency. Molecular dynamics studies showed motional coupling between the INS and protein segments containing the catalytically important proline-binding loop (PBL, residues 199–206). In particular, the complete deletion of INS, as well as mutation of G217 or E218 to alanine, exhibited significant effects on the motion of the PBL. The presence of coupled-dynamics between neighboring protein segments was also observed through in silico mutations and essential dynamics analysis. Taken together, the present study demonstrates that structural elements at the editing domain-activation domain interface participate in coupled motions that facilitate amino acid binding and catalysis by bacterial ProRSs, which may explain why truncated or defunct editing domains have been maintained in some systems, despite the lack of catalytic activity. PMID:22356126

Investigation of Accelerated Methods for the Determination of Available Alkali in Pozzolans

DTIC Science & Technology

1974-02-01

181 p PC$9.50/MFS3.O0 Guidelines for Documentation of Computer Pro - Evaluation of Home Solar Heating System grams and Automated Data Systems UCL5...GrANT NO. 90, ORIGINATOR S REPORT NUMVIEEISI .PROJECT NO. Miscellaneous Pdper C-74-1 C. S. OTHER REPORT NOISP (AIr .dborms"M .0# Gmo Meol o SOl reo") tO...specification limit of 1.5 percent wifll not be exceeded when the pozzolan is evaluated by the present Standard Con - dition, 28 days at 38 C. In order to

Application of the Constant Exposure Time Technique to Transformation Experiments with Fission Neutrons; Failure to Demonstrate Dose-Rate Dependence

DTIC Science & Technology

1994-01-01

ive pro gramming or ltc’utrolns tld -, iii tile mixe’d field (’c)lthl(’ betet-- F-valer (calculation.is f’roni transfiirmiation data sets in min~ed...1991) but not all in vivo and fractions of the hypersensitive cells are expected at in vitro studies of radiation carcinogenesis (Ullrich the end of...fbrt donating beam time’ and dosimetry ticetrolls H. ( ;’suii berg. mauituscript ill prep- support and io the4 ntimerotis AFR RI staff members ara it

Cartographic projection procedures for the UNIX environment; a user's manual

USGS Publications Warehouse

Evenden, Gerald I.

1990-01-01

A tutorial description of the general usage of the cartographic projection program proj (release 3) along with specic cartographic parameters and illustrations of the ap- proximately 70 cartographic projections supported by the program is presented. The program is designed as a standard Unix lter utility to be employed with other pro- grams in the generation of maps and charts and, in many cases, used in map digitizing applications. Tables and shell scripts are also provided for conversion of State Plane Coordinate Systems to and from geographic coordinates.

Federal Agency Satellite Requirements.

DTIC Science & Technology

1985-07-01

and data from DCPs within 20 minutes of ground station reception. 3. Weather Modification Proiect ( Morocco ) The goal of this project is to assist the...Government of Morocco " .’ in establishing a scientifically based weather modification pro- gram, especially for long-term precipitation enhancement. A...066J rl N -- m 0 ~ ~ ~ * VL. N~~E U E EE E E C C ~ E~W I ~~ S or. cc H O-0 3 q id IQ r.~ 0 w ni 0 633 ~.-.~ -1-, >’ %i~9 -9~S -- cSr .- t*~’* - ~- .nm

Intentions of Women (18-25 Years Old) to Join the Military: Results of a National Survey.

DTIC Science & Technology

1978-09-01

MILITARY : RESULTS OF A NATIONAL SURVEY __________________________ S . PERFORMING ORG. N~PQRT NUMUER 7. Au fllON(.) S CONTRACT OR GRANT NUNSER(.) Jules...I. Borack S . PERFORMING ORGANI ZAtION N AME~~~~D ADDRE SS ~~~~. PRO GRAM ELEMENT. PROJECT. TaS~- AREA & WÔRK UNIT NUMSERS Navy Personnel Research and...non— Be interested in hiking. traditional women ’ s activities a- Marital status Be married . Be single. Financial Have financial responsibility Have no

Product quality and microbial dynamics during vermicomposting and maturation of compost from pig manure.

PubMed

Villar, Iria; Alves, David; Mato, Salustiano

2017-11-01

This research evaluates, through microbial dynamics, the use of earthworms Eisenia andrei for maturation of pre-composted pig manure in comparison with maturation under static conditions and with vermicomposting of fresh pig manure. Therefore, two substrates were used (fresh and pre-composted pig manure) and four treatments were developed: fresh manure vermicomposting, control of fresh manure without earthworms, pre-composting followed by vermicomposting and static maturation of pre-composted manure. In order to determine the microbial dynamics, the enzymatic activities and profiles of phospholipid fatty acids (PLFAs) were evaluated over a 112-days period. Physicochemical and biological parameters of the obtained products were also analyzed. The presence of earthworms significantly reduced (p<0.05) microbial biomass and all the microbial groups (Gram+bacteria, Gram-bacteria, and fungi) in both substrates. The enzymatic activities (cellulase, β-glucosidase and acid phosphatase) behaved in a significantly distinctive manner (p<0.05) depending on the treatment. Microbial communities had significant correlations (p<0.05) with hydrolytic activities during static maturation of pre-composted manure. This indicates a direct effect of microbiota evolution on the degradative processes; however, complex earthworm-microbiota interactions were established in the presence of E. andrei. After earthworms' removal from vermicompost of fresh substrate at 70day, an increase in Gram + (4.4 times), Gram - (3.8 times) and fungi (2.8 times) were observed and, although the vermicompost achieved quality values, it is necessary to optimize the vermicompost aging phase period to improve the stability. Static maturation presented stability on microbial dynamics that indicated a slow degradation of organic compounds so that, maturation of pre-composted manure through vermicomposting is better option. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rank Dynamics of Word Usage at Multiple Scales

NASA Astrophysics Data System (ADS)

Morales, José A.; Colman, Ewan; Sánchez, Sergio; Sánchez-Puig, Fernanda; Pineda, Carlos; Iñiguez, Gerardo; Cocho, Germinal; Flores, Jorge; Gershenson, Carlos

2018-05-01

The recent dramatic increase in online data availability has allowed researchers to explore human culture with unprecedented detail, such as the growth and diversification of language. In particular, it provides statistical tools to explore whether word use is similar across languages, and if so, whether these generic features appear at different scales of language structure. Here we use the Google Books N-grams dataset to analyze the temporal evolution of word usage in several languages. We apply measures proposed recently to study rank dynamics, such as the diversity of N-grams in a given rank, the probability that an N-gram changes rank between successive time intervals, the rank entropy, and the rank complexity. Using different methods, results show that there are generic properties for different languages at different scales, such as a core of words necessary to minimally understand a language. We also propose a null model to explore the relevance of linguistic structure across multiple scales, concluding that N-gram statistics cannot be reduced to word statistics. We expect our results to be useful in improving text prediction algorithms, as well as in shedding light on the large-scale features of language use, beyond linguistic and cultural differences across human populations.

The role of loop ZA and Pro371 in the function of yeast Gcn5p bromodomain revealed through molecular dynamics and experiment.

PubMed

Pizzitutti, Francesco; Giansanti, Andrea; Ballario, Paola; Ornaghi, Prisca; Torreri, Paola; Ciccotti, Giovanni; Filetici, Patrizia

2006-01-01

Biological experiments were combined with molecular dynamics simulations to understand the importance of amino acidic residues present in the bromodomain of the yeast histone acetyltransferase Gcn5p. It was found that residue Pro371 plays an important role in the molecular recognition of the acetylated histone H4 tail by Gcn5p bromodomain. Crystallographic analysis of the complex showed that this residue does not directly interact with the histone substrate. It has been demonstrated that a double mutation Pro371Thr and Met372Ala in the Gcn5p bromodomain impairs chromatin remodeling activity. It is demonstrated here that, in this double mutant and in the fully deleted bromodomain strain, there is lower growth under amino acid deprivation conditions. By in vitro surface plasmon resonance (Biacore) experiments it is shown that the binding affinity of the double mutation to acetyl lysine 16 histone H4 peptide decreases. Molecular dynamics simulations were used to explain this loss in acetyl lysine-Gcn5p bromodomain affinity, in the double mutant. By comparing nanosecond molecular dynamics trajectories of the native as well as the single and doubly mutated bromodomain, it is concluded that the presence of Pro371 is important to the functionality of the Gcn5p bromodomain. In the simulation a point mutation involving this highly conserved residue induced an increase in the flexibility of the ZA loop, which in turn modulated the exposure of the binding pocket to the acetyl lysine. The combined double mutations (Pro371Thr-Met372Ala) not only markedly perturb the motion of the ZA loop but also destabilize the entire structure of the bromodomain. Copyright 2005 John Wiley & Sons, Ltd.

In vitro evaluation of tigemonam, a novel oral monobactam.

PubMed Central

Tanaka, S K; Summerill, R A; Minassian, B F; Bush, K; Visnic, D A; Bonner, D P; Sykes, R B

1987-01-01

Tigemonam, a novel, orally administered monobactam, exhibited potent and specific activity in vitro against members of the family Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae. Its activity was variable to poor against gram-positive bacteria, Acinetobacter spp., Pseudomonas aeruginosa, and anaerobes. Within its spectrum of activity, tigemonam was far superior to oral antibiotics currently available, including amoxicillin-clavulanic acid, cefaclor, and trimethoprim-sulfamethoxazole. In addition, tigemonam was superior to cefuroxime, which is under development as an oral pro-drug, and more active than cefixime against several genera of the Enterobacteriaceae. The activity of tigemonam against the enteric bacteria, Haemophilus species, and Neisseria species was, in general, comparable to that of the quinolone norfloxacin. The excellent activity of tigemonam against beta-lactamase-producing bacteria reflected its marked stability to hydrolysis by isolated enzymes. The expanded spectrum of activity against gram-negative bacteria observed with tigemonam thus extends oral beta-lactam coverage to include members of the Enterobacteriaceae that are intrinsically or enzymatically resistant to broad-spectrum penicillins and cephalosporins. PMID:3105448

In vitro and in vivo antimicrobial efficacy of natural plant-derived compounds against Vibrio cholerae of O1 El Tor Inaba serotype.

PubMed

Kim, Hyung-Ip; Kim, Ji-Ae; Choi, Eun-Jin; Harris, Jason B; Jeong, Seong-Yeop; Son, Seok-Jun; Kim, Younghoon; Shin, Ok Sarah

2015-01-01

In this study, we investigated antibacterial activities of 20 plant-derived natural compounds against Gram-negative enteric pathogens. We found that both flavonoids and non-flavonoids, including honokiol and magnolol, possess specific antibacterial activities against V. cholerae, but not against other species of Gram-negative bacterium which we tested. Using various antibacterial assays, we determined that there was a dose-dependent bactericidal and biofilm inhibitory activity of honokiol and magnolol against Vibrio cholerae. In addition to antibacterial activities, these molecules also induced an attenuating effect on reactive oxygen species (ROS) production and pro-inflammatory responses generated by macrophages in response to lipopolysaccharides (LPS). Additionally, Caenorhabditis elegans lethality assay revealed that honokiol and magnolol have an ability to extend a lifespan of V. cholerae-infected worms, contributing to prolonged survival of worms after lethal infection. Altogether, our data show for the first time that honokiol and magnolol may be considered as attractive protective or preventive food adjuncts for cholera.

A novel C-type lectin with two CRD domains from Chinese shrimp Fenneropenaeus chinensis functions as a pattern recognition protein.

PubMed

Zhang, Xiao-Wen; Xu, Wen-Teng; Wang, Xian-Wei; Mu, Yi; Zhao, Xiao-Fan; Yu, Xiao-Qiang; Wang, Jin-Xing

2009-05-01

Lectins are regarded as potential immune recognition proteins. In this study, a novel C-type lectin (Fc-Lec2) was cloned from the hepatopancreas of Chinese shrimp, Fenneropenaeus chinensis. The cDNA of Fc-Lec2 is 1219 bp with an open reading frame (ORF) of 1002 bp that encodes a protein of 333 amino acids. Fc-Lec2 contains a signal peptide and two different carbohydrate recognition domains (CRDs) arranged in tandem. The first CRD contains a QPD (Gln-Pro-Asp) motif that has a predicted binding specificity for galactose and the second CRD contains a EPN (Glu-Pro-Asn) motif for mannose. Fc-Lec2 was constitutively expressed in the hepatopancreas of normal shrimp, and its expression was up-regulated in the hepatopancreas of shrimp challenged with bacteria or viruses. Recombinant mature Fc-Lec2 and its two individual CRDs (CRD1 and 2) did not have hemagglutinating activity against animal red blood cells, but agglutinated some gram-positive and gram-negative bacteria in a calcium-dependent manner. The three recombinant proteins also bound to bacteria in the absence of calcium. Fc-Lec2 seems to have broader specificity and higher affinity for bacteria and polysaccharides (peptidoglycan, lipoteichoic acid and lipopolysaccharide) than each of the two individual CRDs. These data suggest that the two CRDs have synergistic effect, and the intact lectin may be more effective in response to bacterial infection, the Fc-Lec2 performs its pattern recognition function by binding to polysaccharides of pathogen cells.

The Propulsive Small Expendable Deployer System (ProSEDS)

NASA Technical Reports Server (NTRS)

Lorenzini, Enrico C.; Cosmo, Mario L.; Estes, Robert D.; Sanmartin, Juan; Pelaez, Jesus; Ruiz, Manuel

2003-01-01

This Final Report covers the following main topics: 1) Brief Description of ProSEDS; 2) Mission Analysis; 3) Dynamics Reference Mission; 4) Dynamics Stability; 5) Deployment Control; 6) Updated System Performance; 7) Updated Mission Analysis; 8) Updated Dynamics Reference Mission; 9) Updated Deployment Control Profiles and Simulations; 10) Updated Reference Mission; 11) Evaluation of Power Delivered by the Tether; 12) Deployment Control Profile Ref. #78 and Simulations; 13) Kalman Filters for Mission Estimation; 14) Analysis/Estimation of Deployment Flight Data; 15) Comparison of ED Tethers and Electrical Thrusters; 16) Dynamics Analysis for Mission Starting at a Lower Altitude; 17) Deployment Performance at a Lower Altitude; 18) Satellite Orbit after a Tether Cut; 19) Deployment with Shorter Dyneema Tether Length; 20) Interactive Software for ED Tethers.

Effect of oscillation dynamics on long-range electron transfer in a helical peptide monolayer.

PubMed

Matsushita, Daisuke; Uji, Hirotaka; Kimura, Shunsaku

2018-06-06

Electron transfer (ET) reactions via helical peptides composed of -(Aib-Pro)n- were studied in self-assembled monolayers and compared with -(Ala-Aib)n- peptides. Short Aib-Pro peptides showed slightly higher ET rates due to the better electronic coupling of the Pro residue. But, the 24mer Aib-Pro peptide showed a smaller ET rate than the corresponding Ala-Aib peptide. On the basis of DFT calculations, the deceleration of the ET rate of the longer Aib-Pro peptide is considered to be due to the smaller number of active modes of accordion-like oscillations than the Ala-Aib peptide, which has a strong influence on a long-range ET reaction.

Myeloid-derived NF-κB negative regulation of PU.1 and cEBPβ-driven pro-inflammatory cytokine production restrains LPS-induced Shock

PubMed Central

Vanoni, Simone; Tsai, Yi Ting; Waddell, Amanda; Waggoner, Lisa; Klarquist, Jared; Divanovic, Senad; Hoebe, Kasper; Steinbrecher, Kris A.; Hogan, Simon P.

2017-01-01

Sepsis is a life-threatening event predominantly caused by gram-negative bacteria. Bacterial infection causes a pronounced macrophage (MΦ) and dendritic cell (DC) activation that leads to excessive pro-inflammatory cytokine interleukin (IL)-1β, IL-6, and Tumor necrosis factor (TNF)-α production (cytokine storm), resulting in endotoxic shock. Previous experimental studies have revealed that inhibiting Nuclear Factor kappa Beta (NF-κB) signaling ameliorates disease symptoms; however, the contribution of myeloid p65 in endotoxic shock remains elusive. In this study, we demonstrate increased mortality in mice lacking p65 in the myeloid lineage (p65Δmye) compared to wild type (WT) mice upon ultra-pure LPS (U-LPS) challenge. We show that increased susceptibility to Lipopolysaccharide (LPS)-induced shock was associated with elevated serum level of IL-1β and IL-6. Mechanistic analyses revealed that LPS-induced pro-inflammatory cytokine production was ameliorated in p65-deficient bone marrow–derived macrophages (BMDMs); however, p65-deficient “activated” peritoneal macrophages (MΦs) exhibited elevated IL-1β and IL-6. We show that the elevated pro-inflammatory cytokine secretion was due in part to increased accumulation of IL-1β mRNA and protein in activated inflammatory MΦs. The increased IL-1β was linked with heightened binding of PU.1 and CCAAT/Enhancer Binding Protein Beta (cEBPβ to Il1b and Il6 promoters in activated inflammatory MΦs. Our data provides insight into a role for NF-κB in the negative regulation of pro-inflammatory cytokines in myeloid cells. PMID:27932520

Envelope Structures of Gram-Positive Bacteria

PubMed Central

Rajagopal, Mithila; Walker, Suzanne

2016-01-01

Gram-positive organisms, including the pathogens Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecalis, have dynamic cell envelopes that mediate interactions with the environment and serve as the first line of defense against toxic molecules. Major components of the cell envelope include peptidoglycan, which is a well-established target for antibiotics, teichoic acids, capsular polysaccharides, surface proteins, and phospholipids. These components can undergo modification to promote pathogenesis, decrease susceptibility to antibiotics and host immune defenses, and enhance survival in hostile environments. This chapter will cover the structure, biosynthesis and important functions of major cell envelope components in Gram-positive bacteria. Possible targets for new antimicrobials will be noted. PMID:26919863

A broad-host range dual-fluorescence reporter system for gene expression analysis in Gram-negative bacteria.

PubMed

Hennessy, Rosanna C; Christiansen, Line; Olsson, Stefan; Stougaard, Peter

2018-01-01

Fluorescence-based reporter systems are valuable tools for studying gene expression dynamics in living cells. Here we describe a dual-fluorescence reporter system carrying the red fluorescent marker mCherry and the blue fluorescent protein EBFP2 enabling the simultaneous analysis of two promoters in broad-host range autofluorescent Gram-negative bacteria. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative experimental infection of Listeria monocytogenes and Listeria ivanovii in bovine trophoblasts.

PubMed

Rocha, Cláudia E; Mol, Juliana P S; Garcia, Luize N N; Costa, Luciana F; Santos, Renato L; Paixão, Tatiane A

2017-01-01

Listeria monocytogenes is a Gram-positive, facultative intracellular and invasive bacterium that has tropism to the placenta, and causes fetal morbidity and mortality in several mammalian species. While infection with L. monocytogenes and L. ivanovii are known as important causes of abortion and reproductive failure in cattle, the pathogenesis of maternal-fetal listeriosis in this species is poorly known. This study used the bovine chorioallantoic membrane explant model to investigate the kinetics of L. monocytogenes, L. ivanovii, and L. innocua infections in bovine trophoblastic cells for up to 8 h post infection. L. monocytogenes and L. ivanovii were able to invade and multiply in trophoblastic cells without causing cell death or inducing expression of pro-inflammatory genes. Although L. innocua was unable to multiply in bovine trophoblastic cells, it induced transcription of the pro-inflammatory mediator CXCL6. This study demonstrated for the first time the susceptibility of bovine trophoblastic cells to L. monocytogenes and L. ivanovii infection.

Comparative experimental infection of Listeria monocytogenes and Listeria ivanovii in bovine trophoblasts

PubMed Central

Rocha, Cláudia E.; Mol, Juliana P. S.; Garcia, Luize N. N.; Costa, Luciana F.; Santos, Renato L.

2017-01-01

Listeria monocytogenes is a Gram-positive, facultative intracellular and invasive bacterium that has tropism to the placenta, and causes fetal morbidity and mortality in several mammalian species. While infection with L. monocytogenes and L. ivanovii are known as important causes of abortion and reproductive failure in cattle, the pathogenesis of maternal-fetal listeriosis in this species is poorly known. This study used the bovine chorioallantoic membrane explant model to investigate the kinetics of L. monocytogenes, L. ivanovii, and L. innocua infections in bovine trophoblastic cells for up to 8 h post infection. L. monocytogenes and L. ivanovii were able to invade and multiply in trophoblastic cells without causing cell death or inducing expression of pro-inflammatory genes. Although L. innocua was unable to multiply in bovine trophoblastic cells, it induced transcription of the pro-inflammatory mediator CXCL6. This study demonstrated for the first time the susceptibility of bovine trophoblastic cells to L. monocytogenes and L. ivanovii infection. PMID:28467447

[Usefulness of brain natriuretic propeptide in the diagnosis and management of patent ductus arteriosus].

PubMed

Montaner Ramón, Alicia; Galve Pradel, Zenaida; Fernández Espuelas, Cristina; Jiménez Montañés, Lorenzo; Samper Villagrasa, María Pilar; Rite Gracia, Segundo

2017-06-01

Patent ductus arteriosus (PDA) is a prevalent condition in preterm infants, and may be related to increased morbidity and mortality in the most immature newborns. Recent studies have examined the usefulness of brain natriuretic propeptide (proBNP) in the diagnosis of this pathology. The aim of the study was to evaluate the diagnostic efficacy of proBNP as a marker of hemodynamic overload in PDA. A retrospective study was conducted on preterm infants less than 32 weeks of gestation and/or weight less than 1500 grams. Echocardiogram and determination of proBNP levels were performed on all patients. Comparison was made by subgroups according to the presence of PDA and their haemodynamic characteristics. Of the 60 patients enrolled, 71.7% had PDA, of which 86% had haemodynamically significant patent ductus arteriosus (HS-PDA). All of them, but one, received medical treatment with ibuprofen or acetaminophen. Surgical closure was required in 29.7% of HS-PDA. Higher values of proBNP were found in patients with HS-PDA (33338±34494.47pg/mL; p=.000) compared with patients with closed or non-haemodynamically significant ductus arteriosus. Higher values were also found in patients who required surgical closure of PDA (30596.8±14910.9; p=.004). A greater decrease inproBNP levels was found in the group of patients which duct closure after pharmacological treatment (68±24.69% vs -12.22±99.4%; p=.030). ProBNP cutoff-level for HS-PDA was calculated by ROC curve and it was 9321.5pg/mL (Specificity: 100%, Sensitivity: 94.6%). ProBNP levels are related to the presence or absence of haemodynamically significant patent ductus arteriosus; and its variations with treatment response. High values are also related to the need for surgical closure of PDA. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Cyclic dipeptides from rhabditid entomopathogenic nematode-associated Bacillus cereus have antimicrobial activities.

PubMed

Nishanth Kumar, S; Nath, Vishnu Sukumari; Pratap Chandran, R; Nambisan, Bala

2014-02-01

The cell free culture filtrate of Bacillus cereus associated with an entomopathogenic nematode, Rhabditis (Oscheius) sp. exhibited strong antimicrobial activity. The ethyl acetate extract of the bacterial culture filtrate was purified by silica gel column chromatography to obtain four bioactive compounds. The structure and absolute stereochemistry of these compounds were determined based on extensive spectroscopic analyses (FABMS, (1)H NMR, (13)C NMR, (1)H-(1)H COSY, (1)H-(13)C HMBC) and Marfey's method. The compounds were identified as cyclic dipeptides (CDPs): cyclo(L-Pro-L-Trp), cyclo(L-Leu-L-Val), cyclo(D-Pro-D-Met), and cyclo(D-Pro-D-Phe), respectively. Compounds recorded significant antibacterial activity against all the test bacteria (Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and methicillin-resistant S. aureus) except cyclo(L-Leu-L-Val). Cyclo(L-Leu-L-Val) recorded activity only against Gram positive bacteria. Best antibacterial activity was recorded by cyclo(L-Pro-L-Trp) against S. aureus (4 μg/ml). The four compounds were active against all the five fungi tested (Trichophyton rubrum, Aspergillus flavus, Candida albicans, Candida tropicalis and Cryptococcus neoformans) and the activity was compared with amphotericin B, the standard fungicide. The highest activity of 1 μg/ml by cyclo(L-Pro-L-Trp) was recorded against T. rubrum, a human pathogen responsible for causing athlete's foot, jock itch, and ringworm. The activity of cyclo(L-Pro-L-Trp) against T. rubrum, C. neoformans and C. albicans were better than amphotericin B, the standard antifungal agent. To our knowledge, this is the first report of antifungal activity of CDPs against the human pathogenic fungi T. rubrum and C. neoformans. The four CDPs are nontoxic to healthy human cell line up to 200 μg/ml. We conclude that the bacterium associated with entomopathogenic nematode is promising sources of natural antimicrobial secondary metabolites, which may receive greater benefit as potential sources of new drugs in the pharmaceutical industry.

Dynamic Modulation of Microglia/Macrophage Polarization by miR-124 after Focal Cerebral Ischemia.

PubMed

Hamzei Taj, Somayyeh; Kho, Widuri; Aswendt, Markus; Collmann, Franziska M; Green, Claudia; Adamczak, Joanna; Tennstaedt, Annette; Hoehn, Mathias

2016-12-01

Mononuclear phagocytes respond to ischemic stroke dynamically, undergoing an early anti-inflammatory and protective phenotype followed by the pro-inflammatory and detrimental type. These dual roles of microglia/macrophages suggest the need of subtle adjustment of their polarization state instead of broad suppression. The most abundant brain-specific miRNA, miR-124, promotes neuronal differentiation but can also modulate microglia activation and keeps them in a quiescent state. We addressed whether the intracerebral injection of miR-124 in a mouse model of ischemic stroke before or after the peak phase of the pro-inflammatory polarization modifies the pro-/anti- inflammatory balance. In the sub-acute phase, 48 h after stroke, liposomated miR-124 shifted the predominantly pro-inflammatory polarized microglia/macrophages toward the anti-inflammatory phenotype. The altered immune response improved neurological deficit at day 6 after stroke. When miR-124 was injected 10 days after stroke, the pro-/anti- inflammatory ratio was still significantly reduced although to a lower degree and had no effect on recovery at day 14. This study indicates that miR-124 administration before the peak of the pro-inflammatory process of stroke is most effective in support of increasing the rehabilitation opportunity in the sub-acute phases of stroke. Our findings highlight the important role of immune cells after stroke and the therapeutic relevance of their polarization balance.

Proline Substitution of Dimer Interface β-strand Residues as a Strategy for the Design of Functional Monomeric Proteins

PubMed Central

Joseph, Prem Raj B.; Poluri, Krishna Mohan; Gangavarapu, Pavani; Rajagopalan, Lavanya; Raghuwanshi, Sandeep; Richardson, Ricardo M.; Garofalo, Roberto P.; Rajarathnam, Krishna

2013-01-01

Proteins that exist in monomer-dimer equilibrium can be found in all organisms ranging from bacteria to humans; this facilitates fine-tuning of activities from signaling to catalysis. However, studying the structural basis of monomer function that naturally exists in monomer-dimer equilibrium is challenging, and most studies to date on designing monomers have focused on disrupting packing or electrostatic interactions that stabilize the dimer interface. In this study, we show that disrupting backbone H-bonding interactions by substituting dimer interface β-strand residues with proline (Pro) results in fully folded and functional monomers, by exploiting proline’s unique feature, the lack of a backbone amide proton. In interleukin-8, we substituted Pro for each of the three residues that form H-bonds across the dimer interface β-strands. We characterized the structures, dynamics, stability, dimerization state, and activity using NMR, molecular dynamics simulations, fluorescence, and functional assays. Our studies show that a single Pro substitution at the middle of the dimer interface β-strand is sufficient to generate a fully functional monomer. Interestingly, double Pro substitutions, compared to single Pro substitution, resulted in higher stability without compromising native monomer fold or function. We propose that Pro substitution of interface β-strand residues is a viable strategy for generating functional monomers of dimeric, and potentially tetrameric and higher-order oligomeric proteins. PMID:24048001

The Sensorial Effect: Dynamics of Emotion in Pro-Environmental Behavior

ERIC Educational Resources Information Center

Hipolito, Joana

2011-01-01

In this article, sensorial effects are introduced as emotional stimuli for shaping environmentally significant behaviors. This research provides a link between sensorial effect as ubiquitous environmental behavior feedback and the effect of sensorial stimuli on emotions that trigger individuals' pro-environment behavior. A case study of using…

Bacterial Pore-Forming Toxins Promote the Activation of Caspases in Parallel to Necroptosis to Enhance Alarmin Release and Inflammation During Pneumonia.

PubMed

Gonzalez-Juarbe, Norberto; Bradley, Kelley M; Riegler, Ashleigh N; Reyes, Luis F; Brissac, Terry; Park, Sang-Sang; Restrepo, Marcos I; Orihuela, Carlos J

2018-04-11

Pore-forming toxins are the most common virulence factor in pathogenic bacteria. They lead to membrane permeabilization and cell death. Herein, we show that respiratory epithelial cells (REC) undergoing bacterial pore-forming toxin (PFT)-induced necroptosis simultaneously experienced caspase activation independently of RIPK3. MLKL deficient REC treated with a pan-caspase inhibitor were protected in an additive manner against PFT-induced death. Subsequently, cleaved versions of caspases-2, -4 and -10 were detected within REC undergoing necroptosis by immunoblots and monoclonal antibody staining. Caspase activation was observed in lung samples from mice and non-human primates experiencing Gram-negative and Gram-positive bacterial pneumonia, respectively. During apoptosis, caspase activation normally leads to cell shrinkage, nuclear condensation, and immunoquiescent death. In contrast, caspase activity during PFT-induced necroptosis increased the release of alarmins to the extracellular milieu. Caspase-mediated alarmin release was found sufficient to activate resting macrophages, leading to Interleukin-6 production. In a mouse model of Gram-negative pneumonia, deletion of caspases -2 and -11, the mouse orthologue of caspase-4, reduced pulmonary inflammation, immune cell infiltration and lung damage. Thus, our study describes a previously unrecognized role for caspase activation in parallel to necroptosis, and indicates that their activity plays a critical pro-inflammatory role during bacterial pneumonia.

Dynamic detailed model of a molten salt tower receiver, with ThermoSysPro library: Impacts of several failures or operational transients on the receiver dynamic behavior

NASA Astrophysics Data System (ADS)

Hefni, Baligh El; Bourdil, Charles

2017-06-01

Molten salt technology represents nowadays the most cost-effective technology for electricity generation for solar power plant. The molten salt tower receiver is based on a field of individually sun-tracking mirrors (heliostats) that reflect the incident sunshine to a receiver at the top of a centrally located tower. The objective of this study is to assess the impact of several transients issued from different scenarios (failure or normal operation mode) on the receiver dynamic behavior. A dynamic detailed model of Solar Two molten salt central receiver has been developed. The component model is meant to be used for receiver modeling with the ThermoSysPro library, developed by EDF. The paper also gives the results of the dynamic simulation for the selected scenarios on Solar Two receiver.

Dynamics of epidemic spreading with vaccination: Impact of social pressure and engagement

NASA Astrophysics Data System (ADS)

Pires, Marcelo A.; Crokidakis, Nuno

2017-02-01

In this work we consider a model of epidemic spreading coupled with an opinion dynamics in a fully-connected population. Regarding the opinion dynamics, the individuals may be in two distinct states, namely in favor or against a vaccination campaign. Individuals against the vaccination follow a standard SIS model, whereas the pro-vaccine individuals can also be in a third compartment, namely Vaccinated. In addition, the opinions change according to the majority-rule dynamics in groups with three individuals. We also consider that the vaccine can give permanent or temporary immunization to the individuals. By means of analytical calculations and computer simulations, we show that the opinion dynamics can drastically affect the disease propagation, and that the engagement of the pro-vaccine individuals can be crucial for stopping the epidemic spreading. The full numerical code for simulating the model is available from the authors' webpage.

Sequence- and structure-based computational analyses of Gram-negative tripartite efflux pumps in the context of bacterial membranes

DOE PAGES

Travers, Timothy; Wang, Katherine J.; Lopez, Cesar A.; ...

2018-02-09

Gram-negative multidrug resistance currently presents a serious threat to public health with infections effectively rendered untreatable. Multiple molecular mechanisms exist that cause antibiotic resistance and in addition, the last three decades have seen slowing rates of new drug development. In this paper, we summarize the use of various computational techniques for investigating the mechanisms of multidrug resistance mediated by Gram-negative tripartite efflux pumps and membranes. Recent work in our lab combines data-driven sequence and structure analyses to study the interactions and dynamics of these bacterial components. Computational studies can complement experimental methodologies for gaining crucial insights into combatting multidrug resistance.

Sequence- and structure-based computational analyses of Gram-negative tripartite efflux pumps in the context of bacterial membranes

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

Travers, Timothy; Wang, Katherine J.; Lopez, Cesar A.

Gram-negative multidrug resistance currently presents a serious threat to public health with infections effectively rendered untreatable. Multiple molecular mechanisms exist that cause antibiotic resistance and in addition, the last three decades have seen slowing rates of new drug development. In this paper, we summarize the use of various computational techniques for investigating the mechanisms of multidrug resistance mediated by Gram-negative tripartite efflux pumps and membranes. Recent work in our lab combines data-driven sequence and structure analyses to study the interactions and dynamics of these bacterial components. Computational studies can complement experimental methodologies for gaining crucial insights into combatting multidrug resistance.

Competition-Level Differences on the Lower Quarter Y-Balance Test in Baseball Players.

PubMed

Butler, Robert J; Bullock, Garrett; Arnold, Todd; Plisky, Phillip; Queen, Robin

2016-12-01

Decreased performance in dynamic balance has previously been associated with a history of ulnar collateral ligament injury in baseball players. Previous research on dynamic balance in soccer players has shown that test performance depends on competition level. However, dynamic balance has yet to be examined in baseball players. To understand normative values and determine differences in dynamic balance, as measured by the Lower Quarter Y-Balance Test, across competition levels in baseball players. Cross-sectional study. Preseason physical examinations. Dynamic balance was measured in 88 high school (HS), 78 collegiate (COL), and 90 professional (PRO) baseball players. All participants completed the Lower Quarter Y-Balance Test using the standard protocol. In unilateral stance, they reached with 1 foot in the anterior, posteromedial, and posterolateral directions. We calculated 1-way analyses of variance to compare performance, composite score, and reach asymmetry for each direction as well as the sum of the asymmetry values (P < .05). Composite score was calculated by averaging the maximum normalized reach scores. Reach asymmetry was determined by calculating bilateral differences in reach ability. In comparison with the HS and COL groups, the PRO players exhibited greater posteromedial (P < .01; effect size index [ESI] HS = 1.06, ESI COL = 0.95) and posterolateral reach (P < .01; ESI HS = 0.82, ESI COL = 0.84) as well as a greater composite score (P < .01; ESI HS = 0.60, ESI COL = 0.87). In contrast, HS baseball players exhibited increased anterior reach (P < .01; ESI COL = 0.60, ESI PRO = 0.39) compared with the COL and PRO cohorts. No significant differences in reach asymmetry were observed among groups. Lower extremity dynamic balance performance differed based on the baseball players' competition level. These baseline data may be helpful in identifying low-performing athletes who might benefit from neuromuscular interventions.

Molecular and cellular characterization of the tomato pollen profilin, LePro1

USDA-ARS?s Scientific Manuscript database

Profilin is an actin-binding protein involved in the dynamic turnover and restructuring of the actin cytoskeleton in all eukaryotic cells. We previously cloned a profilin gene, designated as LePro1 from tomato pollen. To investigate its biological role, in the present study, We investigated the tem...

Proline substitution of dimer interface β-strand residues as a strategy for the design of functional monomeric proteins.

PubMed

Joseph, Prem Raj B; Poluri, Krishna Mohan; Gangavarapu, Pavani; Rajagopalan, Lavanya; Raghuwanshi, Sandeep; Richardson, Ricardo M; Garofalo, Roberto P; Rajarathnam, Krishna

2013-09-17

Proteins that exist in monomer-dimer equilibrium can be found in all organisms ranging from bacteria to humans; this facilitates fine-tuning of activities from signaling to catalysis. However, studying the structural basis of monomer function that naturally exists in monomer-dimer equilibrium is challenging, and most studies to date on designing monomers have focused on disrupting packing or electrostatic interactions that stabilize the dimer interface. In this study, we show that disrupting backbone H-bonding interactions by substituting dimer interface β-strand residues with proline (Pro) results in fully folded and functional monomers, by exploiting proline's unique feature, the lack of a backbone amide proton. In interleukin-8, we substituted Pro for each of the three residues that form H-bonds across the dimer interface β-strands. We characterized the structures, dynamics, stability, dimerization state, and activity using NMR, molecular dynamics simulations, fluorescence, and functional assays. Our studies show that a single Pro substitution at the middle of the dimer interface β-strand is sufficient to generate a fully functional monomer. Interestingly, double Pro substitutions, compared to single Pro substitution, resulted in higher stability without compromising native monomer fold or function. We propose that Pro substitution of interface β-strand residues is a viable strategy for generating functional monomers of dimeric, and potentially tetrameric and higher-order oligomeric proteins. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Mars Global Reference Atmospheric Model (Mars-GRAM 2005) Applications for Mars Science Laboratory Mission Site Selection Processes

NASA Technical Reports Server (NTRS)

Justh, H. L.; Justus, C. G.

2007-01-01

The new Mars-GRAM auxiliary profile capability, using data from TES observations, mesoscale model output, or other sources, allows a potentially higher fidelity representation of the atmosphere, and a more accurate way of estimating inherent uncertainty in atmospheric density and winds. Figure 3 indicates that, with nominal value rpscale=1, Mars-GRAM perturbations would tend to overestimate observed or mesoscale-modeled variability. To better represent TES and mesoscale model density perturbations, rpscale values as low as about 0.4 could be used. Some trajectory model implementations of Mars-GRAM allow the user to dynamically change rpscale and rwscale values with altitude. Figure 4 shows that an mscale value of about 1.2 would better replicate wind standard deviations from MRAMS or MMM5 simulations at the Gale, Terby, or Melas sites. By adjusting the rpscale and rwscale values in Mars-GRAM based on figures such as Figure 3 and 4, we can provide more accurate end-to-end simulations for EDL at the candidate MSL landing sites.

Antimicrobial proline-rich peptides from the hemolymph of marine snail Rapana venosa.

PubMed

Dolashka, Pavlina; Moshtanska, Vesela; Borisova, Valika; Dolashki, Aleksander; Stevanovic, Stefan; Dimanov, Tzvetan; Voelter, Wolfgang

2011-07-01

Hemolymph of Rapana venosa snails is a complex mixture of biochemically and pharmacologically active components such as peptides and proteins. Antimicrobial peptides are gaining attention as antimicrobial alternatives to chemical food preservatives and commonly used antibiotics. Therefore, for the first time we have explored the isolation, identification and characterisation of 11 novel antimicrobial peptides produced by the hemolymph of molluscs. The isolated peptides from the hemolymph applying ultrafiltration and reverse-phase high-performance liquid chromatography (RP-HPLC) have molecular weights between 3000 and 9500 Da, determined by mass spectrometric analysis. The N-terminal sequences of the peptides identified by Edman degradation matched no peptides in the MASCOT search database, indicating novel proline-rich peptides. UV spectra revealed that these substances possessed the characteristics of protein peptides with acidic isoelectric points. However, no Cotton effects were observed between 190 and 280 nm by circular dichroism spectroscopy. Four of the pro-rich peptides also showed strong antimicrobial activities against tested microorganisms including Gram-positive and Gram-negative bacteria. Copyright © 2011 Elsevier Inc. All rights reserved.

Dynamic modeling of the neck muscles during horizontal head movement. Part II: Model construction in Pro/Engineer.

PubMed

Haapala, Stephenie A; Enderle, John D

2003-01-01

This paper describes the next phase of research on a parametric model of the head-neck system for dynamic simulation of horizontal head rotation. A skull has been imported into Pro/Engineer software and has been assigned mass properties such as density, surface area and moments of inertia. The origin of a universal coordinate system has been located at the center of gravity of the T1 vertebrae. Identification of this origin allows insertion and attachment points of the sternocleidomastoid (SCOM) and splenius capitis to be located. An assembly has been created, marking the location of both muscle sets. This paper will also explore the obstacles encountered when working with an imported feature in Pro/E and attempts to resolve some of these issues. The goal of this work involves the creation of a 3D homeomorphic saccadic eye and head movement system.

Simulation of linear mechanical systems

NASA Technical Reports Server (NTRS)

Sirlin, S. W.

1993-01-01

A dynamics and controls analyst is typically presented with a structural dynamics model and must perform various input/output tests and design control laws. The required time/frequency simulations need to be done many times as models change and control designs evolve. This paper examines some simple ways that open and closed loop frequency and time domain simulations can be done using the special structure of the system equations usually available. Routines were developed to run under Pro-Matlab in a mixture of the Pro-Matlab interpreter and FORTRAN (using the .mex facility). These routines are often orders of magnitude faster than trying the typical 'brute force' approach of using built-in Pro-Matlab routines such as bode. This makes the analyst's job easier since not only does an individual run take less time, but much larger models can be attacked, often allowing the whole model reduction step to be eliminated.

Sharing the skies: the Gemini Observatory international time allocation process

NASA Astrophysics Data System (ADS)

Margheim, Steven J.

2016-07-01

Gemini Observatory serves a diverse community of four partner countries (United States, Canada, Brazil, and Argentina), two hosts (Chile and University of Hawaii), and limited-term partnerships (currently Australia and the Republic of Korea). Observing time is available via multiple opportunities including Large and Long Pro- grams, Fast-turnaround programs, and regular semester queue programs. The slate of programs for observation each semester must be created by merging programs from these multiple, conflicting sources. This paper de- scribes the time allocation process used to schedule the overall science program for the semester, with emphasis on the International Time Allocation Committee and the software applications used.

Shape-dependent bactericidal activity of copper oxide nanoparticle mediated by DNA and membrane damage

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

Laha, Dipranjan; Pramanik, Arindam; Laskar, Aparna

Highlights: • Spherical and sheet shaped copper oxide nanoparticles were synthesized. • Physical characterizations of these nanoparticles were done by TEM, DLS, XRD, FTIR. • They showed shape dependent antibacterial activity on different bacterial strain. • They induced both membrane damage and ROS mediated DNA damage in bacteria. - Abstract: In this work, we synthesized spherical and sheet shaped copper oxide nanoparticles and their physical characterizations were done by the X-ray diffraction, fourier transform infrared spectroscopy, transmission electron microscopy and dynamic light scattering. The antibacterial activity of these nanoparticles was determined on both gram positive and gram negative bacterial. Sphericalmore » shaped copper oxide nanoparticles showed more antibacterial property on gram positive bacteria where as sheet shaped copper oxide nanoparticles are more active on gram negative bacteria. We also demonstrated that copper oxide nanoparticles produced reactive oxygen species in both gram negative and gram positive bacteria. Furthermore, they induced membrane damage as determined by atomic force microscopy and scanning electron microscopy. Thus production of and membrane damage are major mechanisms of the bactericidal activity of these copper oxide nanoparticles. Finally it was concluded that antibacterial activity of nanoparticles depend on physicochemical properties of copper oxide nanoparticles and bacterial strain.« less

Highly Enantioselective Synthesis of syn-β-Hydroxy α-Dibenzylamino Esters via DKR Asymmetric Transfer Hydrogenation and Gram-Scale Preparation of Droxidopa.

PubMed

Sun, Guodong; Zhou, Zihong; Luo, Zhonghua; Wang, Hailong; Chen, Lei; Xu, Yongbo; Li, Shun; Jian, Weilin; Zeng, Jiebin; Hu, Benquan; Han, Xiaodong; Lin, Yicao; Wang, Zhongqing

2017-08-18

A highly efficient preparation of enantiomerically pure syn aryl β-hydroxy α-dibenzylamino esters is reported. The outcome was achieved via dynamic kinetic resolution and asymmetric transfer hydrogenation of aryl α-dibenzylamino β-keto esters. The desired products were obtained in high yields (up to 98%) with excellent diastereoselectivity (>20:1 dr) and enantioselectivity (up to >99% ee). Furthermore, this method was applied for the gram-scale preparation of droxidopa.

Biomolecule Sequencer: Next-Generation DNA Sequencing Technology for In-Flight Environmental Monitoring, Research, and Beyond

NASA Technical Reports Server (NTRS)

Smith, David J.; Burton, Aaron; Castro-Wallace, Sarah; John, Kristen; Stahl, Sarah E.; Dworkin, Jason Peter; Lupisella, Mark L.

2016-01-01

On the International Space Station (ISS), technologies capable of rapid microbial identification and disease diagnostics are not currently available. NASA still relies upon sample return for comprehensive, molecular-based sample characterization. Next-generation DNA sequencing is a powerful approach for identifying microorganisms in air, water, and surfaces onboard spacecraft. The Biomolecule Sequencer payload, manifested to SpaceX-9 and scheduled on the Increment 4748 research plan (June 2016), will assess the functionality of a commercially-available next-generation DNA sequencer in the microgravity environment of ISS. The MinION device from Oxford Nanopore Technologies (Oxford, UK) measures picoamp changes in electrical current dependent on nucleotide sequences of the DNA strand migrating through nanopores in the system. The hardware is exceptionally small (9.5 x 3.2 x 1.6 cm), lightweight (120 grams), and powered only by a USB connection. For the ISS technology demonstration, the Biomolecule Sequencer will be powered by a Microsoft Surface Pro3. Ground-prepared samples containing lambda bacteriophage, Escherichia coli, and mouse genomic DNA, will be launched and stored frozen on the ISS until experiment initiation. Immediately prior to sequencing, a crew member will collect and thaw frozen DNA samples, connect the sequencer to the Surface Pro3, inject thawed samples into a MinION flow cell, and initiate sequencing. At the completion of the sequencing run, data will be downlinked for ground analysis. Identical, synchronous ground controls will be used for data comparisons to determine sequencer functionality, run-time sequence, current dynamics, and overall accuracy. We will present our latest results from the ISS flight experiment the first time DNA has ever been sequenced in space and discuss the many potential applications of the Biomolecule Sequencer for environmental monitoring, medical diagnostics, higher fidelity and more adaptable Space Biology Human Research Program investigations, and even life detection experiments for astrobiology missions.

ProXL (Protein Cross-Linking Database): A Platform for Analysis, Visualization, and Sharing of Protein Cross-Linking Mass Spectrometry Data

PubMed Central

2016-01-01

ProXL is a Web application and accompanying database designed for sharing, visualizing, and analyzing bottom-up protein cross-linking mass spectrometry data with an emphasis on structural analysis and quality control. ProXL is designed to be independent of any particular software pipeline. The import process is simplified by the use of the ProXL XML data format, which shields developers of data importers from the relative complexity of the relational database schema. The database and Web interfaces function equally well for any software pipeline and allow data from disparate pipelines to be merged and contrasted. ProXL includes robust public and private data sharing capabilities, including a project-based interface designed to ensure security and facilitate collaboration among multiple researchers. ProXL provides multiple interactive and highly dynamic data visualizations that facilitate structural-based analysis of the observed cross-links as well as quality control. ProXL is open-source, well-documented, and freely available at https://github.com/yeastrc/proxl-web-app. PMID:27302480

ProXL (Protein Cross-Linking Database): A Platform for Analysis, Visualization, and Sharing of Protein Cross-Linking Mass Spectrometry Data.

PubMed

Riffle, Michael; Jaschob, Daniel; Zelter, Alex; Davis, Trisha N

2016-08-05

ProXL is a Web application and accompanying database designed for sharing, visualizing, and analyzing bottom-up protein cross-linking mass spectrometry data with an emphasis on structural analysis and quality control. ProXL is designed to be independent of any particular software pipeline. The import process is simplified by the use of the ProXL XML data format, which shields developers of data importers from the relative complexity of the relational database schema. The database and Web interfaces function equally well for any software pipeline and allow data from disparate pipelines to be merged and contrasted. ProXL includes robust public and private data sharing capabilities, including a project-based interface designed to ensure security and facilitate collaboration among multiple researchers. ProXL provides multiple interactive and highly dynamic data visualizations that facilitate structural-based analysis of the observed cross-links as well as quality control. ProXL is open-source, well-documented, and freely available at https://github.com/yeastrc/proxl-web-app .

The lipid A of Burkholderia multivorans C1576 smooth-type lipopolysaccharide and its pro-inflammatory activity in a cystic fibrosis airways model.

PubMed

Ieranò, Teresa; Cescutti, Paola; Leone, Maria Rosaria; Luciani, Alessandro; Rizzo, Roberto; Raia, Valeria; Lanzetta, Rosa; Parrilli, Michelangelo; Maiuri, Luigi; Silipo, Alba; Molinaro, Antonio

2010-12-01

Cystic fibrosis is an autosomal recessive disorder and it is characterised by chronic bacterial airway infection which leads to progressive lung deterioration, sometimes with fatal outcome. Burkholderia multivorans and Burkholderia cenocepacia are the species responsible for most of the infections of cystic fibrosis patients. Lipopolysaccharide endotoxins (LPSs) are among the foremost factors of pathogenesis of Gram-negative infection and, in particular, lipid A is the endotoxic portion of LPS responsible for eliciting host innate immune response. In this work, the complete primary structure of the lipid A from B. multivorans C1576 has been defined and, further, its pro-inflammatory activity in a cystic fibrosis airways model is shown. The structure of B. multivorans lipid A was attained by chemical, mass spectrometry and nuclear magnetic resonance analyses whereas its biological activity was assessed on the intestinal epithelial cell line CACO-2 cells, on the airway epithelial IB3-1 cells, carrying the ΔF508/W1282X CFTR mutation and on an ex vivo model of culture explants of nasal polyps.

Functional characterization of bovine TIRAP and MyD88 in mediating bacterial lipopolysaccharide-induced endothelial NF-kappaB activation and apoptosis.

PubMed

Cates, Elizabeth A; Connor, Erin E; Mosser, David M; Bannerman, Douglas D

2009-11-01

Mastitis is a prevalent disease in dairy cows. Gram-negative bacteria, which express the pro-inflammatory molecule lipopolysaccharide (LPS), are responsible for the majority of acute clinical cases of mastitis. Previous studies have identified differential susceptibility of human and bovine endothelial cells (EC) to the pro-inflammatory and injury-inducing effects of LPS. The Toll-like receptor (TLR)-4 signaling pathway, which is activated by LPS, has been well studied in humans, but not in ruminants. Human myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-kappaB and apoptotic signaling pathways. To assess the role of the bovine orthologs of these proteins in bovine TLR-4 signaling, dominant-negative constructs were expressed in bovine EC, and LPS-induced NF-kappaB activation and apoptosis evaluated. The results from this study indicate that bovine MyD88 and TIRAP play functional roles in transducing LPS signaling from TLR-4 to downstream effector molecules involved in NF-kappaB activation, and that TIRAP promotes apoptotic signaling.

Tyrocidine A Analogues Bearing the Planar d-Phe-2-Abz Turn Motif: How Conformation Impacts Bioactivity.

PubMed

Cameron, Alan J; Edwards, Patrick J B; Harjes, Elena; Sarojini, Vijayalekshmi

2017-12-14

The d-Phe-Pro β-turn of the cyclic β-hairpin antimicrobial decapeptide tyrocidine A, (Tyrc A) was substituted with the d-Phe-2-aminobenzoic acid (2-Abz) motif in a synthetic analogue (1). The NMR structure of 1 demonstrated that compound 1 retained the β-hairpin structure of Tyrc A with additional planarity, resulting in approximately 30-fold reduced hemolysis than Tyrc A. Although antibacterial activity was partially compromised, a single Gln to Lys substitution (2) restored activity equivalent to Tyrc A against S. aureus, enhanced activity against two Gram negative strains and maintained the reduced hemeloysis of 1. Analysis by transmission electron microscopy (TEM) suggested a membrane lytic mechanism of action for these peptides. Compound 2 also exhibits nanomolar antifungal activity in synergy with amphotericin B. The d-Phe-2-Abz turn may serve as a tool for the synthesis of structurally predictable β-hairpin libraries. Unlike traditional β-turn motifs such as d-Pro-Gly, both the 2-Abz and d-Phe rings may be further functionalized.

Inhibitor Bound Dengue NS2B-NS3pro Reveals Multiple Dynamic Binding Modes.

PubMed

Gibbs, Alan C; Steele, Ruth; Liu, Gaohua; Tounge, Brett A; Montelione, Gaetano T

2018-03-13

Dengue virus poses a significant global health threat as the source of increasingly deleterious dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. As no specific antiviral treatment exists for dengue infection, considerable effort is being applied to discover therapies and drugs for maintenance and prevention of these afflictions. The virus is primarily transmitted by mosquitoes, and infection occurs following viral endocytosis by host cells. Upon entering the cell, viral RNA is translated into a large multisubunit polyprotein which is post-translationally cleaved into mature, structural and nonstructural (NS) proteins. The viral genome encodes the enzyme to carry out cleavage of the large polyprotein, specifically the NS2B-NS3pro cofactor-protease complex-a target of high interest for drug design. One class of recently discovered NS2B-NS3pro inhibitors is the substrate-based trifluoromethyl ketone containing peptides. These compounds interact covalently with the active site Ser135 via a hemiketal adduct. A detailed picture of the intermolecular protease/inhibitor interactions of the hemiketal adduct is crucial for rational drug design. We demonstrate, through the use of protein- and ligand-detected solution-state 19 F and 1 H NMR methods, an unanticipated multibinding mode behavior of a representative of this class of inhibitors to dengue NS2B-NS3pro. Our results illustrate the highly dynamic nature of both the covalently bound ligand and protease protein structure, and the need to consider these dynamics when designing future inhibitors in this class.

Molecular Level Characterization of the Structure and Interactions in Peptide-Functionalized Metal-Organic Frameworks.

PubMed

Todorova, Tanya K; Rozanska, Xavier; Gervais, Christel; Legrand, Alexandre; Ho, Linh N; Berruyer, Pierrick; Lesage, Anne; Emsley, Lyndon; Farrusseng, David; Canivet, Jérôme; Mellot-Draznieks, Caroline

2016-11-07

We use density functional theory, newly parameterized molecular dynamics simulations, and last generation 15 N dynamic nuclear polarization surface enhanced solid-state NMR spectroscopy (DNP SENS) to understand graft-host interactions and effects imposed by the metal-organic framework (MOF) host on peptide conformations in a peptide-functionalized MOF. Focusing on two grafts typified by MIL-68-proline (-Pro) and MIL-68-glycine-proline (-Gly-Pro), we identified the most likely peptide conformations adopted in the functionalized hybrid frameworks. We found that hydrogen bond interactions between the graft and the surface hydroxyl groups of the MOF are essential in determining the peptides conformation(s). DNP SENS methodology shows unprecedented signal enhancements when applied to these peptide-functionalized MOFs. The calculated chemical shifts of selected MIL-68-NH-Pro and MIL-68-NH-Gly-Pro conformations are in a good agreement with the experimentally obtained 15 N NMR signals. The study shows that the conformations of peptides when grafted in a MOF host are unlikely to be freely distributed, and conformational selection is directed by strong host-guest interactions. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dynamic NETosis is Carried Out by Live Neutrophils in Human and Mouse Bacterial Abscesses and During Severe Gram-Positive Infection

PubMed Central

Yipp, Bryan G.; Petri, Björn; Salina, Davide; Jenne, Craig N.; Scott, Brittney N. V.; Zbytnuik, Lori D.; Pittman, Keir; Asaduzzaman, Muhammad; Wu, Kaiyu; Meijndert, H. Christopher; Malawista, Stephen E.; de Boisfleury Chevance, Anne; Zhang, Kunyan; Conly, John; Kubes, Paul

2013-01-01

Neutrophil extracellular traps (NETs) are released, as neutrophils die in vitro, in a process requiring hours, leaving a temporal gap for invasive microbes to exploit. Functional neutrophils undergoing NETosis have not been documented. During Gram-positive skin infections, we directly visualized live PMN in vivo rapidly releasing NETs, which prevented bacterial dissemination. NETosis occurred during crawling thereby casting large areas of NETs. NET-releasing PMN developed diffuse decondensed nuclei ultimately becoming devoid of DNA. Cells with abnormal nuclei displayed unusual crawling behavior highlighted by erratic pseudopods and hyperpolarization consistent with the nucleus being a fulcrum for crawling. A combined requirement of Tlr2 and complement mediated opsonization tightly regulated NET release. Additionally live human PMN developed decondensed nuclei and formed NETS in vivo and intact anuclear neutrophils were abundant in Gram-positive human abscesses. Therefore early in infection, non-cell death NETosis occurs in vivo during Gram-positive infection in mice and humans. PMID:22922410

Site-Specific Dynamics of β-Sheet Peptides with (D) Pro-Gly Turns Probed by Laser-Excited Temperature-Jump Infrared Spectroscopy.

PubMed

Popp, Alexander; Scheerer, David; Chi, Heng; Keiderling, Timothy A; Hauser, Karin

2016-05-04

Turn residues and side-chain interactions play an important role for the folding of β-sheets. We investigated the conformational dynamics of a three-stranded β-sheet peptide ((D) P(D) P) and a two-stranded β-hairpin (WVYY-(D) P) by time-resolved temperature-jump (T-jump) infrared spectroscopy. Both peptide sequences contain (D) Pro-Gly residues that favor a tight β-turn. The three-stranded β-sheet (Ac-VFITS(D) PGKTYTEV(D) PGOKILQ-NH2 ) is stabilized by the turn sequences, whereas the β-hairpin (SWTVE(D) PGKYTYK-NH2 ) folding is assisted by both the turn sequence and hydrophobic cross-strand interactions. Relaxation times after the T-jump were monitored as a function of temperature and occur on a sub-microsecond time scale, (D) P(D) P being faster than WVYY-(D) P. The Xxx-(D) Pro tertiary amide provides a detectable IR band, allowing us to probe the dynamics site-specifically. The relative importance of the turn versus the intrastrand stability in β-sheet formation is discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Effects of several inhibitors of intracellular signaling on production of cytokines and signal proteins in RAW 264.7 cells cultivated with low dose ammonium].

PubMed

Novoselova, E G; Parfeniuk, S B; Glushkova, O V; Khrenov, M O; Novoselova, T V; Lunin, S M; Fesenko, E E

2012-01-01

Effects of four inhibitors of NF-kappaB, SAPK/JNK and TLR4 signaling, namely, inhibitor XII, SP600125, CLI-095 and Oxpapc on a macrophage response to low dose ammonium were studied in RAW 264.7 cells. Low dose ammonium induced pro-inflammatory response in cells as judged from enhanced production of TNF-alpha, IF-gamma, and IL-6, and by activation of signal cascades. The increase in production of cytokines, namely TNF, IFN, and IL-6, demonstrated that low-dose ammonium induced a pro-inflammatory cellular response. In addition, an activation of NF-kappaB and SAPK/JNK cascades, as well as enhancement of TLR4 expression was shown. Each of used inhibitors reduced to a variable degree the pro-inflammatory response of RAW 264.7 cells on chemical toxin by decreasing cytokine production. The inhibitor of NF-kappaB cascade, IKK Inhibitor XII, was more effective, and not only prevented the development of pro-inflammatory response induced by ammonium, but also decreased cytokine production below control values. The inhibitor of extra cellular domains of TLR2 and TLR4 (OxPAPC) had almost the same anti-inflammatory effect, and an addition of the inhibitor of JNK cascade (SP600125) to cell culture practically neutralized effect of ammonium ions by decreasing cytokine production to control level. Inhibitory analysis showed that activation of RAW 264.7 cells induced by chemical toxin coincide incompletely with intracellular signaling pathways that were early determined regarding macrophage's response to toxin from gram-negative bacteria. Nevertheless, application of the inhibitors defended RAW 264.7 from toxic effect of the low dose ammonium.

Spectroscopic analysis and molecular docking of imidazole derivatives and investigation of its reactive properties by DFT and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Thomas, Renjith; Hossain, Mossaraf; Mary, Y. Sheena; Resmi, K. S.; Armaković, Stevan; Armaković, Sanja J.; Nanda, Ashis Kumar; Ranjan, Vivek Kumar; Vijayakumar, G.; Van Alsenoy, C.

2018-04-01

Solvent-free synthesis pathway for obtaining two imidazole derivatives (2-chloro-1-(4-methoxyphenyl)-4,5-dimethyl-1H-imidazole (CLMPDI) and 1-(4-bromophenyl)-2-chloro-4,5-dimethyl-1H-imidazole (BPCLDI) has been reported in this work, followed by detailed experimental and computational spectroscopic characterization and reactivity study. Spectroscopic methods encompassed IR, FT-Raman and NMR techniques, with the mutual comparison of experimentally and computationally obtained results at DFT/B3LYP level of theory. Reactivity study based on DFT calculations encompassed molecular orbitals analysis, followed by calculations of molecular electrostatic potential (MEP) and average local ionization energy (ALIE) values, Fukui functions and bond dissociation energies (BDE). Additionally, the stability of title molecules in water has been investigated via molecular dynamics (MD) simulations, while interactivity with aspulvinonedimethylallyl transferase protein has been evaluated by molecular docking procedure. CLMPDI compound showed antimicrobial activity against all four bacterial strain in both gram positive and gram negative bacteria while, BPCLDI showed only in gram positive bacteria, Staphylococcus Aureus (MTCC1144). The first order hyperpolarizability of CLMPDI and BPCLDI are 20.15 and 6.10 times that of the standard NLO material urea.

High-throughput hydrophilic interaction chromatography coupled to tandem mass spectrometry for the optimized quantification of the anti-Gram-negatives antibiotic colistin A/B and its pro-drug colistimethate.

PubMed

Mercier, Thomas; Tissot, Fréderic; Gardiol, Céline; Corti, Natascia; Wehrli, Stéphane; Guidi, Monia; Csajka, Chantal; Buclin, Thierry; Couet, William; Marchetti, Oscar; Decosterd, Laurent A

2014-11-21

Colistin is a last resort's antibacterial treatment in critically ill patients with multi-drug resistant Gram-negative infections. As appropriate colistin exposure is the key for maximizing efficacy while minimizing toxicity, individualized dosing optimization guided by therapeutic drug monitoring is a top clinical priority. Objective of the present work was to develop a rapid and robust HPLC-MS/MS assay for quantification of colistin plasma concentrations. This novel methodology validated according to international standards simultaneously quantifies the microbiologically active compounds colistin A and B, plus the pro-drug colistin methanesulfonate (colistimethate, CMS). 96-well micro-Elution SPE on Oasis Hydrophilic-Lipophilic-Balanced (HLB) followed by direct analysis by Hydrophilic Interaction Liquid Chromatography (HILIC) with Ethylene Bridged Hybrid--BEH--Amide phase column coupled to tandem mass spectrometry allows a high-throughput with no significant matrix effect. The technique is highly sensitive (limit of quantification 0.014 and 0.006 μg/mL for colistin A and B), precise (intra-/inter-assay CV 0.6-8.4%) and accurate (intra-/inter-assay deviation from nominal concentrations -4.4 to +6.3%) over the clinically relevant analytical range 0.05-20 μg/mL. Colistin A and B in plasma and whole blood samples are reliably quantified over 48 h at room temperature and at +4°C (<6% deviation from nominal values) and after three freeze-thaw cycles. Colistimethate acidic hydrolysis (1M H2SO4) to colistin A and B in plasma was completed in vitro after 15 min of sonication while the pro-drug hydrolyzed spontaneously in plasma ex vivo after 4 h at room temperature: this information is of utmost importance for interpretation of analytical results. Quantification is precise and accurate when using serum, citrated or EDTA plasma as biological matrix, while use of heparin plasma is not appropriate. This new analytical technique providing optimized quantification in real-life conditions of the microbiologically active compounds colistin A and B offers a highly efficient tool for routine therapeutic drug monitoring aimed at individualizing drug dosing against life-threatening infections. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of the Levels of Pro-Inflammatory Cytokines Released in the Vastus Lateralis Muscle of Patients with Fibromyalgia and Healthy Controls during Contractions of the Quadriceps Muscle – A Microdialysis Study

PubMed Central

Christidis, Nikolaos; Ghafouri, Bijar; Larsson, Anette; Palstam, Annie; Mannerkorpi, Kaisa; Bileviciute-Ljungar, Indre; Löfgren, Monika; Bjersing, Jan; Kosek, Eva; Gerdle, Björn; Ernberg, Malin

2015-01-01

Objective Fibromyalgia is associated with central hyperexcitability, but it is suggested that peripheral input is important to maintain central hyperexcitability. The primary aim was to investigate the levels of pro-inflammatory cytokines released in the vastus lateralis muscle during repetitive dynamic contractions of the quadriceps muscle in patients with fibromyalgia and healthy controls. Secondarily, to investigate if the levels of pro-inflammatory cytokines were correlated with pain or fatigue during these repetitive dynamic contractions. Material and Methods 32 women with fibromyalgia and 32 healthy women (controls) participated in a 4 hour microdialysis session, to sample IL-1β, IL-6, IL-8, and TNF from the most painful point of the vastus lateralis muscle before, during and after 20 minutes of repeated dynamic contractions. Pain (visual analogue scale; 0–100) and fatigue Borg’s Rating of Perceived Exertion Scale; 6–20) were assessed before and during the entire microdialysis session. Results The repetitive dynamic contractions increased pain in the patients with fibromyalgia (P < .001) and induced fatigue in both groups (P < .001). Perceived fatigue was significantly higher among patients with fibromyalgia than controls (P < .001). The levels of IL-1β did not change during contractions in either group. The levels of TNF did not change during contractions in patients with fibromyalgia, but increased in controls (P < .001) and were significantly higher compared to patients with fibromyalgia (P = .033). The levels of IL-6 and IL-8 increased in both groups alike during and after contractions (P’s < .001). There were no correlations between pain or fatigue and cytokine levels after contractions. Conclusion There were no differences between patients with fibromyalgia and controls in release of pro-inflammatory cytokines, and no correlations between levels of pro-inflammatory cytokines and pain or fatigue. Thus, this study indicates that IL-1β, IL-6, IL-8, and TNF do not seem to play an important role in maintenance of muscle pain in fibromyalgia. PMID:26624891

Bacteriocins from Gram-Negative Bacteria: A Classification?

NASA Astrophysics Data System (ADS)

Rebuffat, Sylvie

Bacteria produce an arsenal of toxic peptides and proteins, which are termed bacteriocins and play a role in mediating the dynamics of microbial populations and communities. Bacteriocins from Gram-negative bacteria arise mainly from Enterobacteriaceae. They assemble into two main families: high molecular mass modular proteins (30-80 kDa) termed colicins and low molecular mass peptides (between 1 and 10 kDa) termed microcins. The production of colicins is mediated by the SOS response regulon, which plays a role in the response of many bacteria to DNA damages. Microcins are highly stable hydrophobic peptides that are produced under stress conditions, particularly nutrient depletion. Colicins and microcins are found essentially in Escherichia coli, but several other Gram-negative species also produce bacteriocin-like substances. This chapter presents the basis of a classification of colicins and microcins.

A mutational analysis and molecular dynamics simulation of quinolone resistance proteins QnrA1 and QnrC from Proteus mirabilis.

PubMed

Guo, Qinglan; Weng, Jingwei; Xu, Xiaogang; Wang, Minghua; Wang, Xiaoying; Ye, Xinyu; Wang, Wenning; Wang, Minggui

2010-10-08

The first report on the transferable, plasmid-mediated quinolone-resistance determinant qnrA1 was in 1998. Since then, qnr alleles have been discovered worldwide in clinical strains of Gram-negative bacilli. Qnr proteins confer quinolone resistance, and belong to the pentapeptide repeat protein (PRP) family. Several PRP crystal structures have been solved, but little is known about the functional significance of their structural arrangement. We conducted random and site-directed mutagenesis on qnrA1 and on qnrC, a newly identified quinolone-resistance gene from Proteus mirabilis. Many of the Qnr mutants lost their quinolone resistance function. The highly conserved hydrophobic Leu or Phe residues at the center of the pentapeptide repeats are known as i sites, and loss-of-function mutations included replacement of the i site hydrophobic residues with charged residues, replacing the i-2 site, N-terminal to the i residues, with bulky side-chain residues, introducing Pro into the β-helix coil, deletion of the N- and C-termini, and excision of a central coil. Molecular dynamics simulations and homology modeling demonstrated that QnrC overall adopts a stable β-helix fold and shares more similarities with MfpA than with other PRP structures. Based on homology modeling and molecular dynamics simulation, the dysfunctional point mutations introduced structural deformations into the quadrilateral β-helix structure of PRPs. Of the pentapeptides of QnrC, two-thirds adopted a type II β-turn, while the rest adopted type IV turns. A gap exists between coil 2 and coil 3 in the QnrC model structure, introducing a structural flexibility that is similar to that seen in MfpA. The hydrophobic core and the β-helix backbone conformation are important for maintaining the quinolone resistance property of Qnr proteins. QnrC may share structural similarity with MfpA.

Experimental verification of force fields for molecular dynamics simulations using Gly-Pro-Gly-Gly.

PubMed

Aliev, Abil E; Courtier-Murias, Denis

2010-09-30

Experimental NMR verification of MD simulations using 12 different force fields (AMBER, CHARMM, GROMOS, and OPLS-AA) and 5 different water models has been undertaken to identify reliable MD protocols for structure and dynamics elucidations of small open chain peptides containing Gly and Pro. A conformationally flexible tetrapeptide Gly-Pro-Gly-Gly was selected for NMR (3)J-coupling, chemical shift, and internuclear distance measurements, followed by their calculations using 2 μs long MD simulations in water. In addition, Ramachandran population maps for Pro-2 and Gly-3 residues of GPGG obtained from MD simulations were used for detailed comparisons with similar maps from the protein data bank (PDB) for large number of Gly and Pro residues in proteins. The MD simulations revealed strong dependence of the populations and geometries of preferred backbone and side chain conformations, as well as the time scales of the peptide torsional transitions on the force field used. On the basis of the analysis of the measured and calculated data, AMBER99SB is identified as the most reliable force field for reproducing NMR measured parameters, which are dependent on the peptide backbone and the Pro side chain geometries and dynamics. Ramachandran maps showing the dependence of conformational populations as a function of backbone ϕ/ψ angles for Pro-2 and Gly-3 residues of GPGG from MD simulations using AMBER99SB, AMBER03, and CHARMM were found to resemble similar maps for Gly and Pro residues from the PDB survey. Three force fields (AMBER99, AMBER99ϕ, and AMBER94) showed the least satisfactory agreement with both the solution NMR and the PDB survey data. The poor performance of these force fields is attributed to their propensity to overstabilize helical peptide backbone conformations at the Pro-2 and Gly-3 residues. On the basis of the similarity of the MD and PDB Ramachandran plots, the following sequence of transitions is suggested for the Gly backbone conformation: α(L) ⇆ β(PR) ⇆ β(S) ⇆ β(P) ⇆ α, where backbone secondary structures α(L) and α are associated with helices and turns, β(P) and β(PR) correspond to the left- and right-handed polyproline II structures and β(S) denotes the fully stretched backbone conformation. Compared to the force field dependence, less significant, but noteworthy, variations in the populations of the peptide backbone conformations were observed. For different solvent models considered, a correlation was noted between the number of torsional transitions in GPGG and the water self-diffusion coefficient on using TIP3P, TIP4P, and TIP5P models. In addition to MD results, we also report DFT derived Karplus relationships for Gly and Pro residues using B972 and B3LYP functionals.

Cell wall elongation mode in Gram-negative bacteria is determined by peptidoglycan architecture.

PubMed

Turner, Robert D; Hurd, Alexander F; Cadby, Ashley; Hobbs, Jamie K; Foster, Simon J

2013-01-01

Cellular integrity and morphology of most bacteria is maintained by cell wall peptidoglycan, the target of antibiotics essential in modern healthcare. It consists of glycan strands, cross-linked by peptides, whose arrangement determines cell shape, prevents lysis due to turgor pressure and yet remains dynamic to allow insertion of new material, and hence growth. The cellular architecture and insertion pattern of peptidoglycan have remained elusive. Here we determine the peptidoglycan architecture and dynamics during growth in rod-shaped Gram-negative bacteria. Peptidoglycan is made up of circumferentially oriented bands of material interspersed with a more porous network. Super-resolution fluorescence microscopy reveals an unexpected discontinuous, patchy synthesis pattern. We present a consolidated model of growth via architecture-regulated insertion, where we propose only the more porous regions of the peptidoglycan network that are permissive for synthesis.

Role of Mitochondria in Methamphetamine-Induced Dopaminergic Neurotoxicity: Involvement in Oxidative Stress, Neuroinflammation, and Pro-apoptosis-A Review.

PubMed

Shin, Eun-Joo; Tran, Hai-Quyen; Nguyen, Phuong-Tram; Jeong, Ji Hoon; Nah, Seung-Yeol; Jang, Choon-Gon; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2018-01-01

Methamphetamine (MA), an amphetamine-type psychostimulant, is associated with dopaminergic toxicity and has a high abuse potential. Numerous in vivo and in vitro studies have suggested that impaired mitochondria are critical in dopaminergic toxicity induced by MA. Mitochondria are important energy-producing organelles with dynamic nature. Evidence indicated that exposure to MA can disturb mitochondrial energetic metabolism by inhibiting the Krebs cycle and electron transport chain. Alterations in mitochondrial dynamic processes, including mitochondrial biogenesis, mitophagy, and fusion/fission, have recently been shown to contribute to dopaminergic toxicity induced by MA. Furthermore, it was demonstrated that MA-induced mitochondrial impairment enhances susceptibility to oxidative stress, pro-apoptosis, and neuroinflammation in a positive feedback loop. Protein kinase Cδ has emerged as a potential mediator between mitochondrial impairment and oxidative stress, pro-apoptosis, or neuroinflammation in MA neurotoxicity. Understanding the role and underlying mechanism of mitochondrial impairment could provide a molecular target to prevent or alleviate dopaminergic toxicity induced by MA.

Dynamic Gaming Platform (DGP)

DTIC Science & Technology

2009-04-01

GAMING PLATFORM (DGP) Lockheed Martin Corporation...YYYY) APR 09 2. REPORT TYPE Final 3. DATES COVERED (From - To) Jul 07 – Mar 09 4. TITLE AND SUBTITLE DYNAMIC GAMING PLATFORM (DGP) 5a...CMU Carnegie Mellon University DGP Dynamic Gaming Platform GA Genetic Algorithm IARPA Intelligence Advanced Research Projects Activity LM ATL Lockheed Martin Advanced Technology Laboratories PAINT ProActive INTelligence

Project CHECO Southeast Asia Report. Rolling Thunder

DTIC Science & Technology

1966-03-28

interdiction pro- grams. In February the USAF bad 18 F-100 ’s and 18 F-105 ’s at ))a Nang, 18 F-105’s at Korat , 18 F-lOO’s at Takhli and eight B-57’s at Bien...force back to its November 1964 strength. In Thailand, the F-105 squadron at Korat was joined in early February by two more squadrons of F-l.05’s, one...135) Ubon 45th Tactical Figbter Squadron Takhli 35th ’l."FS (F-105~ 563rd ’fFS (F-105 Korat 357th ’l."FS (F-105) 12th TJ’S (F-105) Udorn 15th

Managing Stigma: Disclosure-Response Communication Patterns in Pro-Anorexic Websites.

PubMed

Chang, Pamara F; Bazarova, Natalya N

2016-01-01

Pro-anorexic websites are a popular online venue for individuals with anorexia, but recent research suggests that they play a role of "online negative enabling support groups" because they can undermine recovery and encourage negative behaviors by validating pro-anorexic views. By analyzing 22,811 messages from 5,590 conversations from the Pro-Ana Nation online discussion board forum, this study examines communicative mechanisms of online negative enabling support through language analysis of disclosure-response sequences, changes in the language of the initial discloser within an interaction exchange, and the role of responses in eliciting those changes. The findings show that initiating disclosures containing stigma-related emotion words, anorexia-specific content, and sociorelational content are typically met with negatively valenced responses from other members of the pro-anorexic community. Moreover, although the act of revealing stigmatized information has some cathartic effects, disclosers use more, not fewer, stigma-related emotion words when they receive negatively valenced responses. These results provide insight into communicative dynamics and effects of online negative enabling support through validation of the pro-anorexic identity and the dangerous cycle of stigma escalation in disclosure-response exchanges on pro-anorexic online communities.

Characterization of molecular interactions between Zika virus protease and peptides derived from the C-terminus of NS2B.

PubMed

Li, Yan; Loh, Ying Ru; Hung, Alvin W; Kang, CongBao

2018-06-21

Zika virus (ZIKV) protease is a two-component complex in which NS3 contains the catalytic triad and NS2B cofactor region is important for protease folding and activity. A protease construct-eZiPro without the transmembrane domains of NS2B was designed. Structural study on eZiPro reveals that the Thr-Gly-Lys-Arg (TGKR) sequence at the C-terminus of NS2B binds to the active site after cleavage. The bZiPro construct only contains NS2B cofactor region and the N-terminus of NS3 without any artificial linker or protease cleavage site, giving rise to an empty pocket accessible to substrate and inhibitor binding. Herein, we demonstrate that the TGKR sequence of NS2B in eZiPro is dynamic. Peptides from NS2B with various lengths exhibit different binding affinities to bZiPro. TGKR binding to the active site in eZiPro does not affect protease binding to small-molecule compounds. Our results suggest that eZiPro will also be useful for evaluating small-molecule protease inhibitors. Copyright © 2018 Elsevier Inc. All rights reserved.

Combined use of susceptibility weighted magnetic resonance imaging sequences and dynamic susceptibility contrast perfusion weighted imaging to improve the accuracy of the differential diagnosis of recurrence and radionecrosis in high-grade glioma patients.

PubMed

Kim, Tae-Hyung; Yun, Tae Jin; Park, Chul-Kee; Kim, Tae Min; Kim, Ji-Hoon; Sohn, Chul-Ho; Won, Jae Kyung; Park, Sung-Hye; Kim, Il Han; Choi, Seung Hong

2017-03-21

Purpose was to assess predictive power for overall survival (OS) and diagnostic performance of combination of susceptibility-weighted MRI sequences (SWMRI) and dynamic susceptibility contrast (DSC) perfusion-weighted imaging (PWI) for differentiation of recurrence and radionecrosis in high-grade glioma (HGG). We enrolled 51 patients who underwent radiation therapy or gamma knife surgeryfollowed by resection for HGG and who developed new measurable enhancement more than six months after complete response. The lesions were confirmed as recurrence (n = 32) or radionecrosis (n = 19). The mean and each percentile value from cumulative histograms of normalized CBV (nCBV) and proportion of dark signal intensity on SWMRI (proSWMRI, %) within enhancement were compared. Multivariate regression was performed for the best differentiator. The cutoff value of best predictor from ROC analysis was evaluated. OS was determined with Kaplan-Meier method and log-rank test. Recurrence showed significantly lower proSWMRI and higher mean nCBV and 90th percentile nCBV (nCBV90) than radionecrosis. Regression analysis revealed both nCBV90 and proSWMRI were independent differentiators. Combination of nCBV90 and proSWMRI achieved 71.9% sensitivity (23/32), 100% specificity (19/19) and 82.3% accuracy (42/51) using best cut-off values (nCBV90 > 2.07 and proSWMRI≤15.76%) from ROC analysis. In subgroup analysis, radionecrosis with nCBV > 2.07 (n = 5) showed obvious hemorrhage (proSWMRI > 32.9%). Patients with nCBV90 > 2.07 and proSWMRI≤15.76% had significantly shorter OS. In conclusion, compared with DSC PWI alone, combination of SWMRI and DSC PWI have potential to be prognosticator for OS and lower false positive rate in differentiation of recurrence and radionecrosis in HGG who develop new measurable enhancement more than six months after complete response.

The CD4+ T cell regulatory network mediates inflammatory responses during acute hyperinsulinemia: a simulation study.

PubMed

Martinez-Sanchez, Mariana E; Hiriart, Marcia; Alvarez-Buylla, Elena R

2017-06-26

Obesity is frequently linked to insulin resistance, high insulin levels, chronic inflammation, and alterations in the behaviour of CD4+ T cells. Despite the biomedical importance of this condition, the system-level mechanisms that alter CD4+ T cell differentiation and plasticity are not well understood. We model how hyperinsulinemia alters the dynamics of the CD4+ T regulatory network, and this, in turn, modulates cell differentiation and plasticity. Different polarizing microenvironments are simulated under basal and high levels of insulin to assess impacts on cell-fate attainment and robustness in response to transient perturbations. In the presence of high levels of insulin Th1 and Th17 become more stable to transient perturbations, and their basin sizes are augmented, Tr1 cells become less stable or disappear, while TGFβ producing cells remain unaltered. Hence, the model provides a dynamic system-level framework and explanation to further understand the documented and apparently paradoxical role of TGFβ in both inflammation and regulation of immune responses, as well as the emergence of the adipose Treg phenotype. Furthermore, our simulations provide new predictions on the impact of the microenvironment in the coexistence of the different cell types, suggesting that in pro-Th1, pro-Th2 and pro-Th17 environments effector and regulatory cells can coexist, but that high levels of insulin severely diminish regulatory cells, especially in a pro-Th17 environment. This work provides a first step towards a system-level formal and dynamic framework to integrate further experimental data in the study of complex inflammatory diseases.

Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4.

PubMed

Asea, Alexzander; Rehli, Michael; Kabingu, Edith; Boch, Jason A; Bare, Olivia; Auron, Philip E; Stevenson, Mary Ann; Calderwood, Stuart K

2002-04-26

Recent studies have initiated a paradigm shift in the understanding of the function of heat shock proteins (HSP). It is now clear that HSP can and do exit mammalian cells, interact with cells of the immune system, and exert immunoregulatory effects. We recently demonstrated that exogenously added HSP70 possesses potent cytokine activity, with the ability to bind with high affinity to the plasma membrane, elicit a rapid intracellular Ca(2+) flux, activate NF-kappaB, and up-regulate the expression of pro-inflammatory cytokines in human monocytes. Here for the first time, we report that HSP70-induced proinflammatory cytokine production is mediated via the MyD88/IRAK/NF-kappaB signal transduction pathway and that HSP70 utilizes both TLR2 (receptor for Gram-positive bacteria) and TLR4 (receptor for Gram-negative bacteria) to transduce its proinflammatory signal in a CD14-dependent fashion. These studies now pave the way for the development of highly effective pharmacological or molecular tools that will either up-regulate or suppress HSP70-induced functions in conditions where HSP70 effects are desirable (cancer) or disorders where HSP70 effects are undesirable (arthritis and arteriosclerosis).

Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes

PubMed Central

Gillette, Devyn D.; Curry, Heather M.; Cremer, Thomas; Ravneberg, David; Fatehchand, Kavin; Shah, Prexy A.; Wewers, Mark D.; Schlesinger, Larry S.; Butchar, Jonathan P.; Tridandapani, Susheela; Gavrilin, Mikhail A.

2014-01-01

Background: Human monocyte inflammatory responses differ between virulent and attenuated Francisella infection. Results: A mixed infection model showed that the virulent F. tularensis Schu S4 can attenuate inflammatory cytokine responses to the less virulent F. novicida in human monocytes. Conclusion: F. tularensis dampens inflammatory response by an active process. Significance: This suppression may contribute to enhanced pathogenicity of F. tularensis. Francisella tularensis is a Gram-negative facultative bacterium that can cause the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. Previous work has shown that monocytes infected with highly virulent F. tularensis subsp. tularensis strain Schu S4 responded with a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes and cytokine production in comparison to those infected with the less virulent related F. novicida. However, it has been unclear whether the virulent Schu S4 was merely evading or actively suppressing monocyte responses. By using mixed infection assays with F. tularensis and F. novicida, we show that F. tularensis actively suppresses monocyte pro-inflammatory responses. Additional experiments show that this suppression occurs in a dose-dependent manner and is dependent upon the viability of F. tularensis. Importantly, F. tularensis was able to suppress pro-inflammatory responses to earlier infections with F. novicida. These results lend support that F. tularensis actively dampens human monocyte responses and this likely contributes to its enhanced pathogenicity. PMID:24783062

Interdisciplinary Discrepancies Between Parenteral Nutrition Macronutrient Prescribing and Recommendations: Is Body Mass Index a Factor?

PubMed

Elliott, Katie L; Kandiah, Jay; Walroth, Todd A

2017-07-01

Formal nutrition training in medical schools and residencies is lacking and needed. Registered dietitians (RDs) are formally trained in nutrition support and considered experts in the nutrition field. Our purpose was to examine prescribing and recommending discrepancies of parenteral nutrition macronutrients between medical residents (MRs) and RDs and compare results with the ASPEN clinical care guidelines. We also looked at discrepancies among obese patients, due to their increased risk of mortality. The primary end point of this retrospective review was discrepancies in nonprotein calories (NPCs) and grams of protein (PRO) between MRs and RDs. The secondary end point was discrepancies in NPCs and PRO between MRs and RDs among patients stratified by body mass index category. MRs prescribed 300 NPCs more versus RDs ( P < .001). When compared with RDs, MRs prescribed fewer NPCs for underweight patients and more for obese patients ( P < .001). The same analysis found that the PRO discrepancies significantly varied by body mass index classification as well ( P = .022). When these results were compared with the ASPEN clinical care guidelines, RDs adhered closer to the guidelines than did MRs in terms of permissive underfeeding of obese patients. It is widely accepted that MRs are in need of increased formal training, and the results of our study confirm this need and suggest a short-term solution of increasing order-writing privileges for the RD. RDs with this privilege may adhere more closely to clinical care guidelines and therefore increase patient safety.

Efficient Conformational Sampling in Explicit Solvent Using a Hybrid Replica Exchange Molecular Dynamics Method

DTIC Science & Technology

2011-12-01

REMD while reproducing the energy landscape of explicit solvent simulations . ’ INTRODUCTION Molecular dynamics (MD) simulations of proteins can pro...Mongan, J.; McCammon, J. A. Accelerated molecular dynamics : a promising and efficient simulation method for biomolecules. J. Chem. Phys. 2004, 120 (24...Chemical Theory and Computation ARTICLE (8) Abraham,M. J.; Gready, J. E. Ensuringmixing efficiency of replica- exchange molecular dynamics simulations . J

Cyberspace: A Selected Bibliography

DTIC Science & Technology

2013-05-01

Implications of the Private Sector’s Role in Cyber Conflict." Texas International Law Journal 47, no. 3 (Summer 2012): 617-640. ProQuest Lucas, George R...Cyberspace." Proceedings: United States Naval Institute 137, no. 2 (February 2011): 32-37. ProQuest Lin, Herbert . "Escalation Dynamics and Conflict...Harold Hongju. "International Law in Cyberspace." USCYBERCOM [United States Cyber Command] Inter-Agency Legal Conference, Ft. Meade , MD, September 18

Parameterization of the proline analogue Aze (azetidine-2-carboxylic acid) for molecular dynamics simulations and evaluation of its effect on homo-pentapeptide conformations.

PubMed

Bessonov, Kyrylo; Vassall, Kenrick A; Harauz, George

2013-02-01

We have parameterized and evaluated the proline homologue Aze (azetidine-2-carboxylic acid) for the gromos56a3 force-field for use in molecular dynamics simulations using GROMACS. Using bi-phasic cyclohexane/water simulation systems and homo-pentapeptides, we measured the Aze solute interaction potential energies, ability to hydrogen bond with water, and overall compaction, for comparison to Pro, Gly, and Lys. Compared to Pro, Aze has a slightly higher H-bonding potential, and stronger electrostatic but weaker non-electrostatic interactions with water. The 20-ns simulations revealed the preferential positioning of Aze and Pro at the interface of the water and cyclohexane layers, with Aze spending more time in the aqueous layer. We also demonstrated through simulations of the homo-pentapeptides that Aze has a greater propensity than Pro to undergo trans→cis peptide bond isomerization, which results in a severe 180° bend in the polypeptide chain. The results provide evidence for the hypothesis that the misincorporation of Aze within proline-rich regions of proteins could disrupt the formation of poly-proline type II structures and compromise events such as recognition and binding by SH3-domains. Copyright © 2012 Elsevier Inc. All rights reserved.

Do we harm others even if we don't need to?

PubMed Central

Cacault, M. Paula; Goette, Lorenz; Lalive, Rafael; Thoenig, Mathias

2015-01-01

Evolutionary explanations of the co-existence of large-scale cooperation and warfare in human societies rest on the hypothesis of parochial altruism, the view that in-group pro-sociality and out-group anti-sociality have co-evolved. We designed an experiment that allows subjects to freely choose between actions that are purely pro-social, purely anti-social, or a combination of the two. We present behavioral evidence on the existence of strong aggression—a pattern of non-strategic behaviors that are welfare-reducing for all individuals (i.e., victims and perpetrators). We also show how strong aggression serves to dynamically stabilize in-group pro-sociality. PMID:26082737

Thr729 in human topoisomerase I modulates anti-cancer drug resistance by altering protein domain communications as suggested by molecular dynamics simulations.

PubMed

Chillemi, Giovanni; D'Annessa, Ilda; Fiorani, Paola; Losasso, Carmen; Benedetti, Piero; Desideri, Alessandro

2008-10-01

The role of Thr729 in modulating the enzymatic function of human topoisomerase I has been characterized by molecular dynamics (MD) simulation. In detail, the structural-dynamical behaviour of the Thr729Lys and the Thr729Pro mutants have been characterized because of their in vivo and in vitro functional properties evidenced in the accompanying paper. Both mutants can bind to the DNA substrate and are enzymatically active, but while Thr729Lys is resistant even at high concentration of the camptothecin (CPT) anti-cancer drug, Thr729Pro shows only a mild reduction in drug sensitivity and in DNA binding. MD simulations show that the Thr729Lys mutation provokes a structural perturbation of the CPT-binding pocket. On the other hand, the Thr729Pro mutant maintains the wild-type structural scaffold, only increasing its rigidity. The simulations also show the complete abolishment, in the Thr729Lys mutant, of the protein communications between the C-terminal domain (where the active Tyr723 is located) and the linker domain, that plays an essential role in the control of the DNA rotation, thus explaining the distributive mode of action displayed by this mutant.

Thr729 in human topoisomerase I modulates anti-cancer drug resistance by altering protein domain communications as suggested by molecular dynamics simulations

PubMed Central

Chillemi, Giovanni; D’Annessa, Ilda; Fiorani, Paola; Losasso, Carmen; Benedetti, Piero; Desideri, Alessandro

2008-01-01

The role of Thr729 in modulating the enzymatic function of human topoisomerase I has been characterized by molecular dynamics (MD) simulation. In detail, the structural–dynamical behaviour of the Thr729Lys and the Thr729Pro mutants have been characterized because of their in vivo and in vitro functional properties evidenced in the accompanying paper. Both mutants can bind to the DNA substrate and are enzymatically active, but while Thr729Lys is resistant even at high concentration of the camptothecin (CPT) anti-cancer drug, Thr729Pro shows only a mild reduction in drug sensitivity and in DNA binding. MD simulations show that the Thr729Lys mutation provokes a structural perturbation of the CPT-binding pocket. On the other hand, the Thr729Pro mutant maintains the wild-type structural scaffold, only increasing its rigidity. The simulations also show the complete abolishment, in the Thr729Lys mutant, of the protein communications between the C-terminal domain (where the active Tyr723 is located) and the linker domain, that plays an essential role in the control of the DNA rotation, thus explaining the distributive mode of action displayed by this mutant. PMID:18765473

Calculation of color difference and measurement of the spectrum of aerosol based on human visual system

NASA Astrophysics Data System (ADS)

Dai, Mengyan; Liu, Jianghai; Cui, Jianlin; Chen, Chunsheng; Jia, Peng

2017-10-01

In order to solve the problem of the quantitative test of spectrum and color of aerosol, the measurement method of spectrum of aerosol based on human visual system was proposed. The spectrum characteristics and color parameters of three different aerosols were tested, and the color differences were calculated according to the CIE1976-L*a*b* color difference formula. Three tested powders (No 1# No 2# and No 3# ) were dispersed in a plexglass box and turned into aerosol. The powder sample was released by an injector with different dosages in each experiment. The spectrum and color of aerosol were measured by the PRO 6500 Fiber Optic Spectrometer. The experimental results showed that the extinction performance of aerosol became stronger and stronger with the increase of concentration of aerosol. While the chromaticity value differences of aerosols in the experiment were so small, luminance was verified to be the main influence factor of human eye visual perception and contributed most in the three factors of the color difference calculation. The extinction effect of No 3# aerosol was the strongest of all and caused the biggest change of luminance and color difference which would arouse the strongest human visual perception. According to the sensation level of chromatic color by Chinese, recognition color difference would be produced when the dosage of No 1# powder was more than 0.10 gram, the dosage of No 2# powder was more than 0.15 gram, and the dosage of No 3# powder was more than 0.05 gram.

Design, synthesis, and biological evaluation of stable β6.3-Helices: Discovery of non-hemolytic antibacterial peptides.

PubMed

Reddy, Damodara N; Singh, Sukrit; Ho, Chris M W; Patel, Janki; Schlesinger, Paul; Rodgers, Stephen; Doctor, Allan; Marshall, Garland R

2018-04-10

Gramicidin A, a topical antibiotic made from alternating L and D amino acids, is characterized by its wide central pore; upon insertion into membranes, it forms channels that disrupts ion gradients. We present helical peptidomimetics with this characteristic wide central pore that have been designed to mimic gramicidin A channels. Mimetics were designed using molecular modeling focused on oligomers of heterochiral dipeptides of proline analogs, in particular azaproline (AzPro). Molecular Dynamics simulations in water confirmed the stability of the designed helices. A sixteen-residue Formyl-(AzPro-Pro) 8 -NHCH 2 CH 2 OH helix was synthesized as well as a full thirty-two residue Cbz-(AzPro-Pro) 16 -O t Bu channels. No liposomal lysis activity was observed suggesting lack of channel formation, possibly due to inappropriate hydrogen-bonding interactions in the membrane. These peptidomimetics also did not hemolyze red blood cells, unlike gramicidin A. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

PGLa-H tandem-repeat peptides active against multidrug resistant clinical bacterial isolates.

PubMed

Rončević, Tomislav; Gajski, Goran; Ilić, Nada; Goić-Barišić, Ivana; Tonkić, Marija; Zoranić, Larisa; Simunić, Juraj; Benincasa, Monica; Mijaković, Marijana; Tossi, Alessandro; Juretić, Davor

2017-02-01

Antimicrobial peptides (AMPs) are promising candidates for new antibiotic classes but often display an unacceptably high toxicity towards human cells. A naturally produced C-terminal fragment of PGLa, named PGLa-H, has been reported to have a very low haemolytic activity while maintaining a moderate antibacterial activity. A sequential tandem repeat of this fragment, diPGLa-H, was designed, as well as an analogue with a Val to Gly substitution at a key position. These peptides showed markedly improved in vitro bacteriostatic and bactericidal activity against both reference strains and multidrug resistant clinical isolates of Gram-negative and Gram-positive pathogens, with generally low toxicity for human cells as assessed by haemolysis, cell viability, and DNA damage assays. The glycine substitution analogue, kiadin, had a slightly better antibacterial activity and reduced haemolytic activity, which may correlate with an increased flexibility of its helical structure, as deduced using molecular dynamics simulations. These peptides may serve as useful lead compounds for developing anti-infective agents against resistant Gram-negative and Gram-positive species. Copyright © 2016 Elsevier B.V. All rights reserved.

Small Body GN and C Research Report: G-SAMPLE - An In-Flight Dynamical Method for Identifying Sample Mass [External Release Version

NASA Technical Reports Server (NTRS)

Carson, John M., III; Bayard, David S.

2006-01-01

G-SAMPLE is an in-flight dynamical method for use by sample collection missions to identify the presence and quantity of collected sample material. The G-SAMPLE method implements a maximum-likelihood estimator to identify the collected sample mass, based on onboard force sensor measurements, thruster firings, and a dynamics model of the spacecraft. With G-SAMPLE, sample mass identification becomes a computation rather than an extra hardware requirement; the added cost of cameras or other sensors for sample mass detection is avoided. Realistic simulation examples are provided for a spacecraft configuration with a sample collection device mounted on the end of an extended boom. In one representative example, a 1000 gram sample mass is estimated to within 110 grams (95% confidence) under realistic assumptions of thruster profile error, spacecraft parameter uncertainty, and sensor noise. For convenience to future mission design, an overall sample-mass estimation error budget is developed to approximate the effect of model uncertainty, sensor noise, data rate, and thrust profile error on the expected estimate of collected sample mass.

Propeptides are sufficient to regulate organelle-specific pH-dependent activation of furin and proprotein convertase 1/3.

PubMed

Dillon, Stephanie L; Williamson, Danielle M; Elferich, Johannes; Radler, David; Joshi, Rajendra; Thomas, Gary; Shinde, Ujwal

2012-10-12

The proprotein convertases (PCs) furin and proprotein convertase 1/3 (PC1) cleave substrates at dibasic residues along the eukaryotic secretory/endocytic pathway. PCs are evolutionarily related to bacterial subtilisin and are synthesized as zymogens. They contain N-terminal propeptides (PRO) that function as dedicated catalysts that facilitate folding and regulate activation of cognate proteases through multiple-ordered cleavages. Previous studies identified a histidine residue (His69) that functions as a pH sensor in the propeptide of furin (PRO(FUR)), which regulates furin activation at pH~6.5 within the trans-Golgi network. Although this residue is conserved in the PC1 propeptide (PRO(PC1)), PC1 nonetheless activates at pH~5.5 within the dense core secretory granules. Here, we analyze the mechanism by which PRO(FUR) regulates furin activation and examine why PRO(FUR) and PRO(PC1) differ in their pH-dependent activation. Sequence analyses establish that while both PRO(FUR) and PRO(PC1) are enriched in histidines when compared with cognate catalytic domains and prokaryotic orthologs, histidine content in PRO(FUR) is ~2-fold greater than that in PRO(PC1), which may augment its pH sensitivity. Spectroscopy and molecular dynamics establish that histidine protonation significantly unfolds PRO(FUR) when compared to PRO(PC1) to enhance autoproteolysis. We further demonstrate that PRO(FUR) and PRO(PC1) are sufficient to confer organelle sensing on folding and activation of their cognate proteases. Swapping propeptides between furin and PC1 transfers pH-dependent protease activation in a propeptide-dictated manner in vitro and in cells. Since prokaryotes lack organelles and eukaryotic PCs evolved from propeptide-dependent, not propeptide-independent prokaryotic subtilases, our results suggest that histidine enrichment may have enabled propeptides to evolve to exploit pH gradients to activate within specific organelles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Influence of Biochemical Features of Burkholderia pseudomallei Strains on Identification Reliability by Vitek 2 System.

PubMed

Zakharova, Irina B; Lopasteyskaya, Yana A; Toporkov, Andrey V; Viktorov, Dmitry V

2018-01-01

Burkholderia pseudomallei is a Gram-negative saprophytic soil bacterium that causes melioidosis, a potentially fatal disease endemic in wet tropical areas. The currently available biochemical identification systems can misidentify some strains of B. pseudomallei . The aim of the present study was to identify the biochemical features of B. pseudomallei , which can affect its correct identification by Vitek 2 system. The biochemical patterns of 40 B. pseudomallei strains were obtained using Vitek 2 GN cards. The average contribution of biochemical tests in overall dissimilarities between correctly and incorrectly identified strains was assessed using nonmetric multidimensional scaling. It was found ( R statistic of 0.836, P = 0.001) that a combination of negative N-acetyl galactosaminidase, β-N-acetyl glucosaminidase, phosphatase, and positive D-cellobiase (dCEL), tyrosine arylamidase (TyrA), and L-proline arylamidase (ProA) tests leads to low discrimination of B. pseudomallei , whereas a set of positive dCEL and negative N-acetyl galactosaminidase, TyrA, and ProA determines the wrong identification of B. pseudomallei as Burkholderia cepacia complex. The further expansion of the Vitek 2 identification keys is needed for correct identification of atypical or regionally distributed biochemical profiles of B. pseudomallei .

Biology of Three ICE Families: SXT/R391, ICEBs1, and ICESt1/ICESt3.

PubMed

Carraro, Nicolas; Burrus, Vincent

2014-12-01

Integrative and Conjugative Elements (ICEs) are bacterial mobile genetic elements that play a key role in bacterial genomes dynamics and evolution. ICEs are widely distributed among virtually all bacterial genera. Recent extensive studies have unraveled their high diversity and complexity. The present review depicts the general conserved features of ICEs and describes more precisely three major families of ICEs that have been extensively studied in the past decade for their biology, their evolution and their impact on genomes dynamics. First, the large SXT/R391 family of ICEs disseminates antibiotic resistance genes and drives the exchange of mobilizable genomic islands (MGIs) between many enteric pathogens such as Vibrio cholerae. Second, ICEBs1 of Bacillus subtilis is the most well understood ICE of Gram-positive bacteria, notably regarding the regulation of its dissemination and its initially unforeseen extrachromosomal replication, which could be a common feature of ICEs of both Gram-positive and Gram-negative bacteria. Finally, ICESt1 and ICESt3 of Streptococcus thermophilus are the prototypes of a large family of ICEs widely distributed among various streptococci. These ICEs carry an original regulation module that associates regulators related to those of both SXT/R391 and ICEBs1. Study of ICESt1 and ICESt3 uncovered the cis-mobilization of related genomic islands (CIMEs) by a mechanism called accretion-mobilization, which likely represents a paradigm for the evolution of many ICEs and genomic islands. These three major families of ICEs give a glimpse about ICEs dynamics and their high impact on bacterial adaptation.

Both the cis-trans equilibrium and isomerization dynamics of a single proline amide modulate β2-microglobulin amyloid assembly

PubMed Central

Torbeev, Vladimir Yu.; Hilvert, Donald

2013-01-01

The human protein β2-microglobulin (β2m) aggregates as amyloid fibrils in patients undergoing long-term hemodialysis. Isomerization of Pro32 from its native cis to a nonnative trans conformation is thought to trigger β2m misfolding and subsequent amyloid assembly. To examine this hypothesis, we systematically varied the free-energy profile of proline cis-trans isomerization by replacing Pro32 with a series of 4-fluoroprolines via total chemical synthesis. We show that β2m’s stability, (un)folding, and aggregation properties are all influenced by the rate and equilibrium of Pro32 cis-trans isomerization. As anticipated, the β2m monomer was either stabilized or destabilized by respective incorporation of (2S,4S)-fluoroproline, which favors the native cis amide bond, or the stereoisomeric (2S,4R)-fluoroproline, which disfavors this conformation. However, substitution of Pro32 with 4,4-difluoroproline, which has nearly the same cis-trans preference as proline but an enhanced isomerization rate, caused pronounced destabilization of the protein and increased oligomerization at neutral pH. More remarkably, these subtle alterations in chemical composition—incorporation of one or two fluorine atoms into a single proline residue in the 99 amino acid long protein—modulated the aggregation properties of β2m, inducing the formation of polymorphically distinct amyloid fibrils. These results highlight the importance of conformational dynamics for molecular assembly of an amyloid cross-β structure and provide insights into mechanistic aspects of Pro32 cis-trans isomerism in β2m aggregation. PMID:24262149

Both the cis-trans equilibrium and isomerization dynamics of a single proline amide modulate β2-microglobulin amyloid assembly.

PubMed

Torbeev, Vladimir Yu; Hilvert, Donald

2013-12-10

The human protein β2-microglobulin (β2m) aggregates as amyloid fibrils in patients undergoing long-term hemodialysis. Isomerization of Pro32 from its native cis to a nonnative trans conformation is thought to trigger β2m misfolding and subsequent amyloid assembly. To examine this hypothesis, we systematically varied the free-energy profile of proline cis-trans isomerization by replacing Pro32 with a series of 4-fluoroprolines via total chemical synthesis. We show that β2m's stability, (un)folding, and aggregation properties are all influenced by the rate and equilibrium of Pro32 cis-trans isomerization. As anticipated, the β2m monomer was either stabilized or destabilized by respective incorporation of (2S,4S)-fluoroproline, which favors the native cis amide bond, or the stereoisomeric (2S,4R)-fluoroproline, which disfavors this conformation. However, substitution of Pro32 with 4,4-difluoroproline, which has nearly the same cis-trans preference as proline but an enhanced isomerization rate, caused pronounced destabilization of the protein and increased oligomerization at neutral pH. More remarkably, these subtle alterations in chemical composition--incorporation of one or two fluorine atoms into a single proline residue in the 99 amino acid long protein--modulated the aggregation properties of β2m, inducing the formation of polymorphically distinct amyloid fibrils. These results highlight the importance of conformational dynamics for molecular assembly of an amyloid cross-β structure and provide insights into mechanistic aspects of Pro32 cis-trans isomerism in β2m aggregation.

ADP/ATP mitochondrial carrier MD simulations to shed light on the structural-dynamical events that, after an additional mutation, restore the function in a pathological single mutant.

PubMed

Di Marino, Daniele; Oteri, Francesco; Morozzo Della Rocca, Blasco; Chillemi, Giovanni; Falconi, Mattia

2010-12-01

Molecular dynamics simulations of the wild type bovine ADP/ATP mitochondrial carrier, and of the single Ala113Pro and double Ala113Pro/Val180Met mutants, embedded in a lipid bilayer, have been carried out for 30ns to shed light on the structural-dynamical changes induced by the Val180Met mutation restoring the carrier function in the Ala113Pro pathologic mutant. Principal component analysis indicates that, for the three systems, the protein dynamics is mainly characterized by the motion of the matrix loops and of the odd-numbered helices having a conserved proline in their central region. Analysis of the motions shows a different behaviour of single pathological mutant with respect of the other two systems. The single mutation induces a regularization and rigidity of the H3 helix, lost upon the introduction of the second mutation. This is directly correlated to the salt bridge distribution involving residues Arg79, Asp134 and Arg234, hypothesized to interact with the substrate. In fact, in the wild type simulation two stable inter-helices salt bridges, crucial for substrate binding, are present almost over all the simulation time. In line with the impaired ADP transport, one salt interaction is lost in the single mutant trajectory but reappears in the double mutant simulation, where a salt bridge network matching the wild type is restored. Other important structural-dynamical properties, such as the trans-membrane helices mobility, analyzed via the principal component analysis, are similar for the wild type and double mutant while are different for the single mutant, providing a mechanistic explanation for their different functional properties. Copyright © 2010 Elsevier Inc. All rights reserved.

Pro-Anorexia and Anti-Pro-Anorexia Videos on YouTube: Sentiment Analysis of User Responses.

PubMed

Oksanen, Atte; Garcia, David; Sirola, Anu; Näsi, Matti; Kaakinen, Markus; Keipi, Teo; Räsänen, Pekka

2015-11-12

Pro-anorexia communities exist online and encourage harmful weight loss and weight control practices, often through emotional content that enforces social ties within these communities. User-generated responses to videos that directly oppose pro-anorexia communities have not yet been researched in depth. The aim was to study emotional reactions to pro-anorexia and anti-pro-anorexia online content on YouTube using sentiment analysis. Using the 50 most popular YouTube pro-anorexia and anti-pro-anorexia user channels as a starting point, we gathered data on users, their videos, and their commentators. A total of 395 anorexia videos and 12,161 comments were analyzed using positive and negative sentiments and ratings submitted by the viewers of the videos. The emotional information was automatically extracted with an automatic sentiment detection tool whose reliability was tested with human coders. Ordinary least squares regression models were used to estimate the strength of sentiments. The models controlled for the number of video views and comments, number of months the video had been on YouTube, duration of the video, uploader's activity as a video commentator, and uploader's physical location by country. The 395 videos had more than 6 million views and comments by almost 8000 users. Anti-pro-anorexia video comments expressed more positive sentiments on a scale of 1 to 5 (adjusted prediction [AP] 2.15, 95% CI 2.11-2.19) than did those of pro-anorexia videos (AP 2.02, 95% CI 1.98-2.06). Anti-pro-anorexia videos also received more likes (AP 181.02, 95% CI 155.19-206.85) than pro-anorexia videos (AP 31.22, 95% CI 31.22-37.81). Negative sentiments and video dislikes were equally distributed in responses to both pro-anorexia and anti-pro-anorexia videos. Despite pro-anorexia content being widespread on YouTube, videos promoting help for anorexia and opposing the pro-anorexia community were more popular, gaining more positive feedback and comments than pro-anorexia videos. Thus, the anti-pro-anorexia content provided a user-generated counterforce against pro-anorexia content on YouTube. Professionals working with young people should be aware of the social media dynamics and versatility of user-generated eating disorder content online.

Pro-Anorexia and Anti-Pro-Anorexia Videos on YouTube: Sentiment Analysis of User Responses

PubMed Central

Garcia, David; Sirola, Anu; Näsi, Matti; Kaakinen, Markus; Keipi, Teo; Räsänen, Pekka

2015-01-01

Background Pro-anorexia communities exist online and encourage harmful weight loss and weight control practices, often through emotional content that enforces social ties within these communities. User-generated responses to videos that directly oppose pro-anorexia communities have not yet been researched in depth. Objective The aim was to study emotional reactions to pro-anorexia and anti-pro-anorexia online content on YouTube using sentiment analysis. Methods Using the 50 most popular YouTube pro-anorexia and anti-pro-anorexia user channels as a starting point, we gathered data on users, their videos, and their commentators. A total of 395 anorexia videos and 12,161 comments were analyzed using positive and negative sentiments and ratings submitted by the viewers of the videos. The emotional information was automatically extracted with an automatic sentiment detection tool whose reliability was tested with human coders. Ordinary least squares regression models were used to estimate the strength of sentiments. The models controlled for the number of video views and comments, number of months the video had been on YouTube, duration of the video, uploader’s activity as a video commentator, and uploader’s physical location by country. Results The 395 videos had more than 6 million views and comments by almost 8000 users. Anti-pro-anorexia video comments expressed more positive sentiments on a scale of 1 to 5 (adjusted prediction [AP] 2.15, 95% CI 2.11-2.19) than did those of pro-anorexia videos (AP 2.02, 95% CI 1.98-2.06). Anti-pro-anorexia videos also received more likes (AP 181.02, 95% CI 155.19-206.85) than pro-anorexia videos (AP 31.22, 95% CI 31.22-37.81). Negative sentiments and video dislikes were equally distributed in responses to both pro-anorexia and anti-pro-anorexia videos. Conclusions Despite pro-anorexia content being widespread on YouTube, videos promoting help for anorexia and opposing the pro-anorexia community were more popular, gaining more positive feedback and comments than pro-anorexia videos. Thus, the anti-pro-anorexia content provided a user-generated counterforce against pro-anorexia content on YouTube. Professionals working with young people should be aware of the social media dynamics and versatility of user-generated eating disorder content online. PMID:26563678

Mars-GRAM 2010: Additions and Resulting Improvements

NASA Technical Reports Server (NTRS)

Justh, Hilary L.; Burns, K. Lee

2013-01-01

The Mars Global Reference Atmospheric Model (Mars-GRAM) is an engineering-level atmospheric model widely used for diverse mission applications. Mars-GRAM has been utilized during previous aerobraking operations in the atmosphere of Mars. Mars-GRAM has also been used in the prediction and validation of Mars Pathfinder hypersonic aerodynamics, the aerothermodynamic and entry dynamics studies for Mars Polar Lander, the landing site selection process for the Mars Science Laboratory (MSL), the Mars Aerocapture System Study (MASS) as well as the Aerocapture Technology Assessment Group (TAG). Most recently, Mars-GRAM 2010 was used to develop the onboard atmospheric density estimator that is part of the Autonomous Aerobraking Development Plan. The most recent release of Mars-GRAM 2010 contains several changes including an update to Fortran 90/95 and the addition of adjustment factors. Following the completion of a comparison analysis between Mars-GRAM, Thermal Emission Spectrometer (TES), as well as Mars Global Surveyor (MGS), Mars Odyssey (ODY), and Mars Reconnaissance Orbiter (MRO) aerobraking density data, adjustment factors were added to Mars-GRAM 2010 that alter the input data from National Aeronautics and Space Administration (NASA) Ames Mars General Circulation Model (MGCM) and the University of Michigan Mars Thermospheric General Circulation Model (MTGCM) for the mapping year 0 user-controlled dust case. The addition of adjustment factors resolved the issue of previous versions of Mars-GRAM being less than realistic when used for sensitivity studies for mapping year 0 and large optical depth values, such as tau equal to 3. Mars-GRAM was evaluated at locations and times of TES limb observations and adjustment factors were determined. For altitudes above 80 km and below 135 km, Mars-GRAM (MTGCM) densities were compared to aerobraking densities measured by Mars Global Surveyor (MGS), Mars Odyssey (ODY), and Mars Reconnaissance Orbiter (MRO) to determine the adjustment factors. The adjustment factors generated by this process had to satisfy the gas law as well as the hydrostatic relation and are expressed as a function of height (z), Latitude (Lat) and areocentric solar longitude (Ls). The greatest adjustments are made at large optical depths such as tau greater than 1. The addition of the adjustment factors has led to better correspondence to TES Limb data from 0-60 km altitude as well as better agreement with MGS, ODY and MRO data at approximately 90-130 km altitude. Improved Mars-GRAM atmospheric simulations for various locations, times and dust conditions on Mars will be presented at the workshop session. The latest results validating Mars-GRAM 2010 versus Mars Climate Sounder data will also be presented. Mars-GRAM 2010 updates have resulted in improved atmospheric simulations which will be very important when beginning systems design, performance analysis, and operations planning for future aerocapture, aerobraking or landed missions to Mars.

The importance of pro-inflammatory signaling in neonatal NEC

PubMed Central

Frost, Brandy L.; Jilling, Tamas; Caplan, Michael S.

2008-01-01

Despite modern medical advances, necrotizing enterocolitis (NEC) remains a significant cause of morbidity and mortality in neonatal intensive care units, affecting 10 percent of premature neonates born weighing less than 1500 grams. Although many advances have been made in the understanding of this disease, the etiology and pathophysiology remain incompletely understood, and treatment is limited to supportive care. In recent years, studies have focused on the role of the inflammatory cascade and its’ impact on the disease process, and investigators are evaluating strategies to attenuate inflammatory signaling that might prevent and/or ameliorate neonatal NEC. In this review, we examine the key points in the signaling pathways involved in NEC, and potential strategies for prevention and treatment of this dreaded disease. PMID:18346533

Direct Detection of Stereospecific Soman Hydrolysis by Wild-Type Human Serum Paraoxonase

DTIC Science & Technology

2007-01-01

was used as Tc = (Ao/VmaA)(1 - (C/Co)( Kmc /KwA)(VmaxA/Vmac)) the carrier gas at a linear velocity of 45 crns-1. The oven + (B0/VmaxB)(1 - (C/Co)( Kmc ...KmB)(VmaxB/Vm.c)) temperature was held initially at 80 ’C for 14 min, pro- + (Co/Vmac)(1 - (C/Co)( Kmc / Kmc )(Vm.c/Vmac)) grammed from 80 to 90 ’C at 5...oC’min-1, and held at + (DO/VmaD)(1 - (C/Co)(K.C/KmD)(Vm.D1/V.aC)) 90 ’C for 3 min. Split injections of 1 tiL volume were made ( Kmc /VmaxC) Log(C/Co

Reasons for 2011 Release of the Evaluated Nuclear Data Library (ENDL2011.0)

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

Brown, D.; Escher, J.; Hoffman, R.

LLNL's Computational Nuclear Physics Group and Nuclear Theory and Modeling Group have collaborated to create the 2011 release of the Evaluated Nuclear Data Library (ENDL2011). ENDL2011 is designed to sup- port LLNL's current and future nuclear data needs. This database is currently the most complete nuclear database for Monte Carlo and deterministic transport of neutrons and charged particles, surpassing ENDL2009.0 [1]. The ENDL2011 release [2] contains 918 transport-ready eval- uations in the neutron sub-library alone. ENDL2011 was assembled with strong support from the ASC program, leveraged with support from NNSA science campaigns and the DOE/Offce of Science US Nuclear Datamore » Pro- gram.« less

Preprocessor that Enables the Use of GridProTM Grids for Unsteady Reynolds-Averaged Navier-Stokes Code TURBO

NASA Technical Reports Server (NTRS)

Shyam, Vikram

2010-01-01

A preprocessor for the Computational Fluid Dynamics (CFD) code TURBO has been developed and tested. The preprocessor converts grids produced by GridPro (Program Development Company (PDC)) into a format readable by TURBO and generates the necessary input files associated with the grid. The preprocessor also generates information that enables the user to decide how to allocate the computational load in a multiple block per processor scenario.

Phosphorus dynamics and phosphatase acitivity of soils under corn production with supplemental irrigation in humid coastal plain region, USA

USDA-ARS?s Scientific Manuscript database

A three-year (2013-2015) field study was conducted to evaluate the effect of integrated nutrient management (NM) and three irrigation scheduling methods (IS): irrigator pro (IPro); normalized difference vegetative index (NDVI) and soil water potentials (SWP) on phosphorus (P) dynamics and phosphatas...

Integration of Molecular Dynamics Based Predictions into the Optimization of De Novo Protein Designs: Limitations and Benefits.

PubMed

Carvalho, Henrique F; Barbosa, Arménio J M; Roque, Ana C A; Iranzo, Olga; Branco, Ricardo J F

2017-01-01

Recent advances in de novo protein design have gained considerable insight from the intrinsic dynamics of proteins, based on the integration of molecular dynamics simulations protocols on the state-of-the-art de novo protein design protocols used nowadays. With this protocol we illustrate how to set up and run a molecular dynamics simulation followed by a functional protein dynamics analysis. New users will be introduced to some useful open-source computational tools, including the GROMACS molecular dynamics simulation software package and ProDy for protein structural dynamics analysis.

A Redundant Role of Human Thyroid Peroxidase Propeptide for Cellular, Enzymatic, and Immunological Activity

PubMed Central

Góra, Monika; Buckle, Ashley M.; Porebski, Benjamin T.; Kemp, E. Helen; Sutton, Brian J.; Czarnocka, Barbara; Banga, J. Paul

2014-01-01

Background: Thyroid peroxidase (TPO) is a dimeric membrane-bound enzyme of thyroid follicular cells, responsible for thyroid hormone biosynthesis. TPO is also a common target antigen in autoimmune thyroid disease (AITD). With two active sites, TPO is an unusual enzyme, and thus there is much interest in understanding its structure and role in AITD. Homology modeling has shown TPO to be composed of different structural modules, as well as a propeptide sequence. During the course of studies to obtain homogeneous preparations of recombinant TPO for structural studies, we investigated the role of the large propeptide sequence in TPO. Methods: An engineered recombinant human TPO preparation expressed in Chinese hamster ovary (CHO) cells lacking the propeptide (TPOΔpro; amino acid residues 21–108) was characterized and its properties compared to wild-type TPO. Plasma membrane localization was determined by cell surface protein biotinylation, and biochemical studies were performed to evaluate enzymatic activity and the effect of deglycosylation. Immunological investigations using autoantibodies from AITD patients and other epitope-specific antibodies that recognize conformational determinants on TPO were evaluated for binding to TPOΔpro by flow cytometry, immunocytochemistry, and capture enzyme-linked immunosorbent assay. Molecular modeling and dynamics simulation of TPOΔpro comprising a dimer of myeloperoxidase-like domains was performed in order to investigate the impact of propeptide removal and the role of glycosylation. Results: The TPOΔpro was expressed on the cell surface at comparable levels to wild-type TPO. The TPOΔpro was enzymatically active and recognized by patients' autoantibodies and a panel of epitope-specific antibodies, confirming structural integrity of the two major conformational determinants recognized by autoantibodies. Faithful intracellular trafficking and N-glycosylation of TPOΔpro was also maintained. Molecular modeling and dynamics simulations were consistent with these observations. Conclusions: Our results point to a redundant role for the propeptide sequence in TPO. The successful expression of TPOΔpro in a membrane-anchored, enzymatically active form that is insensitive to intramolecular proteolysis, and importantly is recognized by patients' autoantibodies, is a key advance for purification of substantial quantities of homogeneous preparation of TPO for crystallization, structural, and immunological studies. PMID:23668778

A redundant role of human thyroid peroxidase propeptide for cellular, enzymatic, and immunological activity.

PubMed

Godlewska, Marlena; Góra, Monika; Buckle, Ashley M; Porebski, Benjamin T; Kemp, E Helen; Sutton, Brian J; Czarnocka, Barbara; Banga, J Paul

2014-02-01

Thyroid peroxidase (TPO) is a dimeric membrane-bound enzyme of thyroid follicular cells, responsible for thyroid hormone biosynthesis. TPO is also a common target antigen in autoimmune thyroid disease (AITD). With two active sites, TPO is an unusual enzyme, and thus there is much interest in understanding its structure and role in AITD. Homology modeling has shown TPO to be composed of different structural modules, as well as a propeptide sequence. During the course of studies to obtain homogeneous preparations of recombinant TPO for structural studies, we investigated the role of the large propeptide sequence in TPO. An engineered recombinant human TPO preparation expressed in Chinese hamster ovary (CHO) cells lacking the propeptide (TPOΔpro; amino acid residues 21-108) was characterized and its properties compared to wild-type TPO. Plasma membrane localization was determined by cell surface protein biotinylation, and biochemical studies were performed to evaluate enzymatic activity and the effect of deglycosylation. Immunological investigations using autoantibodies from AITD patients and other epitope-specific antibodies that recognize conformational determinants on TPO were evaluated for binding to TPOΔpro by flow cytometry, immunocytochemistry, and capture enzyme-linked immunosorbent assay. Molecular modeling and dynamics simulation of TPOΔpro comprising a dimer of myeloperoxidase-like domains was performed in order to investigate the impact of propeptide removal and the role of glycosylation. The TPOΔpro was expressed on the cell surface at comparable levels to wild-type TPO. The TPOΔpro was enzymatically active and recognized by patients' autoantibodies and a panel of epitope-specific antibodies, confirming structural integrity of the two major conformational determinants recognized by autoantibodies. Faithful intracellular trafficking and N-glycosylation of TPOΔpro was also maintained. Molecular modeling and dynamics simulations were consistent with these observations. Our results point to a redundant role for the propeptide sequence in TPO. The successful expression of TPOΔpro in a membrane-anchored, enzymatically active form that is insensitive to intramolecular proteolysis, and importantly is recognized by patients' autoantibodies, is a key advance for purification of substantial quantities of homogeneous preparation of TPO for crystallization, structural, and immunological studies.

Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cδ*

PubMed Central

Farnsworth, Nikki L.; Walter, Rachelle L.; Hemmati, Alireza; Westacott, Matthew J.; Benninger, Richard K. P.

2016-01-01

Pro-inflammatory cytokines contribute to the decline in islet function during the development of diabetes. Cytokines can disrupt insulin secretion and calcium dynamics; however, the mechanisms underlying this are poorly understood. Connexin36 gap junctions coordinate glucose-induced calcium oscillations and pulsatile insulin secretion across the islet. Loss of gap junction coupling disrupts these dynamics, similar to that observed during the development of diabetes. This study investigates the mechanisms by which pro-inflammatory cytokines mediate gap junction coupling. Specifically, as cytokine-induced NO can activate PKCδ, we aimed to understand the role of PKCδ in modulating cytokine-induced changes in gap junction coupling. Isolated mouse and human islets were treated with varying levels of a cytokine mixture containing TNF-α, IL-1β, and IFN-γ. Islet dysfunction was measured by insulin secretion, calcium dynamics, and gap junction coupling. Modulators of PKCδ and NO were applied to determine their respective roles in modulating gap junction coupling. High levels of cytokines caused cell death and decreased insulin secretion. Low levels of cytokine treatment disrupted calcium dynamics and decreased gap junction coupling, in the absence of disruptions to insulin secretion. Decreases in gap junction coupling were dependent on NO-regulated PKCδ, and altered membrane organization of connexin36. This study defines several mechanisms underlying the disruption to gap junction coupling under conditions associated with the development of diabetes. These mechanisms will allow for greater understanding of islet dysfunction and suggest ways to ameliorate this dysfunction during the development of diabetes. PMID:26668311

Discovery of the type VII ESX-1 secretion needle?

PubMed

Ates, Louis S; Brosch, Roland

2017-01-01

Mycobacterium tuberculosis, the etiological agent of human tuberculosis, harbours five ESAT-6/type VII secretion (ESX/T7S) systems. The first esx gene clusters were identified during the genome-sequencing project of M. tuberculosis H37Rv. Follow-up studies revealed additional genes playing important roles in ESX/T7S systems. Among the latter genes, one can find those that encode Pro-Glu (PE) and Pro-Pro-Glu (PPE) proteins as well as a gene cluster that is encoded >260 kb upstream of the esx-1 locus and encodes ESX-1 secretion-associated proteins EspA (Rv3616c), EspC (Rv3615c) and EspD (Rv3614c). The espACD cluster has been suggested to have an important function in ESX-1 secretion since EspA-EspC and EsxA-EsxB are mutually co-dependent on each other for secretion. However, the molecular mechanism of this co-dependence and interaction between the substrates remained unknown. In this issue of Molecular Microbiology, Lou and colleagues show that EspC forms high-molecular weight polymerization complexes that resemble selected components of type II, III and/or IV secretion systems of Gram-negative bacteria. Indeed, EspC-multimeric complexes form filamentous structures that could well represent a secretion needle of ESX-1 type VII secretion systems. This exciting observation opens new avenues for research to discover and characterize ESX/T7S components and elucidates the co-dependence of EsxA/B secretion with EspA/C. © 2016 John Wiley & Sons Ltd.

Competition-Level Differences on the Lower Quarter Y-Balance Test in Baseball Players

PubMed Central

Butler, Robert J.; Bullock, Garrett; Arnold, Todd; Plisky, Phillip; Queen, Robin

2016-01-01

Context: Decreased performance in dynamic balance has previously been associated with a history of ulnar collateral ligament injury in baseball players. Previous research on dynamic balance in soccer players has shown that test performance depends on competition level. However, dynamic balance has yet to be examined in baseball players. Objective: To understand normative values and determine differences in dynamic balance, as measured by the Lower Quarter Y-Balance Test, across competition levels in baseball players. Design: Cross-sectional study. Setting: Preseason physical examinations. Patients or Other Participants: Dynamic balance was measured in 88 high school (HS), 78 collegiate (COL), and 90 professional (PRO) baseball players. Main Outcome Measure(s): All participants completed the Lower Quarter Y-Balance Test using the standard protocol. In unilateral stance, they reached with 1 foot in the anterior, posteromedial, and posterolateral directions. We calculated 1-way analyses of variance to compare performance, composite score, and reach asymmetry for each direction as well as the sum of the asymmetry values (P < .05). Composite score was calculated by averaging the maximum normalized reach scores. Reach asymmetry was determined by calculating bilateral differences in reach ability. Results: In comparison with the HS and COL groups, the PRO players exhibited greater posteromedial (P < .01; effect size index [ESI]HS = 1.06, ESICOL = 0.95) and posterolateral reach (P < .01; ESIHS = 0.82, ESICOL = 0.84) as well as a greater composite score (P < .01; ESIHS = 0.60, ESICOL = 0.87). In contrast, HS baseball players exhibited increased anterior reach (P < .01; ESICOL = 0.60, ESIPRO = 0.39) compared with the COL and PRO cohorts. No significant differences in reach asymmetry were observed among groups. Conclusions: Lower extremity dynamic balance performance differed based on the baseball players' competition level. These baseline data may be helpful in identifying low-performing athletes who might benefit from neuromuscular interventions. PMID:27849388

Cardiac natriuretic peptides in plasma increase after dietary induced weight loss in obesity.

PubMed

Kistorp, Caroline; Bliddal, Henning; Goetze, Jens P; Christensen, Robin; Faber, Jens

2014-01-01

Cardiac natriuretic peptides are established biomarkers in heart disease, but are also affected by body mass index (BMI). The purpose of the present study was to examine the impact of weight loss and changes in body composition following dietary intervention on plasma concentrations of the prohormones to A- and B-type natriuretic peptides (proANP and proBNP) and adrenomedullin (proADM). A total of 52 healthy obese subjects, 47 women and 5 men (BMI 36.5 ± 5.6 kg/m(2)) were randomised to either an intensive weight reduction programme using a combination of very low calorie diet (810 kcal/day) and conventional hypo-energetic diet (1200 kcal/day) for 52 weeks, or to a control group that was offered diet-related counselling. N-terminal proBNP (NT-proBNP), mid-regional proANP (MR-proANP) and proADM (MR-proADM) and body composition using dual-energy x-ray absorptiometry (DEXA) scanning were determined at baseline and after 52 weeks. Comparisons between groups were analysed using t-tests. Changes from the baseline within the groups were analysed with paired tests. Changes in the variables, delta (∆), were calculated as 52 weeks minus the baseline. In the intervention group, BMI decreased by almost 20% (31.6 ± 6.2 vs. 37.1 ± 6.1 kg/m(2); P <0.001) with a loss of body fat of 23.5 ± 15.5% (P < 0.001). Plasma concentrations of NT-proBNP and MR-proANP increased (from 55 ± 31 to 97 ± 55 pg/ml; P < 0.001, and from 59 ± 21 to 74 ± 26 pmol/L; P < 0.001), whereas MR-proADM decreased (from 573 ± 153 to 534 ± 173 pmol/L; P <0.001). Changes (Δ) in MR-proANP correlated with Δfat mass (r = -0.359; P = 0.011) and Δglucose (r = -0.495; P <0.001), while increases in NT-proBNP were primarily associated with reduced plasma glucose (r = -0.462; P <0.001). A modest but significant weight loss of 6% (P < 0.001) was found in the control group with no changes in plasma concentrations of NT-proBNP or MR-proANP, and a minor change in MR-proADM. Plasma NT-proBNP and MR-proANP concentrations increase and MR-proADM concentration decreases during weight loss, underlining the dynamic impact of BMI, body composition and glucose metabolism on these cardiovascular biomarkers.

Neisseria meningitidis elicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model.

PubMed

Borkowski, Julia; Li, Li; Steinmann, Ulrike; Quednau, Natascha; Stump-Guthier, Carolin; Weiss, Christel; Findeisen, Peter; Gretz, Norbert; Ishikawa, Hiroshi; Tenenbaum, Tobias; Schroten, Horst; Schwerk, Christian

2014-09-13

The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis worldwide. The blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus (CP), has been suggested as one of the potential entry sites of Nm into the CSF and can contribute to the inflammatory response during infectious diseases of the brain. Toll-like receptors (TLRs) are involved in mediating signal transduction caused by the pathogens. Using a recently established in vitro model of the human BCSFB based on human malignant CP papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain, MC58, employing transcriptome and RT-PCR analysis, cytokine bead array, and enzyme-linked immunosorbent assay (ELISA). In comparison, we analyzed the answer to the closely related unencapsulated carrier isolate Nm α14. The presence of TLRs in HIBCPP and their role during signal transduction caused by Nm was studied by RT-PCR and the use of specific agonists and mutant bacteria. We observed a stronger transcriptional response after infection with strain MC58, in particular with its capsule-deficient mutant MC58siaD-, which correlated with bacterial invasion levels. Expression evaluation and Gene Set Enrichment Analysis pointed to a NFκB-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IκBζ. Infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, including, among others, IL8, CXCL1-3, and the IκBζ target gene product IL6. The expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2/TLR6, rather than TLR4 or TLR2/TLR1, is involved in the cellular reaction following Nm infection. Our data show that Nm can initiate a pro-inflammatory response in human CP epithelial cells probably involving TLR2/TLR6 signaling and the transcriptional regulator IκBζ.

Sorption isotherms, kinetic and optimization process of amino acid proline based polymer nanocomposite for the removal of selected textile dyes from industrial wastewater.

PubMed

Raghunath, Sharista; Anand, K; Gengan, R M; Nayunigari, Mithil Kumar; Maity, Arjun

2016-12-01

In this article, adsorption and kinetic studies were carried out on three textile dyes, namely Reactive Blue 222 (RB 222), Reactive Red 195 (RR 195) and Reactive Yellow 145 (RY 145). The dyes studied in a mixture were adsorbed under various conditions onto PRO-BEN, a bentonite modified with a new cationic proline polymer (l-proline-epichlorohydrin polymer). The proline polymer was characterized by 1 H NMR, Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) and TEM. The PRO-BEN composite was characterized by FT-IR, dynamic light scattering (DLS) (zeta potential), TEM imaging, SEM/EDX and X-ray photoelectron spectroscopy (characterize the binding energy). During adsorption studies, factors involving pH, temperature, the initial concentrations of the dyes and the quantity of PRO-BEN used during adsorption were established. The results revealed that the adsorption mechanism was categorized by the Langmuir type 1 isotherm. The adsorption data followed the pseudo-second order kinetic model. The intraparticle diffusion model indicated that adsorption did not only depend on the intraparticle diffusion of the dyes. The thermodynamic parameters verified that the adsorption process was spontaneous and exothermic. The Gibbs free energy values indicated that physisorption had occurred. Successful adsorption of dyes from an industrial effluent was achieved. Desorption studies concluded that PRO-BEN desorbed the dyes better than alumina. This can thereby be viewed as a recyclable remediation material. The PRO-BEN composite could be a cost efficient alternative towards the removal of organic dyes in wastewater treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

ProBDNF inhibits collective migration and chemotaxis of rat Schwann cells.

PubMed

Ding, You-Quan; Li, Xuan-Yang; Xia, Guan-Nan; Ren, Hong-Yi; Zhou, Xin-Fu; Su, Bing-Yin; Qi, Jian-Guo

2016-10-01

Schwann cell migration, including collective migration and chemotaxis, is essential for the formation of coordinate interactions between Schwann cells and axons during peripheral nerve development and regeneration. Moreover, limited migration of Schwann cells imposed a serious obstacle on Schwann cell-astrocytes intermingling and spinal cord repair after Schwann cell transplantation into injured spinal cords. Recent studies have shown that mature brain-derived neurotrophic factor, a member of the neurotrophin family, inhibits Schwann cell migration. The precursor form of brain-derived neurotrophic factor, proBDNF, was expressed in the developing or degenerating peripheral nerves and the injured spinal cords. Since "the yin and yang of neurotrophin action" has been established as a common sense, proBDNF would be expected to promote Schwann cell migration. However, we found, in the present study, that exogenous proBDNF also inhibited in vitro collective migration and chemotaxis of RSC 96 cells, a spontaneously immortalized rat Schwann cell line. Moreover, proBDNF suppressed adhesion and spreading of those cells. At molecular level, proBDNF inhibits F-actin polymerization and focal adhesion dynamics in cultured RSC 96 cells. Therefore, our results suggested a special case against the classical opinion of "the yin and yang of neurotrophin action" and implied that proBDNF might modulate peripheral nerve development or regeneration and spinal cord repair through perturbing native or transplanted Schwann cell migration. Copyright © 2016 Elsevier Ltd. All rights reserved.

New antibiotics for bad bugs: where are we?

PubMed Central

2013-01-01

Bacterial resistance to antibiotics is growing up day by day in both community and hospital setting, with a significant impact on the mortality and morbidity rates and the financial burden that is associated. In the last two decades multi drug resistant microorganisms (both hospital- and community-acquired) challenged the scientific groups into developing new antimicrobial compounds that can provide safety in use according to the new regulation, good efficacy patterns, and low resistance profile. In this review we made an evaluation of present data regarding the new classes and the new molecules from already existing classes of antibiotics and the ongoing trends in antimicrobial development. Infectious Diseases Society of America (IDSA) supported a proGram, called “the ′10 × ´20′ initiative”, to develop ten new systemic antibacterial drugs within 2020. The microorganisms mainly involved in the resistance process, so called the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and enterobacteriaceae) were the main targets. In the era of antimicrobial resistance the new antimicrobial agents like fifth generation cephalosporins, carbapenems, monobactams, β-lactamases inhibitors, aminoglycosides, quinolones, oxazolidones, glycopeptides, and tetracyclines active against Gram-positive pathogens, like vancomycin-resistant S. aureus (VRSA) and MRSA, penicillin-resistant streptococci, and vancomycin resistant Enterococcus (VRE) but also against highly resistant Gram-negative organisms are more than welcome. Of these compounds some are already approved by official agencies, some are still in study, but the need of new antibiotics still does not cover the increasing prevalence of antibiotic-resistant bacterial infections. Therefore the management of antimicrobial resistance should also include fostering coordinated actions by all stakeholders, creating policy guidance, support for surveillance and technical assistance. PMID:23984642

Tenebrio molitor Gram-negative-binding protein 3 (TmGNBP3) is essential for inducing downstream antifungal Tenecin 1 gene expression against infection with Beauveria bassiana JEF-007.

PubMed

Yang, Yi-Ting; Lee, Mi Rong; Lee, Se Jin; Kim, Sihyeon; Nai, Yu-Shin; Kim, Jae Su

2017-05-23

The Toll signaling pathway is responsible for defense against both Gram-positive bacteria and fungi. Gram-negative binding protein 3 (GNBP3) has a strong affinity for the fungal cell wall component, β-1,3-glucan, which can activate the prophenoloxidase (proPO) cascade and induce the Toll signaling pathway. Myeloid differentiation factor 88 (MyD88) is an intracellular adaptor protein involved in the Toll signaling pathway. In this study, we monitored the response of 5 key genes (TmGNBP3, TmMyD88, and Tenecin 1, 2, and 3) in the Toll pathway of the mealworm Tenebrio molitor immune system against the fungus Beauveria bassiana JEF-007 using RT-PCR. TmGNBP3, Tenecin 1, and Tenecin 2 were significantly upregulated after fungal infection. To better understand the roles of the Toll signaling pathway in the mealworm immune system, TmGNBP3 and TmMyD88 were knocked down by RNAi silencing. Target gene expression levels decreased at 2 d postknockdown and were dramatically reduced at 6 d post-dsRNA injection. Therefore, mealworms were compromised by B. bassiana JEF-007 at 6 d post-dsRNA injection. Silencing of TmMyD88 and TmGNBP3 resulted in reduced resistance of the host to fungal infection. Particularly, reducing TmGNBP3 levels obviously downregulated Tenecin 1 and Tenecin 2 expression levels, whereas silencing TmMyD88 expression resulted in decreased Tenecin 2 expression. These results indicate that TmGNBP3 is essential to induce downstream antifungal peptide Tenecin 1 expression against B. bassiana JEF-007. © 2017 Institute of Zoology, Chinese Academy of Sciences.

A Regional Real-time Forecast of Marine Boundary Layers During VOCALS-REx

DTIC Science & Technology

2011-01-01

Condensation Nuclei) concentration pro- motes more precipitation, leading to the destruction and structural change of the clouds (e.g., Stevens et al...and Muñoz, 2004), investigations of cloud and dynamic pro- cesses in case studies (Mocko and Cotton , 1995; Mechem and Kogan, 2003; Thompson et al...land breeze, Geophys. Res. Lett., 32, L05605, doi:10.1029/2004GL022139, 2005. Golaz, J.-C., Larson, V. E., and Cotton ,W. R: A PDF-based model for

The Propulsive Small Expendable Deployer System (ProSEDS)

NASA Technical Reports Server (NTRS)

Lorenzini, Enrico C.; Estes, Robert D.; Cosmo, Mario L.

2001-01-01

This is the Annual Report #2 entitled "The Propulsive Small Expendable Deployer System (ProSEDS)" prepared by the Smithsonian Astrophysical Observatory for NASA Marshall Space Flight Center. This report covers the period of activity from 1 August 2000 through 30 July 2001. The topics include: 1) Updated System Performance; 2) Mission Analysis; 3) Updated Dynamics Reference Mission; 4) Updated Deployment Control Profiles and Simulations; 5) Comparison of ED tethers and electrical thrusters; 6) Kalman filters for mission estimation; and 7) Delivery of interactive software for ED tethers.

A novel approach for emerging and antibiotic resistant infections: Innate Defense Regulators as an agnostic therapy

PubMed Central

North, John R.; Takenaka, Shunsuke; Rozek, Annett; Kielczewska, Agnieszka; Opal, Steven; Morici, Lisa A.; Finlay, B. Brett; Schaber, Christopher J.; Straube, Richard; Donini, Oreola

2016-01-01

Innate Defense Regulators (IDRs) are short synthetic peptides that target the host innate immune system via an intracellular adaptor protein which functions at key signaling nodes. In this work, further details of the mechanism of action of IDRs have been discovered. The studies reported here show that the lead clinical IDR, SGX94, has broad-spectrum activity against Gram-negative and Gram-positive bacterial infections caused by intracellular or extracellular bacteria and also complements the actions of standard of care antibiotics. Based on in vivo and primary cell culture studies, this activity is shown to result from the primary action of SGX94 on tissue-resident cells and subsequent secondary signaling to activate myeloid-derived cells, resulting in enhanced bacterial clearance and increased survival. Data from non-clinical and clinical studies also show that SGX94 treatment modulates pro-inflammatory and anti-inflammatory cytokine levels, thereby mitigating the deleterious inflammatory consequences of innate immune activation. Since they act through host pathways to provide both broad-spectrum anti-infective capability as well as control of inflammation, IDRs are unlikely to be impacted by resistance mechanisms and offer potential clinical advantages in the fight against emerging and antibiotic resistant bacterial infections. PMID:27015977

A novel approach for emerging and antibiotic resistant infections: Innate defense regulators as an agnostic therapy.

PubMed

North, John R; Takenaka, Shunsuke; Rozek, Annett; Kielczewska, Agnieszka; Opal, Steven; Morici, Lisa A; Finlay, B Brett; Schaber, Christopher J; Straube, Richard; Donini, Oreola

2016-05-20

Innate Defense Regulators (IDRs) are short synthetic peptides that target the host innate immune system via an intracellular adaptor protein which functions at key signaling nodes. In this work, further details of the mechanism of action of IDRs have been discovered. The studies reported here show that the lead clinical IDR, SGX94, has broad-spectrum activity against Gram-negative and Gram-positive bacterial infections caused by intracellular or extracellular bacteria and also complements the actions of standard of care antibiotics. Based on in vivo and primary cell culture studies, this activity is shown to result from the primary action of SGX94 on tissue-resident cells and subsequent secondary signaling to activate myeloid-derived cells, resulting in enhanced bacterial clearance and increased survival. Data from non-clinical and clinical studies also show that SGX94 treatment modulates pro-inflammatory and anti-inflammatory cytokine levels, thereby mitigating the deleterious inflammatory consequences of innate immune activation. Since they act through host pathways to provide both broad-spectrum anti-infective capability as well as control of inflammation, IDRs are unlikely to be impacted by resistance mechanisms and offer potential clinical advantages in the fight against emerging and antibiotic resistant bacterial infections. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Differential induction of pro- and anti-inflammatory cytokines in whole blood by bacteria: effects of antibiotic treatment.

PubMed

Frieling, J T; Mulder, J A; Hendriks, T; Curfs, J H; van der Linden, C J; Sauerwein, R W

1997-07-01

The in vitro production of interleukin-1beta (IL-1beta), IL-6, and the IL-1 receptor antagonist (IL-1ra) in whole blood upon stimulation with different bacterial strains was measured to study the possible relationship between disease severity and the cytokine-inducing capacities of these strains. Escherichia coli, Neisseria meningitidis, Neisseria gonorrhoeae, Bacteroides fragilis, Capnocytophaga canimorsus, Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Streptococcus pyogenes induced the cytokines IL-1beta, IL-6, and IL-1ra. Gram-negative bacteria induced significantly higher levels of proinflammatory cytokine production than gram-positive bacteria. These differences were less pronounced for the anti-inflammatory cytokine IL-1ra. In addition, blood was stimulated with E. coli killed by different antibiotics to study the effect of the antibiotics on the cytokine-inducing capacity of the bacterial culture. E. coli treated with cefuroxime and gentamicin induced higher levels of IL-1beta and IL-6 production but levels of IL-1ra production similar to that of heat-killed E. coli. In contrast, ciprofloxacin- and imipenem-cilastatin-mediated killing showed a decreased or similar level of induction of cytokine production as compared to that by heat-killed E. coli; polymyxin B decreased the level of production of the cytokines.

Molecular cloning and characterization of a C-type lectin in yellow catfish Tachysurus fulvidraco.

PubMed

Ke, F; Zhang, H B; Wang, Y; Hou, L F; Dong, H J; Wang, Z F; Pan, G W; Cao, X Y

2016-09-01

This study represents the first report of a C-type lectin (ctl) in yellow catfish Tachysurus fulvidraco. The complete sequence of ctl complementary (c)DNA consisted of 685 nucleotides. The open reading frame potentially encoded a protein of 177 amino acids with a calculated molecular mass of c.y 20.204 kDa. The deduced amino-acid sequence contained a signal peptide and a single carbohydrate recognition domain with four cysteine residues and GlnProAsp (QPD) and TrpAsnAsp (WND) motifs. Ctl showed the highest identity (56.0%) to the predicted lactose binding lectin from channel catfish Ictalurus punctatus. Quantitative real-time (qrt)-PCR analysis showed that ctl messenger (m)RNA was constitutively expressed in all examined tissues in normal fish, with high expression in trunk kidney and head kidney, which was increased following Aeromonas hydrophila challenge in a duration-dependent manner. Purified recombinant Ctl (rCtl) from Escherichia coli BL21 was able to bind and agglutinate Gram-positive and Gram-negative bacteria in a calcium-dependent manner. These results suggested that Ctl might be a C-type lectin of T. fulvidraco involved in innate immune responses as receptors (PRR). © 2016 The Fisheries Society of the British Isles.

Dynamic Environmental Qualification Techniques.

DTIC Science & Technology

1981-12-01

environments peculiar to military operations and requirements. numerous dynamic qualification test methods have been established. It was the purpose...requires the achievement of the highest practicable degree in the standard- ization of items, materials and engineering practices within the...standard is described as "A document that established engineering and technical requirements for processes, pro’cedures, practices and methods that have

Transcriptional and Chromatin Dynamics of Muscle Regeneration After Severe Trauma

DTIC Science & Technology

2016-10-12

performed pathway analysis of the time-clustered RNA- Seq data16 and showed an initial burst of pro-inflammatory and immune-response transcripts in the...143 showed dynamic behavior (See Methods) and analysis of the dynamic miRNAs reinforced many of the results observed from the RNA-Seq datasets...excellent agreement was viewed. Hierarchical clustering of the datasets through time revealed 5 clusters, and gene ontology (GO) analysis of the

Bottom-up and top-down controls on picoplankton in the East China Sea

NASA Astrophysics Data System (ADS)

Guo, C.; Liu, H.; Zheng, L.; Song, S.; Chen, B.; Huang, B.

2013-05-01

Dynamics of picoplankton population distribution in the East China Sea (ECS), a marginal sea in the western North Pacific Ocean, were studied during two "CHOICE-C" cruises in August 2009 (summer) and January 2010 (winter). Dilution experiments were conducted during the two cruises to investigate the growth and grazing among picophytoplantkon populations. Picoplankton accounted for an average of ~29% (2% to 88%) of community carbon biomass in the ECS on average, with lower percentages in plume region than in shelf and kuroshio regions. Averaged growth rates (μ) for Prochlorococcus (Pro), Synechococcus (Syn) and picoeukaryotes (peuk) were 0.36, 0.89, 0.90 d-1, respectively, in summer, and 0.46, 0.58, 0.56 d-1, respectively, in winter. Seawater salinity and nutrient availability exerted significant controls on picoplankton growth rate. Averaged grazing mortality (m) were 0.46, 0.63, 0.68 d-1 in summer, and 0.22, 0.32, 0.22 d-1 in winter for Pro, Syn and peuk respectively. The three populations demonstrated very different distribution patterns regionally and seasonally affected by both bottom-up and top-down controls. In summer, Pro, Syn and peuk were dominant in Kuroshio, transitional and plume regions respectively. Protist grazing consumed 84%, 78%, 73% and 45%, 47%, 57% of production for Pro, Syn and peuk in summer and winter respectively, suggesting more significant top-down controls in summer. In winter, all three populations tended to distribute in offshore regions, although the area of coverage was different (peuk > Syn > Pro). Bottom-up factors can explain as much as 91.5%, 82% and 81.2% of Pro, Syn and peuk abundance variance in winter, while only 59.1% and 43.7% for Pro and peuk in summer. Regionally, Yangtze River discharge plays a significant role in affecting the intensity of top-down control, indicated by significant and negative association between salinity and grazing mortality of all three populations and higher grazing mortality to growth rate ratio (m / μ) in plume region than Kuroshio region in summer. The gradient of bottom-up factors caused by Yangtze River input and Kuroshio warm current intrusion also exerted important influence on picoplankton abundance evidenced by the significant correlations. Vertically, picoplankton exhibited highest abundance at subsurface layer around 20 m thick in summer, while at surface in winter. Both growth rate and grazing mortality were higher at surface than at the deep chlorophyll maximum (DCM) layer. Our study first systematically described the bottom-up and top-down regulations of different picoplankton populations between contrasting seasons, different depths, and among different regions in the ECS, which provide insights for better understanding the population dynamics of picoplankton and trophic transfer in microbial food web in highly dynamic shelf ecosystems and in general.

On the role of the optimization algorithm of RapidArc(®) volumetric modulated arc therapy on plan quality and efficiency.

PubMed

Vanetti, Eugenio; Nicolini, Giorgia; Nord, Janne; Peltola, Jarkko; Clivio, Alessandro; Fogliata, Antonella; Cozzi, Luca

2011-11-01

The RapidArc volumetric modulated arc therapy (VMAT) planning process is based on a core engine, the so-called progressive resolution optimizer (PRO). This is the optimization algorithm used to determine the combination of field shapes, segment weights (with dose rate and gantry speed variations), which best approximate the desired dose distribution in the inverse planning problem. A study was performed to assess the behavior of two versions of PRO. These two versions mostly differ in the way continuous variables describing the modulated arc are sampled into discrete control points, in the planning efficiency and in the presence of some new features. The analysis aimed to assess (i) plan quality, (ii) technical delivery aspects, (iii) agreement between delivery and calculations, and (iv) planning efficiency of the two versions. RapidArc plans were generated for four groups of patients (five patients each): anal canal, advanced lung, head and neck, and multiple brain metastases and were designed to test different levels of planning complexity and anatomical features. Plans from optimization with PRO2 (first generation of RapidArc optimizer) were compared against PRO3 (second generation of the algorithm). Additional plans were optimized with PRO3 using new features: the jaw tracking, the intermediate dose and the air cavity correction options. Results showed that (i) plan quality was generally improved with PRO3 and, although not for all parameters, some of the scored indices showed a macroscopic improvement with PRO3. (ii) PRO3 optimization leads to simpler patterns of the dynamic parameters particularly for dose rate. (iii) No differences were observed between the two algorithms in terms of pretreatment quality assurance measurements and (iv) PRO3 optimization was generally faster, with a time reduction of a factor approximately 3.5 with respect to PRO2. These results indicate that PRO3 is either clinically beneficial or neutral in terms of dosimetric quality while it showed significant advantages in speed and technical aspects.

pH-Dependent Activation of Streptomyces hygroscopicus Transglutaminase Mediated by Intein

PubMed Central

Du, Kun; Liu, Zhongmei; Cui, Wenjing; Zhou, Li; Liu, Yi; Chen, Jian

2014-01-01

Microbial transglutaminase (MTG) from Streptomyces is naturally secreted as a zymogen (pro-MTG), which is then activated by the removal of its N-terminal proregion by additional proteases. Inteins are protein-intervening sequences that catalyze protein splicing without cofactors. In this study, a pH-dependent Synechocystis sp. strain PCC6803 DnaB mini-intein (SDB) was introduced into pro-MTG to simplify its activation process by controlling pH. The recombinant protein (pro-SDB-MTG) was obtained, and the activation process was determined to take 24 h at pH 7 in vitro. To investigate the effect of the first residue in MTG on the activity and the cleavage time, two variants, pro-SDB-MTG(D1S) and pro-SDB-MTG(ΔD1), were expressed, and the activation time was found to be 6 h and 30 h, respectively. The enzymatic property and secondary structure of the recombinant MTG and two variants were similar to those of the wild type, indicating that the insertion of mini-intein did not affect the function of MTG. This insignificant effect was further illustrated by molecular dynamics simulations. This study revealed a controllable and effective strategy to regulate the activation process of pro-MTG mediated by a mini-intein, and it may have great potential for industrial MTG production. PMID:24242235

Proline Hydroxylation in Cell Wall Proteins: Is It Yet Possible to Define Rules?

PubMed

Duruflé, Harold; Hervé, Vincent; Balliau, Thierry; Zivy, Michel; Dunand, Christophe; Jamet, Elisabeth

2017-01-01

Cell wall proteins (CWPs) play critical and dynamic roles in plant cell walls by contributing to developmental processes and response to environmental cues. Since the CWPs go through the secretion pathway, most of them undergo post-translational modifications (PTMs) which can modify their biological activity. Glycosylation is one of the major PTMs of CWPs and refers to N -glycosylation, O -glycosylation and glypiation. Each of these PTMs occurs in different amino acid contexts which are not all well defined. This article deals with the hydroxylation of Pro residues which is a prerequisite for O -glycosylation of CWPs on hydroxyproline (Hyp) residues. The location of Hyp residues is well described in several structural CWPs, but yet rarely described in other CWPs. In this article, it is studied in detail in five Arabidopsis thaliana proteins using mass spectrometry data: one of them (At4g38770, AtPRP4) is a structural CWP containing 32.5% of Pro residues arranged in typical motifs, the others are either rich (27-28%, At1g31580 and At2g10940) or poor (6-8%, At1g09750 and At3g08030) in Pro residues. The known rules of Pro hydroxylation allowed a good prediction of Hyp location in AtPRP4. However, they could not be applied to the other proteins whatever their Pro content. In addition, variability of the Pro hydroxylation patterns was observed within some amino acid motifs in all the proteins and new patterns of Pro hydroxylation are described. Altogether, this work shows that Hyp residues are present in more protein families than initially described, and that Pro hydroxylation patterns could be different in each of them. This work paves the way for completing the existing Pro hydroxylation code.

Crystal structures reveal an induced-fit binding of a substrate-like Aza-peptide epoxide to SARS coronavirus main peptidase.

PubMed

Lee, Ting-Wai; Cherney, Maia M; Liu, Jie; James, Karen Ellis; Powers, James C; Eltis, Lindsay D; James, Michael N G

2007-02-23

The SARS coronavirus main peptidase (SARS-CoV M(pro)) plays an essential role in the life-cycle of the virus and is a primary target for the development of anti-SARS agents. Here, we report the crystal structure of M(pro) at a resolution of 1.82 Angstroms, in space group P2(1) at pH 6.0. In contrast to the previously reported structure of M(pro) in the same space group at the same pH, the active sites and the S1 specificity pockets of both protomers in the structure of M(pro) reported here are in the catalytically competent conformation, suggesting their conformational flexibility. We report two crystal structures of M(pro) having an additional Ala at the N terminus of each protomer (M(+A(-1))(pro)), both at a resolution of 2.00 Angstroms, in space group P4(3)2(1)2: one unbound and one bound by a substrate-like aza-peptide epoxide (APE). In the unbound form, the active sites and the S1 specificity pockets of both protomers of M(+A(-1))(pro) are observed in a collapsed (catalytically incompetent) conformation; whereas they are in an open (catalytically competent) conformation in the APE-bound form. The observed conformational flexibility of the active sites and the S1 specificity pockets suggests that these parts of M(pro) exist in dynamic equilibrium. The structural data further suggest that the binding of APE to M(pro) follows an induced-fit model. The substrate likely also binds in an induced-fit manner in a process that may help drive the catalytic cycle.

Molecular dynamics simulations of trans- and cis- N-acetyl- N'-methylamides of XaaPro dipeptides

NASA Astrophysics Data System (ADS)

Hoon Choi, Seung; Yun Yu, Jeong; Kwang Shin, Jae; Shik Jhon, Mu

1994-07-01

The occurrence of cis imide bonds in proteins is much higher than that of cis amide bonds due to the unique properties of proline. In order to examine the relationship between the high occurrence of these cis imide bonds and the residues preceding the proline, we perform molecular dynamics simulations of trans- and cis- N-acetyl- N'-methylamides of XaaPro dipeptides (AcXaaProNHMe). We investigate the conformational energies and structures of trans- and cis-AcXaa where Xaa has 12 amino acids in the vacuum state and 5 amino acids in the solution state. It is found that the occurrence of the cis imide bonds is strongly affected by the residue preceding the proline, and the dihedral angles (φ,ψ) of the backbone in AcXaaProNHMe are influenced by the configuration of the imide bond. We also find that the equilibrium properties of XaaPro in solution simulations are more similar to the statistics of X-ray crystallographic data than are those in vacuum simulations and solvation causes a remarkable change in the conformation of the pyrrolidine ring from the endo to the exo form.

[Optimization of education for laparoendoscopic technologies in Ukraine].

PubMed

Lesovoĭ, V N; Savenkov, V I; Tomin, M S

2014-09-01

International experience of training of surgeons, including urologists, in laparoendoscopic technologies, was analyzed. Practical course "The Fundamentals of aparoscopic Surgery" (FLS) and the European program of education for basic laparoscopic urologic skills (E-BLUS), which are used in specialized centers, constitute a standard programs of development of basic endosurgical skills. Such centers in Ukraine are absent. The project of complex system of a simulating education, testing and certification of surgeons, who are trained in endovideosurgical technologies, is proposed. While performing surveying of Ukrainian surgeons there were revealed the problems in a process of their education and introduction of highly technological methods: insufficient equipment with modern apparatuses, absence of a standardized pro- gram of education. The staged program of education was elaborated, taking into account progressive international experience and adopted to our environment and con ditions.

Large-Eddy Simulation of the Base Flow of a Cylindrical Space Vehicle Configuration

NASA Astrophysics Data System (ADS)

Meiß, J.-H.; Schröder, W.

2009-01-01

A Large-Eddy Simulation (LES) is performed out to in- vestigate high Reynolds number base flow of an axisymmetric rocket-like configuration having an underex- panded nozzle flow. The subsonic base region of low pressure levels is characterized and bounded by the interaction of the freestream of Mach 5.3 and the wide plume of the hot exhaust jet of Mach 3.8. An analysis of the base flow shows that the system of base area vortices determines the highly time-dependent pressure distribution and causes an upstream convection of hot exhaust gas. A comparison of the results with experiments conducted at the German Aerospace Center (DLR) Cologne shows good agreement. The investigation is part of the German RESPACE Pro- gram, which focuses on Key Technologies for Reusable Space Systems.

National water summary 1983: Hydrologic events and issues

USGS Publications Warehouse

,

1984-01-01

The United States as a Nation possesses abundant water resources and has developed and used those resources extensively. The national renewable supply of water is about 1,400 billion gallons per day (for the conterminous 48 States). Approximately 380 billion gallons per day of freshwater is withdrawn for use by the Nation's homes, farms, and industries, and about 280 billion gallons per day is returned to streams. Although a large percentage of the Nation's waste is carried in this return flow, the quality of water in streams has improved in many respects as a result of the pollution-control pro- grams of recent years. However, much remains to be learned about water quality particularly the extent of contamination by synthetic organic chemicals and heavy metals, and the effects of these contaminants on human health.

Anti-cancer, immunoregulatory, and antimicrobial activities of the frog skin host-defense peptides pseudhymenochirin-1Pb and pseudhymenochirin-2Pa.

PubMed

Mechkarska, Milena; Attoub, Samir; Sulaiman, Shahrazad; Pantic, Jelena; Lukic, Miodrag L; Conlon, J Michael

2014-11-01

Pseudhymenochirin-1Pb (Ps-1Pb) and pseudhymenochirin-2Pa (Ps-2Pa) are host-defense peptides, first isolated from skin secretions of the frog Pseudhymenochirus merlini (Pipidae). Ps-1Pb and Ps-2Pa are highly cytotoxic (LC50<12 μM) against non-small cell lung adenocarcinoma A549 cells, breast adenocarcinoma MDA-MB-231 cells, and colorectal adenocarcinoma HT-29 cells but are also hemolytic against human erythrocytes (LC50=28±2 μM for Ps-1Pb and LC50=6±1 μM for Ps-2Pa). Ps-2Pa shows selective cytotoxicity for tumor cells (LC50 against non-neoplastic human umbilical vein (HUVEC) cells=68±2 μM). Ps-1Pb and Ps-2Pa (5 μg/mL) significantly inhibit production of the anti-inflammatory cytokine IL-10 and the multifunctional cytokine IL-6 from lipopolysaccharide (LPS)-stimulated peritoneal macrophages from C57BL/6 mice and enhance the production of the pro-inflammatory cytokine IL-23 from both unstimulated and LPS-stimulated macrophages. Ps-1Pb potently (MIC≤10 μM) inhibits growth of multidrug-resistant clinical isolates of the Gram-positive bacteria methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, and the Gram-negative bacteria Acinetobacter baumannii and Stenotrophomonas maltophilia. Ps-2Pa shows the same high potency (MIC≤10 μM) against the Gram-positive bacteria but is 2-4 fold less potent against the Gram-negative isolates. Ps-1Pb at 4×MIC kills 99.9% of Escherichia coli within 30 min and 99.9% of S. aureus within 180 min. In conclusion, cytotoxicity against tumor cells, cytokine-mediated immunomodulatory properties, and broad-spectrum antimicrobial activity suggest that the Ps-1Pb and Ps-2Pa represent templates for design of non-hemolytic analogs for tumor therapy and for treatment of infections in cancer patients produced by multidrug-resistant pathogens. Copyright © 2014 Elsevier B.V. All rights reserved.

Biological evaluation, docking and molecular dynamic simulation of some novel diaryl urea derivatives bearing quinoxalindione moiety

PubMed Central

Sadeghian-Rizi, Sedighe; Khodarahmi, Ghadamali Ali; Sakhteman, Amirhossein; Jahanian-Najafabadi, Ali; Rostami, Mahboubeh; Mirzaei, Mahmoud; Hassanzadeh, Farshid

2017-01-01

In this study a series of diarylurea derivatives containing quinoxalindione group were biologically evaluated for their cytotoxic activities using MTT assay against MCF-7 and HepG2 cell lines. Antibacterial activities of these compounds were also evaluated by Microplate Alamar Blue Assay (MABA) against three Gram-negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi), three Gram-positive (Staphylococcus aureus, Bacillus subtilis and Listeria monocitogenes) and one yeast-like fungus (Candida albicans) strain. Furthermore, molecular docking was carried out to study the binding pattern of the compounds to the active site of B-RAF kinase (PDB code: 1UWH). Molecular dynamics simulation was performed on the best ligand (16e) to investigate the ligand binding dynamics in the physiological environment. Cytotoxic evaluation revealed the most prominent cytotoxicity for 6 compounds with IC50 values of 10-18 μM against two mentioned cell lines. None of the synthesized compounds showed significant antimicrobial activity. The obtained results of the molecular docking study showed that all compounds fitted in the binding site of enzyme with binding energy range of -11.22 to -12.69 kcal/mol vs sorafenib binding energy -11.74 kcal/mol as the lead compound. Molecular dynamic simulation indicated that the binding of ligand (16e) was stable in the active site of B-RAF during the simulation. PMID:29204178

Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cδ.

PubMed

Farnsworth, Nikki L; Walter, Rachelle L; Hemmati, Alireza; Westacott, Matthew J; Benninger, Richard K P

2016-02-12

Pro-inflammatory cytokines contribute to the decline in islet function during the development of diabetes. Cytokines can disrupt insulin secretion and calcium dynamics; however, the mechanisms underlying this are poorly understood. Connexin36 gap junctions coordinate glucose-induced calcium oscillations and pulsatile insulin secretion across the islet. Loss of gap junction coupling disrupts these dynamics, similar to that observed during the development of diabetes. This study investigates the mechanisms by which pro-inflammatory cytokines mediate gap junction coupling. Specifically, as cytokine-induced NO can activate PKCδ, we aimed to understand the role of PKCδ in modulating cytokine-induced changes in gap junction coupling. Isolated mouse and human islets were treated with varying levels of a cytokine mixture containing TNF-α, IL-1β, and IFN-γ. Islet dysfunction was measured by insulin secretion, calcium dynamics, and gap junction coupling. Modulators of PKCδ and NO were applied to determine their respective roles in modulating gap junction coupling. High levels of cytokines caused cell death and decreased insulin secretion. Low levels of cytokine treatment disrupted calcium dynamics and decreased gap junction coupling, in the absence of disruptions to insulin secretion. Decreases in gap junction coupling were dependent on NO-regulated PKCδ, and altered membrane organization of connexin36. This study defines several mechanisms underlying the disruption to gap junction coupling under conditions associated with the development of diabetes. These mechanisms will allow for greater understanding of islet dysfunction and suggest ways to ameliorate this dysfunction during the development of diabetes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Bactericidal action mechanism of negatively charged food grade clove oil nanoemulsions.

PubMed

Majeed, Hamid; Liu, Fei; Hategekimana, Joseph; Sharif, Hafiz Rizwan; Qi, Jing; Ali, Barkat; Bian, Yuan-Yuan; Ma, Jianguo; Yokoyama, Wallace; Zhong, Fang

2016-04-15

Clove oil (CO) anionic nanoemulsions were prepared with varying ratios of CO to canola oil (CA), emulsified and stabilized with purity gum ultra (PGU), a newly developed succinylated waxy maize starch. Interfacial tension measurements showed that CO acted as a co-surfactant and there was a gradual decrease in interfacial tension which favored the formation of small droplet sizes on homogenization until a critical limit (5:5% v/v CO:CA) was reached. Antimicrobial activity of the negatively charged CO nanoemulsion was determined against Gram positive GPB (Listeria monocytogenes and Staphylococcus aureus) and Gram negative GNB (Escherichia coli) bacterial strains using minimum inhibitory concentration (MIC) and a time kill dynamic method. Negatively charged PGU emulsified CO nanoemulsion showed prolonged antibacterial activities against Gram positive bacterial strains. We concluded that negatively charged CO nanoemulsion droplets self-assemble with GPB cell membrane, and facilitated interaction with cellular components of bacteria. Moreover, no electrostatic interaction existed between negatively charged droplets and the GPB membrane. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis of Metal Contents in Portland Type V and MTA-Based Cements

PubMed Central

Dorileo, Maura Cristiane Gonçales Orçati; Bandeca, Matheus Coelho; Pedro, Fábio Luis Miranda; Volpato, Luiz Evaristo Ricci; Guedes, Orlando Aguirre; Villa, Ricardo Dalla; Tonetto, Mateus Rodrigues; Borges, Alvaro Henrique

2014-01-01

The aim of this study was to determine, by Atomic Absorption Spectrometry (AAS), the concentration levels of 11 metals in Type V gray and structural white PC, ProRoot MTA, and MTA Bio. Samples, containing one gram of each tested cement, were prepared and transferred to a 100 mL Teflon tube with a mixture of 7.0 mL of nitric acid and 21 mL of hydrochloric acid. After the reaction, the mixture was filtered and then volumed to 50 mL of distilled water. For each metal, specific patterns were determined from universal standards. Arsenic quantification was performed by hydride generator. The analysis was performed five times and the data were statistically analyzed at 5% level of significance. Only the cadmium presented concentration levels of values lower than the quantification limit of the device. The AAS analysis showed increased levels of calcium, nickel, and zinc in structural white PC. Type V PC presented the greatest concentration levels of arsenic, chromium, copper, iron, lead, and manganese (P < 0.05). Bismuth was found in all cements, and the lowest concentration levels were observed in Portland cements, while the highest were observed in ProRoot MTA. Both PC and MTA-based cements showed evidence of metals inclusion. PMID:25436238

Influence of Biochemical Features of Burkholderia pseudomallei Strains on Identification Reliability by Vitek 2 System

PubMed Central

Zakharova, Irina B; Lopasteyskaya, Yana A; Toporkov, Andrey V; Viktorov, Dmitry V

2018-01-01

Background: Burkholderia pseudomallei is a Gram-negative saprophytic soil bacterium that causes melioidosis, a potentially fatal disease endemic in wet tropical areas. The currently available biochemical identification systems can misidentify some strains of B. pseudomallei. The aim of the present study was to identify the biochemical features of B. pseudomallei, which can affect its correct identification by Vitek 2 system. Materials and Methods: The biochemical patterns of 40 B. pseudomallei strains were obtained using Vitek 2 GN cards. The average contribution of biochemical tests in overall dissimilarities between correctly and incorrectly identified strains was assessed using nonmetric multidimensional scaling. Results: It was found (R statistic of 0.836, P = 0.001) that a combination of negative N-acetyl galactosaminidase, β-N-acetyl glucosaminidase, phosphatase, and positive D-cellobiase (dCEL), tyrosine arylamidase (TyrA), and L-proline arylamidase (ProA) tests leads to low discrimination of B. pseudomallei, whereas a set of positive dCEL and negative N-acetyl galactosaminidase, TyrA, and ProA determines the wrong identification of B. pseudomallei as Burkholderia cepacia complex. Conclusion: The further expansion of the Vitek 2 identification keys is needed for correct identification of atypical or regionally distributed biochemical profiles of B. pseudomallei. PMID:29563716

Multifaceted Role of Pneumolysin in the Pathogenesis of Myocardial Injury in Community-Acquired Pneumonia.

PubMed

Anderson, Ronald; Nel, Jan G; Feldman, Charles

2018-04-11

Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol-dependent, β-barrel pore-forming cytolysins, is the major protein virulence factor of the dangerous respiratory pathogen, Streptococcus pneumoniae (pneumococcus). PLY plays a major role in the pathogenesis of community-acquired pneumonia (CAP), promoting colonization and invasion of the upper and lower respiratory tracts respectively, as well as extra-pulmonary dissemination of the pneumococcus. Notwithstanding its role in causing acute lung injury in severe CAP, PLY has also been implicated in the development of potentially fatal acute and delayed-onset cardiovascular events, which are now recognized as being fairly common complications of this condition. This review is focused firstly on updating mechanisms involved in the immunopathogenesis of PLY-mediated myocardial damage, specifically the direct cardiotoxic and immunosuppressive activities, as well as the indirect pro-inflammatory/pro-thrombotic activities of the toxin. Secondly, on PLY-targeted therapeutic strategies including, among others, macrolide antibiotics, natural product antagonists, cholesterol-containing liposomes, and fully humanized monoclonal antibodies, as well as on vaccine-based preventive strategies. These sections are preceded by overviews of CAP in general, the role of the pneumococcus as the causative pathogen, the occurrence and types of CAP-associated cardiac complication, and the structure and biological activities of PLY.

OPTICON: Pro-Matlab software for large order controlled structure design

NASA Technical Reports Server (NTRS)

Peterson, Lee D.

1989-01-01

A software package for large order controlled structure design is described and demonstrated. The primary program, called OPTICAN, uses both Pro-Matlab M-file routines and selected compiled FORTRAN routines linked into the Pro-Matlab structure. The program accepts structural model information in the form of state-space matrices and performs three basic design functions on the model: (1) open loop analyses; (2) closed loop reduced order controller synthesis; and (3) closed loop stability and performance assessment. The current controller synthesis methods which were implemented in this software are based on the Generalized Linear Quadratic Gaussian theory of Bernstein. In particular, a reduced order Optimal Projection synthesis algorithm based on a homotopy solution method was successfully applied to an experimental truss structure using a 58-state dynamic model. These results are presented and discussed. Current plans to expand the practical size of the design model to several hundred states and the intention to interface Pro-Matlab to a supercomputing environment are discussed.

Elucidating proline dynamics in spider dragline silk fibre using 2H-13C HETCOR MAS NMR.

PubMed

Shi, Xiangyan; Yarger, Jeffery L; Holland, Gregory P

2014-05-14

(2)H-(13)C HETCOR MAS NMR is performed on (2)H/(13)C/(15)N-Pro enriched A. aurantia dragline silk. Proline dynamics are extracted from (2)H NMR line shapes and T1 in a site-specific manner to elucidate the backbone and side chain molecular dynamics for the MaSp2 GPGXX β-turn regions for spider dragline silk in the dry and wet, supercontracted states.

Amazing "Speaking Dynamically" Tools Utilized in High School Special Education Classroom.

ERIC Educational Resources Information Center

Robinson, Deann A.; Attix, Gerald V.

This paper describes how Alameda High School in California is using the Speaking Dynamically Pro v2.0 software by Mayer-Johnson to help 13 special education students (ages 14-18) communicate and make the world more accessible. The students have a range of disabilities and skill levels. This computer program enables the students to make choices,…

Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics.

PubMed

Tanzi, Luana; Ramondo, Fabio; Caminiti, Ruggero; Campetella, Marco; Di Luca, Andrea; Gontrani, Lorenzo

2015-09-21

We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations and anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features.

Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics

NASA Astrophysics Data System (ADS)

Tanzi, Luana; Ramondo, Fabio; Caminiti, Ruggero; Campetella, Marco; Di Luca, Andrea; Gontrani, Lorenzo

2015-09-01

We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations and anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features.

N-terminal pro-B-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes.

PubMed

Heeschen, Christopher; Hamm, Christian W; Mitrovic, Veselin; Lantelme, Nicte-Ha; White, Harvey D

2004-11-16

Elevated baseline levels of B-type natriuretic peptide (BNP) and the N-terminal fragments of its prohormone, N-terminal-pro-BNP (NT-proBNP), have been associated with adverse long-term outcome in patients with acute coronary syndromes, whereas the prognostic implications of serial NT-proBNP measurements have not been investigated to date. NT-proBNP, troponin T, and C-reactive protein were measured at baseline and at 48 and 72 hours in 1791 patients with non-ST-elevation acute coronary syndromes. Death and myocardial infarction were recorded during 30 days of follow-up. After adjustment for independent predictors of cardiac risk, baseline NT-proBNP levels >250 ng/L were associated with higher event rates (adjusted OR, 3.7; 95% CI, 2.3 to 5.7; P<0.001). In troponin T-negative patients, NT-proBNP identified a subgroup of high-risk patients (OR, 5.9; 95% CI, 2.6 to 13.3; P<0.001). The risk in those patients (7.2%) did not significantly differ from that in troponin T-positive patients (9.8%; P=0.25). Importantly, clinical stabilization without refractory ischemia was associated with a rapid (as soon as 48 hours after onset of symptoms) and significant (48 hours; -24%; 72 hours, -49%; both P<0.001) decline in NT-proBNP levels. In patients with high NT-proBNP baseline levels, lack of a rapid decline in NT-proBNP levels (< or =250 ng/L) was linked to an adverse short-term prognosis (OR, 33.7; 95% CI, 8.2 to 138.8; P<0.001). In patients with low NT-proBNP baseline levels, a rise in NT-proBNP levels over 72 hours to >250 ng/L was also linked to an adverse 30-day prognosis (OR, 24.0; 95% CI, 8.4 to 68.5; P<0.001). Neurohumoral activation as evidenced by NT-proBNP appears as a unifying feature that is independent of other biochemical markers (myocardial necrosis, inflammation) and is a powerful and independent determinant of the short-term cardiac risk in patients with acute coronary syndromes. Whether serial measurements of NT-proBNP in patients with ACS may be used to more rapidly identify patients suitable for early discharge or more intensive therapy deserves future prospective studies.

Antimicrobial Peptide Potency is Facilitated by Greater Conformational Flexibility when Binding to Gram-negative Bacterial Inner Membranes

NASA Astrophysics Data System (ADS)

Amos, Sarah-Beth T. A.; Vermeer, Louic S.; Ferguson, Philip M.; Kozlowska, Justyna; Davy, Matthew; Bui, Tam T.; Drake, Alex F.; Lorenz, Christian D.; Mason, A. James

2016-11-01

The interaction of antimicrobial peptides (AMPs) with the inner membrane of Gram-negative bacteria is a key determinant of their abilities to exert diverse bactericidal effects. Here we present a molecular level understanding of the initial target membrane interaction for two cationic α-helical AMPs that share structural similarities but have a ten-fold difference in antibacterial potency towards Gram-negative bacteria. The binding and insertion from solution of pleurocidin or magainin 2 to membranes representing the inner membrane of Gram-negative bacteria, comprising a mixture of 128 anionic and 384 zwitterionic lipids, is monitored over 100 ns in all atom molecular dynamics simulations. The effects of the membrane interaction on both the peptide and lipid constituents are considered and compared with new and published experimental data obtained in the steady state. While both magainin 2 and pleurocidin are capable of disrupting bacterial membranes, the greater potency of pleurocidin is linked to its ability to penetrate within the bacterial cell. We show that pleurocidin displays much greater conformational flexibility when compared with magainin 2, resists self-association at the membrane surface and penetrates further into the hydrophobic core of the lipid bilayer. Conformational flexibility is therefore revealed as a key feature required of apparently α-helical cationic AMPs for enhanced antibacterial potency.

Bordetella Pertussis Toxin does not induce the release of pro-inflammatory cytokines in human whole blood.

PubMed

Bache, Christina; Spreitzer, Ingo; Becker, Bjoern; Loeschner, Bettina; Rosskopf, Ute; Hanschmann, Kay-Martin; Schwanig, Michael; Schneider, Christian K; Lieb, Bernhard; Montag, Thomas

2012-08-01

Pertussis Toxin (PTx) is one of the most important virulence factors of Bordetella pertussis, the cause of whooping cough. Therefore, the inactivated toxin is an obligatory constituent of acellular pertussis vaccines. It is described in the literature that both native PTx and recombinant Pertussis Toxin (PTg) activate human monocytes whereas others report an inhibition of mammalian monocytes during pertussis infection. B. pertussis, as a Gram-negative bacterium, harbours naturally lipopolysaccharide (LPS, also known as endotoxin), one of the strongest stimulators of monocytes. The latter is triggered via the interaction of endotoxin with inter alia the surface receptor CD14. Consequently, it is necessary to consider a potential contamination of Pertussis Toxin preparations with LPS. First, we determined the LPS content in different preparations of PTx and PTg. All preparations examined were contaminated with LPS; therefore, possible PTx- and PTg-driven monocyte activation independently of LPS was investigated. To meet these aims, we examined monocyte response to PTx and PTg while blocking the LPS receptor CD14 with a specific monoclonal antibody (anti-CD14 mAb). In addition, all toxin preparations examined underwent an LPS depletion. Our results show that it is contaminating LPS, not Pertussis Toxin, which activates human monocytes. Blocking the CD14 receptor prevents Pertussis Toxin-mediated induction of pro-inflammatory cytokines in human monocytes. The depletion of LPS from Pertussis Toxin leads to the same effect. Additionally, the PTx toxicity after LPS depletion procedure was confirmed by animal tests. In contrast, the original Pertussis Toxin preparations not treated as mentioned above generate strong monocyte activation. The results in this publication allow the conclusion that purified Pertussis Toxin preparations do not induce the release of pro-inflammatory cytokines in human whole blood.

Conformational flexibility of DENV NS2B/NS3pro: from the inhibitor effect to the serotype influence

NASA Astrophysics Data System (ADS)

Piccirillo, Erika; Merget, Benjamin; Sotriffer, Christoph A.; do Amaral, Antonia T.

2016-03-01

The dengue virus (DENV) has four well-known serotypes, namely DENV1 to DENV4, which together cause 50-100 million infections worldwide each year. DENV NS2B/NS3pro is a protease recognized as a valid target for DENV antiviral drug discovery. However, NS2B/NS3pro conformational flexibility, involving in particular the NS2B region, is not yet completely understood and, hence, a big challenge for any virtual screening (VS) campaign. Molecular dynamics (MD) simulations were performed in this study to explore the DENV3 NS2B/NS3pro binding-site flexibility and obtain guidelines for further VS studies. MD simulations were done with and without the Bz-nKRR-H inhibitor, showing that the NS2B region stays close to the NS3pro core even in the ligand-free structure. Binding-site conformational states obtained from the simulations were clustered and further analysed using GRID/PCA, identifying four conformations of potential importance for VS studies. A virtual screening applied to a set of 31 peptide-based DENV NS2B/NS3pro inhibitors, taken from literature, illustrated that selective alternative pharmacophore models can be constructed based on conformations derived from MD simulations. For the first time, the NS2B/NS3pro binding-site flexibility was evaluated for all DENV serotypes using homology models followed by MD simulations. Interestingly, the number of NS2B/NS3pro conformational states differed depending on the serotype. Binding-site differences could be identified that may be crucial to subsequent VS studies.

Bacterial Community Dynamics during Production of Registered Designation of Origin Salers Cheese as Evaluated by 16S rRNA Gene Single-Strand Conformation Polymorphism Analysis

PubMed Central

Duthoit, Frédérique; Godon, Jean-Jacques; Montel, Marie-Christine

2003-01-01

Microbial dynamics during processing and ripening of traditional cheeses such as registered designation of origin Salers cheese, an artisanal cheese produced in France, play an important role in the elaboration of sensory qualities. The aim of the present study was to obtain a picture of the dynamics of the microbial ecosystem of RDO Salers cheese by using culture-independent methods. This included DNA extraction, PCR, and single-strand conformation polymorphism (SSCP) analysis. Bacterial and high-GC% gram-positive bacterial primers were used to amplify V2 or V3 regions of the 16S rRNA gene. SSCP patterns revealed changes during the manufacturing of the cheese. Patterns of the ecosystems of cheeses that were provided by three farmers were also quite different. Cloning and sequencing of the 16S rRNA gene revealed sequences related to lactic acid bacteria (Lactococcus lactis, Streptococcus thermophilus, Enterococcus faecium, Leuconostoc mesenteroides, Leuconostoc pseudomesenteroides, Lactobacillus plantarum, and Lactobacillus pentosus), which were predominant during manufacturing and ripening. Bacteria belonging to the high-GC% gram-positive group (essentially corynebacteria) were found by using specific primers. The present molecular approach can effectively describe the ecosystem of artisanal dairy products. PMID:12839752

In-Culture Cross-Linking of Bacterial Cells Reveals Large-Scale Dynamic Protein-Protein Interactions at the Peptide Level.

PubMed

de Jong, Luitzen; de Koning, Edward A; Roseboom, Winfried; Buncherd, Hansuk; Wanner, Martin J; Dapic, Irena; Jansen, Petra J; van Maarseveen, Jan H; Corthals, Garry L; Lewis, Peter J; Hamoen, Leendert W; de Koster, Chris G

2017-07-07

Identification of dynamic protein-protein interactions at the peptide level on a proteomic scale is a challenging approach that is still in its infancy. We have developed a system to cross-link cells directly in culture with the special lysine cross-linker bis(succinimidyl)-3-azidomethyl-glutarate (BAMG). We used the Gram-positive model bacterium Bacillus subtilis as an exemplar system. Within 5 min extensive intracellular cross-linking was detected, while intracellular cross-linking in a Gram-negative species, Escherichia coli, was still undetectable after 30 min, in agreement with the low permeability in this organism for lipophilic compounds like BAMG. We were able to identify 82 unique interprotein cross-linked peptides with <1% false discovery rate by mass spectrometry and genome-wide database searching. Nearly 60% of the interprotein cross-links occur in assemblies involved in transcription and translation. Several of these interactions are new, and we identified a binding site between the δ and β' subunit of RNA polymerase close to the downstream DNA channel, providing a clue into how δ might regulate promoter selectivity and promote RNA polymerase recycling. Our methodology opens new avenues to investigate the functional dynamic organization of complex protein assemblies involved in bacterial growth. Data are available via ProteomeXchange with identifier PXD006287.

m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.

PubMed

Consolato, Francesco; Maltecca, Francesca; Tulli, Susanna; Sambri, Irene; Casari, Giorgio

2018-04-09

The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation of mitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and auto-proteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 [matrix (m) - AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m - AAA and i - AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

Computational investigation of the conformational profile of the four stereomers of Ac-L-Pro-c3Phe-NHMe (c3Phe= 2,3-methanophenylalanine).

PubMed

Rodriguez, Alejandro; Canto, Josep; Corcho, Francesc J; Perez, Juan J

2009-01-01

The present report regards a computational study aimed at assessing the conformational profile of the four stereoisomers of the peptide Ace-Pro-c3Phe-NMe, previously reported to exhibit beta-turn structures in dichloromethane with different type I/type II beta-turn profiles. Molecular systems were represented at the molecular mechanics level using the parm96 parameterization of the AMBER force field. Calculations were carried out in dichloromethane using an implicit solvent approach. Characterization of the conformational features of the peptide analogs was carried out using simulated annealing (SA), molecular dynamics (MD) and replica exchange molecular dynamics (REMD). Present results show that MD calculations do not provide a reasonable sampling after 300 ns. In contrast, both SA and REMD provide similar results and agree well with experimental observations. Copyright 2009 Wiley Periodicals, Inc.

Activating and Attenuating the Amicoumacin Antibiotics.

PubMed

Park, Hyun Bong; Perez, Corey E; Perry, Elena Kim; Crawford, Jason M

2016-06-24

The amicoumacins belong to a class of dihydroisocoumarin natural products and display antibacterial, antifungal, anticancer, and anti-inflammatory activities. Amicoumacins are the pro-drug activation products of a bacterial nonribosomal peptide-polyketide hybrid biosynthetic pathway and have been isolated from Gram-positive Bacillus and Nocardia species. Here, we report the stimulation of a "cryptic" amicoumacin pathway in the entomopathogenic Gram-negative bacterium Xenorhabdus bovienii, a strain not previously known to produce amicoumacins. X. bovienii participates in a multi-lateral symbiosis where it is pathogenic to insects and mutualistic to its Steinernema nematode host. Waxmoth larvae are common prey of the X. bovienii-Steinernema pair. Employing a medium designed to mimic the amino acid content of the waxmoth circulatory fluid led to the detection and characterization of amicoumacins in X. bovienii. The chemical structures of the amicoumacins were supported by 2D-NMR, HR-ESI-QTOF-MS, tandem MS, and polarimeter spectral data. A comparative gene cluster analysis of the identified X. bovienii amicoumacin pathway to that of the Bacillus subtilis amicoumacin pathway and the structurally-related Xenorhabdus nematophila xenocoumacin pathway is presented. The X. bovienii pathway encodes an acetyltransferase not found in the other reported pathways, which leads to a series of N-acetyl-amicoumacins that lack antibacterial activity. N-acetylation of amicoumacin was validated through in vitro protein biochemical studies, and the impact of N-acylation on amicoumacin's mode of action was examined through ribosomal structural analyses.

Co-occurrence of anaerobic bacteria in colorectal carcinomas.

PubMed

Warren, René L; Freeman, Douglas J; Pleasance, Stephen; Watson, Peter; Moore, Richard A; Cochrane, Kyla; Allen-Vercoe, Emma; Holt, Robert A

2013-05-15

Numerous cancers have been linked to microorganisms. Given that colorectal cancer is a leading cause of cancer deaths and the colon is continuously exposed to a high diversity of microbes, the relationship between gut mucosal microbiome and colorectal cancer needs to be explored. Metagenomic studies have shown an association between Fusobacterium species and colorectal carcinoma. Here, we have extended these studies with deeper sequencing of a much larger number (n = 130) of colorectal carcinoma and matched normal control tissues. We analyzed these data using co-occurrence networks in order to identify microbe-microbe and host-microbe associations specific to tumors. We confirmed tumor over-representation of Fusobacterium species and observed significant co-occurrence within individual tumors of Fusobacterium, Leptotrichia and Campylobacter species. This polymicrobial signature was associated with over-expression of numerous host genes, including the gene encoding the pro-inflammatory chemokine Interleukin-8. The tumor-associated bacteria we have identified are all Gram-negative anaerobes, recognized previously as constituents of the oral microbiome, which are capable of causing infection. We isolated a novel strain of Campylobacter showae from a colorectal tumor specimen. This strain is substantially diverged from a previously sequenced oral Campylobacter showae isolate, carries potential virulence genes, and aggregates with a previously isolated tumor strain of Fusobacterium nucleatum. A polymicrobial signature of Gram-negative anaerobic bacteria is associated with colorectal carcinoma tissue.

Acyloxyacyl hydrolase promotes the resolution of lipopolysaccharide-induced acute lung injury

PubMed Central

Tang, Zihui; Yang, Qian; Qian, Guojun; Qian, Jing; Zeng, Wenjiao; Gu, Jie; Chu, Tianqing; Zhu, Ning; Zhang, Wenhong; Yan, Dapeng; He, Rui; Chu, Yiwei

2017-01-01

Pulmonary infection is the most common risk factor for acute lung injury (ALI). Innate immune responses induced by Microbe-Associated Molecular Pattern (MAMP) molecules are essential for lung defense but can lead to tissue injury. Little is known about how MAMP molecules are degraded in the lung or how MAMP degradation/inactivation helps prevent or ameliorate the harmful inflammation that produces ALI. Acyloxyacyl hydrolase (AOAH) is a host lipase that inactivates Gram-negative bacterial endotoxin (lipopolysaccharide, or LPS). We report here that alveolar macrophages increase AOAH expression upon exposure to LPS and that Aoah+/+ mice recover more rapidly than do Aoah-/- mice from ALI induced by nasally instilled LPS or Klebsiella pneumoniae. Aoah-/- mouse lungs had more prolonged leukocyte infiltration, greater pro- and anti-inflammatory cytokine expression, and longer-lasting alveolar barrier damage. We also describe evidence that the persistently bioactive LPS in Aoah-/- alveoli can stimulate alveolar macrophages directly and epithelial cells indirectly to produce chemoattractants that recruit neutrophils to the lung and may prevent their clearance. Distinct from the prolonged tolerance observed in LPS-exposed Aoah-/- peritoneal macrophages, alveolar macrophages that lacked AOAH maintained or increased their responses to bioactive LPS and sustained inflammation. Inactivation of LPS by AOAH is a previously unappreciated mechanism for promoting resolution of pulmonary inflammation/injury induced by Gram-negative bacterial infection. PMID:28622363

The alyteserins: two families of antimicrobial peptides from the skin secretions of the midwife toad Alytes obstetricans (Alytidae).

PubMed

Conlon, J Michael; Demandt, Anni; Nielsen, Per F; Leprince, Jérôme; Vaudry, Hubert; Woodhams, Douglas C

2009-06-01

Two families of structurally related C-terminally alpha-amidated antimicrobial peptides have been identified in norepinephrine-stimulated skin secretions of the midwife toad Alytes obstetricans (Alytidae). The alyteserin-1 peptides (Gly-Leu-Lys-(Asp/Glu)-Ile-Phe-Lys-Ala-Gly-Leu-Gly-Ser-Leu-Val-Lys-(Gly/Asn)-Ile-Ala-Ala-His-Val-Ala-(Asn/Ser).NH(2)) show limited structural similarity to the ascaphins from the skins of frogs of the family Leiopelmatidae. Alyteserin-2a (Ile-Leu-Gly-Lys-Leu-Leu-Ser-Thr-Ala-Ala-Gly-Leu-Leu-Ser-Asn-Leu.NH(2)) and alyteserin-2b and -2c (Ile-Leu-Gly-Ala-Ile-Leu-Pro-Leu-Val-Ser-Gly-Leu-Leu-Ser-(Asn/Ser)-Lys-Leu x NH(2)) show limited sequence identity with bombinin H6, present in the skins of frogs of the family Bombinatoridae. The alyteserin-1 peptides show selective growth inhibitory activity against the Gram-negative bacteria Escherichia coli (MIC=25 microM) whereas alyteserin-2a is more potent against the Gram-positive bacteria Staphylococcus aureus (MIC=50 microM). The hemolytic activity against human erythrocytes of all peptides tested is relatively weak (LC(50)>100 microM). The data demonstrate that the frogs belonging to the family Alytidae are among those producing dermal antimicrobial peptides that may represent a component of the animal's system of innate immunity.

Stage-specific control of early B cell development by the transcription factor Ikaros

PubMed Central

Gültekin, Sinan; Dakic, Aleksandar; Axelsson, Elin; Minnich, Martina; Ebert, Anja; Werner, Barbara; Roth, Mareike; Cimmino, Luisa; Dickins, Ross A.; Zuber, Johannes; Jaritz, Markus; Busslinger, Meinrad

2018-01-01

Ikaros is an essential regulator of lymphopoiesis. Here, we studied the B-cell-specific function of Ikaros by conditional Ikzf1 inactivation in pro-B cells. B-cell development was arrested at an aberrant ‘pro-B’ cell stage characterized by increased cell adhesion and loss of pre-B cell receptor signaling. Ikaros was found to activate genes coding for pre-BCR signal transducers and to repress genes involved in the downregulation of pre-BCR signaling and upregulation of the integrin signaling pathway. Unexpectedly, derepression of Aiolos expression could not compensate for the loss of Ikaros in pro-B cells. Ikaros induced or suppressed active chromatin at regulatory elements of activated or repressed target genes. Notably, Ikaros binding and target gene expression was dynamically regulated at distinct stages of early B-lymphopoiesis. PMID:24509509

Athlete's foot caused by pseudomonas aeruginosa.

PubMed

Abramson, C

1983-01-01

An enzymatically active pigment-producing clinical isolate of Pseudomonas aeruginosa was found to produce a diffusible antifungal product that was shown to be inhibitory to the growth of several dermatophytes, specifically, Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum gypseum, and Microsporum audouini. In this study, Trichophyton rubrum was used as the test organism. The antifungal product was partially purified by Sephadex column chromatography and was found to be stable at 5 degrees, 25 degrees, and 37 degrees C. Several investigators have alluded to the fact that as asymptomatic cases of dermatophytosis simplex progress to symptomatic dermatophytosis complex, the bacterial profile changes from a gram-positive bacterial ecosystem to a gram-negative bacterial over-growth. The primary event in the pathogenesis of interdigital athlete's foot is the invasion of the horny layer by dermatophytes. This presents as a mild to moderate scaly lesion and is asymptomatic. As a result of predisposing factors, such as hyperhidrosis, occlusion by tight shoes, minute abrasions due to friction, and fungal-infected skin surfaces, dynamic overgrowth of opportunistic gram-negative bacilli prevails. As the gram-negative population increases, the recovery of dermatophytes dramatically diminishes, until a point is reached when no dermatophytes can be recovered from clinically symptomatic tinea pedis. Pseudomonas aeruginosa is inhibiting its fungal competitor Trichophyton rubrum by producing a diffusible antifungal agent into the infectious environment of the intertriginous foot lesion. Clinically, the patient is diagnosed as having tinea pedis; laboratory culture for fungus and KOH are negative, and what was a paradox just a few years ago can currently be identified and treated appropriately as gram-negative athlete's foot.

Comparison of self-processing of foot-and-mouth disease virus leader proteinase and porcine reproductive and respiratory syndrome virus leader proteinase nsp1α

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

Steinberger, Jutta; Kontaxis, Georg; Rancan, Chiara

The foot-and-mouth disease virus leader proteinase (Lb{sup pro}) cleaves itself off the nascent viral polyprotein. NMR studies on the monomeric variant Lb{sup pro} L200F provide structural evidence for intramolecular self-processing. {sup 15}N-HSQC measurements of Lb{sup pro} L200F showed specifically shifted backbone signals in the active and substrate binding sites compared to the monomeric variant sLb{sup pro}, lacking six C-terminal residues. This indicates transient intramolecular interactions between the C-terminal extension (CTE) of one molecule and its own active site. Contrastingly, the porcine reproductive and respiratory syndrome virus (PRRSV) leader proteinase nsp1α, with a papain-like fold like Lb{sup pro}, stably binds itsmore » own CTE. Parts of the β-sheet domains but none of the α-helical domains of Lb{sup pro} and nsp1α superimpose; consequently, the α-helical domain of nsp1α is oriented differently relative to its β-sheet domain. This provides a large interaction surface for the CTE with the globular domain, stabilising the intramolecular complex. Consequently, self-processing inactivates nsp1α but not Lb{sup pro}. - Highlights: • We examine self-processing of the leader protease of foot-and-mouth disease virus. • NMR analysis strongly supports intramolecular self-processing. • Self-processing is a dynamic process with no stable complex. • Structural comparison with nsp1α of PRRSV which forms stable intramolecular complex. • Subdomain orientation explains differences in stability of intramolecular complexes.« less

Immunotherapy in the management of sepsis.

PubMed

Sikora, Janusz Piotr

2002-01-01

This work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so-called "respiratory burst" of neutrophils and the antioxidant mechanisms of the host are also discussed. The work focuses on possible approaches to the management of sepsis connected with immunotherapy. Neutralization of endotoxin lipopolysaccharide (LPS), anti-tumor necrosis factor alpha (TNF-alpha) therapy with monoclonal antibodies or pentoxifylline (PTXF), as well as soluble recombinant cytokine agonists and antagonists used in clinical trials are taken into consideration. In addition, cytokine manipulation therapy, anti-adhesion techniques, glucocorticoides and antioxidant barrier interference are also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts an aggressive examination of the immune system aimed at affecting its function.

History of the Field Army Ballistic Missile Defense System Project, 1959-1962

DTIC Science & Technology

1963-01-01

design and/or development. The t o t a l funding of t he program under con- t r a c t a s of November 1959 was $4,984,000, An immediate te rmina t...p a b i l i t y of defending a g a i n s t a n a l l - a l t i t u d e , a i r - suppor t ed t h r e a t . Under t he se i n s t r u c t i o...ion of t he development phase i n t he . fol lowing f i s c a l year were t o be pro- grammed under t he l i n e i tem F i e l d Army B a l

Dynamic technique for measuring adsorption in a gas chromatograph

NASA Technical Reports Server (NTRS)

Deuel, C. L.; Hultgren, N. W.; Mobert, M. L.

1973-01-01

Gas-chromatographic procedure, together with mathematical analysis of adsorption isotherm, allows relative surface areas and adsorptive powers for trace concentrations to be determined in a few minutes. Technique may be used to evaluate relative surface areas of different adsorbates, expressed as volume of adsorbent/gram of adsorbate, and to evaluate their relative adsorptive power.

Photophysical studies on curcumin-sophorolipid nanostructures: applications in quorum quenching and imaging

PubMed Central

2018-01-01

Sophorolipid biosurfactants are biodegradable, less toxic and FDA approved. The purified acidic form of sophorolipid is stimuli-responsive with self-assembling properties and used for solubilizing hydrophobic drugs. This study encapsulated curcumin (CU) with acidic sophorolipid (ASL) micelles and analysed using photophysical studies like UV-visible spectroscopy, photoluminescence (PL) spectroscopy and time-correlated single photon counting (TCSPC). TEM images have revealed ellipsoid micelles of approximately 100 nm size and were confirmed by dynamic light scattering. The bacterial fluorescence uptake studies showed the uptake of formed CUASL nanostructures into both Gram-positive and Gram-negative bacteria. They also showed quorum quenching activity against Pseudomonas aeruginosa. The results have demonstrated this system has potential theranostic applications. PMID:29515826

Aspects of eukaryotic-like signaling in Gram-positive cocci: a focus on virulence

PubMed Central

Burnside, Kellie; Rajagopal, Lakshmi

2011-01-01

Living organisms adapt to the dynamic external environment for their survival. Environmental adaptation in prokaryotes is thought to be primarily accomplished by signaling events mediated by two-component systems, consisting of histidine kinases and response regulators. However, eukaryotic-like serine/threonine kinases (STKs) have recently been described to regulate growth, antibiotic resistance and virulence of pathogenic bacteria. This article summarizes the role of STKs and their cognate phosphatases (STPs) in Gram-positive cocci that cause invasive infections in humans. Given that a large number of inhibitors to eukaryotic STKs are approved for use in humans, understanding how serine/threonine phosphorylation regulates virulence and antibiotic resistance will be beneficial for the development of novel therapeutic strategies against bacterial infections. PMID:21797690

Molecular modeling of Gram-positive bacteria peptidoglycan layer, selected glycopeptide antibiotics and vancomycin derivatives modified with sugar moieties.

PubMed

Ślusarz, Rafał; Szulc, Monika; Madaj, Janusz

2014-05-07

Proper understanding of the mechanisms of binding to Gram-positive bacteria cell wall layers-especially to the peptidoglycan (PG) layer, seems to be crucial for proper development of new drug candidates which are effective against these bacteria. In this work we have constructed two different models of the Gram-positive bacteria PG layer: the layered and the scaffold models. PG conformational changes during geometry optimization, models relaxation, and molecular dynamics were described and discussed. We have found that the border surface of both PG layer models differs from the surface located away from the edge of models and the chains formed by disaccharide units prefer helix-like conformation. This curling of PG chains significantly affects the shape of antibiotic-accessible surface and the process is thus crucial for new drug development. Glycopeptide antibiotics effective against Gram-positive bacteria, such as vancomycin and its semisynthetic derivatives-oritavancin and telavancin, bind to d-alanyl-d-alanine stem termini on the peptidoglycan precursors of the cell wall. This binding inhibits cross-linking between the peptides and subsequently prevents cell wall synthesis. In this study some of the aspects of conformational freedom of vancomycin and restrictions from the modifications of vancomycin structure introduced into oritavancin and telavancin and five other vancomycin derivatives (with addition of 2-acetamido-2-deoxy-β-d-galactopyranosylamine, 2-acetamido-2-deoxy-β-d-glucopyranosylamine, 1-amine-1-deoxy-d-glucitol, 2-amino-2-deoxy-d-galactitol, or 2-amino-2-deoxy-d-glucitol to the C-terminal amino acid group in the vancomycin) are presented and discussed. The resulting molecular dynamics trajectories, root mean square deviation changes of aglycon and saccharide moieties as well as a comparative study of possible interactions with cyclic and chain forms of modified groups have been carried out, measured, and analyzed. Energetically advantageous conformations show close similarity to the structures known from the experimental data, but the diversity of others suggest very high conformational freedom of all modeled antibiotics and vancomycin derivatives. Alditol derivatives move closer to the peptidoglycan chain more easily but they also form intramolecular interactions more frequently than their homologous cyclic forms. One of the proposed derivatives seems to be a promising agent which is efficient in treatment of infections caused by Gram-positive bacteria. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hexapeptide fragment of carcinoembryonic antigen which acts as an agonist of heterogeneous ribonucleoprotein M.

PubMed

Palermo, Nicholas Y; Thomas, Peter; Murphy, Richard F; Lovas, Sándor

2012-04-01

Colorectal cancers with metastatic potential secrete the glycoprotein carcinoembryonic antigen (CEA). CEA has been implicated in colorectal cancer metastasis by inducing Kupffer cells to produce inflammatory cytokines which, in turn, make the hepatic micro-environment ideal for tumor cell implantation. CEA binds to the heterogeneous ribonucleoprotein M (hnRNP M) which acts as a cell surface receptor in Kupffer cells. The amino acid sequence in CEA, which binds the hnRNP M receptor, is Tyr-Pro-Glu-Leu-Pro-Lys. In this study, the structure of Ac-Tyr-Pro-Glu-Leu-Pro-Lys-NH₂ (YPELPK) was investigated using electronic circular dichroism, vibrational circular dichroism, and molecular dynamics simulations. The binding of the peptide to hnRNP M was also investigated using molecular docking calculations. The biological activity of YPELPK was studied using differentiated human THP-1 cells, which express hnRNP M on their surface and secrete IL-6 when stimulated by CEA. YPELPK forms a stable polyproline-II helix and stimulates IL-6 production of THP-1 cells at micromolar concentrations. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

Enantioselective complexation of chiral propylene oxide by an enantiopure water-soluble cryptophane.

PubMed

Bouchet, Aude; Brotin, Thierry; Linares, Mathieu; Ågren, Hans; Cavagnat, Dominique; Buffeteau, Thierry

2011-05-20

ECD and NMR experiments show that the complexation of propylene oxide (PrO) within the cavity of an enantiopure water-soluble cryptophane 1 in NaOH solution is enantioselective and that the (R)-PrO@PP-1 diastereomer is more stable than the (S)-PrO@PP-1 diastereomer with a free energy difference of 1.7 kJ/mol. This result has been confirmed by molecular dynamics (MD) and ab initio calculations. The enantioselectivity is preserved in LiOH and KOH solutions even though the binding constants decrease, whereas PrO is not complexed in CsOH solution.

Dynamic self-guiding analysis of Alzheimer's disease

PubMed Central

Kurakin, Alexei; Bredesen, Dale E.

2015-01-01

We applied a self-guiding evolutionary algorithm to initiate the synthesis of the Alzheimer's disease-related data and literature. A protein interaction network associated with amyloid-beta precursor protein (APP) and a seed model that treats Alzheimer's disease as progressive dysregulation of APP-associated signaling were used as dynamic “guides” and structural “filters” in the recursive search, analysis, and assimilation of data to drive the evolution of the seed model in size, detail, and complexity. Analysis of data and literature across sub-disciplines and system-scale discovery platforms suggests a key role of dynamic cytoskeletal connectivity in the stability, plasticity, and performance of multicellular networks and architectures. Chronic impairment and/or dysregulation of cell adhesions/synapses, cytoskeletal networks, and/or reversible epithelial-to-mesenchymal-like transitions, which enable and mediate the stable and coherent yet dynamic and reconfigurable multicellular architectures, may lead to the emergence and persistence of the disordered, wound-like pockets/microenvironments of chronically disconnected cells. Such wound-like microenvironments support and are supported by pro-inflammatory, pro-secretion, de-differentiated cellular phenotypes with altered metabolism and signaling. The co-evolution of wound-like microenvironments and their inhabitants may lead to the selection and stabilization of degenerated cellular phenotypes, via acquisition of epigenetic modifications and mutations, which eventually result in degenerative disorders such as cancer and Alzheimer's disease. PMID:26041885

Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics

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

Tanzi, Luana; Ramondo, Fabio, E-mail: fabio.ramondo@univaq.it; Caminiti, Ruggero

2015-09-21

We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations andmore » anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features.« less

Acute ileitis facilitates infection with multidrug resistant Pseudomonas aeruginosa in human microbiota-associated mice.

PubMed

von Klitzing, Eliane; Ekmekciu, Ira; Bereswill, Stefan; Heimesaat, Markus M

2017-01-01

The rising incidence of multidrug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa has become a serious issue in prevention of its spread particularly among hospitalized patients. It is, however, unclear whether distinct conditions such as acute intestinal inflammation facilitate P. aeruginosa infection of vertebrate hosts. To address this, we analysed P. aeruginosa infection in human microbiota-associated (hma) mice with acute ileitis induced by peroral Toxoplasma gondii challenge. When perorally infected with P. aeruginosa at day 3 post ileitis induction, hma mice displayed higher intestinal P. aeruginosa loads as compared to hma mice without ileitis. However, the overall intestinal microbiota composition was not disturbed by P. aeruginosa (except for lowered bifidobacterial populations), and the infection did not further enhance ileal immune cell responses. Pro-inflammatory cytokines including IFN-γ and IL-12p70 were similarly increased in ileum and mesenteric lymph nodes of P. aeruginosa infected and uninfected hma mice with ileitis. The anti-inflammatory cytokine IL-10 increased multifold upon ileitis induction, but interestingly more distinctly in P. aeruginosa infected as compared to uninfected controls. Immune responses were not restricted to the intestines as indicated by elevated pro-inflammatory cytokine levels in liver and kidney upon ileitis induction. However, except for hepatic TNF-α levels, P. aeruginosa infection did not result in more distinct pro-inflammatory cytokine secretion in liver and kidney of hma mice with ileitis. Whereas viable intestinal bacteria were more frequently detected in systemic compartments such as spleen and cardiac blood of P. aeruginosa infected than uninfected mice at day 7 following ileitis induction, P. aeruginosa infection did not exacerbate systemic pro-inflammatory sequelae, but resulted in lower IL-10 serum levels. Acute intestinal inflammation facilitates infection of the vertebrate host with MDR bacteria including P. aeruginosa and might also pose particularly hospitalized patients at risk for acquisition. Since acute T. gondii induced inflammation might mask immunopathology caused by P. aeruginosa , a subacute or chronic inflammation model might be better suited to investigate the potential role of P. aeruginosa infection in the aggravation of intestinal disease.

Propulsive Small Expendable Deployer System (ProSEDS)

NASA Technical Reports Server (NTRS)

Curtis, Leslie; Johnson, Les; Brown, Norman S. (Technical Monitor)

2002-01-01

The Propulsive Small Expendable Deployer System (ProSEDS) space experiment will demonstrate the use of an electrodynamic tether propulsion system to generate thrust in space by decreasing the orbital altitude of a Delta 11 Expendable Launch Vehicle second stage. ProSEDS, which is planned on an Air Force GPS Satellite replacement mission in June 2002, will use the flight proven Small Expendable Deployer System (SEDS) to deploy a tether (5 km bare wire plus 10 km non-conducting Dyneema) from a Delta 11 second stage to achieve approx. 0.4N drag thrust. ProSEDS will utilize the tether-generated current to provide limited spacecraft power. The ProSEDS instrumentation includes Langmuir probes and Differential Ion Flux Probes, which will determine the characteristics of the ambient ionospheric plasma. Two Global Positioning System (GPS) receivers will be used (one on the Delta and one on the endmass) to help determine tether dynamics and to limit transmitter operations to occasions when the spacecraft is over selected ground stations. The flight experiment is a precursor to the more ambitious electrodynamic tether upper stage demonstration mission, which will be capable of orbit raising, lowering and inclination changes-all using electrodynamic thrust. An immediate application of ProSEDS technology is for the removal of spent satellites for orbital debris mitigation. In addition to the use of this technology to provide orbit transfer and debris mitigation it may also be an attractive option for future missions to Jupiter and any other planetary body with a magnetosphere.

Propulsive Small Expendable Deployer System (ProSEDS)

NASA Technical Reports Server (NTRS)

Ballance, Judy; Johnson, Les; Rogacki, John R. (Technical Monitor)

2000-01-01

The Propulsive Small Expendable Deployer System (ProSEDS) space experiment will demonstrate the use of an electrodynamic tether propulsion system to generate thrust in space by decreasing the orbital altitude of a Delta II Expendable Launch Vehicle (ELV) second stage. ProSEDS, which is planned to fly in 2001, will use the flight proven Small Expendable Deployer System (SEDS) to deploy a tether (5km bare wire plus 10 km spectra or dyneema) from a Delta II second stage to achieve approximately 0.4N drag thrust. ProSEDS will utilize the tether-generated current to provide limited spacecraft power. The ProSEDs instrumentation includes a Langmuir probe and Differential Ion Flux Probe, which will determine the characteristics of the ambient ionospheric plasma. Two Global Positioning System (GPS) receivers will be used (one on the Delta and one on the endmass) to help determine tether dynamics and to limit transmitter operations to occasions when the spacecraft is over selected ground stations, The flight experiment is a precursor to the more ambitious electrodynamic tether upper stage demonstration mission, which will be capable of orbit raising, lowering and inclination changes-all using electrodynamic thrust. An immediate application of ProSEDS technology is for the deorbit of spent satellites for orbital debris mitigation. In addition to the use of this technology to provide orbit transfer and debris mitigation it may also be an attractive option for future missions to Jupiter and any other planetary body with a magnetosphere.

Inactivation dynamics of 222 nm krypton-chlorine excilamp irradiation on Gram-positive and Gram-negative foodborne pathogenic bacteria.

PubMed

Kang, Jun-Won; Kim, Sang-Soon; Kang, Dong-Hyun

2018-07-01

The object of this study was to elucidate the bactericidal mechanism of a 222 nm Krypton Chlorine (KrCl) excilamp compared with that of a 254 nm Low Pressure mercury (LP Hg) lamp. The KrCl excilamp had higher bactericidal capacity against Gram-positive pathogenic bacteria (Staphylococcus aureus and L. monocytogenes) and Gram-negative pathogenic bacteria (S. Typhimurium and E. coli O157:H7) than did the LP Hg lamp when cell suspensions in PBS were irradiated with each type of UV lamp. It was found out that the KrCl excilamp induced cell membrane damage as a form of depolarization. From the study of respiratory chain dehydrogenase activity and the lipid peroxidation assay, it was revealed that cell membrane damage was attributed to inactivation of enzymes related to generation of membrane potential and occurrence of lipid peroxidation. Direct absorption of UV radiation which led to photoreaction through formation of an excited state was one of the causes inducing cell damage. Additionally, generation of ROS and thus occurrence of secondary damage can be another cause. The LP Hg lamp only induced damage to DNA but not to other components such as lipids or proteins. This difference was derived from differences of UV radiation absorption by cellular materials. Copyright © 2018 Elsevier Ltd. All rights reserved.

Challenges of including nitrogen effects on decomposition in earth system models

NASA Astrophysics Data System (ADS)

Hobbie, S. E.

2011-12-01

Despite the importance of litter decomposition for ecosystem fertility and carbon balance, key uncertainties remain about how this fundamental process is affected by nitrogen (N) availability. Nevertheless, resolving such uncertainties is critical for mechanistic inclusion of such processes in earth system models, towards predicting the ecosystem consequences of increased anthropogenic reactive N. Towards that end, we have conducted a series of experiments examining nitrogen effects on litter decomposition. We found that both substrate N and externally supplied N (regardless of form) accelerated the initial decomposition rate. Faster initial decomposition rates were linked to the higher activity of carbohydrate-degrading enzymes associated with externally supplied N and the greater relative abundances of Gram negative and Gram positive bacteria associated with green leaves and externally supplied organic N (assessed using phospholipid fatty acid analysis, PLFA). By contrast, later in decomposition, externally supplied N slowed decomposition, increasing the fraction of slowly decomposing litter and reducing lignin-degrading enzyme activity and relative abundances of Gram negative and Gram positive bacteria. Our results suggest that elevated atmospheric N deposition may have contrasting effects on the dynamics of different soil carbon pools, decreasing mean residence times of active fractions comprising very fresh litter, while increasing those of more slowly decomposing fractions including more processed litter. Incorporating these contrasting effects of N on decomposition processes into models is complicated by lingering uncertainties about how these effects generalize across ecosystems and substrates.

Effect of Cycling Skills on Bicycle Safety and Comfort Associated with Bicycle Infrastructure and Environment

DOT National Transportation Integrated Search

2017-08-31

This study seeks to improve the methodology for determining the relationship between cycling dynamic performance and roadway environment characteristics across different bicyclists' skill levels. To achieve the goal of this study, an Instrumented Pro...

Macrophage Pro-Inflammatory Response to Francisella novicida Infection Is Regulated by SHIP

PubMed Central

Parsa, Kishore V. L; Ganesan, Latha P; Rajaram, Murugesan V. S; Gavrilin, Mikhail A; Balagopal, Ashwin; Mohapatra, Nrusingh P; Wewers, Mark D; Schlesinger, Larry S; Gunn, John S; Tridandapani, Susheela

2006-01-01

Francisella tularensis, a Gram-negative facultative intracellular pathogen infecting principally macrophages and monocytes, is the etiological agent of tularemia. Macrophage responses to F. tularensis infection include the production of pro-inflammatory cytokines such as interleukin (IL)-12, which is critical for immunity against infection. Molecular mechanisms regulating production of these inflammatory mediators are poorly understood. Herein we report that the SH2 domain-containing inositol phosphatase (SHIP) is phosphorylated upon infection of primary murine macrophages with the genetically related F. novicida, and negatively regulates F. novicida–induced cytokine production. Analyses of the molecular details revealed that in addition to activating the MAP kinases, F. novicida infection also activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in these cells. Interestingly, SHIP-deficient macrophages displayed enhanced Akt activation upon F. novicida infection, suggesting elevated PI3K-dependent activation pathways in absence of SHIP. Inhibition of PI3K/Akt resulted in suppression of F. novicida–induced cytokine production through the inhibition of NFκB. Consistently, macrophages lacking SHIP displayed enhanced NFκB-driven gene transcription, whereas overexpression of SHIP led to decreased NFκB activation. Thus, we propose that SHIP negatively regulates F. novicida–induced inflammatory cytokine response by antagonizing the PI3K/Akt pathway and suppressing NFκB-mediated gene transcription. A detailed analysis of phosphoinositide signaling may provide valuable clues for better understanding the pathogenesis of tularemia. PMID:16848641

Core-oscillator model of Caulobacter crescentus

NASA Astrophysics Data System (ADS)

Vandecan, Yves; Biondi, Emanuele; Blossey, Ralf

2016-06-01

The gram-negative bacterium Caulobacter crescentus is a powerful model organism for studies of bacterial cell cycle regulation. Although the major regulators and their connections in Caulobacter have been identified, it still is a challenge to properly understand the dynamics of its circuitry which accounts for both cell cycle progression and arrest. We show that the key decision module in Caulobacter is built from a limit cycle oscillator which controls the DNA replication program. The effect of an induced cell cycle arrest is demonstrated to be a key feature to classify the underlying dynamics.

Composition and immuno-stimulatory properties of extracellular DNA from mouse gut flora.

PubMed

Qi, Ce; Li, Ya; Yu, Ren-Qiang; Zhou, Sheng-Li; Wang, Xing-Guo; Le, Guo-Wei; Jin, Qing-Zhe; Xiao, Hang; Sun, Jin

2017-11-28

To demonstrate that specific bacteria might release bacterial extracellular DNA (eDNA) to exert immunomodulatory functions in the mouse small intestine. Extracellular DNA was extracted using phosphate buffered saline with 0.5 mmol/L dithiothreitol combined with two phenol extractions. TOTO-1 iodide, a cell-impermeant and high-affinity nucleic acid stain, was used to confirm the existence of eDNA in the mucus layers of the small intestine and colon in healthy Male C57BL/6 mice. Composition difference of eDNA and intracellular DNA (iDNA) of the small intestinal mucus was studied by Illumina sequencing and terminal restriction fragment length polymorphism (T-RFLP). Stimulation of cytokine production by eDNA was studied in RAW264.7 cells in vitro . TOTO-1 iodide staining confirmed existence of eDNA in loose mucus layer of the mouse colon and thin surface mucus layer of the small intestine. Illumina sequencing analysis and T-RFLP revealed that the composition of the eDNA in the small intestinal mucus was significantly different from that of the iDNA of the small intestinal mucus bacteria. Illumina Miseq sequencing showed that the eDNA sequences came mainly from Gram-negative bacteria of Bacteroidales S24-7. By contrast, predominant bacteria of the small intestinal flora comprised Gram-positive bacteria. Both eDNA and iDNA were added to native or lipopolysaccharide-stimulated Raw267.4 macrophages, respectively. The eDNA induced significantly lower tumor necrosis factor-α/interleukin-10 (IL-10) and IL-6/IL-10 ratios than iDNA, suggesting the predominance for maintaining immune homeostasis of the gut. Our results indicated that degraded bacterial genomic DNA was mainly released by Gram-negative bacteria, especially Bacteroidales-S24-7 and Stenotrophomonas genus in gut mucus of mice. They decreased pro-inflammatory activity compared to total gut flora genomic DNA.

Evolutionary emergence of angiogenesis in avascular tumors using a spatial public goods game

PubMed Central

Salimi Sartakhti, Javad; Manshaei, Mohammad Hossein; Sadeghi, Mehdi

2017-01-01

Natural selection in cancer often results in the emergence of increasingly malignant tumor cells that display many if not all of the hallmarks of cancer. One of the most important traits acquired during cancer progression is angiogenesis. Tumor cells capable of secreting pro-angiogenic factors can be seen as cooperators where the improved oxygenation, nutrient delivery and waste disposal resulting from angiogenesis could be seen as a public good. Under this view, the relatively costly secretion of molecular signals required to orchestrate angiogenesis would be undertaken exclusively by cooperating tumor cells but the benefits of angiogenesis would be felt by neighboring tumor cells regardless of their contribution to the process. In this work we detail a mathematical model to better understand how clones capable of secreting pro-angiogenic factors can emerge in a tumor made of non-cooperative tumor cells. Given the importance of the spatial configuration of the tumor in determining the efficacy of the secretion of pro-angiogenic factors as well as the benefits of angiogenesis we have developed a spatial game theoretic approach where interactions and public good diffusion are described by graphs. The results show that structure of the population affects the evolutionary dynamics of the pro-angiogenic clone. Specifically, when the benefit of angiogenesis is represented by sigmoid function with regards to the number of pro-angiogenic clones then the probability of the coexistence of pro-angiogenic and angiogenesis-neutral clones increases. Our results demonstrate that pro-angiogenic clone equilibrates into clusters that appear from surrounding vascular tissues towards the center of tumor. These clusters appear notably less dense after anti-angiogenic therapy. PMID:28399181

Cyclic fatigue of three types of rotary nickel-titanium files in a dynamic model.

PubMed

Yao, James H; Schwartz, Scott A; Beeson, Thomas J

2006-01-01

The cyclic fatigue resistance of three types of nickel-titanium rotary files was compared in a model using reciprocating axial movement. The influence of file size and taper was also investigated and fracture patterns were examined under SEM. The 10 experimental groups consisted of ProFiles, K3s, and RaCe files, size 25 in .04 and .06 tapers, as well as ProFiles and K3s, size 40 in .04 and .06 tapers. Each file was rotated freely at 300 rpm inside a stainless steel tube with a 60 degree and 5 mm radius of curvature. A continuous 3 mm oscillating axial motion was applied at 1 cycle per second by attaching an electric dental handpiece to the most inferior load cell of an Instron machine using a custom-made jig. The number of rotations to failure was determined and analyzed using analysis of variance and Tukey's post hoc tests. Overall, K3 25/.04 files were significantly more resistant to cyclic fatigue compared to any other group in this study. In the 25/.04 category, K3s were significantly more resistant to failure than ProFiles and RaCe files. Also in the same category, ProFiles significantly outlasted RaCe files. In the 25/.06 group, K3s and ProFiles were significantly more resistant to failure than RaCe files, but K3s were not significantly different than ProFiles. In the 40/.04 and 40/.06 groups, K3s were significantly more resistant to cyclic fatigue than ProFiles. SEM observations demonstrated mostly a ductile mode of fracture. The results suggest that different cross-sectional designs, diameters, and tapers all contribute to a nickel-titanium instrument's vulnerability to cyclic failure.

Dynamic impact of brief electrical nerve stimulation on the neural immune axis-polarization of macrophages toward a pro-repair phenotype in demyelinated peripheral nerve.

PubMed

McLean, Nikki A; Verge, Valerie M K

2016-09-01

Demyelinating peripheral nerves are infiltrated by cells of the monocyte lineage, including macrophages, which are highly plastic, existing on a continuum from pro-inflammatory M1 to pro-repair M2 phenotypic states. Whether one can therapeutically manipulate demyelinated peripheral nerves to promote a pro-repair M2 phenotype remains to be elucidated. We previously identified brief electrical nerve stimulation (ES) as therapeutically beneficial for remyelination, benefits which include accelerated clearance of macrophages, making us theorize that ES alters the local immune response. Thus, the impact of ES on the immune microenvironment in the zone of demyelination was examined. Adult male rat tibial nerves were focally demyelinated via 1% lysophosphatidyl choline (LPC) injection. Five days later, half underwent 1 hour 20 Hz sciatic nerve ES proximal to the LPC injection site. ES had a remarkable and significant impact, shifting the macrophage phenotype from predominantly pro-inflammatory/M1 toward a predominantly pro-repair/M2 one, as evidenced by an increased incidence of expression of M2-associated phenotypic markers in identified macrophages and a decrease in M1-associated marker expression. This was discernible at 3 days post-ES (8 days post-LPC) and continued at the 5 day post-ES (10 days post-LPC) time point examined. ES also affected chemokine (C-C motif) ligand 2 (CCL2; aka MCP-1) expression in a manner that correlated with increases and decreases in macrophage numbers observed in the demyelination zone. The data establish that briefly increasing neuronal activity favorably alters the immune microenvironment in demyelinated nerve, rapidly polarizing macrophages toward a pro-repair phenotype, a beneficial therapeutic concept that may extend to other pathologies. GLIA 2016;64:1546-1561. © 2016 Wiley Periodicals, Inc.

Risk assessment and subsequent nursing interventions in a forensic mental health inpatient setting: Associations and impact on aggressive behaviour.

PubMed

Maguire, Tessa; Daffern, Michael; Bowe, Steven J; McKenna, Brian

2018-03-01

To examine associations between risk of aggression and nursing interventions designed to prevent aggression. There is scarce empirical research exploring the nature and effectiveness of interventions designed to prevent inpatient aggression. Some strategies may be effective when patients are escalating, whereas others may be effective when aggression is imminent. Research examining level of risk for aggression and selection and effectiveness of interventions and impact on aggression is necessary. Archival case file. Data from clinical files of 30 male and 30 female patients across three forensic acute units for the first 60 days of hospitalisation were collected. Risk for imminent aggression as measured by the Dynamic Appraisal of Situational Aggression, documented nursing interventions following each assessment, and acts of aggression within the 24-hours following assessment were collected. Generalised estimating equations were used to investigate whether intervention strategies were associated with reduction in aggression. When a Dynamic Appraisal of Situational Aggression assessment was completed, nurses intervened more frequently compared to days when no Dynamic Appraisal of Situational Aggression assessment was completed. Higher Dynamic Appraisal of Situational Aggression assessments were associated with a greater number of interventions. The percentage of interventions selected for males differed from females; males received more pro re nata medication and observation, and females received more limit setting, one-to-one nursing and reassurance. Pro re nata medication was the most commonly documented intervention (35.9%) in this study. Pro re nata medication, limit setting and reassurance were associated with an increased likelihood of aggression in some risk bands. Structured risk assessment prompts intervention, and higher risk ratings result in more interventions. Patient gender influences the type of interventions. Some interventions are associated with increased aggression, although this depends upon gender and risk level. When structured risk assessments are used, there is greater likelihood of intervention. Intervention should occur early using least restrictive interventions. © 2017 John Wiley & Sons Ltd.

Role of the Outer Pore Domain in Transient Receptor Potential Vanilloid 1 Dynamic Permeability to Large Cations*

PubMed Central

Munns, Clare H.; Chung, Man-Kyo; Sanchez, Yuly E.; Amzel, L. Mario; Caterina, Michael J.

2015-01-01

Transient receptor potential vanilloid 1 (TRPV1) has been shown to alter its ionic selectivity profile in a time- and agonist-dependent manner. One hallmark of this dynamic process is an increased permeability to large cations such as N-methyl-d-glucamine (NMDG). In this study, we mutated residues throughout the TRPV1 pore domain to identify loci that contribute to dynamic large cation permeability. Using resiniferatoxin (RTX) as the agonist, we identified multiple gain-of-function substitutions within the TRPV1 pore turret (N628P and S629A), pore helix (F638A), and selectivity filter (M644A) domains. In all of these mutants, maximum NMDG permeability was substantially greater than that recorded in wild type TRPV1, despite similar or even reduced sodium current density. Two additional mutants, located in the pore turret (G618W) and selectivity filter (M644I), resulted in significantly reduced maximum NMDG permeability. M644A and M644I also showed increased and decreased minimum NMDG permeability, respectively. The phenotypes of this panel of mutants were confirmed by imaging the RTX-evoked uptake of the large cationic fluorescent dye YO-PRO1. Whereas none of the mutations selectively altered capsaicin-induced changes in NMDG permeability, the loss-of-function phenotypes seen with RTX stimulation of G618W and M644I were recapitulated in the capsaicin-evoked YO-PRO1 uptake assay. Curiously, the M644A substitution resulted in a loss, rather than a gain, in capsaicin-evoked YO-PRO1 uptake. Modeling of our mutations onto the recently determined TRPV1 structure revealed several plausible mechanisms for the phenotypes observed. We conclude that side chain interactions at a few specific loci within the TRPV1 pore contribute to the dynamic process of ionic selectivity. PMID:25568328

Role of the outer pore domain in transient receptor potential vanilloid 1 dynamic permeability to large cations.

PubMed

Munns, Clare H; Chung, Man-Kyo; Sanchez, Yuly E; Amzel, L Mario; Caterina, Michael J

2015-02-27

Transient receptor potential vanilloid 1 (TRPV1) has been shown to alter its ionic selectivity profile in a time- and agonist-dependent manner. One hallmark of this dynamic process is an increased permeability to large cations such as N-methyl-D-glucamine (NMDG). In this study, we mutated residues throughout the TRPV1 pore domain to identify loci that contribute to dynamic large cation permeability. Using resiniferatoxin (RTX) as the agonist, we identified multiple gain-of-function substitutions within the TRPV1 pore turret (N628P and S629A), pore helix (F638A), and selectivity filter (M644A) domains. In all of these mutants, maximum NMDG permeability was substantially greater than that recorded in wild type TRPV1, despite similar or even reduced sodium current density. Two additional mutants, located in the pore turret (G618W) and selectivity filter (M644I), resulted in significantly reduced maximum NMDG permeability. M644A and M644I also showed increased and decreased minimum NMDG permeability, respectively. The phenotypes of this panel of mutants were confirmed by imaging the RTX-evoked uptake of the large cationic fluorescent dye YO-PRO1. Whereas none of the mutations selectively altered capsaicin-induced changes in NMDG permeability, the loss-of-function phenotypes seen with RTX stimulation of G618W and M644I were recapitulated in the capsaicin-evoked YO-PRO1 uptake assay. Curiously, the M644A substitution resulted in a loss, rather than a gain, in capsaicin-evoked YO-PRO1 uptake. Modeling of our mutations onto the recently determined TRPV1 structure revealed several plausible mechanisms for the phenotypes observed. We conclude that side chain interactions at a few specific loci within the TRPV1 pore contribute to the dynamic process of ionic selectivity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Three Dimensional Dynamics of Freshwater Lenses in the Oceans Near Surface Layer

DTIC Science & Technology

2016-09-14

a third new front appeared…” However, this striking effect was observed only when the following con- ditions for the Froude number (Fr) and the... Coriolis forces and, strictly speaking, is valid only for the equatorial region. CONCLUSIONS Convective rains within the ITCZ pro- duce localized...freshwater plumes under the influence of both ambient stratification and wind stress and how they interact to affect plume dynam- ics. The Coriolis

An Assessment of Team Development at the Air Force Flight Dynamics Laboratory.

DTIC Science & Technology

1980-09-01

FLIGHT DYNAMICS LABORATORY S. PERFORMING OG. REPORT NUMGER 7. AUTHOR(*) S. CONTRACT ON GRANT NUMBER(s) illiam D. Rutley, Captain, USAF _. PERFORMING ...the change from 1978 to 1980 on eleven criterion variables, employee job satisfaction, job motivation and absenteeism ; five organizational climate...variables except absenteeism . Absenteeism data were obtained from AFFDL intern~al records. The four main pro- duct divisions of AFlDL se.-ve-i as subjects

System Dynamics Modeling for Proactive Intelligence

DTIC Science & Technology

2010-01-01

5  4. Modeling Resources as Part of an Integrated Multi- Methodology System .................. 16  5. Formalizing Pro-Active...Observable Data With and Without Simulation Analysis ............................... 15  Figure 13. Summary of Probe Methodology and Results...Strategy ............................................................................. 22  Figure 22. Overview of Methodology

Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis.

PubMed

Treibel, Thomas A; Bandula, Steve; Fontana, Marianna; White, Steven K; Gilbertson, Janet A; Herrey, Anna S; Gillmore, Julian D; Punwani, Shonit; Hawkins, Philip N; Taylor, Stuart A; Moon, James C

2015-01-01

Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed. To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT. Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area). ECVCT and ECVCMR results were well correlated (r(2) = 0.85 vs r(2) = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone scintigraphy amyloid burden (p<0.001). Dynamic Equilibrium CT, a 5 minute contrast-enhanced gated cardiac CT, has potential for non-invasive diagnosis and quantification of cardiac amyloidosis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Interactions of 2-phenyl-benzotriazole xenobiotic compounds with human Cytochrome P450-CYP1A1 by means of docking, molecular dynamics simulations and MM-GBSA calculations.

PubMed

Mena-Ulecia, Karel; MacLeod-Carey, Desmond

2018-06-01

2-phenyl-benzotriazole xenobiotic compounds (PBTA-4, PBTA-6, PBTA-7 and PBTA-8) that were previously isolated and identified in waters of the Yodo river, in Japan (Nukaya et al., 2001; Ohe et al., 2004; Watanabe et al., 2001) were characterized as powerful pro-mutagens. In order to predict the activation mechanism of these pro-mutagens, we designed a computational biochemistry protocol, which includes, docking experiments, molecular dynamics simulations and free energy decomposition calculations to obtain information about the interaction of 2-phenyl-benzotriazole molecules into the active center of cytochrome P450-CYP1A1 (CYP1A1). Molecular docking calculations using AutoDock Vina software shows that PBTAs are proportionally oriented in the pocket of CYP1A1, establishing π-π stacking attractive interactions between the triazole group and the Phe224, as well as, the hydrogen bonds of the terminal NH 2 over the benzotriazole units with the Asn255 and Ser116 amino acids. Molecular dynamics simulations using NAMD package showed that these interactions are stable along 100.0 ns of trajectories. Into this context, free binding energy calculations employing the MM-GBSA approach, shows that some differences exists among the interaction of PBTAs with CYP1A1, regarding the solvation, electrostatic and van der Waals interaction energy components. These results suggest that PBTA molecules might be activated by CYP1A1. Thus, enhancing their mutagenicity when compared with the pro-mutagen parent species. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Shock and Vibration Bulletin: Proceedings on the Symposium on ShocK and Vibration (52nd) Held in New Orleans, Louisiana on 26-28 October 1981. Part 2. Invited Papers, Space Shuttle Loads and Dynamics, Space Shuttle Data Systems, Shock Testing, Shock Analysis Space Shuttle Thermal Protection Systems

DTIC Science & Technology

1982-05-01

discovered during posttest inspection. The unit had experienced 2 As- designed damper, 0.92-1-.14 grams 8 tests for a total of 330 seconds of opera- 3...a Modeling DAMPED STRUCTURE DESIGN USING FINITE ELEMENT ANALYSIS M. F. Klunmner and M. L. Drake, University of Dayti-n Resatch Institute, Dayton, OH...IN DYNAMICS T. E. Simkins, U.S. Army Armament Research and Development Command, Watervliet, NY Stucturd Dynamics A PROCEDURE FOR DESIGNING OVERDAMPED

Simulation of Non-resonant Internal Kink Mode with Toroidal Rotation in NSTX

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

Fu, Guoyong

2013-07-16

Plasmas in spherical and conventional tokamaks, with weakly reversed shear q pro le and minimum q above but close to unity, are susceptible to an non-resonant (m, n ) = (1, 1) internal kink mode. This mode can saturate and persist and can induce a (2; 1) seed island for Neoclassical Tearing Mode (NTMs)1 . The mode can also lead to large energetic particle transport and signi cant broadening of beam-driven current. Motivated by these important e ects, we have carried out extensive nonlinear simulations of the mode with nite toroidal rotation using parameters and pro les of an NTSXmore » plasma with a weakly reversed shear pro le. The numerical results show that, at the experimental level, plasma rotation has little e ect on either equilibrium or linear stability. However, rotation can signi cantly inuence the nonlinear dynamics of the (1, 1) mode and the the induced (2, 1) magnetic island. The simulation results show that a rotating helical equilibrium is formed and maintained in the nonlinear phase at nite plasma rotation. In contrast, for non-rotating cases, the nonlinear evolution exhibits dynamic oscillations between a quasi-2D state and a helical state. Furthermore, the e ects of rotation are found to greatly suppress the (2, 1) magnetic island even at a low level.« less

The Propulsive Small Expendable Deployer System (ProSEDS)

NASA Technical Reports Server (NTRS)

Lorenzini, Enrico C.

2002-01-01

This Annual Report covers the following main topics: 1) Updated Reference Mission. The reference ProSEDS (Propulsive Small Expendable Deployer System) mission is evaluated for an updated launch date in the Summer of 2002 and for the new 80-s current operating cycle. Simulations are run for nominal solar activity condition at the time of launch and for extreme conditions of dynamic forcing. Simulations include the dynamics of the system, the electrodynamics of the bare tether, the neutral atmosphere and the thermal response of the tether. 2) Evaluation of power delivered by the tether system. The power delivered by the tethered system during the battery charging mode is computed under the assumption of minimum solar activity for the new launch date. 3) Updated Deployment Control Profiles and Simulations. A number of new deployment profiles were derived based on the latest results of the deployment ground tests. The flight profile is then derived based on the friction characteristics obtained from the deployment tests of the F-1 tether. 4) Analysis/estimation of deployment flight data. A process was developed to estimate the deployment trajectory of the endmass with respect to the Delta and the final libration amplitude from the data of the deployer turn counters. This software was tested successfully during the ProSEDS mission simulation at MSFC (Marshall Space Flight Center) EDAC (Environments Data Analysis Center).

Molecular basis of thermal stability in truncated (2/2) hemoglobins.

PubMed

Bustamante, Juan P; Bonamore, Alessandra; Nadra, Alejandro D; Sciamanna, Natascia; Boffi, Alberto; Estrin, Darío A; Boechi, Leonardo

2014-07-01

Understanding the molecular mechanism through which proteins are functional at extreme high and low temperatures is one of the key issues in structural biology. To investigate this phenomenon, we have focused on two instructive truncated hemoglobins from Thermobifida fusca (Tf-trHbO) and Mycobacterium tuberculosis (Mt-trHbO); although the two proteins are structurally nearly identical, only the former is stable at high temperatures. We used molecular dynamics simulations at different temperatures as well as thermal melting profile measurements of both wild type proteins and two mutants designed to interchange the amino acid residue, either Pro or Gly, at E3 position. The results show that the presence of a Pro at the E3 position is able to increase (by 8°) or decrease (by 4°) the melting temperature of Mt-trHbO and Tf-trHbO, respectively. We observed that the ProE3 alters the structure of the CD loop, making it more flexible. This gain in flexibility allows the protein to concentrate its fluctuations in this single loop and avoid unfolding. The alternate conformations of the CD loop also favor the formation of more salt-bridge interactions, together augmenting the protein's thermostability. These results indicate a clear structural and dynamical role of a key residue for thermal stability in truncated hemoglobins. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular Hydrogen Formation from Proximal Glycol Pairs on TiO2(110)

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

Chen, Long; Li, Zhenjun; Smith, R. Scott

2014-04-16

Understanding hydrogen formation on TiO2 surfaces is of great importance as it could provide fundamental insight into water splitting for hydrogen production using solar energy. In this work, hydrogen formation from glycols having different numbers of methyl end-groups have been studied using temperature pro-grammed desorption on reduced, hydroxylated, and oxidized TiO2(110) surfaces. The results from OD-labeled glycols demon-strate that gas-phase molecular hydrogen originates exclusively from glycol hydroxyl groups. The yield is controlled by a combi-nation of glycol coverage, steric hindrance, TiO2(110) order and the amount of subsurface charge. Combined, these results show that proximal pairs of hydroxyl aligned glycol moleculesmore » and subsurface charge are required to maximize the yield of this redox reaction. These findings highlight the importance of geometric and electronic effects in hydrogen formation from adsorbates on TiO2(110).« less

[New antibiotics produced by Bacillus subtilis strains].

PubMed

Malanicheva, I A; Kozlov, D G; Efimenko, T A; Zenkova, V A; Kastrukha, G S; Reznikova, M I; Korolev, A M; Borshchevskaia, L N; Tarasova, O D; Sineokiĭ, S P; Efremenkova, O V

2014-01-01

Two Bacillus subtilis strains isolated from the fruiting body of a basidiomycete fungus Pholiota squarrosa exhibited a broad range of antibacterial activity, including those against methicillin-resistant Staphylococcus aureus INA 00761 (MRSA) and Leuconostoc mes6nteroides VKPM B-4177 resistant to glycopep-> tide antibiotics, as well as antifungal activity. The strains were identified as belonging to the "B. subtilis" com- plex based on their morphological and physiological characteristics, as well as by sequencing of the 16S rRNA gene fragments. Both strains (INA 01085 and INA 01086) produced insignificant amounts of polyene antibiotics (hexaen and pentaen, respectively). Strain INA 01086 produced also a cyclic polypeptide antibiotic containing Asp, Gly, Leu, Pro, Tyr, Thr, Trp, and Phe, while the antibiotic of strain INA 01085 contained, apart from these, two unidentified nonproteinaceous amino acids. Both polypeptide antibiotics were new compounds efficient against gram-positive bacteria and able to override the natural bacterial antibiotic resistance.

Chemical synthesis, NMR analysis and evaluation on a cancer xenograft model (HL-60) of the aminosteroid derivative RM-133.

PubMed

Maltais, René; Hospital, Audrey; Delhomme, Audrey; Roy, Jenny; Poirier, Donald

2014-04-01

The aminosteroid derivative RM-133 has been reported to be a promising pro-apoptotic agent showing activity on various cancer cell lines. Following the development of solid-phase synthesis that generated a series of libraries of aminosteroid derivatives, we now report the development of a convenient liquid phase chemical synthesis of RM-133, the most promising candidate, in order to obtain sufficient quantities to proceed with the first preclinical assays. A simple and convergent six-step synthesis was designed and allowed the preparation of a gram-quantity scale of RM-133. This aminosteroid derivative was also fully characterized by NMR experiments which revealed an interesting mixture of conformers. Finally, the in vivo potency of RM-133 was evaluated on a xenograft model in nude mice with HL-60 tumors, which has resulted in the blocking of tumor progression by 57%. Copyright © 2014 Elsevier Inc. All rights reserved.

DYNAMIC TUNING OF INSECT AND BIRD WINGS AND COPEPOD AND DAPHNIA APPENDAGES

EPA Science Inventory

Compressible flow theory suggests, and dimensional analysis and growing empirical evidence confirm that, to aid flight, many insects and even some birds, notably hummingbirds, tune their wing-beat frequency to a corresponding characteristic harmonic frequency of air. The same pro...

CHLORDANES IN THE MID-ATLANTIC ATMOSPHERE: NEW JERSEY 1997-1999

EPA Science Inventory

To characterize the atmospheric dynamics and behavior of chlordane compounds in the mid-Atlantic region of the United States, atmospheric concentrations were measured in 1997-1999 at three New Jersey locations as part of the New Jersey Atmospheric Deposition Network (NJADN) pro...

7 CFR 51.306 - Tolerances.

Code of Federal Regulations, 2013 CFR

2013-01-01

... inches or 65 grams 63 grams 21/4 inches or 75 grams 70 grams 23/8 inches or 84 grams 82 grams 21/2 inches or 100 grams 95 grams 25/8 inches or 115 grams 109 grams 23/4 inches or 139 grams 134 grams...

7 CFR 51.306 - Tolerances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... inches or 65 grams 63 grams 21/4 inches or 75 grams 70 grams 23/8 inches or 84 grams 82 grams 21/2 inches or 100 grams 95 grams 25/8 inches or 115 grams 109 grams 23/4 inches or 139 grams 134 grams...

Mixed pro and antisaccade performance in children and adults.

PubMed

Irving, Elizabeth L; Tajik-Parvinchi, Diana J; Lillakas, Linda; González, Esther G; Steinbach, Martin J

2009-02-19

Pro and antisaccades are usually presented in blocks of similar type but they can also be presented such that prosaccade and antisaccade eye movements are mixed and a cue, usually the shape/colour of the fixation target or the peripheral target, determines which type of eye movement is required in a particular trial. A mixed-saccade task theoretically equalizes the inhibitory requirements for pro and antisaccades. Using a mixed-saccade task paradigm the aims of the study were to: 1) compare pro and antisaccades of children, 2) compare performance of children and adults and 3) explore the effect of increased working memory load in adults. The eye movements of 22 children (5-12 years) and 22 adults (20-51 years) were examined using a video-based eye tracking system (El-Mar Series 2020 Eye Tracker, Toronto, Canada). The task was a mixed-saccade task of pro and antisaccades and the colour of the peripheral target was the cue for whether the required saccade was to be a pro or an antisaccade. The children performed the mixed-saccade task and 11 adults performed the same mixed-saccade task alone and in a dual-task paradigm (together with mental subtraction or number repetition). A second group of 11 adults performed the mixed-saccade task alone. Children made mainly antisaccade errors. The adults' error rates increased in the mental subtraction dual-task condition but both antisaccade and prosaccade errors were made. It was concluded that the increased error rates of these two groups are reflective of different processing dynamics.

Quantum Spin Dynamics with Pairwise-Tunable, Long-Range Interactions

DTIC Science & Technology

2016-08-05

rection of the arrows. Dashed (dotted) lines mark the NNN hopping terms (coefficients ±t2). NNNN long -range hopping along curved lines are included to...Quantum spin dynamics with pairwise-tunable, long -range interactions C.-L. Hunga,b,1,2, Alejandro González-Tudelac,1,2, J. Ignacio Ciracc, and H. J...atoms) that interact by way of a variety of processes, such as atomic collisions. Such pro- cesses typically lead to short -range, nearest-neighbor

A biogenesis step upstream of Microprocessor controls miR-17~92 expression

PubMed Central

Du, Peng; Wang, Longfei; Sliz, Piotr; Gregory, Richard I.

2015-01-01

SUMMARY The precise control of miR-17~92 microRNA (miRNA) is essential for normal development and overexpression of certain miRNAs from this cluster is oncogenic. Here we find the relative expression of the six miRNAs processed from the primary (pri-miR-17~92) transcript is dynamically regulated during embryonic stem cell (ESC) differentiation. Pri-miR-17~92 is processed to a biogenesis intermediate, termed ‘progenitor-miRNA’ (pro-miRNA). Pro-miRNA is an efficient substrate for Microprocessor and is required to selectively license production of pre-miR-17, -18a, -19a, 20a, and -19b from this cluster. Two complementary cis-regulatory repression domains within pri-miR-17~92 are required for the blockade of miRNA processing through the formation of an autoinhibitory RNA conformation. The endonuclease CPSF3 (CPSF73), and the Spliceosome-associated ISY1 are responsible for pro-miRNA biogenesis and expression of all miRNAs within the cluster except miR-92. Thus, developmentally regulated pro-miRNA processing is key step controlling miRNA expression and explains the posttranscriptional control of miR-17~92 expression in development. PMID:26255770

Fluorescence probe of polypeptide conformational dynamics in gas phase and in solution

NASA Astrophysics Data System (ADS)

Iavarone, Anthony T.; Meinen, Jan; Schulze, Susanne; Parks, Joel H.

2006-07-01

Fluorescence measurements of polypeptides derivatized with the fluorescent dye BODIPY TMR have been used to probe the polypeptide conformational dynamics as a function of temperature and charge state. Measurements of (BODIPY TMR)-[Pro]n-Arg-Trp and (BODIPY TMR)-[Gly-Ser]m-Arg-Trp have been performed for charge states 1+ and 2+ of n = 4 and 10 and m = 2 and 5. The 2+ charge states of both of these polypeptides exhibit similar temperature dependences for equal chain lengths (n = 4, m = 2 and n = 10, m = 5) and suggest conformations dominated by Coulomb repulsion. In the absence of such Coulomb repulsion, the 1+ charge state conformations appear to be characterized by the flexibility of the polypeptide chain for which [Gly-Ser]m > [Pro]n. Comparisons of these gas phase polypeptide measurements with corresponding measurements in solution provide a direct measure of the effects of solvent on the conformational dynamics. The change in fluorescence as a function of temperature in the gas phase is two orders of magnitude greater than that in solution, a dramatic result we attribute to the restrictions on intramolecular dynamics imposed by diffusion-limited kinetics and the lack of shielding by solvent. Measurements were also made of unsolvated Pron peptides without the tryptophan (Trp) residue to isolate the interaction of the fluorescent dye with charges.

Anti-endotoxic and antibacterial effects of a dermal substitute coated with host defense peptides.

PubMed

Kasetty, Gopinath; Kalle, Martina; Mörgelin, Matthias; Brune, Jan C; Schmidtchen, Artur

2015-01-01

Biomaterials used during surgery and wound treatment are of increasing importance in modern medical care. In the present study we set out to evaluate the addition of thrombin-derived host defense peptides to human acellular dermis (hAD, i.e. epiflex(®)). Antimicrobial activity of the functionalized hAD was demonstrated using radial diffusion and viable count assays against Gram-negative Escherichia coli, Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus bacteria. Electron microscopy analyses showed that peptide-mediated bacterial killing led to reduced hAD degradation. Furthermore, peptide-functionalized hAD displayed endotoxin-binding activity in vitro, as evidenced by inhibition of NF-κB activation in human monocytic cells (THP-1 cells) and a reduction of pro-inflammatory cytokine production in whole blood in response to lipopolysaccharide stimulation. The dermal substitute retained its anti-endotoxic activity after washing, compatible with results showing that the hAD bound a significant amount of peptide. Furthermore, bacteria-induced contact activation was inhibited by peptide addition to the hAD. E. coli infected hAD, alone, or after treatment with the antiseptic substance polyhexamethylenebiguanide (PHMB), yielded NF-κB activation in THP-1 cells. The activation was abrogated by peptide addition. Thus, thrombin-derived HDPs should be of interest in the further development of new biomaterials with combined antimicrobial and anti-endotoxic functions for use in surgery and wound treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A periplasmic D-alanyl-D-alanine dipeptidase in the gram-negative bacterium Salmonella enterica.

PubMed

Hilbert, F; García-del Portillo, F; Groisman, E A

1999-04-01

The VanX protein is a D-alanyl-D-alanine (D-Ala-D-Ala) dipeptidase essential for resistance to the glycopeptide antibiotic vancomycin. While this enzymatic activity has been typically associated with vancomycin- and teicoplainin-resistant enterococci, we now report the identification of a D-Ala-D-Ala dipeptidase in the gram-negative species Salmonella enterica. The Salmonella enzyme is only 36% identical to VanX but exhibits a similar substrate specificity: it hydrolyzes D-Ala-D-Ala, DL-Ala-DL-Phe, and D-Ala-Gly but not the tripeptides D-Ala-D-Ala-D-Ala and DL-Ala-DL-Lys-Gly or the dipeptides L-Ala-L-Ala, N-acetyl-D-Ala-D-Ala, and L-Leu-Pro. The Salmonella dipeptidase gene, designated pcgL, appears to have been acquired by horizontal gene transfer because pcgL-hybridizing sequences were not detected in related bacterial species and the G+C content of the pcgL-containing region (41%) is much lower than the overall G+C content of the Salmonella chromosome (52%). In contrast to wild-type Salmonella, a pcgL mutant was unable to use D-Ala-D-Ala as a sole carbon source. The pcgL gene conferred D-Ala-D-Ala dipeptidase activity upon Escherichia coli K-12 but did not allow growth on D-Ala-D-Ala. The PcgL protein localizes to the periplasmic space of Salmonella, suggesting that this dipeptidase participates in peptidoglycan metabolism.

Bacterial growth rates are influenced by cellular characteristics of individual species when immersed in electromagnetic fields.

PubMed

Tessaro, Lucas W E; Murugan, Nirosha J; Persinger, Michael A

2015-03-01

Previous studies have shown that exposure to extremely low-frequency electromagnetic fields (ELF-EMFs) have negative effects on the rate of growth of bacteria. In the present study, two Gram-positive and two Gram-negative species were exposed to six magnetic field conditions in broth cultures. Three variations of the 'Thomas' pulsed frequency-modulated pattern; a strong-static "puck" magnet upwards of 5000G in intensity; a pair of these magnets rotating opposite one another at ∼30rpm; and finally a strong dynamic magnetic field generator termed the 'Resonator' with an average intensity of 250μT were used. Growth rate was discerned by optical density (OD) measurements every hour at 600nm. ELF-EMF conditions significantly affected the rates of growth of the bacterial cultures, while the two static magnetic field conditions were not statistically significant. Most interestingly, the 'Resonator' dynamic magnetic field increased the rates of growth of three species (Staphylococcus epidermidis, Staphylococcus aureus, and Escherichia coli), while slowing the growth of one (Serratia marcescens). We suggest that these effects are due to individual biophysical characteristics of the bacterial species. Copyright © 2015 Elsevier GmbH. All rights reserved.

Dynamics of mono- and dual-species biofilm formation and interactions between Staphylococcus aureus and Gram-negative bacteria.

PubMed

Makovcova, Jitka; Babak, Vladimir; Kulich, Pavel; Masek, Josef; Slany, Michal; Cincarova, Lenka

2017-07-01

Microorganisms are not commonly found in the planktonic state but predominantly form dual- and multispecies biofilms in almost all natural environments. Bacteria in multispecies biofilms cooperate, compete or have neutral interactions according to the involved species. Here, the development of mono- and dual-species biofilms formed by Staphylococcus aureus and other foodborne pathogens such as Salmonella enterica subsp. enterica serovar Enteritidis, potentially pathogenic Raoultella planticola and non-pathogenic Escherichia coli over the course of 24, 48 and 72 h was studied. Biofilm formation was evaluated by the crystal violet assay (CV), enumeration of colony-forming units (CFU cm -2 ) and visualization using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). In general, Gram-negative bacterial species and S. aureus interacted in a competitive manner. The tested Gram-negative bacteria grew better in mixed dual-species biofilms than in their mono-species biofilms as determined using the CV assay, CFU ml -2 enumeration, and CLSM and SEM visualization. In contrast, the growth of S. aureus biofilms was reduced when cultured in dual-species biofilms. CLSM images revealed grape-like clusters of S. aureus and monolayers of Gram-negative bacteria in both mono- and dual-species biofilms. S. aureus clusters in dual-species biofilms were significantly smaller than clusters in S. aureus mono-species biofilms. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

7 CFR 51.306 - Tolerances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... largest fruit. Table II Red delicious Golden delicious 21/8 inches or 65 grams 63 grams 21/4 inches or 75 grams 70 grams 23/8 inches or 84 grams 82 grams 21/2 inches or 100 grams 95 grams 25/8 inches or 115 grams 109 grams 23/4 inches or 139 grams 134 grams Application of Tolerances ...

7 CFR 51.306 - Tolerances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... largest fruit. Table II Red delicious Golden delicious 21/8 inches or 65 grams 63 grams 21/4 inches or 75 grams 70 grams 23/8 inches or 84 grams 82 grams 21/2 inches or 100 grams 95 grams 25/8 inches or 115 grams 109 grams 23/4 inches or 139 grams 134 grams Application of Tolerances ...

7 CFR 51.306 - Tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... largest fruit. Table II Red delicious Golden delicious 21/8 inches or 65 grams 63 grams 21/4 inches or 75 grams 70 grams 23/8 inches or 84 grams 82 grams 21/2 inches or 100 grams 95 grams 25/8 inches or 115 grams 109 grams 23/4 inches or 139 grams 134 grams Application of Tolerances ...

Anti-cancer, anti-inflammatory and anti-microbial activities of plant extracts used against hematological tumors in traditional medicine of Jordan.

PubMed

Assaf, Areej M; Haddadin, Randa N; Aldouri, Nedhal A; Alabbassi, Reem; Mashallah, Sundus; Mohammad, Mohammad; Bustanji, Yasser

2013-02-13

Mercurialis annua L., Bongardia chrysogonum L., and Viscum cruciatum Sieb have been traditionally used by local herbalists in Jordan for the treatment of hematopoietic neoplasms. To determine the anti-cancer, anti-inflammatory and anti-microbial potentials of the three extracts against two of the most common hematopoietic malignancies in the Jordanian populations; Burkitt's lymphoma and Multiple myeloma. The anti-cancer activity was tested against the two cell lines (BJAB Burkitt's lymphoma and U266 multiple myeloma) using the MTT and trypan blue assays. The agar dilution assay was used to study the anti-microbial activity against Gram-positive bacteria, Gram-negative bacteria, anaerobic bacteria and yeast. The pro-inflammatory cytokines interleukin (IL) -1β, IL-8 and tumor necrosis factor-α (TNF-α) were measured in the pretreated cell lines using ELISA assay to determine the anti-inflammatory activity of Viscum cruciatum Sieb against the two cell lines. The results show no evidence of stimulation of tumor growth by any of the three extracts comprising cell lines from hematological malignancies, but Viscum cruciatum Sieb showed a selective anticancer activity against BJAB cells, with IC(50) value of 14.21μg/ml. The antimicrobial effect was only noticed with Viscum cruciatum extract by inhibiting Staphylococcus aureus, Candida albicans and Propionibacterium acne, but not Pseudomonas aeruginosa at MIC of 1.25, 1.25, 0.625 and <5mg/ml, respectively. The highest activity was against the anaerobic bacteria Propionibacterium acne. Viscum cruciatum Sieb extract showed an inhibitory effect on the pro-inflammatory cytokine IL-8, but it increased TNF-α and IL-1β secretions in BJAB cells. Whereas, it had an inhibitory effect on TNF-α and IL-1β cytokines while it enhanced IL-8 secretions in U266 cells. Among the three tested herbal extracts used in the traditional medicine in Jordan, only Viscum cruciatum Sieb showed high anti-cancer and anti-microbial potentials. They also had an anti-inflammatory effect. These observations raise the prospects of using Viscum cruciatum Sieb for treatment of diseases associated with some bacterial and fungal infections, for imbalanced cytokine production and for enhancing cancer and other immunotherapies. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The functional characterization and comparison of two single CRD containing C-type lectins with novel and typical key motifs from Portunus trituberculatus.

PubMed

Huang, Mengmeng; Mu, Changkao; Wu, Yuehong; Ye, Fei; Wang, Dan; Sun, Cong; Lv, Zhengbing; Han, Bingnan; Wang, Chunlin; Xu, Xue-Wei

2017-11-01

C-type lectins are a superfamily of Ca 2+ -dependent carbohydrate-recognition proteins, which play crucial roles in innate immunity including nonself-recognition and pathogen elimination. In the present study, two single-CRD containing C-type lectins were identified from swimming crab Portunus trituberculatus (designated as PtCTL-2 and PtCTL-3). The open reading frame (ORF) of PtCTL-2 encoded polypeptides of 485 amino acids with a signal peptide and a single carbohydrate-recognition domain (CRD), while PtCTL-3's ORF encoded polypeptides of 241 amino acids with a coiled-coil region and a single-CRD. The key motifs determining carbohydrate binding specificity in PtCTL-2 and PtCTL-3 were EPR (Glu-Pro-Arg) and QPD (Gln-Pro-Asp). EPR is a motif being identified for the first time, whereas QPD is a typical motif in C-type lectins. Different PAMPs binding features of the two recombinant proteins - PtCTL-2 (rPtCTL-2) and PtCTL-3 (rPtCTL-3) have been observed in our experiments. rPtCTL-2 could bind three pathogen-associated molecular patterns (PAMPs) with relatively high affinity, including glucan, lipopolysaccharide (LPS) and peptidoglycan (PGN), while rPtCTL-3 could barely bind any of them. However, rPtCTL-2 could bind seven kinds of microbes and rPtCTL-3 could bind six kinds in microbe binding assay. Moreover, rPtCTL-2 and rPtCTL-3 exhibited similar agglutination activity against Gram-positive bacteria, Gram-negative bacteria and fungi in agglutination assay. All these results illustrated that PtCTL-2 and PtCTL-3 could function as important pattern-recognition receptors (PRR) with broad nonself-recognition spectrum involved in immune defense against invaders. In addition, the results of carbohydrate binding specificity showed that PtCTL-2 with novel key motif had broad carbohydrate binding specificity, while PtCTL-3 with typical key motif possessed different carbohydrate binding specificity from the classical binding rule. Furthermore, PtCTL-2 and PtCTL-3 could also function as opsonin to enhance encapsulation of hemocytes against Ni-NTA beads. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota

PubMed Central

von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A.; Bereswill, Stefan

2017-01-01

Background Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Methodology/Principal findings Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. Conclusion/Significance With respect to the intestinal microbiota composition “humanized” mice display acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation. PMID:28414794

Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota.

PubMed

von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A; Bereswill, Stefan; Heimesaat, Markus M

2017-01-01

Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. With respect to the intestinal microbiota composition "humanized" mice display acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation.

Recognition of microbial molecular patterns and stimulation of prophenoloxidase activation by a β-1,3-glucanase-related protein in Manduca sexta larval plasma

PubMed Central

Wang, Yang; Sumathipala, Niranji; Rayaprolu, Subrahmanyam; Jiang, Haobo

2011-01-01

Detection of pathogenic invaders is the essential first step of a successful defense response in multicellular organisms. In this study, we have identified a new member of the β-1,3-glucanase-related protein superfamily from the tobacco hornworm Manduca sexta. This protein, designated microbe binding protein (MBP), is 61% identical in sequence to Bombyx mori Gram-negative bacteria binding protein, but only 34-36% identical to M. sexta β-1,3-glucan recognition protein-1 and 2. Its mRNA levels were strongly up-regulated in hemocytes and fat body of immune challenged larvae, along with an increase in concentration of the plasma protein. We expressed M. sexta MBP in a baculovirus-insect cell system. The purified protein associated with intact bacteria and fungi. It specifically bound to lipoteichoic acid, lipopolysaccharide, diaminopimelic acid-type peptidoglycans (DAP-PGs) from Escherichia coli and Bacillus subtilis, but less so to laminarin or Lys-type PG from Staphylococcus aureus. The complex binding pattern was influenced by other plasma factors and additional microbial surface molecules. After different amounts of MBP had been incubated with larval plasma on ice, a concentration-dependent increase in phenoloxidase (PO) activity occurred in the absence of any microbial elicitor. The activity increase was also observed in the mixture of plasma and a bacterial or fungal cell wall component. The prophenoloxidase (proPO) activation became more prominent when DAP-PGs, Micrococcus luteus Lys-PG, or lipoteichoic acid was included in the mixture of MBP and plasma. Statistic analysis suggested that a synergistic enhancement of proPO activation was caused by an interaction between MBP and these elicitors, but not S. aureus Lys-PG, lipopolysaccharide, curdlan, or laminarin. These data indicate that M. sexta MBP is a component of the surveillance mechanism and, by working together with other pattern recognition molecules and serine proteinases, triggers the proPO activation system. PMID:21296155

Imaging Thromboembolism with Fibrin-Avid 99mTc-Peptide: Evaluation in Swine

PubMed Central

Aruva, Mohan R.; Daviau, Judy; Sharma, Shubh S.; Thakur, Mathew L.

2006-01-01

A pentapeptide, Gly-Pro-Arg-Pro-Pro, with high affinity for α-chain-fibrin was labeled with 99mTc (99mTc-TP850) and evaluated in swine to image experimental venous thromboembolism (deep vein thrombosis [DVT]) and pulmonary embolism (PE). Methods Scatchard analysis was performed to determine fibrin affinity for TP850 and the number of binding sites (receptors) per milligram of fibrin. DVT was induced in the left jugular vein and PE was induced by introducing a preformed autologous blood clot into the right atrium using a 7-French introducer sheath inserted into the right jugular vein. 99mTc-TP850 was injected at 4, 24, 48, 72, 96, or 120 h later. Animals were imaged for up to 4 h after injection, heparinized, and sacrificed. Lungs were extirpated, radiographed, and imaged, and the PE was removed. Other tissues, including blood and normal lungs, were harvested and, concomitantly, 99mTc was counted for determination of target-to-tissue ratios and the percentage injected dose per gram of tissue. Results The affinity for human fibrin was 10−9 mol/L and there were >1015 receptors per milligram of fibrin. DVT and PE were visualized for up to 4 h after injection with high DVT/blood (7.9–22.6), DVT/muscle (31.1–89.4), PE/blood (1–155), and PE/lung (0.8–245) ratios. Thereafter, the PEs fragmented spontaneously below the spatial resolution of the γ-camera and, despite the high associated radioactivity, could not be localized in vivo. The fragmented clots were detectable by scintigraphy on excised lungs and provided excellent concordance with radiograms. Conclusion 99mTc-TP850 with its modest affinity (10−9 mol/L), rapid blood clearance, and high DVT and PE uptake is a promising agent for imaging vascular thrombosis. PMID:16391200

Dynamic Control of Radiative Heat Transfer with Tunable Materials for Thermal Management in Both Far and Near Fields

NASA Astrophysics Data System (ADS)

Yang, Yue

The proposed research mainly focuses on employing tunable materials to achieve dynamic control of radiative heat transfer in both far and near fields for thermal management. Vanadium dioxide (VO2), which undergoes a phase transition from insulator to metal at the temperature of 341 K, is one tunable material being applied. The other one is graphene, whose optical properties can be tuned by chemical potential through external bias or chemical doping. (Abstract shortened by ProQuest.).

DYNALIST II : A Computer Program for Stability and Dynamic Response Analysis of Rail Vehicle Systems : Volume 2. User's Manual.

DOT National Transportation Integrated Search

1975-02-01

A methodology and a computer program, DYNALIST II, have been developed for computing the response of rail vehicle systems to sinusoidal or stationary random rail irregularities. The computer program represents an extension of the earlier DYNALIST pro...

Gender-Linked Perceptions and Causal Attributions of Female/Male Competencies.

ERIC Educational Resources Information Center

Major, Harriet; Plake, Barbara S.

Undergraduate students (N=518) rated graduate application materials for males or females applying to traditionally perceived masculine or feminine fields. Independent variables were rater's pro/anti feminism, sex of subject, sex of referent, sex of field, and sex of attributes. Dependent variables were academic competence, personal dynamics,…

DYNALIST II : A Computer Program for Stability and Dynamic Response Analysis of Rail Vehicle Systems : Volume 1. Technical Report.

DOT National Transportation Integrated Search

1975-02-01

A methodology and a computer program, DYNALIST II, have been developed for computing the response of rail vehicle systems to sinusoidal or stationary random rail irregularities. The computer program represents an extension of the earlier DYNALIST pro...

Conformational and receptor-binding properties of the insect neuropeptide proctolin and its analogues

NASA Astrophysics Data System (ADS)

Odell, Barbara; Hammond, Stephen J.; Osborne, Richard; Goosey, Michael W.

1996-04-01

Proctolin (Arg-Tyr-Leu-Pro-Thr) was the first insect neuropeptide to be chemically characterised. It plays an essential role in insect neurophysiology and is involved in muscular contraction and neuromodulation. Elements of secondary structure in solution have been studied by comparing data obtained from NMR and molecular dynamics simulations. Different secondary structural requirements are associated with agonist and antagonist activities. A favoured conformation of proctolin has an inverse γ-turn, comprising an intramolecular hydrogen bond near the C-terminal end between Thr NH and Leu CO. Antagonists have a more compact structure resembling a `paperclip' loop, containing an intramolecular hydrogen bond between Tyr NH and Pro CO, possibly stabilised by a salt bridge between the N- and C-terminal groups. A cyclic analogue retains antagonist activity and resembles a β-bulge loop, also comprising intramolecular hydrogen bonds between Tyr NH and Pro CO and Thr CO. These models may offer feasible starting points for designing novel compounds with proctolinergic activity.

Dynamics of the BH3-Only Protein Binding Interface of Bcl-xL.

PubMed

Liu, Xiaorong; Beugelsdijk, Alex; Chen, Jianhan

2015-09-01

The balance and interplay between pro-death and pro-survival members of the B-cell lymphoma-2 (Bcl-2) family proteins play key roles in regulation of the mitochondrial pathway of programmed cell death. Recent NMR and biochemical studies have revealed that binding of the proapoptotic BH3-only protein PUMA induces significant unfolding of antiapoptotic Bcl-xL at the interface, which in turn disrupts the Bcl-xL/p53 interaction to activate apoptosis. However, the molecular mechanism of such regulated unfolding of Bcl-xL is not fully understood. Analysis of the existing Protein Data Bank structures of Bcl-xL in both bound and unbound states reveal substantial intrinsic heterogeneity at its BH3-only protein binding interface. Large-scale atomistic simulations were performed in explicit solvent for six representative structures to further investigate the intrinsic conformational dynamics of Bcl-xL. The results support that the BH3-only protein binding interface of Bcl-xL is much more dynamic compared to the rest of the protein, both unbound and when bound to various BH3-only proteins. Such intrinsic interfacial conformational dynamics likely provides a physical basis that allows Bcl-xL to respond sensitively to detailed biophysical properties of the ligand. The ability of Bcl-xL to retain or even enhance dynamics at the interface in bound states could further facilitate the regulation of its interactions with various BH3-only proteins such as through posttranslational modifications. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

A Comparative biochemical study on two marine endophytes, Bacterium SRCnm and Bacillus sp. JS, Isolated from red sea algae.

PubMed

Ahmed, Eman Fadl; Hassan, Hossam Mokhtar; Rateb, Mostafa Ezzat; Abdel-Wahab, Noha; Sameer, Somayah; Aly Taie, Hanan Anwar; Abdel-Hameed, Mohammed Sayed; Hammouda, Ola

2016-01-01

Two marine endophytic bacteria were isolated from the Red Sea algae; a red alga; Acanthophora dendroides and the brown alga Sargassum sabrepandum. The isolates were identified based on their 16SrRNA sequences as Bacterium SRCnm and Bacillus sp. JS. The objective of this study was to investigate the potential anti-microbial and antioxidant activities of the extracts of the isolated bacteria grown in different nutrient conditions. Compared to amoxicillin (25μg/disk) and erythromycin (15μg/disk), the extracts of Bacterium SRCn min media II, III, IV and V were potent inhibitors of the gram-positive bacterium Sarcina maxima even at low concentrations. Also, the multidrug resistant Staphylococcus aureus(MRSA) was more sensitive to the metabolites produced in medium (II) of the same endophyte than erythromycin (15μg/disk). A moderate activity of the Bacillus sp. JS extracts of media I and II was obtained against the same pathogen. The total compounds (500ug/ml) of both isolated endophytes showed moderate antioxidant activities (48.9% and 46.1%, respectively). LC/MS analysis of the bacterial extracts was carried out to investigate the likely natural products produced. Cyclo(D-cis-Hyp-L-Leu), dihydrosphingosine and 2-Amino-1,3-hexadecanediol were identified in the fermentation medium of Bacterium SRCnm, whereas cyclo (D-Pro-L-Tyr) and cyclo (L-Leu-L-Pro) were the suggested compounds of Bacillus sp. JS.

A mobile loop near the active site acts as a switch between the dual activities of a viral protease/deubiquitinase

PubMed Central

Ayach, Maya; Fieulaine, Sonia

2017-01-01

The positive-strand RNA virus Turnip yellow mosaic virus (TYMV) encodes an ovarian tumor (OTU)-like protease/deubiquitinase (PRO/DUB) protein domain involved both in proteolytic processing of the viral polyprotein through its PRO activity, and in removal of ubiquitin chains from ubiquitylated substrates through its DUB activity. Here, the crystal structures of TYMV PRO/DUB mutants and molecular dynamics simulations reveal that an idiosyncratic mobile loop participates in reversibly constricting its unusual catalytic site by adopting "open", "intermediate" or "closed" conformations. The two cis-prolines of the loop form a rigid flap that in the most closed conformation zips up against the other side of the catalytic cleft. The intermediate and closed conformations also correlate with a reordering of the TYMV PRO/DUB catalytic dyad, that then assumes a classical, yet still unusually mobile, OTU DUB alignment. Further structure-based mutants designed to interfere with the loop's mobility were assessed for enzymatic activity in vitro and in vivo, and were shown to display reduced DUB activity while retaining PRO activity. This indicates that control of the switching between the dual PRO/DUB activities resides prominently within this loop next to the active site. Introduction of mutations into the viral genome revealed that the DUB activity contributes to the extent of viral RNA accumulation both in single cells and in whole plants. In addition, the conformation of the mobile flap was also found to influence symptoms severity in planta. Such mutants now provide powerful tools with which to study the specific roles of reversible ubiquitylation in viral infection. PMID:29117247

Cyclic fatigue resistance of R-Pilot, WaveOne Gold Glider, and ProGlider glide path instruments.

PubMed

Keskin, Cangül; İnan, Uğur; Demiral, Murat; Keleş, Ali

2018-02-17

The aim of the present study was to compare the cyclic fatigue resistance of R-Pilot (VDW; Munich, Germany) with ProGlider (Denstply Sirona; Ballaigues, Switzerland) and WaveOne Gold Glider (Denstply Sirona; Ballaigues, Switzerland) glide path instruments. R-Pilot, ProGlider, and WaveOne Gold Glider instruments were collected (n = 15) and tested in a dynamic cyclic fatigue test device, which has an artificial canal with 60° angle of curvature and a 5-mm radius of curvature. All instruments were operated until fracture occurred, and both time to fracture (TF) and the lengths of the fractured fragments were recorded. Mean and standard deviations of TF and fragment length were calculated for each reciprocating system. TF data and fractured fragment length data were subjected to one-way ANOVA and post-hoc Tukey tests (P < 0.05). Also a Weibull analysis was performed on TF data. The cyclic fatigue resistance values of the WaveOne Gold Glider and R-Pilot were significantly higher than those of the ProGlider (P < 0.05), with no significant difference between them (P > 0.05). Weibull analysis revealed that WaveOne Gold Glider showed the highest predicted TF value for 99% survival rate, which was followed by R-Pilot and ProGlider. Regarding the length of the fractured tips, there were no significant differences among the instruments (P > 0.05). The reciprocating WaveOne Gold Glider and R-Pilot instruments had significantly higher cyclic fatigue resistance than rotary ProGlider instruments. This study reported that novel reciprocating glide path instruments exhibited higher cyclic fatigue resistance than rotating glide path instrument.

In silico molecular engineering for a targeted replacement in a tumor-homing peptide

PubMed Central

Zanuy, David; Flores-Ortega, Alejandra; Jiménez, Ana I.; Calaza, M. Isabel; Cativiela, Carlos; Nussinov, Ruth; Ruoslahti, Erkki; Alemán, Carlos

2009-01-01

A new amino acid has been designed as a replacement for arginine (Arg, R) to protect the tumor-homing pentapeptide CREKA from proteases. This amino acid, denoted (Pro)hArg, is characterized by a proline skeleton bearing a specifically oriented guanidinium side chain. This residue combines the ability of Pro to induce turn-like conformations with the Arg side-chain functionality. The conformational profile of the CREKA analogue incorporating this Arg substitute has been investigated by a combination of simulated annealing and Molecular Dynamics. Comparison of the results with those previously obtained for the natural CREKA shows that (Pro)hArg significantly reduces the conformational flexibility of the peptide. Although some changes are observed in the backbone···backbone and side chain···side chain interactions, the modified peptide exhibits a strong tendency to accommodate turn conformations centered at the (Pro)hArg residue and the overall shape of the molecule in the lowest energy conformations characterized for the natural and the modified peptide exhibit a high degree of similarity. In particular, the turn orients the backbone such that the Arg, Glu and Lys side chains face the same side of the molecule, which is considered essential for bioactivity. These results suggest that replacement of Arg by (Pro)hArg in CREKA may be useful in providing resistance against proteolytic enzymes while retaining conformational features which are essential for tumor-homing activity. PMID:19432404

Analysis of ProSEDS Test of Bare-Tether Collection

NASA Technical Reports Server (NTRS)

Sanmartin, J. R.; Lorenzini, E. C.; Estes, R. D.; Charro, M.; Cosmo, M. L.

2003-01-01

NASA's tether experiment ProSEDS will be placed in orbit on board a Delta-II rocket to test bare-tether electron collection, deorbiting of the rocket second stage, and the system dynamic stability. ProSEDS performance will vary because ambient conditions change along the orbit and tether-circuit bulk elements at the cathodic end follow the step-by-step sequence for the current cycles of operating modes (open-circuit, shunt and resistor modes for primary cycles; shunt and battery modes for secondary cycles). In this work we discuss expected ProSEDS values of the ratio L,/L*, which jointly with cathodic bulk elements determines bias and current tether profiles; L, is tether length, and L* (changing with tether temperature and ionospheric plasma density and magnetic field) is a characteristic length gauging ohmic versus baretether collection impedances. We discuss how to test bare-tether electron collection during primary cycles, using probe measurements of plasma density, measurements of cathodic current in resistor and shunt modes, and an estimate of tether temperature based on ProSEDS orbital position at the particular cycle concerned. We discuss how a temperature misestimate might occasionally affect the test of bare-tether collection, and how introducing the battery mode in some primary cycles, for an additional current measurement, could obviate the need of a temperature estimate. We also show how to test bare-tether collection by estimating orbit-decay rate from measurements of cathodic current for the shunt and battery modes of secondary cycles.

The role of proline residues in the dynamics of transmembrane helices: the case of bacteriorhodopsin.

PubMed

Perálvarez-Marín, Alex; Bourdelande, José-Luis; Querol, Enric; Padrós, Esteve

2006-01-01

Proline residues in transmembrane helices have been found to have important roles in the functioning of membrane proteins. Moreover, Pro residues occur with high frequency in transmembrane alpha-helices, as compared to alpha-helices for soluble proteins. Here, we report several properties of the bacteriorhodopsin mutants P50A (helix B), P91A (helix C) and P186A (helix F). Compared to wild type, strongly perturbed behaviour has been found for these mutants. In the resting state, increased hydroxylamine accessibility and altered Asp-85 pKa and light-dark adaptation were observed. On light activation, hydroxylamine accessibility was increased and proton transport activity, M formation kinetics and FTIR difference spectra of M and N intermediates showed clear distortions. On the basis of these alterations and the near identity of the crystalline structures of mutants with that of wild type, we conclude that the transmembrane proline residues of bacteriorhodopsin fulfil a dynamic role in both the resting and the light-activated states. Our results are consistent with the notion that mutation of Pro to Ala allows the helix to increase its flexibility towards the direction originally hindered by the steric clash between the ring Cgamma and the carbonyl O of the i-4 residue, at the same time decreasing the mobility towards the opposite direction. Due to their properties, transmembrane Pro residues may serve as transmission elements of conformational changes during the transport process. We propose that these concepts can be extended to other transmembrane proteins.

40 CFR 86.166-12 - Method for calculating emissions due to air conditioning leakage.

Code of Federal Regulations, 2012 CFR

2012-07-01

... determine a refrigerant leakage rate in grams per year from vehicle-based air conditioning units. The... using the following equation: Grams/YRTOT = Grams/YRRP + Grams/YRSP + Grams/YRFH + Grams/YRMC + Grams/YRC Where: Grams/YRTOT = Total air conditioning system emission rate in grams per year and rounded to...

A dynamical systems model of progesterone receptor interactions with inflammation in human parturition.

PubMed

Brubaker, Douglas; Barbaro, Alethea; R Chance, Mark; Mesiano, Sam

2016-08-19

Progesterone promotes uterine relaxation and is essential for the maintenance of pregnancy. Withdrawal of progesterone activity and increased inflammation within the uterine tissues are key triggers for parturition. Progesterone actions in myometrial cells are mediated by two progesterone receptor (PR) isoforms, PR-A and PR-B, that function as ligand-activated transcription factors. PR-B mediates relaxatory actions of progesterone, in part, by decreasing myometrial cell responsiveness to pro-inflammatory stimuli. These same pro-inflammatory stimuli promote the expression of PR-A which inhibits the anti-inflammatory activity of PR-B. Competitive interaction between the progesterone receptors then augments myometrial responsiveness to pro-inflammatory stimuli. The interaction between PR-B transcriptional activity and inflammation in the pregnancy myometrium is examined using a dynamical systems model in which quiescence and labor are represented as phase-space equilibrium points. Our model shows that PR-B transcriptional activity and the inflammatory load determine the stability of the quiescent and laboring phenotypes. The model is tested using published transcriptome datasets describing the mRNA abundances in the myometrium before and after the onset of labor at term. Surrogate transcripts were selected to reflect PR-B transcriptional activity and inflammation status. The model coupling PR-B activity and inflammation predicts contractile status (i.e., laboring or quiescent) with high precision and recall and outperforms uncoupled single and two-gene classifiers. Linear stability analysis shows that phase space bifurcations exist in our model that may reflect the phenotypic states of the pregnancy uterus. The model describes a possible tipping point for the transition of the quiescent to the contractile laboring phenotype. Our model describes the functional interaction between the PR-A:PR-B hypothesis and tissue level inflammation in the pregnancy uterus and is a first step in more sophisticated dynamical systems modeling of human partition. The model explains observed biochemical dynamics and as such will be useful for the development of a range of systems-based models using emerging data to predict preterm birth and identify strategies for its prevention.

Molecular Mechanisms That Underlie the Dynamic Adaptation of Innate Monocyte Memory to Varying Stimulant Strength of TLR Ligands.

PubMed

Yuan, Ruoxi; Geng, Shuo; Li, Liwu

2016-01-01

In adaptation to rising stimulant strength, innate monocytes can be dynamically programed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programing may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS. Mechanistically, monocytes adapted by super-low dose LPS exhibited higher levels of transcription factor, interferon regulatory factor 5 (IRF5), and reduced levels of transcriptional modulator B lymphocyte-induced maturation protein-1 (Blimp-1). Intriguingly, the inflammatory monocyte adaptation by super-low dose LPS is dependent upon TRAM/TRIF but not MyD88. Similar to LPS, we also observed biphasic inflammatory adaptation and tolerance in monocytes challenged with varying dosages of TLR7 agonist. In sharp contrast, rising doses of TLR3 agonist preferentially caused inflammatory adaptation without inducing tolerance. At the molecular level, the differential regulation of IRF5 and Blimp-1 coincides with unique monocyte adaptation dynamics by TLR4/7 and TLR3 agonists. Our study provides novel clue toward the understanding of monocyte adaptation and memory toward distinct TLR ligands.

[Estimation of activity of pharmakopeal disinfectants and antiseptics against Gram-negative and Gram-positive bacteria isolated from clinical specimens, drugs and environment].

PubMed

Grzybowska, Wanda; Młynarczyk, Grazyna; Młynarczyk, Andrzej; Bocian, Ewa; Luczak, Mirosław; Tyski, Stefan

2007-01-01

The MIC of nine different disinfectants and antiseptics were determined for the Gram-negative and Gram-positive bacteria. Strains originated from clinical specimens, drugs and environment. A sensitivity was determined against chlorhexidinum digluconate (Gram-negative: 0,625-80 mg/L, Gram-positive: 0,3-10 mg/L), benzalconium chloride (Gram-negative: 2,5-1280 mg/L, Gram-positive: 1,25-20 mg/L), salicilic acid (Gram-negative and Gram-positive: 400-1600 mg/L), benzoic acid (Gram-negative: 800-1600 mg/L, Gram-positive: 400-1 600 mg/L), boric acid (Gram-negative: 800-12 800 mg/L, Gram-positive: 1 600-6400 mg/L), chloramine B (Gram-negative: 1600-6400 mg/L, Gram-positive:800- 6400 mg/L), jodine (Gram-negative: 200-1600 mg/L, Gram-positive: 200-1600 mg/L), etacridine lactate (Gram-negative: 40 do > 20480 mg/L, Gram-positive: 40-1280 mg/L) and resorcine (Gram-negative: 1600-6400 mg/L, Gram-positive: 800-6400 mg/L). Diversified values of MIC for different strains were obtained, especially in the case of benzalconium chloride, etacridine lactate, chlorhexidinum digluconate, boric acid and iodine. Strains isolated from environment were usually more susceptible to examined compounds than clinical strains. The biggest diversification of sensitivity was observed among strains originated from drugs where besides sensitive appeared strains characterizing by very high MIC values of some substances, eg. boric acid.

Computational modeling predicts simultaneous targeting of fibroblasts and epithelial cells is necessary for treatment of pulmonary fibrosis

DOE PAGES

Warsinske, Hayley C.; Wheaton, Amanda K.; Kim, Kevin K.; ...

2016-06-23

Pulmonary fibrosis is pathologic remodeling of lung tissue that can result in difficulty breathing, reduced quality of life, and a poor prognosis for patients. Fibrosis occurs as a result of insult to lung tissue, though mechanisms of this response are not well-characterized. The disease is driven in part by dysregulation of fibroblast proliferation and differentiation into myofibroblast cells, as well as pro-fibrotic mediator-driven epithelial cell apoptosis. The most well-characterized pro-fibrotic mediator associated with pulmonary fibrosis is TGF-β1. Excessive synthesis of, and sensitivity to, pro-fibrotic mediators as well as insufficient production of and sensitivity to anti-fibrotic mediators has been credited withmore » enabling fibroblast accumulation. Available treatments neither halt nor reverse lung damage. In this study we have two aims: to identify molecular and cellular scale mechanisms driving fibroblast proliferation and differentiation as well as epithelial cell survival in the context of fibrosis, and to predict therapeutic targets and strategies. We combine in vitro studies with a multi-scale hybrid agent-based computational model that describes fibroblasts and epithelial cells in co-culture. Within this model TGF-β1 represents a pro-fibrotic mediator and we include detailed dynamics of TGFβ1 receptor ligand signaling in fibroblasts. PGE 2 represents an anti-fibrotic mediator. Using uncertainty and sensitivity analysis we identify TGF-β1 synthesis, TGF-β1 activation, and PGE 2 synthesis among the key mechanisms contributing to fibrotic outcomes. We further demonstrate that intervention strategies combining potential therapeutics targeting both fibroblast regulation and epithelial cell survival can promote healthy tissue repair better than individual strategies. Combinations of existing drugs and compounds may provide significant improvements to the current standard of care for pulmonary fibrosis. In conclusion, a two-hit therapeutic intervention strategy may prove necessary to halt and reverse disease dynamics.« less

Computational modeling predicts simultaneous targeting of fibroblasts and epithelial cells is necessary for treatment of pulmonary fibrosis

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

Warsinske, Hayley C.; Wheaton, Amanda K.; Kim, Kevin K.

Pulmonary fibrosis is pathologic remodeling of lung tissue that can result in difficulty breathing, reduced quality of life, and a poor prognosis for patients. Fibrosis occurs as a result of insult to lung tissue, though mechanisms of this response are not well-characterized. The disease is driven in part by dysregulation of fibroblast proliferation and differentiation into myofibroblast cells, as well as pro-fibrotic mediator-driven epithelial cell apoptosis. The most well-characterized pro-fibrotic mediator associated with pulmonary fibrosis is TGF-β1. Excessive synthesis of, and sensitivity to, pro-fibrotic mediators as well as insufficient production of and sensitivity to anti-fibrotic mediators has been credited withmore » enabling fibroblast accumulation. Available treatments neither halt nor reverse lung damage. In this study we have two aims: to identify molecular and cellular scale mechanisms driving fibroblast proliferation and differentiation as well as epithelial cell survival in the context of fibrosis, and to predict therapeutic targets and strategies. We combine in vitro studies with a multi-scale hybrid agent-based computational model that describes fibroblasts and epithelial cells in co-culture. Within this model TGF-β1 represents a pro-fibrotic mediator and we include detailed dynamics of TGFβ1 receptor ligand signaling in fibroblasts. PGE 2 represents an anti-fibrotic mediator. Using uncertainty and sensitivity analysis we identify TGF-β1 synthesis, TGF-β1 activation, and PGE 2 synthesis among the key mechanisms contributing to fibrotic outcomes. We further demonstrate that intervention strategies combining potential therapeutics targeting both fibroblast regulation and epithelial cell survival can promote healthy tissue repair better than individual strategies. Combinations of existing drugs and compounds may provide significant improvements to the current standard of care for pulmonary fibrosis. In conclusion, a two-hit therapeutic intervention strategy may prove necessary to halt and reverse disease dynamics.« less

Gram staining for the treatment of peritonsillar abscess.

PubMed

Takenaka, Yukinori; Takeda, Kazuya; Yoshii, Tadashi; Hashimoto, Michiko; Inohara, Hidenori

2012-01-01

Objective. To examine whether Gram staining can influence the choice of antibiotic for the treatment of peritonsillar abscess. Methods. Between 2005 and 2009, a total of 57 cases of peritonsillar abscess were analyzed with regard to cultured bacteria and Gram staining. Results. Only aerobes were cultured in 16% of cases, and only anaerobes were cultured in 51% of cases. Mixed growth of aerobes and anaerobes was observed in 21% of cases. The cultured bacteria were mainly aerobic Streptococcus, anaerobic Gram-positive cocci, and anaerobic Gram-negative rods. Phagocytosis of bacteria on Gram staining was observed in 9 cases. The bacteria cultured from these cases were aerobic Streptococcus, anaerobic Gram-positive cocci, and anaerobic Gram-negative rods. The sensitivity of Gram staining for the Gram-positive cocci and Gram-negative rods was 90% and 64%, respectively. The specificity of Gram staining for the Gram-positive cocci and Gram-negative rods was 62% and 76%, respectively. Most of the Gram-positive cocci were sensitive to penicillin, but some of anaerobic Gram-negative rods were resistant to penicillin. Conclusion. When Gram staining shows only Gram-positive cocci, penicillin is the treatment of choice. In other cases, antibiotics effective for the penicillin-resistant organisms should be used.

Biosynthesis of silver nanoparticles using Ocimum sanctum (Tulsi) leaf extract and screening its antimicrobial activity

NASA Astrophysics Data System (ADS)

Singhal, Garima; Bhavesh, Riju; Kasariya, Kunal; Sharma, Ashish Ranjan; Singh, Rajendra Pal

2011-07-01

Development of green nanotechnology is generating interest of researchers toward ecofriendly biosynthesis of nanoparticles. In this study, biosynthesis of stable silver nanoparticles was done using Tulsi ( Ocimum sanctum) leaf extract. These biosynthesized nanoparticles were characterized with the help of UV-vis spectrophotometer, Atomic Absorption Spectroscopy (AAS), Dynamic light scattering (DLS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Transmission electron microscopy (TEM). Stability of bioreduced silver nanoparticles was analyzed using UV-vis absorption spectra, and their antimicrobial activity was screened against both gram-negative and gram-positive microorganisms. It was observed that O. sanctum leaf extract can reduce silver ions into silver nanoparticles within 8 min of reaction time. Thus, this method can be used for rapid and ecofriendly biosynthesis of stable silver nanoparticles of size range 4-30 nm possessing antimicrobial activity suggesting their possible application in medical industry.

In vitro transport activity of the fully assembled MexAB-OprM efflux pump from Pseudomonas aeruginosa

NASA Astrophysics Data System (ADS)

Verchère, Alice; Dezi, Manuela; Adrien, Vladimir; Broutin, Isabelle; Picard, Martin

2015-04-01

Antibiotic resistance is a major public health issue and many bacteria responsible for human infections have now developed a variety of antibiotic resistance mechanisms. For instance, Pseudomonas aeruginosa, a disease-causing Gram-negative bacteria, is now resistant to almost every class of antibiotics. Much of this resistance is attributable to multidrug efflux pumps, which are tripartite membrane protein complexes that span both membranes and actively expel antibiotics. Here we report an in vitro procedure to monitor transport by the tripartite MexAB-OprM pump. By combining proteoliposomes containing the MexAB and OprM portions of the complex, we are able to assay energy-dependent substrate translocation in a system that mimics the dual-membrane architecture of Gram-negative bacteria. This assay facilitates the study of pump transport dynamics and could be used to screen pump inhibitors with potential clinical use in restoring therapeutic activity of old antibiotics.

Antimicrobial activity of silver nanoparticles impregnated wound dressing

NASA Astrophysics Data System (ADS)

Shinde, V. V.; Jadhav, P. R.; Patil, P. S.

2013-06-01

In this work, silver nanoparticles were synthesized by simple wet chemical reduction method. The silver nitrate was reduced by Sodium borohydride used as reducing agent and Poly (vinyl pyrrolidone) (PVP) as stabilizing agent. The formation of silver nanoparticles was evaluated by UV-visible spectroscope and transmission electron microscope (TEM). Absorption spectrum consist two plasmon peaks at 410 and 668 nm revels the formation of anisotropic nanoparticles confirmed by TEM. The formation of silver nanoparticles was also evidenced by dynamic light scattering (DLS) study. DLS showed polydisperse silver nanoparticles with hydrodynamic size 32 nm. Protecting mechanism of PVP was manifested by FT-Raman study. Silver nanoparticles were impregnated into wound dressing by sonochemical method. The Kirby-Bauer disc diffusion methods were used for antimicrobial susceptibility testing. The antimicrobial activity of the samples has been tested against gram-negative bacterium Escherichia coli and gram-positive bacterium Staphylococcus aureus.

Microbial decontamination of cosmetic raw materials and personal care products by irradiation

NASA Astrophysics Data System (ADS)

Katušin-Ražem, Branka; Mihaljević, Branka; Ražem, Dušan

2003-03-01

Typical levels of sporadically occurring (dynamic) microbial contamination of cosmetic raw materials: pigments, abrasives and liposomes, as well as of final products for personal care: toothpaste, crayons, shampoos, cleansers and creams, were evaluated. In most cases the contamination was dominated by a single population of microorganisms, either Gram-negative bacteria or molds. The feasibility of microbial decontamination by irradiation was studied by determining the resistance to gamma radiation of contaminating microflora in situ. It was expressed as a dose required for the first 90% reduction, D first 90% red . The values in the range 1-2 kGy for molds and 0.1-0.6 kGy for Gram-negative bacteria were obtained. This relatively high susceptibility to irradiation allowed inactivation factors close to 6 to be achieved with doses generally not exceeding 3 kGy, and yielding endpoint contamination less than 10/g.

Kinetics of bacterial fluorescence staining with 3,3'-diethylthiacyanine.

PubMed

Thomas, Marlon S; Nuñez, Vicente; Upadhyayula, Srigokul; Zielins, Elizabeth R; Bao, Duoduo; Vasquez, Jacob M; Bahmani, Baharak; Vullev, Valentine I

2010-06-15

For more than a century, colorimetric and fluorescence staining have been the foundation of a broad range of key bioanalytical techniques. The dynamics of such staining processes, however, still remains largely unexplored. We investigated the kinetics of fluorescence staining of two gram-negative and two gram-positive species with 3,3'-diethylthiacyanine (THIA) iodide. An increase in the THIA fluorescence quantum yield, induced by the bacterial dye uptake, was the principal reason for the observed emission enhancement. The fluorescence quantum yield of THIA depended on the media viscosity and not on the media polarity, which suggested that the microenvironment of the dye molecules taken up by the cells was restrictive. The kinetics of fluorescence staining did not manifest a statistically significant dependence neither on the dye concentration, nor on the cell count. In the presence of surfactant additives, however, the fluorescence-enhancement kinetic patterns manifested species specificity with statistically significant discernibility.

A landscape based, systems dynamic model for assessing impacts of urban development on water quality for sustainable seagrass growth in Tampa Bay, Florida

EPA Science Inventory

We present an integrated assessment model to predict potential unintended consequences of urban development on the sustainability of seagrasses and preservation of ecosystem services, such as catchable fish, in Tampa Bay. Ecosystem services are those ecological functions and pro...

Moisture-Absorption and Water Dynamics in the Powder of Egg Albumen Peptide, Met-Pro-Asp-Ala-His-Leu.

PubMed

Yang, Shuailing; Liu, Xuye; Zhang, Mingdi; Lin, Songyi; Chen, Feng

2017-01-01

Moisture absorbed into the powder of Met-Pro-Asp-Ala-His-Leu (MPDAHL)-a novel egg albumen antioxidant peptide-profoundly affects its properties. In this study, we elucidated water dynamics in MPDAHL using DVS, DSC, and low-field 1 H NMR. Based on the DVS data, we found that MPDAHL sorption kinetics obey a parallel exponential model. DSC results indicated that both water and heating could change the microstructure of MPDAHL. The T 2 parameters of NMR reflected the different phases of moisture absorption revealed that there were 4 categories of water with different states or mobility in the MPDAHL during the moisture absorption process. The fastest fraction T 2b mainly dominated the hygroscopicity of MPDAHL and the absorbed water significantly changed the proton distribution and structure of MPDAHL. Thus, this study shows that DVS, DSC, and low-field 1 H NMR are effective methods for monitoring water mobility and distribution in synthetic peptides. It can be used to improve the quality assurance of functional peptides. © 2016 Institute of Food Technologists®.

Structural analysis and the effect of cyclo(His-Pro) dipeptide on neurotoxins--a dynamics and density functional theory study.

PubMed

Abiram, Angamuthu; Kolandaivel, Ponmalai

2010-02-01

The switching propensity and maximum probability of occurrence of the side chain imidazole group in the dipeptide cyclo(His-Pro) (CHP) were studied by applying molecular dynamics simulations and density functional theory. The atomistic behaviour of CHP with the neurotoxins glutamate (E) and paraquat (Pq) were also explored; E and Pq engage in hydrogen bond formation with the diketopiperazine (DKP) ring of the dipeptide, with which E shows a profound interaction, as confirmed further by NH and CO stretching vibrational frequencies. The effect of CHP was found to be greater on E than on Pq neurotoxin. A ring puckering study indicated a twist boat conformation for the six-membered DKP ring. Molecular electrostatic potential (MESP) mapping was also used to explore the hydrogen bond interactions prevailing between the neurotoxins and the DKP ring. The results of this study reveal that the DKP ring of the dipeptide CHP can be expected to play a significant role in reducing effects such as oxidative stress and cell death caused by neurotoxins.

Altered self-assembly and apatite binding of amelogenin induced by N-terminal proline mutation

PubMed Central

Zhu, Li; Uskoković, Vuk; Le, Thuan; DenBesten, Pamela; Huang, Yulei; Habelitz, Stefan; Li, Wu

2012-01-01

Objective A single Pro-70 to Thr (p.P70T) mutation of amelogenin is known to result in hypomineralized amelogenesis imperfecta (AI). This study aims to test the hypothesis that the given mutation affects the self-assembly of amelogenin molecules and impairs their ability to conduct the growth of apatite crystals. Design Recombinant human full-length wild-type (rh174) and p.P70T mutated amelogenins were analyzed using dynamic light scattering (DLS), protein quantification assay and atomic force microscopy (AFM) before and after the binding of amelogenins to hydroxyapatite crystals. The crystal growth modulated by both amelogenins in a dynamic titration system was observed using AFM. Results As compared to rh174 amelogenin, p.P70T mutant displayed significantly increased sizes of the assemblies, higher binding affinity to apatite, and decreased crystal height. Conclusions Pro-70 plays an important structural role in the biologically relevant amelogenin self-assembly. The disturbed regularity of amelogenin nanospheres by this single mutation resulted in an increased binding to apatite and inhibited crystal growth. PMID:21081224

Essential uncontrollability of discrete linear, time-invariant, dynamical systems

NASA Technical Reports Server (NTRS)

Cliff, E. M.

1975-01-01

The concept of a 'best approximating m-dimensional subspace' for a given set of vectors in n-dimensional whole space is introduced. Such a subspace is easily described in terms of the eigenvectors of an associated Gram matrix. This technique is used to approximate an achievable set for a discrete linear time-invariant dynamical system. This approximation characterizes the part of the state space that may be reached using modest levels of control. If the achievable set can be closely approximated by a proper subspace of the whole space then the system is 'essentially uncontrollable'. The notion finds application in studies of failure-tolerant systems, and in decoupling.

Perchlorate Detection at Nanomolar Concentrations by Surface-Enhanced Raman Scattering

DTIC Science & Technology

2009-01-01

grooves/mm grating light path controlled by Renishaw WiRE software and analyzed by Galactic GRAMS software. RESULTS AND DISCUSSION Quantitative... Federal Rights License 14. ABSTRACT Perchlorate (ClO4 ) has emerged as a widespread environmental contaminant and has been detected in various food...by means of dynamic light scattering using a ZetaPlus particle size analyzer (Brookhaven Instruments, Holtsville, NY). Data were collected for every

Characterization of Bacterial Community Dynamics during the Decomposition of Pig Carcasses in Simulated Soil Burial and Composting Systems.

PubMed

Ki, Bo-Min; Kim, Yu Mi; Jeon, Jun Min; Ryu, Hee Wook; Cho, Kyung-Suk

2017-12-28

Soil burial is the most widely used disposal method for infected pig carcasses, but composting has gained attention as an alternative disposal method because pig carcasses can be decomposed rapidly and safely by composting. To understand the pig carcass decomposition process in soil burial and by composting, pilot-scale test systems that simulated soil burial and composting were designed and constructed in the field. The envelope material samples were collected using special sampling devices without disturbance, and bacterial community dynamics were analyzed by high-throughput pyrosequencing for 340 days. Based on the odor gas intensity profiles, it was estimated that the active and advanced decay stages were reached earlier by composting than by soil burial. The dominant bacterial communities in the soil were aerobic and/or facultatively anaerobic gram-negative bacteria such as Pseudomonas, Gelidibacter, Mucilaginibacter , and Brevundimonas . However, the dominant bacteria in the composting system were anaerobic, thermophilic, endospore-forming, and/or halophilic gram-positive bacteria such as Pelotomaculum, Lentibacillus, Clostridium , and Caldicoprobacter . Different dominant bacteria played important roles in the decomposition of pig carcasses in the soil and compost. This study provides useful comparative date for the degradation of pig carcasses in the soil burial and composting systems.

Asymmetric phospholipid: lipopolysaccharide bilayers; a Gram-negative bacterial outer membrane mimic

PubMed Central

Clifton, Luke A.; Skoda, Maximilian W. A.; Daulton, Emma L.; Hughes, Arwel V.; Le Brun, Anton P.; Lakey, Jeremy H.; Holt, Stephen A.

2013-01-01

The Gram-negative bacterial outer membrane (OM) is a complex and highly asymmetric biological barrier but the small size of bacteria has hindered advances in in vivo examination of membrane dynamics. Thus, model OMs, amenable to physical study, are important sources of data. Here, we present data from asymmetric bilayers which emulate the OM and are formed by a simple two-step approach. The bilayers were deposited on an SiO2 surface by Langmuir–Blodgett deposition of phosphatidylcholine as the inner leaflet and, via Langmuir–Schaefer deposition, an outer leaflet of either Lipid A or Escherichia coli rough lipopolysaccharides (LPS). The membranes were examined using neutron reflectometry (NR) to examine the coverage and mixing of lipids between the bilayer leaflets. NR data showed that in all cases, the initial deposition asymmetry was mostly maintained for more than 16 h. This stability enabled the sizes of the headgroups and bilayer roughness of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and Lipid A, Rc-LPS and Ra-LPS to be clearly resolved. The results show that rough LPS can be manipulated like phospholipids and used to fabricate advanced asymmetric bacterial membrane models using well-known bilayer deposition techniques. Such models will enable OM dynamics and interactions to be studied under in vivo-like conditions. PMID:24132206

Gram-negative, but not Gram-positive, bacteria elicit strong PGE2 production in human monocytes.

PubMed

Hessle, Christina C; Andersson, Bengt; Wold, Agnes E

2003-12-01

Gram-positive and Gram-negative bacteria induce different cytokine patterns in human mononuclear cells. We have seen that Gram-positives preferentially induce IL-12 and TNF-alpha, whereas Gram-negatives induce more IL-10, IL-6, and IL-8. In this study, we compared the capacity of these two groups of bacteria to induce PGE2. Monocytes stimulated with Gram-negative bacterial species induced much more PGE2 than did Gram-positive bacteria (5600 +/- 330 vs. 1700 +/- 670 pg/mL, p < 0.001). Blocking of COX-2 by NS398 abolished PGE2 production, but did not alter the cytokine patterns induced by Gram-positive and Gram-negative bacteria. We suggest that Gram-positive and Gram-negative bacteria may stimulate different innate effector functions; Gram-positive bacteria promoting cell-mediated effector functions whereas Gram-negative bacteria inducing mediators inhibiting the same.

NprR-NprX Quorum-Sensing System Regulates the Algicidal Activity of Bacillus sp. Strain S51107 against Bloom-Forming Cyanobacterium Microcystis aeruginosa.

PubMed

Wu, Lishuang; Guo, Xingliang; Liu, Xianglong; Yang, Hong

2017-01-01

Harmful cyanobacterial blooms have severely impaired freshwater quality and threatened human health worldwide. Here, a Gram-positive bacterium, Bacillus sp. strain S51107, which exhibits strong algicidal activity against Microcystis aeruginosa , was isolated from Lake Taihu. We found that the algicidal activity of strain S51107 was regulated primarily by NprR-NprX quorum sensing (QS), in which the mature form of the signaling peptide NprX was identified as the SKPDIVG heptapeptide. Disruption of the nprR-nprX cassette markedly decreased the algicidal activity, and complemented strains showed significantly recovered algicidal activity. Strain S51107 produced low-molecular-weight algicidal compounds [indole-3-carboxaldehyde and cyclo(Pro-Phe)] and high-molecular-weight algicidal substance(s) (>3 kDa). Moreover, the production of high-molecular-weight algicidal substance(s) was regulated by NprR-NprX QS, but the production of low-molecular-weight algicidal compounds was not. High-molecular-weight algicidal substance(s) played a more important role than low-molecular-weight algicidal compounds in the algicidal activity of strain S51107. The results of this study could increase our knowledge about algicidal characteristics of a potential algicidal bacterium, Bacillus sp. strain S51107, and provide the first evidence that the algicidal activity of Gram-positive algicidal bacteria is regulated by QS, which will greatly enhance our understanding of the interactions between algae and indigenous algicidal bacteria, thereby providing aid in the design and optimization of strategies to control harmful algae blooms.

NprR-NprX Quorum-Sensing System Regulates the Algicidal Activity of Bacillus sp. Strain S51107 against Bloom-Forming Cyanobacterium Microcystis aeruginosa

PubMed Central

Wu, Lishuang; Guo, Xingliang; Liu, Xianglong; Yang, Hong

2017-01-01

Harmful cyanobacterial blooms have severely impaired freshwater quality and threatened human health worldwide. Here, a Gram-positive bacterium, Bacillus sp. strain S51107, which exhibits strong algicidal activity against Microcystis aeruginosa, was isolated from Lake Taihu. We found that the algicidal activity of strain S51107 was regulated primarily by NprR-NprX quorum sensing (QS), in which the mature form of the signaling peptide NprX was identified as the SKPDIVG heptapeptide. Disruption of the nprR-nprX cassette markedly decreased the algicidal activity, and complemented strains showed significantly recovered algicidal activity. Strain S51107 produced low-molecular-weight algicidal compounds [indole-3-carboxaldehyde and cyclo(Pro-Phe)] and high-molecular-weight algicidal substance(s) (>3 kDa). Moreover, the production of high-molecular-weight algicidal substance(s) was regulated by NprR-NprX QS, but the production of low-molecular-weight algicidal compounds was not. High-molecular-weight algicidal substance(s) played a more important role than low-molecular-weight algicidal compounds in the algicidal activity of strain S51107. The results of this study could increase our knowledge about algicidal characteristics of a potential algicidal bacterium, Bacillus sp. strain S51107, and provide the first evidence that the algicidal activity of Gram-positive algicidal bacteria is regulated by QS, which will greatly enhance our understanding of the interactions between algae and indigenous algicidal bacteria, thereby providing aid in the design and optimization of strategies to control harmful algae blooms. PMID:29075240

The Impact of Meal Timing on Cardiometabolic Syndrome Indicators in Shift Workers

PubMed Central

Molzof, Hylton E.; Wirth, Michael D.; Burch, James B.; Shivappa, Nitin; Hébert, James R.; Johnson, Russell L.; Gamble, Karen L.

2017-01-01

The aims of this study were to 1) compare the inflammatory potential of night- and day-shift nurses’ diets in regard to time-of-day and work status, and 2) explore how the timing of food intake during work and off-work is associated with cardiometabolic syndrome (CMS) risk factors between these two groups. Female nurses (N = 17; 8 day-shift and 9 night-shift) reported food intake over 9 days. On a middle day off of work, metabolic parameters were measured after an overnight fast. Energy/macronutrient intake and inflammatory potential of dietary intake (as assessed via the Dietary Inflammatory IndexTM) were calculated for nurses’ workdays, work nights, off-work days, and off-work nights. Work-night total food intake (grams) accounted for a significant amount of variance in CMS risk factors for night-shift nurses only. Increased total gram consumption during night-shift nurses’ work nights was associated with increased lipid levels – independent of the macronutrient composition of the food consumed. Alternatively, for night-shift nurses, work-day intake of several food parameters accounted for a significant proportion of variance in HDL cholesterol levels, with higher intake associated with higher HDL levels. For both day- and night-shift nurses, food intake during the day was more pro-inflammatory regardless of shift-type or work status. Our novel approach of combining time-of-day-specific and work-day-specific analyses of dietary inflammatory factors and macronutrient composition with measurement of CMS risk factors suggests a link between meal timing and cardiometabolic health for shift-working nurses. PMID:28107043

Outer Membrane Vesicles Prime and Activate Macrophage Inflammasomes and Cytokine Secretion In Vitro and In Vivo

PubMed Central

Cecil, Jessica D.; O’Brien-Simpson, Neil M.; Lenzo, Jason C.; Holden, James A.; Singleton, William; Perez-Gonzalez, Alexis; Mansell, Ashley; Reynolds, Eric C.

2017-01-01

Outer membrane vesicles (OMVs) are proteoliposomes blebbed from the surface of Gram-negative bacteria. Chronic periodontitis is associated with an increase in subgingival plaque of Gram-negative bacteria, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. In this study, we investigated the immune-modulatory effects of P. gingivalis, T. denticola, and T. forsythia OMVs on monocytes and differentiated macrophages. All of the bacterial OMVs were phagocytosed by monocytes, M(naïve) and M(IFNγ) macrophages in a dose-dependent manner. They also induced NF-κB activation and increased TNFα, IL-8, and IL-1β cytokine secretion. P. gingivalis OMVs were also found to induce anti-inflammatory IL-10 secretion. Although unprimed monocytes and macrophages were resistant to OMV-induced cell death, lipopolysaccharide or OMV priming resulted in a significantly reduced cell viability. P. gingivalis, T. denticola, and T. forsythia OMVs all activated inflammasome complexes, as monitored by IL-1β secretion and ASC speck formation. ASC was critical for OMV-induced inflammasome formation, while AIM2−/− and Caspase-1−/− cells had significantly reduced inflammasome formation and NLRP3−/− cells exhibited a slight reduction. OMVs were also found to provide both priming and activation of the inflammasome complex. High-resolution microscopy and flow cytometry showed that P. gingivalis OMVs primed and activated macrophage inflammasomes in vivo with 80% of macrophages exhibiting inflammasome complex formation. In conclusion, periodontal pathogen OMVs were found to have significant immunomodulatory effects upon monocytes and macrophages and should therefore influence pro-inflammatory host responses associated with disease. PMID:28890719

Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis

PubMed Central

Treibel, Thomas A.; Bandula, Steve; Fontana, Marianna; White, Steven K.; Gilbertson, Janet A.; Herrey, Anna S.; Gillmore, Julian D.; Punwani, Shonit; Hawkins, Philip N.; Taylor, Stuart A.; Moon, James C.

2015-01-01

Background Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed. Objectives To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT. Methods Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area). Results ECVCT and ECVCMR results were well correlated (r2 = 0.85 vs r2 = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone scintigraphy amyloid burden (p<0.001). Conclusion Dynamic Equilibrium CT, a 5 minute contrast-enhanced gated cardiac CT, has potential for non-invasive diagnosis and quantification of cardiac amyloidosis. PMID:26209459

In Vitro Anti/Pro-oxidant Activities of R. ferruginea Extract and Its Effect on Glioma Cell Viability: Correlation with Phenolic Compound Content and Effects on Membrane Dynamics.

PubMed

Dos Santos, Desirée Magalhães; Rocha, Camila Valesca Jardim; da Silveira, Elita Ferreira; Marinho, Marcelo Augusto Germani; Rodrigues, Marisa Raquel; Silva, Nichole Osti; da Silva Ferreira, Ailton; de Moura, Neusa Fernandes; Darelli, Gabriel Jorge Sagrera; Braganhol, Elizandra; Horn, Ana Paula; de Lima, Vânia Rodrigues

2018-04-01

Rapanea ferruginea antioxidant and antitumoral properties were not explored before in literature. This study aimed to investigate these biological activities for the R. ferruginea leaf extract and correlate them with its phenolic content and influence in biological membrane dynamics. Thus, in this study, anti/pro-oxidative properties of R. ferruginea leaf extract by in vitro DPPH and TBARS assays, with respect to the free radical reducing potential and to its activity regarding membrane free radical-induced peroxidation, respectively. Furthermore, preliminary tests related to the extract effect on in vitro glioma cell viability were also performed. In parallel, the phenolic content was detected by HPLC-DAD and included syringic and trans-cinnamic acids, quercetrin, catechin, quercetin, and gallic acid. In an attempt to correlate the biological activity of R. ferruginea extract and its effect on membrane dynamics, the molecular interaction between the extract and a liposomal model with natural-sourced phospholipids was investigated. Location and changes in vibrational, rotational, and translational lipid motions, as well as in the phase state of liposomes, induced by R. ferruginea extract, were monitored by Fourier-transform infrared spectroscopy, nuclear magnetic resonance, differential scanning calorimetry, and UV-visible spectroscopy. In its free form, the extract showed promising in vitro antioxidant properties. Free-form extract (at 1000µ g/mL) exposure reduced glioma cell in vitro viability in 40%, as evidenced by MTT tests. Pro-oxidant behavior was observed when the extract was loaded into liposomes. A 70.8% cell viability reduction was achieved with 500 µg/mL of liposome-loaded extract. The compounds of R. ferruginea extract ordered liposome interface and disorder edits a polar region. Phenolic content, as well as membrane interaction and modulation may have an important role in the oxidative and antitumoral activities of the R. ferruginea leaf extract.

Ex-gay rhetoric and the politics of sexuality: the Christian antigay/pro-family movement's "truth in love" ad campaign.

PubMed

Fetner, Tina

2005-01-01

In 1998, a coalition of antigay, pro-family activist organizations published a set of full-page print advertisements in several nationally recognized newspapers. These ads promoted sexual (ex-gay) conversion therapy for homosexuals. I examine these advertisements as a contest over cultural symbols and values, and over the very definition of lesbian and gay identity. This discursive contest had the potential to impact activist politics greatly, but this impact was mitigated significantly by a similar set of ads produced in response by an opposing movement: the lesbian, gay, bisexual and transgender movement. The interactive dynamics between opposing movements impact the political field in which activists on each side pursue their goals.

Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC.

PubMed

Ladurelle, Nataly; Gabriel, Cecilia; Viggiano, Adela; Mocaër, Elisabeth; Baulieu, Etienne E; Bianchi, Massimiliano

2012-06-01

Agomelatine is described as a novel and clinical effective antidepressant drug with melatonergic (MT(1)/MT(2)) agonist and 5-HT(2C) receptor antagonist properties. Previous studies suggest that modulation of neuronal plasticity and microtubule dynamics may be involved in the treatment of depression. The present study investigated the effects of agomelatine on microtubular, synaptic and brain-derived neurotrophic factor (BDNF) proteins in selected rat brain regions. Adult male rats received agomelatine (40 mg/kg i.p.) once a day for 22 days. The pro-cognitive effect of agomelatine was tested in the novel object recognition task and antidepressant activity in the forced swimming test. Microtubule dynamics markers, microtubule-associated protein type 2 (MAP-2), phosphorylated MAP-2, synaptic markers [synaptophysin, postsynaptic density-95 (PSD-95) and spinophilin] and BDNF were measured by Western blot in the hippocampus, amygdala and prefrontal cortex (PFC). Agomelatine exerted pro-cognitive and antidepressant activity and induced molecular changes in the brain areas examined. Agomelatine enhanced microtubule dynamics in the hippocampus and to a higher magnitude in the amygdala. By contrast, in the PFC, a decrease in microtubule dynamics was observed. Spinophilin (dendritic spines marker) was decreased, and BDNF increased in the hippocampus. Synaptophysin (presynaptic) and spinophilin were increased in the PFC and amygdala, while PSD-95 (postsynaptic marker) was increased in the amygdala, consistent with the phenomena of synaptic remodelling. Agomelatine modulates cytoskeletal microtubule dynamics and synaptic markers. This may play a role in its pharmacological behavioural effects and may result from the melatonergic agonist and 5-HT(2C) antagonist properties of the compound.

Cerebral Lateralization of Pro- and Anti-Social Tendencies

PubMed Central

2014-01-01

Mounting evidence suggest that the right-hemisphere (RH) has a relative advantage, over the left-hemisphere (LH), in mediating social intelligence - identifying social stimuli, understanding the intentions of other people, awareness of the dynamics in social relationships, and successful handling of social interactions. Furthermore, a review and synthesis of the literature suggest that pro-social attitudes and behaviors are associated with physiological activity in the RH, whereas unsocial and anti-social tendencies are mediated primarily by the LH. This hemispheric asymmetry is rooted in several neurobiological and functional differences between the two hemispheres. (I) Positive social interactions often require inhibiting one's immediate desires and considering the perspectives and needs of others. Given that self-control is mediated by the RH, pro-social emotions and behaviors are, therefore, inherently associated with the RH as it subserves the brain's self-restraint mechanisms. (II) The RH mediates experiences of vulnerability. It registers the relative clumsiness and motor weakness of the left limbs, and it is involved, more than the LH, in processing threats and mediating fear. Emotional states of vulnerability trigger the need for affiliation and sociality, therefore the RH has a greater role in mediating pro-social attitudes and behaviors. (III) The RH mediates a holistic mode of representing the world. Holistic perception emphasizes similarities rather than differences, takes a long-term perspective, is associated with divergent thinking and seeing other points-of-view, and it mediates a personal mode of relating to people. All these features of holistic perception facilitate a more empathetic attitude toward others and pro-social behaviors. PMID:24737936

Multiple binding modes for palmitate to barley lipid transfer protein facilitated by the presence of proline 12.

PubMed

Smith, Lorna J; Gunsteren, Wilfred F Van; Allison, Jane R

2013-01-01

Molecular dynamics simulations have been used to characterise the binding of the fatty acid ligand palmitate in the barley lipid transfer protein 1 (LTP) internal cavity. Two different palmitate binding modes (1 and 2), with similar protein-ligand interaction energies, have been identified using a variety of simulation strategies. These strategies include applying experimental protein-ligand atom-atom distance restraints during the simulation, or protonating the palmitate ligand, or using the vacuum GROMOS 54B7 force-field parameter set for the ligand during the initial stages of the simulations. In both the binding modes identified the palmitate carboxylate head group hydrogen bonds with main chain amide groups in helix A, residues 4 to 19, of the protein. In binding mode 1 the hydrogen bonds are to Lys 11, Cys 13, and Leu 14 and in binding mode 2 to Thr 15, Tyr 16, Val 17, Ser 24 and also to the OH of Thr 15. In both cases palmitate binding exploits irregularity of the intrahelical hydrogen-bonding pattern in helix A of barley LTP due to the presence of Pro 12. Simulations of two variants of barley LTP, namely the single mutant Pro12Val and the double mutant Pro12Val Pro70Val, show that Pro 12 is required for persistent palmitate binding in the LTP cavity. Overall, the work identifies key MD simulation approaches for characterizing the details of protein-ligand interactions in complexes where NMR data provide insufficient restraints. Copyright © 2012 The Protein Society.

Effect of biostimulants on 2,4,6-trinitrotoluene (TNT) degradation and bacterial community composition in contaminated aquifer sediment enrichments.

PubMed

Fahrenfeld, Nicole; Zoeckler, Jeffrey; Widdowson, Mark A; Pruden, Amy

2013-04-01

2,4,6-Trinitrotoluene (TNT) is a toxic and persistent explosive compound occurring as a contaminant at numerous sites worldwide. Knowledge of the microbial dynamics driving TNT biodegradation is limited, particularly in native aquifer sediments where it poses a threat to water resources. The purpose of this study was to quantify the effect of organic amendments on anaerobic TNT biodegradation rate and pathway in an enrichment culture obtained from historically contaminated aquifer sediment and to compare the bacterial community dynamics. TNT readily biodegraded in all microcosms, with the highest biodegradation rate obtained under the lactate amended condition followed by ethanol amended and naturally occurring organic matter (extracted from site sediment) amended conditions. Although a reductive pathway of TNT degradation was observed across all conditions, denaturing gradient gel electrophoresis (DGGE) analysis revealed distinct bacterial community compositions. In all microcosms, Gram-negative γ- or β-Proteobacteria and Gram-positive Negativicutes or Clostridia were observed. A Pseudomonas sp. in particular was observed to be stimulated under all conditions. According to non-metric multidimensional scaling analysis of DGGE profiles, the microcosm communities were most similar to heavily TNT-contaminated field site sediment, relative to moderately and uncontaminated sediments, suggesting that TNT contamination itself is a major driver of microbial community structure. Overall these results provide a new line of evidence of the key bacteria driving TNT degradation in aquifer sediments and their dynamics in response to organic carbon amendment, supporting this approach as a promising technology for stimulating in situ TNT bioremediation in the subsurface.

Identification of key genes in Gram-positive and Gram-negative sepsis using stochastic perturbation

PubMed Central

Li, Zhenliang; Zhang, Ying; Liu, Yaling; Liu, Yanchun; Li, Youyi

2017-01-01

Sepsis is an inflammatory response to pathogens (such as Gram-positive and Gram-negative bacteria), which has high morbidity and mortality in critically ill patients. The present study aimed to identify the key genes in Gram-positive and Gram-negative sepsis. GSE6535 was downloaded from Gene Expression Omnibus, containing 17 control samples, 18 Gram-positive samples and 25 Gram-negative samples. Subsequently, the limma package in R was used to screen the differentially expressed genes (DEGs). Hierarchical clustering was conducted for the specific DEGs in Gram-negative and Gram-negative samples using cluster software and the TreeView software. To analyze the correlation of samples at the gene level, a similarity network was constructed using Cytoscape software. Functional and pathway enrichment analyses were conducted for the DEGs using DAVID. Finally, stochastic perturbation was used to determine the significantly differential functions between Gram-positive and Gram-negative samples. A total of 340 and 485 DEGs were obtained in Gram-positive and Gram-negative samples, respectively. Hierarchical clustering revealed that there were significant differences between control and sepsis samples. In Gram-positive and Gram-negative samples, myeloid cell leukemia sequence 1 was associated with apoptosis and programmed cell death. Additionally, NADH:ubiquinone oxidoreductase subunit S4 was associated with mitochondrial respiratory chain complex I assembly. Stochastic perturbation analysis revealed that NADH:ubiquinone oxidoreductase subunit B2 (NDUFB2), NDUFB8 and ubiquinol-cytochrome c reductase hinge protein (UQCRH) were associated with cellular respiration in Gram-negative samples, whereas large tumor suppressor kinase 2 (LATS2) was associated with G1/S transition of the mitotic cell cycle in Gram-positive samples. NDUFB2, NDUFB8 and UQCRH may be biomarkers for Gram-negative sepsis, whereas LATS2 may be a biomarker for Gram-positive sepsis. These findings may promote the therapies of sepsis caused by Gram-positive and Gram-negative bacteria. PMID:28714002

Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis

NASA Astrophysics Data System (ADS)

Li, Yongxin; Li, Zhongrui; Yamanaka, Kazuya; Xu, Ying; Zhang, Weipeng; Vlamakis, Hera; Kolter, Roberto; Moore, Bradley S.; Qian, Pei-Yuan

2015-03-01

Bacilli are ubiquitous low G+C environmental Gram-positive bacteria that produce a wide assortment of specialized small molecules. Although their natural product biosynthetic potential is high, robust molecular tools to support the heterologous expression of large biosynthetic gene clusters in Bacillus hosts are rare. Herein we adapt transformation-associated recombination (TAR) in yeast to design a single genomic capture and expression vector for antibiotic production in Bacillus subtilis. After validating this direct cloning ``plug-and-play'' approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation process involving the N-acyl-asparagine pro-drug intermediates preamicoumacins, which are hydrolyzed by the asparagine-specific peptidase into the active component amicoumacin A. This work represents the first direct cloning based heterologous expression of natural products in the model organism B. subtilis and paves the way to the development of future genome mining efforts in this genus.

Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis.

PubMed

Li, Yongxin; Li, Zhongrui; Yamanaka, Kazuya; Xu, Ying; Zhang, Weipeng; Vlamakis, Hera; Kolter, Roberto; Moore, Bradley S; Qian, Pei-Yuan

2015-03-24

Bacilli are ubiquitous low G+C environmental Gram-positive bacteria that produce a wide assortment of specialized small molecules. Although their natural product biosynthetic potential is high, robust molecular tools to support the heterologous expression of large biosynthetic gene clusters in Bacillus hosts are rare. Herein we adapt transformation-associated recombination (TAR) in yeast to design a single genomic capture and expression vector for antibiotic production in Bacillus subtilis. After validating this direct cloning "plug-and-play" approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation process involving the N-acyl-asparagine pro-drug intermediates preamicoumacins, which are hydrolyzed by the asparagine-specific peptidase into the active component amicoumacin A. This work represents the first direct cloning based heterologous expression of natural products in the model organism B. subtilis and paves the way to the development of future genome mining efforts in this genus.

Diabetes education project: community networking in rural Utah.

PubMed

DeBry, S M; Smith, A; Wittenberg, M; Mortensen, V

1996-01-01

People in rural areas often lack the financial resources, workforce, and professional network needed to sustain a diabetes education pro gram in their own community. HealthInsight, a nonprofit organization that works to improve the quality of health care in its community, developed a 2-day seminar in an effort to facilitate the networking of rural health professionals who educate patients with diabetes and to help those educators better learn how to use existing resources. Participants included nurses, dietitians, diabetes educators, quality managers, and education directors from hospitals and home health agencies in both rural and metropolitan areas. Speakers presented information on a variety of topics related to program development, and a resource manual containing numerous materials was given to each participant. At the end of the seminar, the group turned in goals for their own programs. Too often, providers of health care compete rather than collaborate with one another. There is a great need for such networking opportunities among health care professionals working on common goals--especially in rural areas.

Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract.

PubMed

Anahtar, Melis N; Byrne, Elizabeth H; Doherty, Kathleen E; Bowman, Brittany A; Yamamoto, Hidemi S; Soumillon, Magali; Padavattan, Nikita; Ismail, Nasreen; Moodley, Amber; Sabatini, Mary E; Ghebremichael, Musie S; Nusbaum, Chad; Huttenhower, Curtis; Virgin, Herbert W; Ndung'u, Thumbi; Dong, Krista L; Walker, Bruce D; Fichorova, Raina N; Kwon, Douglas S

2015-05-19

Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining genital health. However, little is known about how genital microbiota influence host immune function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women and found that the majority of participants had genital communities with low Lactobacillus abundance and high ecological diversity. High-diversity communities strongly correlated with genital pro-inflammatory cytokine concentrations in both cross-sectional and longitudinal analyses. Transcriptional profiling suggested that genital antigen-presenting cells sense gram-negative bacterial products in situ via Toll-like receptor 4 signaling, contributing to genital inflammation through activation of the NF-κB signaling pathway and recruitment of lymphocytes by chemokine production. Our study proposes a mechanism by which cervicovaginal microbiota impact genital inflammation and thereby might affect a woman's reproductive health, including her risk of acquiring HIV. Copyright © 2015 Elsevier Inc. All rights reserved.

Experimental evaluation of cyclic fatigue resistance of four different nickel-titanium instruments after immersion in sodium hypochlorite and/or sterilization

PubMed Central

BULEM, Üreyen Kaya; KECECI, Ayse Diljin; GULDAS, Hilmi Egemen

2013-01-01

NiTi instruments have a high risk of separation due to torsional or flexural fatigue (cyclic fatigue). Chemomechanical preparation, cleaning procedures, chemical disinfection and sterilization cause the corrosion of endodontic instruments that may weaken the fracture resistance of the instruments. Objective To assess the effects of NaOCl immersion and autoclave sterilization on the cyclic fatigue resistance of ProFile, FlexMaster, Mtwo and TwistedFiles NiTi instruments (tip size 25, 0.06 taper, n=160). Material and Methods The instruments (n=10 for each subgroup) were dynamically immersed in NaOCl; immersed in NaOCl and sterilized in one autoclave cycle; 5 cycles immersed in NaOCl and sterilized in autoclave and not immersed in NaOCl and not sterilized (control group). Dynamic cyclic fatigue resistance was tested. The number of cycles to failure (NCF) were statistically analyzed (P<0.05). Results Kruskall-Wallis test indicated significant differences among the tested instruments in terms of NCF (P=0.000). The mean NCF of Mtwo (556.75) was higher than that of the Twisted File, Flexmaster and ProFile, 483.1, 376.12, 365.25, respectively. NaOCl immersion and autoclave sterilization have no effect on the NCF values of the tested instruments (P>.05). Conclusions Cyclic fatigue resistance of the tested NiTi instruments cannot be adversely affected by NaOCl immersion and autoclave sterilization. Production process (TwistedFiles) or design (Twisted Files, FlexMaster, Mtwo and ProFile) of the instruments can influence their cyclic fatigue resistance. PMID:24473715

Microbial community structures in algae cultivation ponds for bioconversion of agricultural wastes from livestock industry for feed production

USDA-ARS?s Scientific Manuscript database

Dynamics of seasonal microbial community compositions in algae cultivation ponds are complex. There is very limited knowledge on community compositions that may play significant roles in the bioconversion of manure nu¬trients to animal feed. Algae production is an alternative where land area for pro...

Accuracy of Tracking Forest Machines with GPS

Treesearch

M.W. Veal; S.E. Taylor; T.P. McDonald; D.K. McLemore; M.R. Dunn

2001-01-01

This paper describes the results of a study that measured the accuracy of using GPS to track movement offorest machines. Two different commercially available GPS receivers (Trimble ProXR and GeoExplorer II) were used to track wheeled skidders under three different canopy conditions at two different vehicle speeds. Dynamic GPS data were compared to position data...

"The Very Unrecognizability of the Other": Edith Stein, Judith Butler, and the Pedagogical Challenge of Empathy

ERIC Educational Resources Information Center

Kukar, Polina

2016-01-01

There is no standard definition of empathy, but the concept is assumed to be innately pro-social and teachable regardless of factors such as power dynamics or other manifestations of social injustice within a society. Such assumptions in discursive practices, whether academic, popular, or pedagogical, obscure the emergence of two important…

Chip-Based Dynamic Real-Time Quantification of Drug-Induced Cytotoxicity in Human Tumor Cells

PubMed Central

Wlodkowic, Donald; Skommer, Joanna; McGuinness, Dagmara; Faley, Shannon; Kolch, Walter; Darzynkiewicz, Zbigniew; Cooper, Jonathan M.

2013-01-01

Cell cytotoxicity tests are among the most common bioassays using flow cytometry and fluorescence imaging analysis. The permeability of plasma membranes to charged fluorescent probes serves, in these assays, as a marker distinguishing live from dead cells. Since it is generally assumed that probes, such as propidium iodide (PI) or 7-amino-actinomycin D (7-AAD), are themselves cytotoxic, they are currently generally used only as the end-point markers of assays for live versus dead cells. In the current study, we provide novel insights into potential applications of these classical plasma membrane integrity markers in the dynamic tracking of drug-induced cytotoxicity. We show that treatment of a number of different human tumor cell lines in cultures for up to 72 h with the PI, 7-AAD, SYTOX Green (SY-G), SYTOX Red (SYR), TO-PRO, and YO-PRO had no effect on cell viability assessed by the integrity of plasma membrane, cell cycle progression, and rate of proliferation. We subsequently explore the potential of dynamic labeling with these markers in real-time analysis, by comparing results from both conventional cytometry and microfluidic chips. Considering the simplicity of the staining protocols and their low cost combined with the potential for real-time data collection, we show how that real-time fluorescent imaging and Lab-on-a-Chip platforms have the potential to be used for automated drug screening routines. PMID:19572560

On the Roles of Substrate Binding and Hinge Unfolding in Conformational Changes of Adenylate Kinase

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

Brokaw, Jason B.; Chu, Jhih-wei

2010-11-17

We characterized the conformational change of adenylate kinase (AK) between open and closed forms by conducting five all-atom molecular-dynamics simulations, each of 100 ns duration. Different initial structures and substrate binding configurations were used to probe the pathways of AK conformational change in explicit solvent, and no bias potential was applied. A complete closed-to-open and a partial open-to-closed transition were observed, demonstrating the direct impact of substrate-mediated interactions on shifting protein conformation. The sampled configurations suggest two possible pathways for connecting the open and closed structures of AK, affirming the prediction made based on available x-ray structures and earlier worksmore » of coarse-grained modeling. The trajectories of the all-atom molecular-dynamics simulations revealed the complexity of protein dynamics and the coupling between different domains during conformational change. Calculations of solvent density and density fluctuations surrounding AK did not show prominent variation during the transition between closed and open forms. Finally, we characterized the effects of local unfolding of an important hinge near Pro177 on the closed-to-open transition of AK and identified a novel mechanism by which hinge unfolding modulates protein conformational change. The local unfolding of Pro177 hinge induces alternative tertiary contacts that stabilize the closed structure and prevent the opening transition.« less

21 CFR 520.550 - Dextrose/glycine/electrolyte.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ingredients: sodium chloride 8.82 grams, potassium phosphate 4.20 grams, citric acid anhydrous 0.5 gram, potassium citrate 0.12 gram, aminoacetic acid (glycine) 6.36 grams, and dextrose 44.0 grams. (b) Sponsor...

21 CFR 520.550 - Glucose/glycine/electrolyte.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ingredients: Sodium chloride 8.82 grams, potassium phosphate 4.20 grams, citric acid anhydrous 0.5 gram, potassium citrate 0.12 gram, aminoacetic acid (glycine) 6.36 grams, and glucose 44.0 grams. (b) Sponsor. See...

21 CFR 520.550 - Glucose/glycine/electrolyte.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ingredients: Sodium chloride 8.82 grams, potassium phosphate 4.20 grams, citric acid anhydrous 0.5 gram, potassium citrate 0.12 gram, aminoacetic acid (glycine) 6.36 grams, and glucose 44.0 grams. (b) Sponsor. See...

21 CFR 520.550 - Glucose/glycine/electrolyte.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ingredients: Sodium chloride 8.82 grams, potassium phosphate 4.20 grams, citric acid anhydrous 0.5 gram, potassium citrate 0.12 gram, aminoacetic acid (glycine) 6.36 grams, and glucose 44.0 grams. (b) Sponsor. See...

21 CFR 520.550 - Glucose/glycine/electrolyte.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ingredients: Sodium chloride 8.82 grams, potassium phosphate 4.20 grams, citric acid anhydrous 0.5 gram, potassium citrate 0.12 gram, aminoacetic acid (glycine) 6.36 grams, and glucose 44.0 grams. (b) Sponsor. See...

Developing Novel Frameworks for Many-Body Ensembles

DTIC Science & Technology

2016-03-17

RETURN YOUR FORM TO THE ABOVE ADDRESS. Massachusetts Institute of Technology (MIT) 77 Massachusetts Ave. NE18-901 Cambridge , MA 02139 -4307 15-Jul-2015...of-equilibrium dynamics and to estimate prob- Page 4 of 9 Figure 2: Illustration of the dendro- gram representation. The rectangle on the left shows...isolation as illustrated in Figure 4. Starting from random initial conditions, an ensemble of particle pairs was simulated to establish the long-time

A Reverse-phase Protein Microarray-based Screen Identifies Host Signaling Dynamics upon Burkholderia spp. Infection

DTIC Science & Technology

2015-07-27

University, Manassas, VA, USA, 4 PerkinElmer, Inc., Waltham, MA, USA Burkholderia is a diverse genus of gram-negative bacteria that causes high...Burkholderia spp. infections. Materials and Methods Bacterial Strains Bm ATCC 23344, NCTC 10247, NCTC 10229, NCTC 3708, NCTC 3709, 2002721278 (Burtnick...macrophage cell line RAW264.7 was obtained from ATCC (Manassas, VA). Cells were cultured in DMEM (Life Technologies) supplemented with 10% fetal

Parallel Group and Sunspot Counts from SDO/HMI and AAVSO Visual Observers (Abstract)

NASA Astrophysics Data System (ADS)

Howe, R.; Alvestad, J.

2015-06-01

(Abstract only) Creating group and sunspot counts from the SDO/HMI detector on the Solar Dynamics Observatory (SDO) satellite requires software that calculates sunspots from a “white light” intensity-gram (CCD image) and group counts from a filtered CCD magneto-gram. Images from the satellite come from here http://jsoc.stanford.edu/data/hmi/images/latest/ Together these two sets of images can be used to estimate the Wolf number as W = (10g + s), which is used to calculate the American Relative index. AAVSO now has approximately two years of group and sunspot counts in the SunEntry database as SDOH observer Jan Alvestad. It is important that we compare these satellite CCD image data with our visual observer daily submissions to determine if the SDO/HMI data should be included in calculating the American Relative index. These satellite data are continuous observations with excellent seeing. This contrasts with “snapshot” earth-based observations with mixed seeing. The SDO/HIM group and sunspot counts could be considered unbiased, except that they show a not normal statistical distribution when compared to the overall visual observations, which show a Poisson distribution. One challenge that should be addressed by AAVSO using these SDO/HMI data is the splitting of groups and deriving group properties from the magneto-grams. The filtered CCD detector that creates the magento-grams is not something our visual observers can relate too, unless they were to take CCD images in H-alpha and/or the Calcium spectrum line. So, questions remain as to how these satellite CCD image counts can be integrated into the overall American Relative index.

Effects of dimethyl sulfoxide in cholesterol-containing lipid membranes: a comparative study of experiments in silico and with cells.

PubMed

de Ménorval, Marie-Amélie; Mir, Lluis M; Fernández, M Laura; Reigada, Ramon

2012-01-01

Dimethyl sulfoxide (DMSO) has been known to enhance cell membrane permeability of drugs or DNA. Molecular dynamics (MD) simulations with single-component lipid bilayers predicted the existence of three regimes of action of DMSO: membrane loosening, pore formation and bilayer collapse. We show here that these modes of action are also reproduced in the presence of cholesterol in the bilayer, and we provide a description at the atomic detail of the DMSO-mediated process of pore formation in cholesterol-containing lipid membranes. We also successfully explore the applicability of DMSO to promote plasma membrane permeability to water, calcium ions (Ca(2+)) and Yo-Pro-1 iodide (Yo-Pro-1) in living cell membranes. The experimental results on cells in culture can be easily explained according to the three expected regimes: in the presence of low doses of DMSO, the membrane of the cells exhibits undulations but no permeability increase can be detected, while at intermediate DMSO concentrations cells are permeabilized to water and calcium but not to larger molecules as Yo-Pro-1. These two behaviors can be associated to the MD-predicted consequences of the effects of the DMSO at low and intermediate DMSO concentrations. At larger DMSO concentrations, permeabilization is larger, as even Yo-Pro-1 can enter the cells as predicted by the DMSO-induced membrane-destructuring effects described in the MD simulations.

Effects of Dimethyl Sulfoxide in Cholesterol-Containing Lipid Membranes: A Comparative Study of Experiments In Silico and with Cells

PubMed Central

de Ménorval, Marie-Amélie; Mir, Lluis M.; Fernández, M. Laura; Reigada, Ramon

2012-01-01

Dimethyl sulfoxide (DMSO) has been known to enhance cell membrane permeability of drugs or DNA. Molecular dynamics (MD) simulations with single-component lipid bilayers predicted the existence of three regimes of action of DMSO: membrane loosening, pore formation and bilayer collapse. We show here that these modes of action are also reproduced in the presence of cholesterol in the bilayer, and we provide a description at the atomic detail of the DMSO-mediated process of pore formation in cholesterol-containing lipid membranes. We also successfully explore the applicability of DMSO to promote plasma membrane permeability to water, calcium ions (Ca2+) and Yo-Pro-1 iodide (Yo-Pro-1) in living cell membranes. The experimental results on cells in culture can be easily explained according to the three expected regimes: in the presence of low doses of DMSO, the membrane of the cells exhibits undulations but no permeability increase can be detected, while at intermediate DMSO concentrations cells are permeabilized to water and calcium but not to larger molecules as Yo-Pro-1. These two behaviors can be associated to the MD-predicted consequences of the effects of the DMSO at low and intermediate DMSO concentrations. At larger DMSO concentrations, permeabilization is larger, as even Yo-Pro-1 can enter the cells as predicted by the DMSO-induced membrane-destructuring effects described in the MD simulations. PMID:22848583

B-type and N-terminal pro-B-type natriuretic peptides are equally useful in assessing patent ductus arteriosus in very preterm infants.

PubMed

König, Kai; Guy, Katelyn J; Drew, Sandra M; Barfield, Charles P

2015-04-01

B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) have been shown to correlate with the size of the patent ductus arteriosus (PDA) in preterm infants. We investigated whether BNP or NTproBNP was more closely correlated with PDA size. This prospective observational study included preterm infants born <32 weeks' gestation who had an echocardiogram performed within the first four days of life. Blood samples were taken simultaneously for BNP and NTproBNP measurements prior to echocardiographic examination. Of the 60 infants recruited, 58 had complete data sets. The cohort's mean and standard deviation (SD) gestational age was 27(+3) (2(+2)) weeks, the mean (SD) birthweight was 1032 (315) grams, and 46 (79.3%) infants had a PDA with a mean (SD) diameter of 3.2 (0.9) mm. Median and interquartile range (IQR) BNP levels were 486.5 (219-1316) pg/mL for infants with a PDA and 190 (95.5-514.5) pg/mL for infants without a PDA. Median (IQR) NTproBNP levels were 10 858.5 (6319-42 108) pg/mL for infants with a PDA and 7488 (3363-14 227.5) pg/mL for infants without a PDA. Both BNP (R = 0.35, p = 0.0066) and NTproBNP (R = 0.31, p = 0.018) were significantly correlated with PDA size. BNP and NTproBNP are similarly useful for assessing PDA size in preterm infants. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Aspirin-triggered resolvin D1 is produced during self-resolving gram-negative bacterial pneumonia and regulates host immune responses for the resolution of lung inflammation.

PubMed

Abdulnour, R E; Sham, H P; Douda, D N; Colas, R A; Dalli, J; Bai, Y; Ai, X; Serhan, C N; Levy, B D

2016-09-01

Bacterial pneumonia is a leading cause of morbidity and mortality worldwide. Host responses to contain infection and mitigate pathogen-mediated lung inflammation are critical for pneumonia resolution. Aspirin-triggered resolvin D1 (AT-RvD1; 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) is a lipid mediator (LM) that displays organ-protective actions in sterile lung inflammation, and regulates pathogen-initiated cellular responses. Here, in a self-resolving murine model of Escherichia coli pneumonia, LM metabololipidomics performed on lungs obtained at baseline, 24, and 72 h after infection uncovered temporal regulation of endogenous AT-RvD1 production. Early treatment with exogenous AT-RvD1 (1 h post infection) enhanced clearance of E. coli and Pseudomonas aeruginosa in vivo, and lung macrophage phagocytosis of fluorescent bacterial particles ex vivo. Characterization of macrophage subsets in the alveolar compartment during pneumonia identified efferocytosis by infiltrating macrophages (CD11b(Hi) CD11c(Low)) and exudative macrophages (CD11b(Hi) CD11c(Hi)). AT-RvD1 increased efferocytosis by these cells ex vivo, and accelerated neutrophil clearance during pneumonia in vivo. These anti-bacterial and pro-resolving actions of AT-RvD1 were additive to antibiotic therapy. Taken together, these findings suggest that the pro-resolving actions of AT-RvD1 during pneumonia represent a novel host-directed therapeutic strategy to complement the current antibiotic-centered approach for combatting infections.

Variation in the ovine cortisol response to systemic bacterial endotoxin challenge is predominantly determined by signalling within the hypothalamic-pituitary-adrenal axis

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

You Qiumei; Karrow, Niel A.; Cao Honghe

Bi-directional communication between the neuroendocrine and immune systems is designed, in part, to maintain or restore homeostasis during physiological stress. Exposure to endotoxin during Gram-negative bacterial infection for example, elicits the release of pro-inflammatory cytokines that activate the hypothalamic-pituitary-adrenal axis (HPAA). The secretion of adrenal glucocorticoids subsequently down regulates the host inflammatory response, minimizing potential tissue damage. Sequence and epigenetic variants in genes involved in regulating the neuroendocrine and immune systems are likely to contribute to individual differences in the HPAA response, and this may influence the host anti-inflammatory response to toxin exposure and susceptibility to inflammatory disease. In thismore » study, high (HCR) and low (LCR) cortisol responders were selected from a normal population of 110 female sheep challenged iv with Escherichia coli endotoxin (400 ng/kg) to identify potential determinants that contribute to variation in the cortisol response phenotype. This phenotype was stable over several years in the HCR and LCR animals, and did not appear to be attributed to differences in expression of hepatic immune-related genes or systemic pro-inflammatory cytokine concentrations. Mechanistic studies using corticotrophin-releasing factor (0.5 {mu}g/kg body weight), arginine vasopressin (0.5 {mu}g/kg), and adrenocorticotropic hormone (0.5 {mu}g/kg) administered iv demonstrated that variation in this phenotype is largely determined by signalling within the HPAA. Future studies will use this ovine HCR/LCR model to investigate potential genetic and epigenetic variants that may contribute to variation in cortisol responsiveness to bacterial endotoxin.« less

gram-scale metafluids and large area tunable metamaterials: design, fabrication, and nano-optical tomographic characterization (Conference Presentation)

NASA Astrophysics Data System (ADS)

Dionne, Jennifer A.

2016-09-01

Advances in metamaterials and metasurfaces have enabled unprecedented control of light-matter interactions. Metamaterial constituents support high-frequency electric and magnetic dipoles, which can be used as building blocks for new materials capable of negative refraction, electromagnetic cloaking, strong visible-frequency circular dichroism, and enhanced magnetic or chiral transitions in ions and molecules. However, most metamaterials to date have been limited to solid-state, static, narrow-band, and/or small-area structures. Here, we introduce the design, fabrication, and three-dimensional nano-optical characterization of large-area, dynamically-tunable metamaterials and gram-scale metafluids. First, we use transformation optics to design a broadband metamaterial constituent - a metallo-dielectric nanocrescent - characterized by degenerate electric and magnetic dipoles. A periodic array of nanocrescents exhibits large positive and negative refractive indices at optical frequencies, confirmed through simulations of plane wave refraction through a metamaterial prism. Simulations also reveal that the metamaterial optical properties are largely insensitive to the wavelength, orientation and polarization of incident light. Then, we introduce a new tomographic technique, cathodoluminescence (CL) spectroscopic tomography, to probe light-matter interactions in individual nanocrescents with nanometer-scale resolution. Two-dimensional CL maps of the three-dimensional nanostructure are obtained at various orientations, while a filtered back projection is used to reconstruct the CL intensity at each wavelength. The resulting tomograms allow us to locate regions of efficient cathodoluminescence in three dimensions across visible and near-infrared wavelengths, with contributions from material luminescence and radiative decay of electromagnetic eigenmodes. Finally, we demonstrate the fabrication of dynamically tunable large-area metamaterials and gram-scale metafluids, using a combination of colloidal synthesis, protein-directed assembly, self-assembly, etching, and stamping. The electric and magnetic response of the bulk metamaterial and metafluid are directly probed with optical scattering and spectroscopy. Using chemical swelling, these metamaterials exhibit reversible, unity-order refractive index changes that may provide a foundation for new adaptive optical materials in sensing, solar, and display applications.

Robust peptidoglycan growth by dynamic and variable multi-protein complexes.

PubMed

Pazos, Manuel; Peters, Katharina; Vollmer, Waldemar

2017-04-01

In Gram-negative bacteria such as Escherichia coli the peptidoglycan sacculus resides in the periplasm, a compartment that experiences changes in pH value, osmolality, ion strength and other parameters depending on the cell's environment. Hence, the cell needs robust peptidoglycan growth mechanisms to grow and divide under different conditions. Here we propose a model according to which the cell achieves robust peptidoglycan growth by employing dynamic multi-protein complexes, which assemble with variable composition from freely diffusing sets of peptidoglycan synthases, hydrolases and their regulators, whereby the composition of the active complexes depends on the cell cycle state - cell elongation or division - and the periplasmic growth conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phaeton Mast Dynamics: On-Orbit Characterization of Deployable Masts

NASA Technical Reports Server (NTRS)

Michaels, Darren J.

2011-01-01

The PMD instrument is a set of three custom-designed triaxial accelerometer systems designed specifically to detect and characterize the modal dynamics of deployable masts in orbit. The instrument was designed and built as a payload for the NuSTAR spacecraft, but it is now sponsored by the Air Force Research Laboratory's DSX project. It can detect acceleration levels from 1 micro gram to 0.12g over a frequency range of 0.1Hz to 30Hz, the results of which can support future modeling and designing of deployable mast structures for space. This paper details the hardware architecture and design, calibration test and results, and current status of the PMD instrument.

Tissue structure characterization of biotissue phantom by use of the speckle-correlometric technique

NASA Astrophysics Data System (ADS)

Isaeva, A. A.; Isaeva, E. A.; Zimnyakov, D. A.; Pantyukov, A. V.; Agapova, Y. V.; Macheyev, M. A.

2017-03-01

Speckle correlometry gives the possibilities to visualize tissue scattering structure analyzing the correlation characteristics of speckle-modulated images. In this work, the inhomogeneous multiple scattering medium with the "dynamic" long inclusions was investigated like a blood vessels in living tissue. The scattering media is 0.28% weight fraction of gelatin dissolved in water and 1 gram per liter (gL-1) and 100 mg per liter (gL-1) of TiO2 for optical scattering. The movement of fluid (distilled water) in the cylindrical hole with given radius simulate a blood motion in the vessel. It was shown the possibility to determinate the depth location of dynamic inhomogeneities inside a scattering medium.

Experimental validation of docking and capture using space robotics testbeds

NASA Technical Reports Server (NTRS)

Spofford, John; Schmitz, Eric; Hoff, William

1991-01-01

This presentation describes the application of robotic and computer vision systems to validate docking and capture operations for space cargo transfer vehicles. Three applications are discussed: (1) air bearing systems in two dimensions that yield high quality free-flying, flexible, and contact dynamics; (2) validation of docking mechanisms with misalignment and target dynamics; and (3) computer vision technology for target location and real-time tracking. All the testbeds are supported by a network of engineering workstations for dynamic and controls analyses. Dynamic simulation of multibody rigid and elastic systems are performed with the TREETOPS code. MATRIXx/System-Build and PRO-MATLAB/Simulab are the tools for control design and analysis using classical and modern techniques such as H-infinity and LQG/LTR. SANDY is a general design tool to optimize numerically a multivariable robust compensator with a user-defined structure. Mathematica and Macsyma are used to derive symbolically dynamic and kinematic equations.

Differential staining of bacteria: gram stain.

PubMed

Moyes, Rita B; Reynolds, Jackie; Breakwell, Donald P

2009-11-01

In 1884, Hans Christian Gram, a Danish doctor, developed a differential staining technique that is still the cornerstone of bacterial identification and taxonomic division. This multistep, sequential staining protocol separates bacteria into four groups based on cell morphology and cell wall structure: Gram-positive cocci, Gram-negative cocci, Gram-positive rods, and Gram-negative rods. The Gram stain is useful for assessing bacterial contamination of tissue culture samples or for examining the Gram stain status and morphological features of bacteria isolated from mixed or isolated bacterial cultures. (c) 2009 by John Wiley & Sons, Inc.

Differential response of TRHergic neurons of the hypothalamic paraventricular nucleus (PVN) in female animals submitted to food-restriction or dehydration-induced anorexia and cold exposure.

PubMed

Jaimes-Hoy, Lorraine; Joseph-Bravo, Patricia; de Gortari, Patricia

2008-02-01

TRH neurons of the hypothalamic paraventricular nucleus (PVN), regulate pituitary-thyroid axis (HPT). Fasting activates expression of orexigenic peptides from the arcuate nucleus, increases corticosterone while reduces leptin, and pro-TRH mRNA levels despite low serum thyroid hormone concentration (tertiary hypothyroidism). TRH synthesis is positively regulated by anorexigenic peptides whose expression is reduced in fasting. The model of dehydration-induced anorexia (DIA) leads to decreased voluntary food intake but peptide expression in the arcuate is similar to forced-food restriction (FFR), where animals remain hungered. We compared the response of HPT axis of female Wistar rats submitted to DIA (2.5% saline solution, food ad libitum, 7 days) with FFR (provided with the amount of food ingested by DIA) and naïve (N) group fed ad libitum, as well as their response to acute cold exposure. Pro-TRH and pro-CRH mRNA levels in the PVN were measured by RT-PCR, TRH content, serum concentration of TSH and thyroid hormones by radioimmunoassay. DIA rats reduced 80% their food consumption compared to N, decreased PVN pro-CRH expression, serum estradiol and leptin levels, increased corticosterone similar to FFR. HPT axis of DIA animals failed to adapt: FFR presented tertiary hypothyroidism and DIA, primary. Response to cold stimulation leading to increased pro-TRH mRNA levels and TRH release was preserved under reduced energy availability in FFR rats but not in DIA, although the dynamics of hormonal release differed: TSH release augmented only in naïve; thyroxine in all but highest in DIA, and triiodothyronine in FFR and DIA suggesting a differential regulation of deiodinases.

Dynamics of Flow in the Region of the Tsugaru Strait.

DTIC Science & Technology

1981-03-01

possessed sufficient initial vrticity at a strait outlet. Beardslev and Hart (1978) pro- duced anal yr i c sol It i ons -t the out t low ci rcul at ion for a...38. ’da , M . , 1934, Hlydrographical studies based on simll taneous oceano - ,graphi cal surveys made in the Japan Sea and i ts adjacent waters during

Misinterpretation of Gram Stain from the Stationary Growth Phase of Positive Blood Cultures for Brucella and Acinetobacter Species.

PubMed

Bazzi, Ali M; Al-Tawfiq, Jaffar A; Rabaan, Ali A

2017-01-01

Acinetobacter baumannii and Brucella species are Gram-negative organisms that are vulnerable to misinterpretation as Gram-positive or Gram-variable in blood cultures. We assess the random errors in gram stain interpretation to reduce the likelihood of such errors and therefore patient harm. Aerobic and anaerobic blood cultures from two patients in an acute care facility in Saudi Arabia were subjected to preliminary Gram-staining. In case 1, VITEK-2 Anaerobe Identification, repeat Gram staining from a blood agar plate, Remel BactiDrop™ Oxidase test, Urea Agar urease test and real-time PCR were used to confirm presence of Brucella and absence of Coryneform species. In case 2, repeat Gram- staining from the plate and the vials, VITEK-2 Gram-Negative Identification, real-time PCR and subculture on to Columbia agar, blood agar, and MacConkey agar were carried out to identify A. baumannii . In case 1, initially pleomorphic Gram-positive bacteria were identified. Coryneform species were suspected. Tiny growth was observed after 24 h on blood agar plates, and good growth by 48 h. Presence of Brucella species was ultimately confirmed. In case 2, preliminary Gram-stain results suggested giant Gram-positive oval cocci. Further testing over 18-24 h identified A. baumannii . Oxidase test from the plate and urease test from the culture vial is recommended after apparent identification of pleomorphic Gram-positive bacilli from blood culture, once tiny growth is observed, to distinguish Brucella from Corynebacterium species. If giant Gram-positive oval cocci are indicated by preliminary Gram-staining, it is recommended that the Gram stain be repeated from the plate after 4-6 h, or culture should be tested in Triple Sugar Iron (TSI) medium and the Gram stain repeated after 2-4 h incubation.

Chemical and Biological Sensor Standards Study

DTIC Science & Technology

2005-01-01

that is utilized in lieu of Bacillus anthracis in testing biological agent sensors; both are gram positive, spore forming bacteria that have similar...for a given agent dosage is as follows: C = D r 3 f B Tη4π 3 ρ See the table for the variable designation. Using Bacillus anthracis as an example...e.g., genetic similarity, aerosol dynamics, size, shape, etc.) of the agent of interest. For example, Bacillus globigii is a widely used bacterium

Computerized video-enhanced high temporal resolution of erythrocytes sedimentation rate (ESR-graphy) reveals complex dynamic and self-organizing properties of whole blood

NASA Astrophysics Data System (ADS)

Voeikov, Vladimir L.; Kondakov, Sergey E.; Buravleva, Ekaterina; Kaganovsky, Isaak; Reznikov, Mikhail

2000-05-01

An automatic device for high-temporal resolution of the process of red blood sedimentation was designed. The position of the boundary between red blood and plasma may be registered each 30 sec in several pipettes simultaneously with +/- 10 mkm precision. Fractional rates of the boundary movement are deduced with high accuracy. Data are processed by a PC and presented as velocity-time curves (ESR-grams) and the curves describing time evolution of the boundary position. Several unexpected phenomena in the process of red blood sedimentation have been revealed. Upward fast movements of the boundary up to 1 mm were noted. In patients' blood sets of 5 - 10 milliHz oscillations of sedimentation rate were usually developing at early stages of blood sedimentation. In non-diluted healthy donors' blood high amplitude periodic oscillations were either absent, or were emerging only after blood resided in pipettes for several hours. When blood was diluted to a certain degree with physiological saline or with own plasma long-term low frequency (1 - 3 milliHz) rate oscillations regularly appeared. Non-trivial dependence of patterns of ESR-grams on diluting of blood with own plasma or saline was observed. Thus, non-linear dynamic behavior of living blood has been revealed due to application of the principles of the system of technical vision for the detailed analysis of red blood sedimentation kinetics.

Angiotensin I-converting-enzyme-inhibitory and antibacterial peptides from Lactobacillus helveticus PR4 proteinase-hydrolyzed caseins of milk from six species.

PubMed

Minervini, F; Algaron, F; Rizzello, C G; Fox, P F; Monnet, V; Gobbetti, M

2003-09-01

Sodium caseinates prepared from bovine, sheep, goat, pig, buffalo or human milk were hydrolyzed by a partially purified proteinase of Lactobacillus helveticus PR4. Peptides in each hydrolysate were fractionated by reversed-phase fast-protein liquid chromatography. The fractions which showed the highest angiotensin I-converting-enzyme (ACE)-inhibitory or antibacterial activity were sequenced by mass spectrum and Edman degradation analyses. Various ACE-inhibitory peptides were found in the hydrolysates: the bovine alpha(S1)-casein (alpha(S1)-CN) 24-47 fragment (f24-47), f169-193, and beta-CN f58-76; ovine alpha(S1)-CN f1-6 and alpha(S2)-CN f182-185 and f186-188; caprine beta-CN f58-65 and alpha(S2)-CN f182-187; buffalo beta-CN f58-66; and a mixture of three tripeptides originating from human beta-CN. A mixture of peptides with a C-terminal sequence, Pro-Gly-Pro, was found in the most active fraction of the pig sodium caseinate hydrolysate. The highest ACE-inhibitory activity of some peptides corresponded to the concentration of the ACE inhibitor (S)-N-(1-[ethoxycarbonyl]-3-phenylpropyl)-ala-pro maleate (enalapril) of 49.253 micro g/ml (100 micro mol/liter). Several of the above sequences had features in common with other ACE-inhibitory peptides reported in the literature. The 50% inhibitory concentration (IC(50)) of some of the crude peptide fractions was very low (16 to 100 micro g/ml). Some identified peptides were chemically synthesized, and the ACE-inhibitory activity and IC(50)s were confirmed. An antibacterial peptide corresponding to beta-CN f184-210 was identified in human sodium caseinate hydrolysate. It showed a very large spectrum of inhibition against gram-positive and -negative bacteria, including species of potential clinical interest, such as Enterococcus faecium, Bacillus megaterium, Escherichia coli, Listeria innocua, Salmonella spp., Yersinia enterocolitica, and Staphylococcus aureus. The MIC for E. coli F19 was ca. 50 micro g/ml. Once generated, the bioactive peptides were resistant to further degradation by proteinase of L. helveticus PR4 or by trypsin and chymotrypsin.

21 CFR 520.2380e - Thiabendazole with trichlorfon.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Thiabendazole with trichlorfon. (a) Specifications. The drug contains 5 grams of thiabendazole with 4.5 grams of trichlorfon, or 20 grams of thiabendazole with 18 grams of trichlorfon. (b) Sponsor. See No. 017135 in § 510... ascarids (Parascaris spp. ) in horses. (2) Administer 2 grams of thiabendazole with 1.8 grams of...

21 CFR 558.635 - Virginiamycin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... activity (5 grams per pound), 2.2 percent activity (10 grams per pound), 4.4 percent activity (20 grams per pound), 11 percent activity (50 grams per pound), and 50 percent activity (227 grams per pound) used as in paragraph (d) of this section; and 30 percent activity (136.2 grams per pound) for the manufacture...

21 CFR 558.635 - Virginiamycin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... activity (5 grams per pound), 2.2 percent activity (10 grams per pound), 4.4 percent activity (20 grams per pound), 11 percent activity (50 grams per pound), and 50 percent activity (227 grams per pound) used as in paragraph (d) of this section; and 30 percent activity (136.2 grams per pound) for the manufacture...

21 CFR 520.1720c - Phenylbutazone paste.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... (a) Specifications—(1) Each gram of paste contains 0.2 grams phenylbutazone. (2) Each gram of paste contains 0.35 grams phenylbutazone. (b) Sponsors. See sponsor numbers in § 510.600(c) of this chapter. (1.... 1 to 2 grams of phenylbutazone per 500 pounds of body weight, not to exceed 4 grams daily. (2...

10 CFR 150.14 - Commission regulatory authority for physical protection.

Code of Federal Regulations, 2012 CFR

2012-01-01

... significance in quantities greater than 15 grams of plutonium or uranium-233 or uranium-235 (enriched to 20 percent or more in the U-235 isotope) or any combination greater than 15 grams when computed by the equation grams=grams uranium-235+grams plutonium+grams uranium-233 shall meet the physical protection...

21 CFR 520.1720c - Phenylbutazone paste.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... (a) Specifications—(1) Each gram of paste contains 0.2 grams phenylbutazone. (2) Each gram of paste contains 0.35 grams phenylbutazone. (b) Sponsors. See sponsor numbers in § 510.600(c) of this chapter. (1.... 1 to 2 grams of phenylbutazone per 500 pounds of body weight, not to exceed 4 grams daily. (2...

21 CFR 558.635 - Virginiamycin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... activity (5 grams per pound), 2.2 percent activity (10 grams per pound), 4.4 percent activity (20 grams per pound), 11 percent activity (50 grams per pound), and 50 percent activity (227 grams per pound) used as in paragraph (d) of this section; and 30 percent activity (136.2 grams per pound) for the manufacture...

10 CFR 150.14 - Commission regulatory authority for physical protection.

Code of Federal Regulations, 2010 CFR

2010-01-01

... significance in quantities greater than 15 grams of plutonium or uranium-233 or uranium-235 (enriched to 20 percent or more in the U-235 isotope) or any combination greater than 15 grams when computed by the equation grams=grams uranium-235+grams plutonium+grams uranium-233 shall meet the physical protection...

21 CFR 558.635 - Virginiamycin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... activity (5 grams per pound), 2.2 percent activity (10 grams per pound), 4.4 percent activity (20 grams per pound), 11 percent activity (50 grams per pound), and 50 percent activity (227 grams per pound) used as in paragraph (d) of this section; and 30 percent activity (136.2 grams per pound) for the manufacture...

21 CFR 558.635 - Virginiamycin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... activity (5 grams per pound), 2.2 percent activity (10 grams per pound), 4.4 percent activity (20 grams per pound), 11 percent activity (50 grams per pound), and 50 percent activity (227 grams per pound) used as in paragraph (d) of this section; and 30 percent activity (136.2 grams per pound) for the manufacture...

10 CFR 150.14 - Commission regulatory authority for physical protection.

Code of Federal Regulations, 2011 CFR

2011-01-01

... significance in quantities greater than 15 grams of plutonium or uranium-233 or uranium-235 (enriched to 20 percent or more in the U-235 isotope) or any combination greater than 15 grams when computed by the equation grams=grams uranium-235+grams plutonium+grams uranium-233 shall meet the physical protection...

21 CFR 520.2380e - Thiabendazole with trichlorfon.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Thiabendazole with trichlorfon. (a) Specifications. The drug contains 5 grams of thiabendazole with 4.5 grams of trichlorfon, or 20 grams of thiabendazole with 18 grams of trichlorfon. (b) Sponsor. See No. 017135 in § 510... ascarids (Parascaris spp. ) in horses. (2) Administer 2 grams of thiabendazole with 1.8 grams of...

21 CFR 520.2380e - Thiabendazole with trichlorfon.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Thiabendazole with trichlorfon. (a) Specifications. The drug contains 5 grams of thiabendazole with 4.5 grams of trichlorfon, or 20 grams of thiabendazole with 18 grams of trichlorfon. (b) Sponsor. See No. 017135 in § 510... ascarids (Parascaris spp. ) in horses. (2) Administer 2 grams of thiabendazole with 1.8 grams of...

10 CFR 150.14 - Commission regulatory authority for physical protection.

Code of Federal Regulations, 2013 CFR

2013-01-01

... significance in quantities greater than 15 grams of plutonium or uranium-233 or uranium-235 (enriched to 20 percent or more in the U-235 isotope) or any combination greater than 15 grams when computed by the equation grams=grams uranium-235+grams plutonium+grams uranium-233 shall meet the physical protection...

21 CFR 520.2380e - Thiabendazole with trichlorfon.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Thiabendazole with trichlorfon. (a) Specifications. The drug contains 5 grams of thiabendazole with 4.5 grams of trichlorfon, or 20 grams of thiabendazole with 18 grams of trichlorfon. (b) Sponsor. See No. 017135 in § 510... ascarids (Parascaris spp. ) in horses. (2) Administer 2 grams of thiabendazole with 1.8 grams of...

10 CFR 150.14 - Commission regulatory authority for physical protection.

Code of Federal Regulations, 2014 CFR

2014-01-01

... significance in quantities greater than 15 grams of plutonium or uranium-233 or uranium-235 (enriched to 20 percent or more in the U-235 isotope) or any combination greater than 15 grams when computed by the equation grams=grams uranium-235+grams plutonium+grams uranium-233 shall meet the physical protection...

21 CFR 520.1720c - Phenylbutazone paste.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... (a) Specifications—(1) Each gram of paste contains 0.2 grams phenylbutazone. (2) Each gram of paste contains 0.35 grams phenylbutazone. (b) Sponsors. See sponsor numbers in § 510.600(c) of this chapter. (1.... 1 to 2 grams of phenylbutazone per 500 pounds of body weight, not to exceed 4 grams daily. (2...

The SMS4 cryptographic system design based on dynamic partial self-reconfiguration technology

NASA Astrophysics Data System (ADS)

Wang, Jianxin; Gao, Xianwei; Li, Xiuying; Sui, Meili

2013-03-01

This paper describes SMS4 algorithm by using dynamic partial self-reconfiguration. The design is implemented on Xilinx VirtexII-Pro XC2VP30 FPGA devices. The partial self-reconfiguration encryption/decryption module data throughput is up to 50Mb/s, key expansion and encryption/decryption modules use 1606 and 1570 slices respectively, and the resource utilization ratio of the key expansion by using partial self-reconfiguration technology is less 32.03% and slices are less 757 than the non-reconfiguration technology. SMS4 implementation gets a good balance between high performance and low complexity in area. The theoretical and practical research of dynamic partial self-reconfiguration has a broad space for development and application prospect.

Comparative activity of ceftobiprole against Gram-positive and Gram-negative isolates from Europe and the Middle East: the CLASS study.

PubMed

Rossolini, Gian M; Dryden, Matthew S; Kozlov, Roman S; Quintana, Alvaro; Flamm, Robert K; Läuffer, Jörg M; Lee, Emma; Morrissey, Ian; CLASS Study Group

2011-01-01

to assess the in vitro activity of ceftobiprole and comparators against a recent collection of Gram-positive and Gram-negative pathogens, in order to detect potential changes in susceptibility patterns, and to evaluate the Etest assay for ceftobiprole susceptibility testing. contemporary Gram-positive and Gram-negative isolates (excluding extended-spectrum β-lactamase-producing isolates) from across Europe and the Middle East were collected, and their susceptibility to ceftobiprole, vancomycin, teicoplanin, linezolid, ceftazidime and cefepime was assessed using the Etest method. Quality testing [using Etest and broth microdilution (BMD)] was conducted at a central reference laboratory. some 5041 Gram-positive and 4026 Gram-negative isolates were included. Against Gram-positive isolates overall, ceftobiprole had the lowest MIC50 (0.5 mg/L), compared with 1 mg/L for its comparators (vancomycin, teicoplanin and linezolid). Against methicillin-resistant Staphylococcus aureus, all four agents had a similar MIC90 (2 mg/L), but ceftobiprole had a 4-fold better MIC90 (0.5 mg/L) against methicillin-susceptible strains. Only 38 Gram-positive isolates were confirmed as ceftobiprole resistant. Among Gram-negative strains, 86.9%, 91.7% and 95.2% were susceptible to ceftobiprole, ceftazidime and cefepime, respectively. Pseudomonas aeruginosa was less susceptible to all three antimicrobials than any other Gram-negative pathogen. There was generally good agreement between local Etest results and those obtained at the reference laboratory (for ceftobiprole: 86.8% with Gram-negatives; and 94.7% with Gram-positives), as well as between results obtained by BMD and Etest methods (for ceftobiprole: 98.2% with Gram-negatives; and 98.4% with Gram-positives). ceftobiprole exhibits in vitro activity against a wide range of Gram-positive and Gram-negative pathogens, including multidrug-resistant strains. No changes in its known susceptibility profile were identified.

Gram staining.

PubMed

Coico, Richard

2005-10-01

Named after Hans Christian Gram who developed the method in 1884, the Gram stain allows one to distinguish between Gram-positive and Gram-negative bacteria on the basis of differential staining with a crystal violet-iodine complex and a safranin counterstain. The cell walls of Gram-positive organisms retain this complex after treatment with alcohol and appear purple, whereas gram-negative organisms decolorize following such treatment and appear pink. The method described here is useful for assessing bacterial contamination of tissue culture samples or for examining the Gram stain status and morphological features of bacteria isolated from mixed or isolated bacterial cultures.

Engineering-Level Model Atmospheres for Titan and Neptune

NASA Technical Reports Server (NTRS)

Justus, C. G.; Duvall, Aleta; Johnson, D. L.

2003-01-01

Engineering-level atmospheric models for Titan and Neptune have been developed for use in NASA s systems analysis studies of aerocapture applications in missions to the outer planets. Analogous to highly successful Global Reference Atmospheric Models for Earth (GRAM, Justus et al., 2000) and Mars (Mars-GRAM, Justus and Johnson, 2001, Justus et al., 2002) the new models are called Titan-GRAM and Neptune-GRAM. Like GRAM and Mars-GRAM, an important feature of Titan-GRAM and Neptune-GRAM is their ability to simulate quasi-random perturbations for Monte- Carlo analyses in developing guidance, navigation and control algorithms, and for thermal systems design.

Gram staining.

PubMed

Coico, R

2001-05-01

Named after Hans Christian Gram who developed the method in 1884, the Gram stain allows one to distinguish between Gram-positive and Gram-negative bacteria on the basis of differential staining with a crystal violet-iodine complex and a safranin counterstain. The cell walls of Gram-positive organisms retain this complex after treatment with alcohol and appear purple, whereas gram-negative organisms decolorize following such treatment and appear pink. The method described here is useful for assessing bacterial contamination of tissue culture samples or for examining the Gram stain status and morphological features of bacteria isolated from mixed or isolated bacterial cultures.

Sex Differences in the Cannabinoid Modulation of Appetite, Body Temperature and Neurotransmission at POMC Synapses

PubMed Central

Diaz, Shanna; Farhang, Borzoo; Hoien, Joshua; Stahlman, Megan; Adatia, Nadira; Cox, Jeremy M.; Wagner, Edward J.

2009-01-01

We sought to determine whether sex differences exist for the cannabinoid modulation of appetite, body temperature and neurotransmission at pro-opiomelanocortin (POMC) synapses. Gonadectomized male and female guinea pigs were outfitted to monitor core body temperature and injected with either the CB1 receptor agonist WIN 55,212-2 (1 mg/kg s.c.), antagonist AM251 (3 mg/kg s.c.) or vehicle (1 ml/kg s.c.) and evaluated for changes in six indices of feeding behavior under ad libitum conditions for 7 days. WIN 55,212-2 elicited an overt, sexually differentiated hyperphagia in which males displayed larger increases in hourly and daily intake, consumption/gram body weight, meal size and meal duration. The agonist also produced a more robust acute hypothermia in males than in females. In addition, males were more sensitive to the hypophagic effect of AM251, manifested by comparatively sizeable decreases in hourly intake, consumption/gram body weight, meal frequency and hyperthermia. To gain additional insight into the cellular mechanism underlying cannabinoid regulation of energy homeostasis, we performed whole-cell patch clamp recordings in hypothalamic slices prepared from gonadectomized male and female guinea pigs, and monitored miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) in arcuate (ARC) neurons. ARC neurons from females exhibited a higher basal mEPSC frequency. WIN 55,212-2 dose-dependently reduced mEPSC and mIPSC frequency; however, cells from males were far less sensitive to the CB1 receptor-mediated decrease in mIPSC frequency. These effects were observed in neurons subsequently identified as POMC neurons. These data reveal pronounced sex differences in how cannabinoids influence the hypothalamic control of homeostasis. PMID:19136814

Antimicrobial/cytolytic peptides from the venom of the North African scorpion, Androctonus amoreuxi: biochemical and functional characterization of natural peptides and a single site-substituted analog.

PubMed

Almaaytah, Ammar; Zhou, Mei; Wang, Lei; Chen, Tianbao; Walker, Brian; Shaw, Chris

2012-06-01

The venoms of scorpions are complex cocktails of polypeptide toxins that fall into two structural categories: those that contain cysteinyl residues with associated disulfide bridges and those that do not. As the majority of lethal toxins acting upon ion channels fall into the first category, most research has been focused there. Here we report the identification and structural characterization of two novel 18-mer antimicrobial peptides from the venom of the North African scorpion, Androctonus amoreuxi. Named AamAP1 and AamAP2, both peptides are C-terminally amidated and differ in primary structure at just two sites: Leu-->Pro at position 2 and Phe-->Ile at position 17. Synthetic replicates of both peptides exhibited a broad-spectrum of antimicrobial activity against a Gram-positive bacterium (Staphylococcus aureus), a Gram-negative bacterium (Escherichia coli) and a yeast (Candida albicans), at concentrations ranging between 20 μM and 150 μM. In this concentration range, both peptides produced significant degrees of hemolysis. A synthetic replicate of AamAP1 containing a single substitution (His-->Lys) at position 8, generated a peptide (AamAP-S1) with enhanced antimicrobial potency (3-5 μM) against the three test organisms and within this concentration range, hemolytic effects were negligible. In addition, this His-->Lys variant exhibited potent growth inhibitory activity (ID(50) 25-40 μm) against several human cancer cell lines and endothelial cells that was absent in both natural peptides. Natural bioactive peptide libraries, such as those that occur in scorpion venoms, thus constitute a unique source of novel lead compounds with drug development potential whose biological properties can be readily manipulated by simple synthetic chemical means. Copyright © 2012 Elsevier Inc. All rights reserved.

Structural and functional characterization of the Mycobacterium tuberculosis uridine monophosphate kinase: insights into the allosteric regulation.

PubMed

Labesse, Gilles; Benkali, Khaled; Salard-Arnaud, Isabelle; Gilles, Anne-Marie; Munier-Lehmann, Hélène

2011-04-01

Nucleoside Monophosphate Kinases (NMPKs) family are key enzymes in nucleotide metabolism. Bacterial UMPKs depart from the main superfamily of NMPKs. Having no eukaryotic counterparts they represent attractive therapeutic targets. They are regulated by GTP and UTP, while showing different mechanisms in Gram(+), Gram(-) and archaeal bacteria. In this work, we have characterized the mycobacterial UMPK (UMPKmt) combining enzymatic and structural investigations with site-directed mutagenesis. UMPKmt exhibits cooperativity toward ATP and an allosteric regulation by GTP and UTP. The crystal structure of the complex of UMPKmt with GTP solved at 2.5 Å, was merely identical to the modelled apo-form, in agreement with SAXS experiments. Only a small stretch of residues was affected upon nucleotide binding, pointing out the role of macromolecular dynamics rather than major structural changes in the allosteric regulation of bacterial UMPKs. We further probe allosteric regulation by site-directed mutagenesis. In particular, a key residue involved in the allosteric regulation of this enzyme was identified.

Fabrication of Metal and Metal Oxide Nanoparticles by Algae and their Toxic Effects

NASA Astrophysics Data System (ADS)

Siddiqi, Khwaja Salahuddin; Husen, Azamal

2016-08-01

Of all the aquatic organisms, algae are a good source of biomolecules. Since algae contain pigments, proteins, carbohydrates, fats, nucleic acids and secondary metabolites such as alkaloids, some aromatic compounds, macrolides, peptides and terpenes, they act as reducing agents to produce nanoparticles from metal salts without producing any toxic by-product. Once the algal biomolecules are identified, the nanoparticles of desired shape or size may be fabricated. The metal and metal oxide nanoparticles thus synthesized have been investigated for their antimicrobial activity against several gram-positive and gram-negative bacterial strains and fungi. Their dimension is controlled by temperature, incubation time, pH and concentration of the solution. In this review, we have attempted to update the procedure of nanoparticle synthesis from algae, their characterization by UV-vis, Fourier transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, x-ray diffraction, energy-dispersive x-ray spectroscopy, dynamic light scattering and application in cutting-edge areas.

Exploring the Effects of Subfreezing Temperature and Salt Concentration on Ice Growth Inhibition of Antarctic Gram-Negative Bacterium Marinomonas Primoryensis Using Coarse-Grained Simulation.

PubMed

Nguyen, Hung; Dac Van, Thanh; Tran, Nhut; Le, Ly

2016-04-01

The aim of this work is to study the freezing process of water molecules surrounding Antarctic Gram-negative bacterium Marinomonas primoryensis antifreeze protein (MpAFP) and the MpAFP interactions to the surface of ice crystals under various marine environments (at different NaCl concentrations of 0.3, 0.6, and 0.8 mol/l). Our result indicates that activating temperature region of MpAFPs reduced as NaCl concentration increased. Specifically, MpAFP was activated and functioned at 0.6 mol/l with temperatures equal or larger 278 K, and at 0.8 mol/l with temperatures equal or larger 270 K. Additionally, MpAFP was inhibited by ice crystal network from 268 to 274 K and solid-liquid hybrid from 276 to 282 K at 0.3 mol/l concentration. Our results shed lights on structural dynamics of MpAFP among different marine environments.

A portable expression resource for engineering cross-species genetic circuits and pathways

PubMed Central

Kushwaha, Manish; Salis, Howard M.

2015-01-01

Genetic circuits and metabolic pathways can be reengineered to allow organisms to process signals and manufacture useful chemicals. However, their functions currently rely on organism-specific regulatory parts, fragmenting synthetic biology and metabolic engineering into host-specific domains. To unify efforts, here we have engineered a cross-species expression resource that enables circuits and pathways to reuse the same genetic parts, while functioning similarly across diverse organisms. Our engineered system combines mixed feedback control loops and cross-species translation signals to autonomously self-regulate expression of an orthogonal polymerase without host-specific promoters, achieving nontoxic and tuneable gene expression in diverse Gram-positive and Gram-negative bacteria. Combining 50 characterized system variants with mechanistic modelling, we show how the cross-species expression resource's dynamics, capacity and toxicity are controlled by the control loops' architecture and feedback strengths. We also demonstrate one application of the resource by reusing the same genetic parts to express a biosynthesis pathway in both model and non-model hosts. PMID:26184393

Healable Antifouling Films Composed of Partially Hydrolyzed Poly(2-ethyl-2-oxazoline) and Poly(acrylic acid).

PubMed

Li, Yixuan; Pan, Tiezheng; Ma, Benhua; Liu, Junqiu; Sun, Junqi

2017-04-26

Antifouling polymeric films can prevent undesirable adhesion of bacteria but are prone to accidental scratches, leading to a loss of their antifouling functions. To solve this problem, we report the fabrication of healable antifouling polymeric films by layer-by-layer assembly of partially hydrolyzed poly(2-ethyl-2-oxazoline) (PEtOx-EI-7%) and poly(acrylic acid) (PAA) based on hydrogen-bonding interaction as the driving force. The thermally cross-linked (PAA/PEtOx-EI-7%)*100 films show strong resistance to adhesion of both Gram-negative Escherichia coli and Gram-positive Bacillus subtilis bacteria due to the high surface and bulk concentration of the antifouling polymer PEtOx-EI-7%. Meanwhile, the dynamic nature of the hydrogen-bonding interactions and the high mobility of the polymers in the presence of water enable repeated healing of cuts of several tens of micrometers wide in cross-linked (PAA/PEtOx-EI-7%)*100 films to fully restore their antifouling function.

Procession to pediatric bacteremia and sepsis: covert operations and failures in diplomacy.

PubMed

Bateman, Stacey L; Seed, Patrick C

2010-07-01

Despite advances in diagnosis and treatment, bacterial sepsis remains a major cause of pediatric morbidity and mortality, particularly among neonates, the critically ill, and the growing immunocompromised patient population. Sepsis is the end point of a complex and dynamic series of events in which both host and microbial factors drive high morbidity and potentially lethal physiologic alterations. In this article we provide a succinct overview of the events that lead to pediatric bloodstream infections (BSIs) and sepsis, with a focus on the molecular mechanisms used by bacteria to subvert host barriers and local immunity to gain access to and persist within the systemic circulation. In the events preceding and during BSI and sepsis, Gram-positive and Gram-negative pathogens use a battery of factors for translocation, inhibition of immunity, molecular mimicry, intracellular survival, and nutrient scavenging. Gaps in understanding the molecular pathogenesis of bacterial BSIs and sepsis are highlighted as opportunities to identify and develop new therapeutics.

Studying the silver nanoparticles influence on thermodynamic behavior and antimicrobial activities of novel amide Gemini cationic surfactants.

PubMed

Shaban, Samy M; Abd-Elaal, Ali A

2017-07-01

Three novels amide Gemini cationic surfactants with various alkyl chains and their silver nanohybrid with silver nanoparticles were synthesized and a confirmation study for surfactant and their nanoparticles formation has been established using IR, 1 HNMR, TEM and UV-Vis spectroscopy. The surface-active properties of these surfactants and their nanoform were investigated through surface tension and electrical conductivity measurements and a comparative study has been established. The thermodynamic parameters of micellization and adsorption were assessed at temperatures range from 25 to 65°C. The effect of silver particles on the surface behavior of the synthesized surfactant has been discussed. The aggregation behavior of silver nanoparticles with these synthesized Gemini surfactants in water were investigated using dynamic light scattering and transmission electron microscopy. Furthermore, the antimicrobial activities of these synthesized amide Gemini surfactants and their nanostructure with silver against both Gram positive and Gram negative bacteria were also investigated. Copyright © 2017 Elsevier B.V. All rights reserved.

21 CFR 520.1720c - Phenylbutazone paste.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... (a) Specifications—(1) Each gram of paste contains 0.2 grams phenylbutazone. (2) Each gram of paste contains 0.35 grams phenylbutazone. (b) Sponsors. See sponsor numbers in § 510.600(c) of this chapter. (1...—(1) Amount. 1 to 2 grams of phenylbutazone per 500 pounds of body weight, not to exceed 4 grams daily...

78 FR 69992 - Withdrawal of Approval of New Animal Drug Applications; Carbarsone; Roxarsone

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-22

...) * * * Combinations in Roxarsone in grams per ton grams per ton Indications for use Limitations Sponsor (i) [Reserved...) * * * Combinations in Roxarsone in grams per ton grams per ton Indications for use Limitations Sponsor (i) [Reserved... Roxarsone in grams per ton grams per ton Indications for use Limitations Sponsor (i) [Reserved] (ii) 22.7 to...

21 CFR 520.1720c - Phenylbutazone paste.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... (a) Specifications—(1) Each gram of paste contains 0.2 grams phenylbutazone. (2) Each gram of paste contains 0.35 grams phenylbutazone. (b) Sponsors. See sponsor numbers in § 510.600(c) of this chapter. (1...—(1) Amount. 1 to 2 grams of phenylbutazone per 500 pounds of body weight, not to exceed 4 grams daily...

Understanding the Impact of Interventions to Prevent Antimicrobial Resistant Infections in the Long-Term Care Facility: A Review and Practical Guide to Mathematical Modeling.

PubMed

Rosello, Alicia; Horner, Carolyne; Hopkins, Susan; Hayward, Andrew C; Deeny, Sarah R

2017-02-01

OBJECTIVES (1) To systematically search for all dynamic mathematical models of infectious disease transmission in long-term care facilities (LTCFs); (2) to critically evaluate models of interventions against antimicrobial resistance (AMR) in this setting; and (3) to develop a checklist for hospital epidemiologists and policy makers by which to distinguish good quality models of AMR in LTCFs. METHODS The CINAHL, EMBASE, Global Health, MEDLINE, and Scopus databases were systematically searched for studies of dynamic mathematical models set in LTCFs. Models of interventions targeting methicillin-resistant Staphylococcus aureus in LTCFs were critically assessed. Using this analysis, we developed a checklist for good quality mathematical models of AMR in LTCFs. RESULTS AND DISCUSSION Overall, 18 papers described mathematical models that characterized the spread of infectious diseases in LTCFs, but no models of AMR in gram-negative bacteria in this setting were described. Future models of AMR in LTCFs require a more robust methodology (ie, formal model fitting to data and validation), greater transparency regarding model assumptions, setting-specific data, realistic and current setting-specific parameters, and inclusion of movement dynamics between LTCFs and hospitals. CONCLUSIONS Mathematical models of AMR in gram-negative bacteria in the LTCF setting, where these bacteria are increasingly becoming prevalent, are needed to help guide infection prevention and control. Improvements are required to develop outputs of sufficient quality to help guide interventions and policy in the future. We suggest a checklist of criteria to be used as a practical guide to determine whether a model is robust enough to test policy. Infect Control Hosp Epidemiol 2017;38:216-225.

Interpersonal ambivalence in obsessive-compulsive disorder.

PubMed

Moritz, Steffen; Niemeyer, Helen; Hottenrott, Birgit; Schilling, Lisa; Spitzer, Carsten

2013-10-01

The social attitudes and interpersonal relationships of patients with obsessive-compulsive disorder (OCD) are subject to a longstanding controversy. Whereas cognitive-behavioural researchers emphasize exaggerated pro-social attitudes in OCD like inflated responsibility and worry for other people (especially significant others), dynamic theories traditionally focus on anti-social attitudes such as latent aggression and hostility. In two recent studies, we gathered support not only for a co-existence of these seemingly opposing attitudes in OCD, but also for a functional connection: inflated responsibility in part appears to serve as a coping strategy (or “defense”) against negative interpersonal feelings. In the present study, we tested a shortened version of the Responsibility and Interpersonal Behaviours and Attitudes Questionnaire (RIBAQ-R). The scale was administered to 34 participants with OCD and 34 healthy controls. The questionnaire concurrently measures pro-social and anti-social interpersonal attitudes across three subscales. In line with our prior studies, patients displayed higher scores on both exaggerated pro-social attitudes (e.g. “I suffer from a strict conscience concerning my relatives”) as well as latent aggression (e.g. “Sometimes I would like to harm strangers on the street“) and suspiciousness/distrust (e.g. “I cannot even trust my own family”). A total of 59% of the patients but only 12% of the healthy controls showed marked interpersonal ambivalence (defined as scores higher than one standard deviation from the mean of the nonclinical controls on both the prosocial and at least one of the two anti-social subscales). The study asserts high interpersonal ambivalence in OCD. Further research is required to pinpoint both the dynamic and causal links between opposing interpersonal styles. Normalization and social competence training may prove beneficial to resolve the apparent problems of patients with OCD regarding anger expression and social conflict management.

Comparison of mechanical compressive properties of commercial and autologous fibrin glues for tissue engineering applications.

PubMed

Cravens, Matthew G; Behn, Anthony W; Dragoo, Jason L

2017-11-01

Fibrin glues are widely used in orthopedic surgery as adhesives and hemostatic agents. We evaluated the compressive properties of selected fibrin glues in order to identify which are appropriate for tissue regeneration applications subject to compression. Uniaxial unconfined compression tests were performed on fibrin gels prepared from commercial and autologous products: (1) Evicel (Ethicon), (2) Tisseel (Baxter), (3) Angel (Arthrex), and (4) ProPlaz (Biorich). Cyclic loads were applied from 0 to 30% strain for 100cycles at 0.5Hz. Following cyclic testing, specimens were subjected to ramp displacement of 1% strain per second to 80% strain. Throughout cyclic loading, Evicel and Tisseel deformed (shortened) less than Angel at all but one time point, and deformed less than ProPlaz at cycles 10 and 20. The dynamic moduli, peak stress, and strain energy were significantly greater in Tisseel than all other groups. Evicel displayed significantly greater dynamic moduli, peak stress, and strain energy than Angel and ProPlaz. Following cyclic testing, Tisseel and Evicel were significantly less deformed than Angel. No specimens exhibited gross failure during ramp loading to 80% strain. Ramp loading trends mirrored those of cyclic loading. The tested commercial glues were significantly more resistant to compression than the autologous products. The compressive properties of Tisseel were approximately twice those of Evicel. All preparations displayed moduli multiple orders of magnitude less than that of native articular cartilage. We conclude that in knee surgeries requiring fibrin glue to undergo compression of daily activity, commercial products are preferable to autologous preparations from platelet-poor plasma, though both will deform significantly. Copyright © 2017 Elsevier Ltd. All rights reserved.

An optimized staining technique for the detection of Gram positive and Gram negative bacteria within tissue.

PubMed

Becerra, Sandra C; Roy, Daniel C; Sanchez, Carlos J; Christy, Robert J; Burmeister, David M

2016-04-12

Bacterial infections are a common clinical problem in both acute and chronic wounds. With growing concerns over antibiotic resistance, treatment of bacterial infections should only occur after positive diagnosis. Currently, diagnosis is delayed due to lengthy culturing methods which may also fail to identify the presence of bacteria. While newer costly bacterial identification methods are being explored, a simple and inexpensive diagnostic tool would aid in immediate and accurate treatments for bacterial infections. Histologically, hematoxylin and eosin (H&E) and Gram stains have been employed, but are far from optimal when analyzing tissue samples due to non-specific staining. The goal of the current study was to develop a modification of the Gram stain that enhances the contrast between bacteria and host tissue. A modified Gram stain was developed and tested as an alternative to Gram stain that improves the contrast between Gram positive bacteria, Gram negative bacteria and host tissue. Initially, clinically relevant strains of Pseudomonas aeruginosa and Staphylococcus aureus were visualized in vitro and in biopsies of infected, porcine burns using routine Gram stain, and immunohistochemistry techniques involving bacterial strain-specific fluorescent antibodies as validation tools. H&E and Gram stain of serial biopsy sections were then compared to a modification of the Gram stain incorporating a counterstain that highlights collagen found in tissue. The modified Gram stain clearly identified both Gram positive and Gram negative bacteria, and when compared to H&E or Gram stain alone provided excellent contrast between bacteria and non-viable burn eschar. Moreover, when applied to surgical biopsies from patients that underwent burn debridement this technique was able to clearly detect bacterial morphology within host tissue. We describe a modification of the Gram stain that provides improved contrast of Gram positive and Gram negative microorganisms within host tissue. The samples used in this study demonstrate that this staining technique has laboratory and clinical applicability. This modification only adds minutes to traditional Gram stain with reusable reagents, and results in a cost- and time-efficient technique for identifying bacteria in any clinical biopsy containing connective tissue.

The Causes of Post-Operative Meningitis: The Comparison Of Gram-Negative and Gram-Positive Pathogens.

PubMed

Kurtaran, Behice; Kuscu, Ferit; Ulu, Aslihan; Inal, Ayse Seza; Komur, Suheyla; Kibar, Filiz; Cetinalp, Nuri Eralp; Ozsoy, Kerem Mazhar; Arslan, Yusuf Kemal; Aksu, Hasan Salih; Tasova, Yesim

2017-06-20

In this study, we aim to determine the microbiological etiology in critically ill neurosurgical patients with nosocomial meningitis (NM) and show the impact of Gram-negative rods and differences of patient's characteristics, clinical and prognostic measures between Gram-negative and Gram-positive meningitis. In this prospective, one center study we reviewed all adult patients hospitalized during a 12-year period and identified pathogens isolated from post-neurosurgical cases of NM. Demographic, clinical, and treatment characteristics were noted from the medical records. Of the 134 bacterial NM patients, 78 were male and 56 were female, with a mean age of 46±15.9 and median age of 50 (18-80) years. 141 strains isolated; 82 (58.2%) were Gram negative, 59 (41.8%) were Gram positive. Most common isolated microorganism was Acinetobacter baumannii (%34.8). In comparison of mortality data shows that the patients who have meningitis with Gram-negative pathogens have higher mortality than with Gram positives (p=0.034). The duration between surgery and meningitis was shorter in Gram negative meningitis cases compared to others (p=0.045) but the duration between the diagnosis and death was shorter in Gram-positive meningitis cases compared to Gram negatives (p= 0.017). CSF protein and lactate level were higher and glucose level was lower in cases of NM with Gram negatives (p value were respectively, 0.022, 0.039 and 0.049). As conclusions; in NM, Gram-negative pathogens were seen more frequently; A.baumanni was the predominant pathogen; and NM caused by Gram negatives had worse clinical and laboratory characteristic and prognostic outcome than Gram positives.

Is the gram stain useful in the microbiologic diagnosis of VAP? A meta-analysis.

PubMed

O'Horo, John C; Thompson, Deb; Safdar, Nasia

2012-08-01

In a meta-analysis examining respiratory specimen Gram stain for diagnosis of ventilator-associated pneumonia, absence of bacteria on Gram stain had a high negative predictive value, but a positive Gram stain correlated poorly with organisms recovered in culture. Rapid and accurate diagnosis of ventilator-associated pneumonia (VAP) is a major challenge and no generally accepted gold standard exists for VAP diagnosis. We conducted a meta-analysis to examine the role of respiratory specimen Gram stain to diagnose VAP, and the correlation with final culture results. In 21 studies, pooled sensitivity of Gram stain for VAP was 0.79 (95% confidence interval [CI], .77-0.81; P < .0001) and specificity was 0.75 (95% CI, .73-.78; P < .0001). Negative predictive value of Gram stain for a VAP prevalence of 20%-30% was 91%, suggesting that VAP is unlikely with a negative Gram stain but the positive predictive value of Gram stain was only 40%. Pooled kappa was 0.42 for gram-positive organisms and 0.34 for gram-negative organisms, suggesting fair concordance between organisms on Gram stain and recovery by culture. Therefore, a positive Gram stain should not be used to narrow anti-infective therapy until culture results become available.

21 CFR 520.1660d - Oxytetracycline powder.

Code of Federal Regulations, 2011 CFR

2011-04-01

....14 grams of powder contains 1 gram of oxytetracycline hydrochloride (OTC HCl) (packets: 4, 6.4, and 16 oz.). (2) Each 4.43 grams of powder contains 1 gram of OTC HCl (packets: 4 and 16 oz.). (3) Each 1.32 grams of powder contains 1 gram of OTC HCl (packets: 2.39, 4.78, and 9.55 oz.; jars: 2.25 lbs...

21 CFR 558.355 - Monensin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... only), 44, 45, 60, or 90.7 grams per pound for use as in paragraphs (f)(1)(i) and (f)(4) of this section. (2) To 000986: 110 grams per lb., paragraphs (f)(1) (i), (iii), (iv), (v), (ix), and (x). (3) To 000986: 44 grams per lb. with 18 grams per lb. of roxarsone, 110 grams per lb. with 45 grams per lb. of...

21 CFR 520.1660d - Oxytetracycline powder.

Code of Federal Regulations, 2013 CFR

2013-04-01

....14 grams of powder contains 1 gram of oxytetracycline hydrochloride (OTC HCl) (packets: 4, 6.4, and 16 oz.). (2) Each 4.43 grams of powder contains 1 gram of OTC HCl (packets: 4 and 16 oz.). (3) Each 1.32 grams of powder contains 1 gram of OTC HCl (packets: 2.39, 4.78, and 9.55 oz.; jars: 2.25 lbs...

21 CFR 520.1660d - Oxytetracycline powder.

Code of Federal Regulations, 2014 CFR

2014-04-01

....14 grams of powder contains 1 gram of oxytetracycline hydrochloride (OTC HCl) (packets: 4, 6.4, and 16 oz.). (2) Each 4.43 grams of powder contains 1 gram of OTC HCl (packets: 4 and 16 oz.). (3) Each 1.32 grams of powder contains 1 gram of OTC HCl (packets: 2.39, 4.78, and 9.55 oz.; jars: 2.25 lbs...

21 CFR 520.1660d - Oxytetracycline powder.

Code of Federal Regulations, 2010 CFR

2010-04-01

....14 grams of powder contains 1 gram of oxytetracycline hydrochloride (OTC HCl) (packets: 4, 6.4, and 16 oz.). (2) Each 4.43 grams of powder contains 1 gram of OTC HCl (packets: 4 and 16 oz.). (3) Each 1.32 grams of powder contains 1 gram of OTC HCl (packets: 2.39, 4.78, and 9.55 oz.; jars: 2.25 lbs...

21 CFR 520.1660d - Oxytetracycline powder.

Code of Federal Regulations, 2012 CFR

2012-04-01

....14 grams of powder contains 1 gram of oxytetracycline hydrochloride (OTC HCl) (packets: 4, 6.4, and 16 oz.). (2) Each 4.43 grams of powder contains 1 gram of OTC HCl (packets: 4 and 16 oz.). (3) Each 1.32 grams of powder contains 1 gram of OTC HCl (packets: 2.39, 4.78, and 9.55 oz.; jars: 2.25 lbs...

Simultaneous Fluorescent Gram Staining and Activity Assessment of Activated Sludge Bacteria

PubMed Central

Forster, Scott; Snape, Jason R.; Lappin-Scott, Hilary M.; Porter, Jonathan

2002-01-01

Wastewater treatment is one of the most important commercial biotechnological processes, and yet the component bacterial populations and their associated metabolic activities are poorly understood. The novel fluorescent dye hexidium iodide allows assessment of Gram status by differential absorption through bacterial cell walls. Differentiation between gram-positive and gram-negative wastewater bacteria was achieved after flow cytometric analysis. This study shows that the relative proportions of gram-positive and gram-negative bacterial cells identified by traditional microscopy and hexidium iodide staining were not significantly different. Dual staining of cells for Gram status and activity proved effective in analyzing mixtures of cultured bacteria and wastewater populations. Levels of highly active organisms at two wastewater treatment plants, both gram positive and gram negative, ranged from 1.5% in activated sludge flocs to 16% in the activated sludge fluid. Gram-positive organisms comprised <5% of the total bacterial numbers but accounted for 19 and 55% of the highly active organisms within flocs at the two plants. Assessment of Gram status and activity within activated sludge samples over a 4-day period showed significant differences over time. This method provides a rapid, quantitative measure of Gram status linked with in situ activity within wastewater systems. PMID:12324319

Simultaneous fluorescent gram staining and activity assessment of activated sludge bacteria.

PubMed

Forster, Scott; Snape, Jason R; Lappin-Scott, Hilary M; Porter, Jonathan

2002-10-01

Wastewater treatment is one of the most important commercial biotechnological processes, and yet the component bacterial populations and their associated metabolic activities are poorly understood. The novel fluorescent dye hexidium iodide allows assessment of Gram status by differential absorption through bacterial cell walls. Differentiation between gram-positive and gram-negative wastewater bacteria was achieved after flow cytometric analysis. This study shows that the relative proportions of gram-positive and gram-negative bacterial cells identified by traditional microscopy and hexidium iodide staining were not significantly different. Dual staining of cells for Gram status and activity proved effective in analyzing mixtures of cultured bacteria and wastewater populations. Levels of highly active organisms at two wastewater treatment plants, both gram positive and gram negative, ranged from 1.5% in activated sludge flocs to 16% in the activated sludge fluid. Gram-positive organisms comprised <5% of the total bacterial numbers but accounted for 19 and 55% of the highly active organisms within flocs at the two plants. Assessment of Gram status and activity within activated sludge samples over a 4-day period showed significant differences over time. This method provides a rapid, quantitative measure of Gram status linked with in situ activity within wastewater systems.

Dynamic Torsional and Cyclic Fracture Behavior of ProFile Rotary Instruments at Continuous or Reciprocating Rotation as Visualized with High-speed Digital Video Imaging.

PubMed

Tokita, Daisuke; Ebihara, Arata; Miyara, Kana; Okiji, Takashi

2017-08-01

This study examined the dynamic fracture behavior of nickel-titanium rotary instruments in torsional or cyclic loading at continuous or reciprocating rotation by means of high-speed digital video imaging. The ProFile instruments (size 30, 0.06 taper; Dentsply Maillefer, Ballaigues, Switzerland) were categorized into 4 groups (n = 7 in each group) as follows: torsional/continuous (TC), torsional/reciprocating (TR), cyclic/continuous (CC), and cyclic/reciprocating (CR). Torsional loading was performed by rotating the instruments by holding the tip with a vise. For cyclic loading, a custom-made device with a 38° curvature was used. Dynamic fracture behavior was observed with a high-speed camera. The time to fracture was recorded, and the fractured surface was examined with scanning electron microscopy. The TC group initially exhibited necking of the file followed by the development of an initial crack line. The TR group demonstrated opening and closing of a crack according to its rotation in the cutting and noncutting directions, respectively. The CC group separated without any detectable signs of deformation. In the CR group, initial crack formation was recognized in 5 of 7 samples. The reciprocating rotation exhibited a longer time to fracture in both torsional and cyclic fatigue testing (P < .05). The scanning electron microscopic images showed a severely deformed surface in the TR group. The dynamic fracture behavior of NiTi rotary instruments, as visualized with high-speed digital video imaging, varied between the different modes of rotation and different fatigue testing. Reciprocating rotation induced a slower crack propagation and conferred higher fatigue resistance than continuous rotation in both torsional and cyclic loads. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Relationship between tumour necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor in human multiple myeloma patients.

PubMed

Bolkun, Lukasz; Lemancewicz, Dorota; Piszcz, Jaroslaw; Moniuszko, Marcin; Bolkun-Skornicka, Urszula; Szkiladz, Malgorzata; Jablonska, Ewa; Kloczko, Janusz; Dzieciol, Janusz

2015-12-01

Tumour necrosis factor-alfa (TNF-α) is an inflammatory cytokine with a wide spectrum of biological activity, including angiogenesis. Tumour necrosis factor-related apoptosis inducing ligand (TRAIL), which belongs to the TNF family of proteins, plays a role in the regulation of vascular responses, but its effect on the formation of new blood vessels (angiogenesis) is unclear. We analysed TRAIL concentrations in parallel with pro-angiogenic cytokines in serum and their expression in trephine biopsy (TB) in 56 patients with newly diagnosed IgG MM and 24 healthy volunteers. The study showed statistically higher concentrations of TRAIL and TNF-α, as well as of VEGF and its receptor, in MM patients compared to healthy volunteers and patients in advanced stages of the disease. Furthermore, we observed a significant decrease in all studied pro-angiogenic cytokines and significant increase of TRAIL concentration after anti-angiogenic therapy, with meaningful differences between responders (at least partial remission) and patients with progression during the induction treatment. It was also established that TRAIL correlated statistically and negatively with pro-angiogenic cytokines such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. In summary, our data indicate that in MM patients, both clinical course and treatment responsiveness are associated with dynamic yet corresponding changes of levels of TRAIL parallel pro-angiogenic mediators such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. Copyright © 2014 John Wiley & Sons, Ltd.

Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization1

PubMed Central

Dale, Matthew A; Xiong, Wanfen; Carson, Jeffrey S; Suh, Melissa K; Karpisek, Andrew D.; Meisinger, Trevor M.; Casale, George P.; Baxter, B. Timothy

2016-01-01

Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Damage to elastin in the ECM results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Pro-inflammatory M1 macrophages initially are recruited to sites of injury but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. AAA tissue reveals a high M1/M2 ratio where pro-inflammatory cells and their associated markers dominate. In the present study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57Bl/6 mice, antibody-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and pro-inflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2 polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a pro-inflammatory environment in aortic tissue by inducing M1 polarization and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

Virtex-II Pro PowerPC SEE Characterization Test Methods and Results

NASA Technical Reports Server (NTRS)

Petrick, David; Powell, Wesley; LaBel, Ken; Howard, James

2005-01-01

The Xilinx Vix-11 Pro is a platform FPGA that embeds multiple microprocessors within the fabric of an SRAM-based reprogrammable FPGA. The variety and quantity of resources provided by this family of devices make them very attractive for spaceflight applications. However,these devices will be susceptible to single event effects (SEE), which must be mitigated. Observations from prior testing of the Xilinx Virtex-II Pro suggest that the PowerPC core has significant vulnerability to SEES. However, these initial tests were not designed to exclusively target the functionality of the PowerPC, therefore making it difficult to distinguish processor upsets from fabric upsets. The main focus of this paper involves detailed SEE testing of the embedded PowerPC core. Due to the complexity of the PowerPC, various custom test applications, both static and dynamic, will be designed to isolate each Unit of the processor. Collective analysis of the test results will provide insight into the exact upset mechanism of the PowerPC. With this information, mitigations schemes can be developed and tested that address the specific susceptibilities of these devices. The test bed will be the Xilinx SEE Consortium Virtex-II Pro test board, which allows for configuration scrubbing, design triplication, and ease of data collection. Testing will be performed at the Indiana University Cyclotron Facility using protons of varying energy levels and fluencies. This paper will present the detailed test approach along with the results.

Serum gonadotropins and gonadal steroids associated with ovulation and egg production in sea turtles.

PubMed

Wibbels, T; Owens, D W; Licht, P; Limpus, C; Reed, P C; Amoss, M S

1992-07-01

Changes in serum concentrations of gonadotropins and gonadal steroids during the periovulatory period were monitored in green, Chelonia mydas, and loggerhead, Caretta caretta, sea turtles. Turtles were from natural populations that nest on a coral island on the Great Barrier Reef. After nesting, each turtle was transferred to a holding tank and held for a maximum of 8 days. A time series of blood samples was obtained from each of five sea turtles (three C. mydas and two C. caretta) starting immediately after nesting and then at approximately 12-hr intervals until the time of release. Prior to release back into the ocean, each turtle was examined by laparoscopy to verify that ovulation had occurred. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (PRO), and testosterone (T) in both species exhibited significant changes during this period. Surges of FSH, LH, and PRO were evident within approximately 20 to 50 hr after each turtle had nested. The significant change in FSH concentration during the periovulatory period is the first such report for a reptile. Coincident with maximal concentrations of FSH, LH, and PRO was a decline in T concentrations in both species. Estradiol-17 beta concentrations were near or below assay sensitivity in the C. mydas, whereas those in the C. caretta were detectable but exhibited no significant changes. The dynamic changes in FSH, LH, PRO, and T concentrations are consistent with the hypothesis that these hormones facilitate specific physiological events during ovulation and egg production.

Conformational Plasticity of the Cell-Penetrating Peptide SAP As Revealed by Solid-State 19F-NMR and Circular Dichroism Spectroscopies.

PubMed

Afonin, Sergii; Kubyshkin, Vladimir; Mykhailiuk, Pavel K; Komarov, Igor V; Ulrich, Anne S

2017-07-13

The cell-penetrating peptide SAP, which was designed as an amphipathic poly-l-proline helix II (PPII), was suggested to self-assemble into regular fibrils that are relevant for its internalization. Herein we have analyzed the structure of SAP in the membrane-bound state by solid-state 19 F-NMR, which revealed other structural states, in addition to the expected surface-aligned PPII. Trifluoromethyl-bicyclopentyl-glycine (CF 3 -Bpg) and two rigid isomers of trifluoromethyl-4,5-methanoprolines (CF 3 -MePro) were used as labels for 19 F-NMR analysis. The equilibria between different conformations of SAP were studied and were found to be shifted by the substituents at Pro-11. Synchrotron-CD results suggested that substituting Pro-11 by CF 3 -MePro governed the coil-to-PPII equilibrium in solution and in the presence of a lipid bilayer. Using CD and 19 F-NMR, we examined the slow kinetics of the association of SAP with membranes and the dependence of the SAP conformational dynamics on the lipid composition. The peptide did not bind to lipids in the solid ordered phase and aggregated only in the liquid ordered "raft"-like bilayers. Self-association could not be detected in solution or in the presence of liquid disordered membranes. Surface-bound amphipathic SAP in a nonaggregated state was structured as a mixture of nonideal extended conformations reflecting the equilibrium already present in solution, i.e., before binding to the membrane.

Intrinsic flexibility of West Nile virus protease in solution characterized using small-angle X-ray scattering.

PubMed

Garces, Andrea P; Watowich, Stanley J

2013-10-01

West Nile virus (WNV) is a mosquito-borne flavivirus with a rapidly expanding global distribution. Infection can cause severe neurological disease and fatality in humans. Efforts are ongoing to develop antiviral drugs that inhibit the WNV protease, a viral enzyme required for polyprotein processing. Unfortunately, little is known about the solution structure of recombinant WNV protease (NS2B-NS3pro) used for antiviral drug discovery and development, although X-ray crystal structures and nuclear magnetic resonance (NMR) studies have provided valuable insights into the interactions between NS2B-NS3pro and peptide-based inhibitors. We completed small-angle X-ray scattering and Fourier transform infrared spectroscopy experiments to determine the solution structure and dynamics of WNV NS2B-NS3pro in the absence of a bound substrate or inhibitor. Importantly, these solution studies suggested that all or most of the NS2B cofactor was highly flexible and formed an ensemble of structures, in contrast to the NS2B tertiary structures observed in crystallographic and NMR studies. The secondary structure of NS2B-NS3pro in solution had high β-content, similar to the secondary structure observed in crystallographic studies. This work provided evidence of the intrinsic flexibility and conformational heterogeneity of the NS2B chain of the WNV protease in the absence of substratelike ligands, which should be considered during antiviral drug discovery and development efforts.

Conformational profile of a proline-arginine hybrid

PubMed Central

Revilla-López, Guillermo; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos; Zanuy, David

2010-01-01

The intrinsic conformational preferences of a new non-proteinogenic amino acid have been explored by computational methods. This tailored molecule, named (βPro)Arg, is conceived as a replacement for arginine in bioactive peptides when the stabilization of folded turn-like conformations is required. The new residue features a proline skeleton that bears the guanidilated side chain of arginine at the Cβ position of the five-membered pyrrolidine ring, either in a cis or a trans orientation with respect to the carboxylic acid. The conformational profile of the N-acetyl-N'-methylamide derivatives of the cis and trans isomers of (βPro)Arg has been examined in the gas phase and in solution by B3LYP/6–31+G(d,p) calculations and molecular dynamics simulations. The main conformational features of both isomers represent a balance between geometric restrictions imposed by the five-membered pyrrolidine ring and the ability of the guanidilated side chain to interact with the backbone through hydrogen-bonds. Thus, both cis and trans (βPro)Arg exhibit a preference for the αL conformation as a consequence of the interactions established between the guanidinium moiety and the main-chain amide groups. PMID:20886854

Conformational profile of a proline-arginine hybrid.

PubMed

Revilla-López, Guillermo; Jiménez, Ana I; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos; Zanuy, David

2010-10-25

The intrinsic conformational preferences of a new nonproteinogenic amino acid have been explored by computational methods. This tailored molecule, named ((β)Pro)Arg, is conceived as a replacement for arginine in bioactive peptides when the stabilization of folded turn-like conformations is required. The new residue features a proline skeleton that bears the guanidilated side chain of arginine at the C(β) position of the five-membered pyrrolidine ring, in either a cis or a trans orientation with respect to the carboxylic acid. The conformational profiles of the N-acetyl-N'-methylamide derivatives of the cis and trans isomers of ((β)Pro)Arg have been examined in the gas phase and in solution by B3LYP/6-31+G(d,p) calculations and molecular dynamics simulations. The main conformational features of both isomers represent a balance between geometric restrictions imposed by the five-membered pyrrolidine ring and the ability of the guanidilated side chain to interact with the backbone through hydrogen bonds. Thus, both cis- and trans-((β)Pro)Arg exhibit a preference for the α(L) conformation as a consequence of the interactions established between the guanidinium moiety and the main-chain amide groups.

40 CFR 86.098-10 - Emission standards for 1998 and later model year Otto-cycle heavy-duty engines and vehicles.

Code of Federal Regulations, 2011 CFR

2011-07-01

....1 grams per brake horsepower-hour (0.41 gram per megajoule), as measured under transient operating conditions. (B) Carbon monoxide. (1) 14.4 grams per brake horsepower-hour (5.36 grams per megajoule), as... flow at curb idle. (C) Oxides of nitrogen (1) 4.0 grams per brake horsepower-hour (1.49 grams per...

40 CFR 86.098-10 - Emission standards for 1998 and later model year Otto-cycle heavy-duty engines and vehicles.

Code of Federal Regulations, 2012 CFR

2012-07-01

....1 grams per brake horsepower-hour (0.41 gram per megajoule), as measured under transient operating conditions. (B) Carbon monoxide. (1) 14.4 grams per brake horsepower-hour (5.36 grams per megajoule), as... flow at curb idle. (C) Oxides of nitrogen (1) 4.0 grams per brake horsepower-hour (1.49 grams per...

40 CFR 86.098-10 - Emission standards for 1998 and later model year Otto-cycle heavy-duty engines and vehicles.

Code of Federal Regulations, 2014 CFR

2014-07-01

....1 grams per brake horsepower-hour (0.41 gram per megajoule), as measured under transient operating conditions. (B) Carbon monoxide. (1) 14.4 grams per brake horsepower-hour (5.36 grams per megajoule), as... flow at curb idle. (C) Oxides of nitrogen (1) 4.0 grams per brake horsepower-hour (1.49 grams per...

40 CFR 86.098-10 - Emission standards for 1998 and later model year Otto-cycle heavy-duty engines and vehicles.

Code of Federal Regulations, 2013 CFR

2013-07-01

....1 grams per brake horsepower-hour (0.41 gram per megajoule), as measured under transient operating conditions. (B) Carbon monoxide. (1) 14.4 grams per brake horsepower-hour (5.36 grams per megajoule), as... flow at curb idle. (C) Oxides of nitrogen (1) 4.0 grams per brake horsepower-hour (1.49 grams per...

Rapid Discrimination of Gram-Positive and Gram-Negative Bacteria in Liquid Samples by Using NaOH-Sodium Dodecyl Sulfate Solution and Flow Cytometry

PubMed Central

Wada, Atsushi; Kono, Mari; Kawauchi, Sawako; Takagi, Yuri; Morikawa, Takashi; Funakoshi, Kunihiro

2012-01-01

Background For precise diagnosis of urinary tract infections (UTI), and selection of the appropriate prescriptions for their treatment, we explored a simple and rapid method of discriminating gram-positive and gram-negative bacteria in liquid samples. Methodology/Principal Findings We employed the NaOH-sodium dodecyl sulfate (SDS) solution conventionally used for plasmid extraction from Escherichia coli and the automated urine particle analyzer UF-1000i (Sysmex Corporation) for our novel method. The NaOH-SDS solution was used to determine differences in the cell wall structures between gram-positive and gram-negative bacteria, since the tolerance to such chemicals reflects the thickness and structural differences of bacterial cell walls. The UF-1000i instrument was used as a quantitative bacterial counter. We found that gram-negative bacteria, including E. coli, in liquid culture could easily be lysed by direct addition of equal volumes of NaOH-SDS solution. In contrast, Enterococcus faecalis, which is a gram-positive bacterium, could not be completely lysed by the solution. We then optimized the reaction time of the NaOH-SDS treatment at room temperature by using 3 gram-positive and 4 gram-negative bacterial strains and determined that the optimum reaction time was 5 min. Finally, in order to evaluate the generalizability of this method, we treated 8 gram-positive strains and 8 gram-negative strains, or 4 gram-positive and 4 gram-negative strains incubated in voluntary urine from healthy volunteers in the same way and demonstrated that all the gram-positive bacteria were discriminated quantitatively from gram negative bacteria using this method. Conclusions/Significance Using our new method, we could easily discriminate gram-positive and gram-negative bacteria in liquid culture media within 10 min. This simple and rapid method may be useful for determining the treatment course of patients with UTIs, especially for those without a prior history of UTIs. The method may be easily applied in order to obtain additional information for clinical prescriptions from bacteriuria. PMID:23077549

Monomicrobial necrotizing fasciitis in a single center: the emergence of Gram-negative bacteria as a common pathogen.

PubMed

Yahav, D; Duskin-Bitan, H; Eliakim-Raz, N; Ben-Zvi, H; Shaked, H; Goldberg, E; Bishara, J

2014-11-01

Necrotizing fasciitis (NF) is a life-threatening soft tissue infection. It is usually caused by Streptococcus pyogenes and other Gram-positive bacteria. Several reports, however, emphasize the importance of Gram-negative rods in this infection. We retrospectively studied all cases of monomicrobial necrotizing fasciitis hospitalized in our center during the years 2002-2012. We compared clinical characteristics and outcomes of patients with Gram-negative versus Gram-positive infection. Forty-five cases were reviewed, 19 caused by Gram-negative organisms, 10 of them Escherichia coli, and 26 caused by Gram-positive organisms, 10 of them S. pyogenes. Compared to Gram-positive infections, patients with Gram-negative infections were more likely to have a baseline malignancy (9/19, 47.4%) or to have undergone recent surgery (4/19, 42.3%). The 30-day mortality was higher among Gram-negative infected patients (8/19, 42.1% vs. 8/26, 30.8%). Creatine phosphokinase (CPK) was elevated in a minority of patients with Gram-negative necrotizing fasciitis, and its absolute value was lower than in Gram-positive necrotizing fasciitis. In our center, 42% of monomicrobial necrotizing fasciitis cases were found to be caused by Gram-negative organisms, mostly E. coli. These infections usually appeared in immunocompromised or postoperative patients, often presented with normal CPK levels, and were associated with high mortality rates.

Investigation of Back-off Based Interpolation Between Recurrent Neural Network and N-gram Language Models (Author’s Manuscript)

DTIC Science & Technology

2016-02-11

INVESTIGATION OF BACK-OFF BASED INTERPOLATION BETWEEN RECURRENT NEURAL NETWORK AND N- GRAM LANGUAGE MODELS X. Chen, X. Liu, M. J. F. Gales, and P. C...As the gener- alization patterns of RNNLMs and n- gram LMs are inherently dif- ferent, RNNLMs are usually combined with n- gram LMs via a fixed...RNNLMs and n- gram LMs as n- gram level changes. In order to fully exploit the detailed n- gram level comple- mentary attributes between the two LMs, a

Evaluation of Marsh/Estuarine Water Quality and Ecological Models: An Interim Guide

DTIC Science & Technology

1982-01-01

benthic oxygen demand, benthic scour and deposition, photosynthesis and respiration of aquatic plants, and nitrification (Dobbins 1964; O’Connor 1967... photosynthesis , algal respiration, decom- position, and mixing processes play dominant roles, the understanding and characterization of significant pro...Adams, S. M. 1979. "A Mathematical Model of Trophic Dynamics in Estuarine Seagrass Communities," Marsh-Estuarine Systems Simulation, Dame, R. F., ed

Helicopter Dynamic Performance Program. Volume 2. User’s Manual

DTIC Science & Technology

1980-07-01

Technologies Corporation Stratford, Connecticut 06602 July 1980 Final Report / • ., . Approved for public release; I distribution unlimited. ; A - Prepared...for : APPLIED TECHNOLOGY LABORATORY U. S. ARMY RESEARCH AND TECHNOLOGY LABORATORIES (AVRADCOM) Fort Eustis, Va. 23604 80 8 27 D APPLIED TECHNOLOGY ... Technology Division. Technic31 review of this report was also pro- vided by Messrs. W_ A. Pleasants of Design Integration and Analysis Technical Area

The role of intrinsic disorder and dynamics in the assembly and function of the type II secretion system.

PubMed

Gu, Shuang; Shevchik, Vladimir E; Shaw, Rosie; Pickersgill, Richard W; Garnett, James A

2017-10-01

Many Gram-negative commensal and pathogenic bacteria use a type II secretion system (T2SS) to transport proteins out of the cell. These exported proteins or substrates play a major role in toxin delivery, maintaining biofilms, replication in the host and subversion of host immune responses to infection. We review the current structural and functional work on this system and argue that intrinsically disordered regions and protein dynamics are central for assembly, exo-protein recognition, and secretion competence of the T2SS. The central role of intrinsic disorder-order transitions in these processes may be a particular feature of type II secretion. Copyright © 2017 Elsevier B.V. All rights reserved.

Gravitational parameters of the Jupiter system from the Doppler tracking of Pioneer 10

NASA Technical Reports Server (NTRS)

Anderson, J. D.; Null, G. W.; Wong, S. K.

1974-01-01

Preliminary analyses of Doppler data from Pioneer 10 during its encounter with Jupiter indicate that the mass of Io is about 20% greater than previously thought and that Io's mean density is about 3.5 grams per cubic centimeter. A determination of the dynamical flattening of Jupiter (a - b)/a (where a is the semimajor axis and b is the semiminor axis) is found to lie in the neighborhood of 0.065, which agrees with the value determined from satellite perturbations.

Minimization of Food Cost on 2000-Calorie Diabetic Diet

NASA Astrophysics Data System (ADS)

Urrutia, J. D.; Mercado, J.; Tampis, R. L.

2017-03-01

This study focuses on minimization of food cost that satisfies the daily nutrients required based on 2000-calorie diet for a diabetic person. This paper attempts to provide a food combination that satisfies the daily nutrient requirements of a diabetic person and its lowest possible dietary food cost. A linear programming diet model is used to determine the cheapest combination of food items that satisfy the recommended daily nutritional requirements of the diabetic persons. According to the findings, a 50 year old and above diabetic male need to spend a minimum of 72.22 pesos for foods that satisfy the daily nutrients they need. In order to attain the minimum spending, the foods must consist of 60.49 grams of anchovy, 91.24 grams of carrot, 121.92 grams of durian, 121.41 grams of chicken egg, 70.82 grams of pork (lean), and 369.70 grams of rice (well-milled). For a 50 year old and above diabetic female, the minimum spending is 64.65 pesos per day and the food must consist of 75.87 grams of anchovy, 43.38 grams of carrot, 160.46 grams of durian, 69.66 grams of chicken egg, 23.16 grams of pork (lean) and 416.19 grams of rice (well-milled).

Bacteremic complications of intravascular catheter tip colonization with Gram-negative micro-organisms in patients without preceding bacteremia.

PubMed

van Eck van der Sluijs, A; Oosterheert, J J; Ekkelenkamp, M B; Hoepelman, I M; Peters, Edgar J G

2012-06-01

Although Gram-negative micro-organisms are frequently associated with catheter-related bloodstream infections, the prognostic value and clinical implication of a positive catheter tip culture with Gram-negative micro-organisms without preceding bacteremia remains unclear. We determined the outcomes of patients with intravascular catheters colonized with these micro-organisms, without preceding positive blood cultures, and identified risk factors for the development of subsequent Gram-negative bacteremia. All patients with positive intravascular catheter tip cultures with Gram-negative micro-organisms at the University Medical Center, Utrecht, The Netherlands, between 2005 and 2009, were retrospectively studied. Patients with Gram-negative bacteremia within 48 h before catheter removal were excluded. The main outcome measure was bacteremia with Gram-negative micro-organisms. Other endpoints were length of the hospital stay, in-hospital mortality, secondary complications of Gram-negative bacteremia, and duration of intensive care admission. A total of 280 catheters from 248 patients were colonized with Gram-negative micro-organisms. Sixty-seven cases were excluded because of preceding positive blood cultures, leaving 213 catheter tips from 181 patients for analysis. In 40 (19%) cases, subsequent Gram-negative bacteremia developed. In multivariate analysis, arterial catheters were independently associated with subsequent Gram-negative bacteremia (odds ratio [OR] = 5.00, 95% confidence interval [CI]: 1.20-20.92), as was selective decontamination of the digestive tract (SDD) (OR = 2.47, 95% CI: 1.07-5.69). Gram-negative bacteremia in patients who received SDD was predominantly caused by cefotaxime (part of the SDD)-resistant organisms. Mortality was significantly higher in the group with subsequent Gram-negative bacteremia (35% versus 20%, OR = 2.12, 95% CI: 1.00-4.49). Patients with a catheter tip colonized with Gram-negative micro-organisms had a high chance of subsequent Gram-negative bacteremia from any cause. This may be clinically relevant, as starting antibiotic treatment pre-emptively in high-risk patients with Gram-negative micro-organisms cultured from arterial intravenous catheters may be beneficial.

Blood glucose meters employing dynamic electrochemistry are stable against hematocrit interference in a laboratory setting.

PubMed

Pfützner, Andreas; Musholt, Petra B; Schipper, Christina; Demircik, Filiz; Hengesbach, Carina; Flacke, Frank; Sieber, Jochen; Forst, Thomas

2013-11-01

Hematocrit (HCT) is known to be a confounding factor that interferes with many blood glucose (BG) measurement technologies, resulting in wrong readings. Dynamic electrochemistry has been identified as one possible way to correct for these potential deviations. The purpose of this laboratory investigation was to assess the HCT stability of four BG meters known to employ dynamic electrochemistry (BGStar and iBGStar, Sanofi; Wavesense Jazz, AgaMatrix; Wellion Linus, MedTrust) in comparison with three other devices (GlucoDock, Medisana; OneTouch Verio Pro, LifeScan; FreeStyle Freedom InsuLinx, Abbott-Medisense). Venous heparinized blood was immediately aliquoted after draw and manipulated to contain three different BG concentrations (60-90, 130-160, and 280-320 mg/dl) and five different HCT levels (25%, 35%, 45%, 55%, and 60%). After careful oxygenation to normal blood oxygen pressure, each of the resulting 15 different samples was measured six times with three devices and three strip lots of each meter. The YSI Stat 2300 served as laboratory reference method. Stability to HCT influence was assumed when less than 10% difference occurred between the highest and lowest mean glucose deviations in relation to HCT concentrations [hematocrit interference factor (HIF)]. Five of the investigated self-test meters showed a stable performance with the different HCT levels tested in this investigation: BGStar (HIF 4.6%), iBGStar (6.6%), Wavesense Jazz (4.1%), Wellion Linus (8.5%), and OneTouch Verio Pro (6.2%). The two other meters were influenced by HCT (FreeStyle InsuLinx 17.8%; GlucoDock 46.5%). In this study, meters employing dynamic electrochemistry, as used in the BGStar and iBGStar devices, were shown to correct for potential HCT influence on the meter results. Dynamic electrochemistry appears to be an effective way to handle this interfering condition. © 2013 Diabetes Technology Society.

Blood Glucose Meters Employing Dynamic Electrochemistry Are Stable against Hematocrit Interference in a Laboratory Setting

PubMed Central

Pfützner, Andreas; Musholt, Petra B.; Schipper, Christina; Demircik, Filiz; Hengesbach, Carina; Flacke, Frank; Sieber, Jochen; Forst, Thomas

2013-01-01

Background Hematocrit (HCT) is known to be a confounding factor that interferes with many blood glucose (BG) measurement technologies, resulting in wrong readings. Dynamic electrochemistry has been identified as one possible way to correct for these potential deviations. The purpose of this laboratory investigation was to assess the HCT stability of four BG meters known to employ dynamic electrochemistry (BGStar and iBGStar, Sanofi; Wavesense Jazz, AgaMatrix; Wellion Linus, MedTrust) in comparison with three other devices (GlucoDock, Medisana; OneTouch Verio Pro, LifeScan; FreeStyle Freedom InsuLinx, Abbott-Medisense). Methods Venous heparinized blood was immediately aliquoted after draw and manipulated to contain three different BG concentrations (60–90, 130–160, and 280–320 mg/dl) and five different HCT levels (25%, 35%, 45%, 55%, and 60%). After careful oxygenation to normal blood oxygen pressure, each of the resulting 15 different samples was measured six times with three devices and three strip lots of each meter. The YSI Stat 2300 served as laboratory reference method. Stability to HCT influence was assumed when less than 10% difference occurred between the highest and lowest mean glucose deviations in relation to HCT concentrations [hematocrit interference factor (HIF)]. Results Five of the investigated self-test meters showed a stable performance with the different HCT levels tested in this investigation: BGStar (HIF 4.6%), iBGStar (6.6%), Wavesense Jazz (4.1%), Wellion Linus (8.5%), and OneTouch Verio Pro (6.2%). The two other meters were influenced by HCT (FreeStyle InsuLinx 17.8%; GlucoDock 46.5%). Conclusions In this study, meters employing dynamic electrochemistry, as used in the BGStar and iBGStar devices, were shown to correct for potential HCT influence on the meter results. Dynamic electrochemistry appears to be an effective way to handle this interfering condition. PMID:24351179

21 CFR 172.802 - Acetone peroxides.

Code of Federal Regulations, 2013 CFR

2013-04-01

... grams to 10 grams of hydrogen peroxide equivalent per 100 grams of the additive, plus carrier, for use in flour maturing and bleaching; or (2) approximately 0.75 gram of hydrogen peroxide equivalent per 100 grams of the additive, plus carrier, for use in dough conditioning. (c) It is used or intended for...