Science.gov

Sample records for multiple organophosphorylated sites

  1. Mass spectrometry identifies multiple organophosphorylated sites on tubulin

    SciTech Connect

    Grigoryan, Hasmik Schopfer, Lawrence M. Peeples, Eric S. Duysen, Ellen G. Grigoryan, Marine Thompson, Charles M. Lockridge, Oksana

    2009-10-15

    Acute toxicity of organophosphorus poisons (OP) is explained by inhibition of acetylcholinesterase in nerve synapses. Low-dose effects are hypothesized to result from modification of other proteins, whose identity is not yet established. The goal of the present work was to obtain information that would make it possible to identify tubulin as a target of OP exposure. Tubulin was selected for study because live mice injected with a nontoxic dose of a biotinylated organophosphorus agent appeared to have OP-labeled tubulin in brain as determined by binding to avidin beads and mass spectrometry. The experiments with live mice were not conclusive because binding to avidin beads could be nonspecific. To be convincing, it is necessary to find and characterize the OP-labeled tubulin peptide. The search for OP-labeled tubulin peptides was begun by identifying residues capable of making a covalent bond with OP. Pure bovine tubulin (0.012 mM) was treated with 0.01-0.5 mM chlorpyrifos oxon for 24 h at 37 {sup o}C in pH 8.3 buffer. The identity of labeled amino acids and percent labeling was determined by mass spectrometry. Chlorpyrifos oxon bound covalently to tyrosines 83, 103, 108, 161, 224, 262, 272, 357, and 399 in bovine alpha tubulin, and to tyrosines 50, 51, 59, 106, 159, 281, 310, and 340 in bovine beta tubulin. The most reactive were tyrosine 83 in alpha and tyrosine 281 in beta tubulin. In the presence of 1 mM GTP, percent labeling increased 2-fold. Based on the crystal structure of the tubulin heterodimer (PDB 1jff) tyrosines 83 and 281 are well exposed to solvent. In conclusion seventeen tyrosines in tubulin have the potential to covalently bind chlorpyrifos oxon. These results will be useful when searching for OP-labeled tubulin in live animals.

  2. Preparation and properties of hybrid direct methanol fuel cell membranes by embedding organophosphorylated titania submicrospheres into a chitosan polymer matrix

    NASA Astrophysics Data System (ADS)

    Wu, Hong; Hou, Weiqiang; Wang, Jingtao; Xiao, Lulu; Jiang, Zhongyi

    Organophosphorylated titania submicrospheres (OPTi) are prepared and incorporated into a chitosan (CS) matrix to fabricate hybrid membranes with enhanced methanol resistance and proton conductivity for application in direct methanol fuel cells (DMFC). The pristine monodispersed titania submicrospheres (TiO 2) of controllable particle size are synthesized through a modified sol-gel method and then phosphorylated by amino trimethylene phosphonic acid (ATMP) via chemical adsorption, which is confirmed by XPS, FTIR and TGA. The morphology and thermal property of the hybrid membranes are explored by SEM and TGA. The ionic cross-linking between the -PO 3H 2 groups on OPTi and the -NH 2 groups on CS lead to better compatibility between the inorganic fillers and the polymer matrix, as well as a decreased fractional free volume (FFV), which is verified by positron annihilation lifetime spectroscopy (PALS). The effects of particle size and content on the methanol permeability, proton conductivity, swelling and FFV of the membranes are investigated. Compared to pure CS membrane, the hybrid membranes exhibit an increased proton conductivity to an acceptable level of 0.01 S cm -1 for DMFC application and a reduced methanol permeability of 5 × 10 -7 cm 2 s -1 at a 2 M methanol feed.

  3. Enzyme-linked immunosorbent assay for detection of organophosphorylated butyrylcholinesterase: A biomarker of exposure to organophosphate agents

    SciTech Connect

    Wang, Liming; Du, Dan; Lu, Donglai; Lin, Chiann Tso; Smith, Jordan N.; Timchalk, Charles; Liu, Fengquan; Wang, Jun; Lin, Yuehe

    2011-05-05

    A sandwich enzyme-linked immunosorbent assay (sELISA) is developed for detection of organophosphorylated butyrylcholinesterase (OP-BChE), a potential biomarker for human exposure to organophosphate insecticides and nerve agents. A pair of antibodies specific to OP-BChE adduct were identified through systematic screening of several anti BChE antibodies (anti-BChE) and anti-phosphoserine antibodies (anti-Pser) from different sources. The selected anti-BChE (set as capture antibody) antibodies recognize both phosphorylated and nonphosphorylated BChE. These antibodies can therefore be used to capture both BChE and OP-BChE from the sample matrices. The anti- Pser (set as detecting antibody) was used to recognize the OP moiety of OP-BChE adducts. With the combination of the selected antibody pair, several key parameters (such as the concentration of anti-BChE and anti-Pser, and the blocking agent) were optimized to enhance the sensitivity and selectivity of the sELISA. Under the optimal conditions, the sELISA has shown a wide linear range from 0.03 nM to 30 nM, with a detection limit of 0.03 nM. Furthermore, the sELISA was successfully applied to detect OP-BChE using in-vitro biological samples such as rat plasma spiked with OP-BChE with excellent adduct recovery (z>99 %). These results demonstrate that this novel approach holds great promise to develop an ELISA kit and offers a simple and cost-effective tool for screening/evaluating exposure to organophosphate insecticides and nerve agents.

  4. HPV Vaccine Effective at Multiple Anatomic Sites

    Cancer.gov

    A new study from NCI researchers finds that the HPV vaccine protects young women from infection with high-risk HPV types at the three primary anatomic sites where persistent HPV infections can cause cancer. The multi-site protection also was observed at l

  5. Multiple instance learning of Calmodulin binding sites

    PubMed Central

    Minhas, Fayyaz ul Amir Afsar; Ben-Hur, Asa

    2012-01-01

    Motivation: Calmodulin (CaM) is a ubiquitously conserved protein that acts as a calcium sensor, and interacts with a large number of proteins. Detection of CaM binding proteins and their interaction sites experimentally requires a significant effort, so accurate methods for their prediction are important. Results: We present a novel algorithm (MI-1 SVM) for binding site prediction and evaluate its performance on a set of CaM-binding proteins extracted from the Calmodulin Target Database. Our approach directly models the problem of binding site prediction as a large-margin classification problem, and is able to take into account uncertainty in binding site location. We show that the proposed algorithm performs better than the standard SVM formulation, and illustrate its ability to recover known CaM binding motifs. A highly accurate cascaded classification approach using the proposed binding site prediction method to predict CaM binding proteins in Arabidopsis thaliana is also presented. Availability: Matlab code for training MI-1 SVM and the cascaded classification approach is available on request. Contact: fayyazafsar@gmail.com or asa@cs.colostate.edu PMID:22962461

  6. Using Multiple Unmanned Systems for a Site Security Task

    SciTech Connect

    Matthew O. Anderson; Curtis W. Nielsen; Mark D. McKay; Derek C. Wadsworth; Ryan C. Hruska; John A. Koudelka

    2009-04-01

    Unmanned systems are often used to augment the ability of humans to perform challenging tasks. While the value of individual unmanned vehicles have been proven for a variety of tasks, it is less understood how multiple unmanned systems should be used together to accomplish larger missions such as site security. The purpose of this paper is to discuss efforts by researchers at the Idaho National Laboratory (INL) to explore the utility and practicality of operating multiple unmanned systems for a site security mission. This paper reviews the technology developed for a multi-agent mission and summarizes the lessons-learned from a technology demonstration.

  7. Myxoid Malignant Fibrous Histiocytoma with Multiple Primary Sites

    PubMed Central

    Muler, Jeffrey H.; Paulino, Augusto F.; Roulston, Diane

    2002-01-01

    Malignant fibrous histiocytoma (MFH) is one of the most common types of soft tissue sarcomas in adults. The most common location of MFH are the extremities and the trunk, with the most common site for distant metastases being the lung. We describe a case with multiple synchronous sites of myxoid MFH but no lung metastases and presence of abnormalities of 19p13. PMID:18521346

  8. Multiple phosphorus chemical sites in heavily phosphorus-doped diamond

    SciTech Connect

    Okazaki, Hiroyuki; Yoshida, Rikiya; Muro, Takayuki; Nakamura, Tetsuya; Hirai, Masaaki; Kato, Hiromitsu; Yamasaki, Satoshi; Takano, Yoshihiko; Ishii, Satoshi; Oguchi, Tamio

    2011-02-21

    We have performed high-resolution core level photoemission spectroscopy on a heavily phosphorus (P)-doped diamond film in order to elucidate the chemical sites of doped-phosphorus atoms in diamond. P 2p core level study shows two bulk components, providing spectroscopic evidence for multiple chemical sites of doped-phosphorus atoms. This indicates that only a part of doped-phosphorus atoms contribute to the formation of carriers. From a comparison with band calculations, possible origins for the chemical sites are discussed.

  9. Protein engineering: single or multiple site-directed mutagenesis.

    PubMed

    Hsieh, Pei-Chung; Vaisvila, Romualdas

    2013-01-01

    Site-directed mutagenesis techniques are invaluable tools in molecular biology to study the structural and functional properties of a protein. To expedite the time required and simplify methods for mutagenesis, we recommend two protocols in this chapter. The first method for single site-directed mutagenesis, which includes point mutations, insertions, or deletions, can be achieved by an inverse PCR strategy with mutagenic primers and the high-fidelity Phusion(®) DNA Polymerase to introduce a site-directed mutation with exceptional efficiency. The second method is for engineering multiple mutations into a gene of interest. This can be completed in one step by PCR with mutagenic primers and by assembling all mutagenized PCR products using the Gibson Assembly™ Master Mix. This method allows multiple nucleotides to be changed simultaneously, which not only saves time but also reagents compared to traditional methods of mutagenesis. PMID:23423897

  10. Hereditary Angioedema Attacks: Local Swelling at Multiple Sites.

    PubMed

    Hofman, Zonne L M; Relan, Anurag; Hack, C Erik

    2016-02-01

    Hereditary angioedema (HAE) patients experience recurrent local swelling in various parts of the body including painful swelling of the intestine and life-threatening laryngeal oedema. Most HAE literature is about attacks located in one anatomical site, though it is mentioned that HAE attacks may also involve multiple anatomical sites simultaneously. A detailed description of such multi-location attacks is currently lacking. This study investigated the occurrence, severity and clinical course of HAE attacks with multiple anatomical locations. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. Visual analog scale scores filled out by the patients for various symptoms at various locations and investigator symptoms scores during the attack were analysed. Data of 219 eligible attacks in 119 patients was analysed. Thirty-three patients (28%) had symptoms at multiple locations in anatomically unrelated regions at the same time during their first attack. Up to five simultaneously affected locations were reported. The observation that severe HAE attacks often affect multiple sites in the body suggests that HAE symptoms result from a systemic rather than from a local process as is currently believed. PMID:25527240

  11. Hereditary Angioedema Attacks: Local Swelling at Multiple Sites.

    PubMed

    Hofman, Zonne L M; Relan, Anurag; Hack, C Erik

    2016-02-01

    Hereditary angioedema (HAE) patients experience recurrent local swelling in various parts of the body including painful swelling of the intestine and life-threatening laryngeal oedema. Most HAE literature is about attacks located in one anatomical site, though it is mentioned that HAE attacks may also involve multiple anatomical sites simultaneously. A detailed description of such multi-location attacks is currently lacking. This study investigated the occurrence, severity and clinical course of HAE attacks with multiple anatomical locations. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. Visual analog scale scores filled out by the patients for various symptoms at various locations and investigator symptoms scores during the attack were analysed. Data of 219 eligible attacks in 119 patients was analysed. Thirty-three patients (28%) had symptoms at multiple locations in anatomically unrelated regions at the same time during their first attack. Up to five simultaneously affected locations were reported. The observation that severe HAE attacks often affect multiple sites in the body suggests that HAE symptoms result from a systemic rather than from a local process as is currently believed.

  12. Multiple-site estimations in probabilistic seismic hazard assessment

    NASA Astrophysics Data System (ADS)

    Sokolov, Vladimir; Ismail-Zadeh, Alik

    2016-04-01

    We analyze specific features of multiple-site probabilistic seismic hazard assessment (PSHA), i.e. annual rate of ground motion level exceedance in at least one site of several sites of interest located within in an area or along a linear extended object. The relation between the multiple-scale hazard estimations and strong ground-motion records obtained during the 2008 Wenchuan (China) Mw 7.9 earthquake is discussed. The ground-motion records may be considered as an example of ground motion exceeding the design level estimated using the classical point-wise PSHA. We showed that the multiple-site hazard (MSH) assessment, when being performed for standard return period 475 years, provide reasonable estimations of the ground motions that may occur during the earthquake, parameters of which are close to maximum possible events accepted in PSHA for the region. Thus the MSH may be useful in estimation of maximum considered earthquake ground motion for the considered territory taking into account its extent.

  13. Multiple postoperative intracerebral haematomas remote from the site of craniotomy.

    PubMed

    Rapanà, A; Lamaida, E; Pizza, V

    1998-08-01

    A postoperative haemorrhage is a common and serious complication of a neurosurgical procedure. It usually occurs at the site of the surgery, but on occasion a postoperative haematoma is found at a distance from the previous craniotomy. Multiple postoperative haemorrhages are extremely rare. We report the case of a 63-year-old woman, operated on for the removal of a supratentorial astrocytoma, who developed in the early post-operative period multiple bilateral intracerebral haematomas without involvement of the surgical bed. PMID:10070433

  14. Gonorrhea and multiple site infection: case report and screening opportunities.

    PubMed

    D'Antuono, Antonietta; Baraldi, Carlotta; Banzola, Nicoletta; Gaspari, Valeria; Filippini, Andrea; Patrizi, Annalisa

    2016-06-01

    Neisseria gonorrhoeae is one of the most prevalent sexually transmitted pathogen with the vast majority of reported cases diagnosed at urogenital sites. While urethral gonococcal infections in men usually present with penile discharge and dysuria, pharynx and rectal infections are often asymptomatic. The Centers for Disease Control and Prevention recommend that sexually active men who have sex with men (MSM) be screened at least annually for urethral, pharyngeal and rectal gonorrhea, considering sexual exposure history, and every 3 to 6 months if higher-risk behaviours are reported. However, despite CDC's guidelines screening recommendations, low rates of testing among MSM are reported, such as urethral-only screening which may entail missing pharyngeal and rectal gonococcal infection. We present a case report of gonorrhea with multiple anatomic sites infection in a young MSM. Inspite of clinical presentation involving urogenital symptoms only, a sexual history based valutation allowed to detect asymptomatic pharyngeal and rectal infections. PMID:27176080

  15. Polypharmacology within CXCR4: Multiple binding sites and allosteric behavior

    NASA Astrophysics Data System (ADS)

    Planesas, Jesús M.; Pérez-Nueno, Violeta I.; Borrell, José I.; Teixidó, Jordi

    2014-10-01

    CXCR4 is a promiscuous receptor, which binds multiple diverse ligands. As usual in promiscuous proteins, CXCR4 has a large binding site, with multiple subsites, and high flexibility. Hence, it is not surprising that it is involved in the phenomenon of allosteric modulation. However, incomplete knowledge of allosteric ligand-binding sites has hampered an in-depth molecular understanding of how these inhibitors work. For example, it is known that lipidated fragments of intracellular GPCR loops, so called pepducins, such as pepducin ATI-2341, modulate CXCR4 activity using an agonist allosteric mechanism. Nevertheless, there are also examples of small organic molecules, such as AMD11070 and GSK812397, which may act as antagonist allosteric modulators. Here, we give new insights into this issue by proposing the binding interactions between the CXCR4 receptor and the above-mentioned allosteric modulators. We propose that CXCR4 has minimum two topographically different allosteric binding sites. One allosteric site would be in the intracellular loop 1 (ICL1) where pepducin ATI-2341 would bind to CXCR4, and the second one, in the extracellular side of CXCR4 in a subsite into the main orthosteric binding pocket, delimited by extracellular loops n° 1, 2, and the N-terminal end, where antagonists AMD11070 and GSK812397 would bind. Prediction of allosteric interactions between CXCR4 and pepducin ATI-2341 were studied first by rotational blind docking to determine the main binding region and a subsequent refinement of the best pose was performed using flexible docking methods and molecular dynamics. For the antagonists AMD11070 and GSK812397, the entire CXCR4 protein surface was explored by blind docking to define the binding region. A second docking analysis by subsites of the identified binding region was performed to refine the allosteric interactions. Finally, we identified the binding residues that appear to be essential for CXCR4 (agonists and antagonists) allosteric

  16. HANFORD SITE WELDING PROGRAM SUCCESSFULLY PROVIDING A SINGLE SITE FUNCTION FOR USE BY MULTIPLE CONTRACTORS

    SciTech Connect

    CANNELL GR

    2009-11-19

    The Department of Energy, Richland Operations (DOE-RL) recently restructured its Hanford work scope, awarding two new contracts over the past several months for a total of three contracts to manage the sites cleanup efforts. DOE-RL met with key contractor personnel prior to and during contract transition to ensure site welding activities had appropriate oversight and maintained code compliance. The transition also provided an opportunity to establish a single site-wide function that would provide welding and materials engineering services to the Hanford site contractors: CH2M HILL Plateau Remediation Company (CHPRC); Mission Support Alliance (MSA); Washington River Protection Solutions (WRPS); and Washington Closure Hanford (WCH). Over the years, multiple and separate welding programs (amongst the several contractors) existed at the Hanford site leading to inefficiencies resulting from duplication of administrative efforts, maintenance of welding procedures, welder performance certifications, etc. The new, single program eliminates these inefficiencies. The new program, co-managed by two of the sites' new contractors, the CHPRC ('owner' of the program and responsible for construction welding services) and the MSA (provides maintenance welding services), provides more than just the traditional construction and maintenance welding services. Also provided, are welding engineering, specialty welding development/qualification for the closure of radioactive materials containers and materials evaluation/failure analysis. The following describes the new Hanford site welding program.

  17. 24 CFR 1710.15 - Regulatory exemption-multiple site subdivision-determination required.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Regulatory exemption-multiple site... PROGRAM) LAND REGISTRATION General Requirements § 1710.15 Regulatory exemption—multiple site subdivision—determination required. (a) General. (1) The sale of lots contained in multiple sites of fewer than 100...

  18. Multiple-Use Site Demand Analysis: An Application to the Boundary Waters Canoe Area Wilderness.

    ERIC Educational Resources Information Center

    Peterson, George L.; And Others

    1982-01-01

    A single-site, multiple-use model for analyzing trip demand is derived from a multiple site regional model based on utility maximizing choice theory. The model is used to analyze and compare trips to the Boundary Waters Canoe Area Wilderness for several types of use. Travel cost elasticities of demand are compared and discussed. (Authors/JN)

  19. Reducing Job Coach Assistance for Supported Workers with Severe Multiple Disabilities: An Alternative Off-Site/On-Site Model.

    ERIC Educational Resources Information Center

    Parsons, Marsha B.; Reid, Dennis H.; Green, Carolyn W.; Browning, Leah B.

    2001-01-01

    A study evaluated an off-site/on-site program for reducing job coach assistance provided for three adults with severe multiple disabilities in a part-time community job. On-the-job assistance was reduced, while the individuals received more traditional day services when not at work. No adverse effects on productivity were observed. (Contains…

  20. Prioritizing functional phosphorylation sites based on multiple feature integration

    PubMed Central

    Xiao, Qingyu; Miao, Benpeng; Bi, Jie; Wang, Zhen; Li, Yixue

    2016-01-01

    Protein phosphorylation is an important type of post-translational modification that is involved in a variety of biological activities. Most phosphorylation events occur on serine, threonine and tyrosine residues in eukaryotes. In recent years, many phosphorylation sites have been identified as a result of advances in mass-spectrometric techniques. However, a large percentage of phosphorylation sites may be non-functional. Systematically prioritizing functional sites from a large number of phosphorylation sites will be increasingly important for the study of their biological roles. This study focused on exploring the intrinsic features of functional phosphorylation sites to predict whether a phosphosite is likely to be functional. We found significant differences in the distribution of evolutionary conservation, kinase association, disorder score, and secondary structure between known functional and background phosphorylation datasets. We built four different types of classifiers based on the most representative features and found that their performances were similar. We also prioritized 213,837 human phosphorylation sites from a variety of phosphorylation databases, which will be helpful for subsequent functional studies. All predicted results are available for query and download on our website (Predict Functional Phosphosites, PFP, http://pfp.biosino.org/). PMID:27090940

  1. Risk Prediction Models for Other Cancers or Multiple Sites

    Cancer.gov

    Developing statistical models that estimate the probability of developing other multiple cancers over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  2. The Hanford Site multiple function badge demonstration project

    SciTech Connect

    Nelson, R.A.

    1993-03-01

    The US Department of Energy Hanford Site is an original defense production site dating from World War II. The US Department of Energy assigned a new waste management mission for the Hanford Site. This mission requires fewer manned security posts and more areas restricted because of safety and environmental concerns. Entry into these areas requires specific safety and environmental qualifications, which could be controlled by automated access control systems. Automated entry reduces costs of managing the Site but requires health physics, safety, employee training, security databases integration, and a network system. Another approach, avoiding integration, is individuals carrying this information on their person as a picture identity badge and access control token. The health physics, safety, employee training, and security regulations that define access requirements may be best served using a smart card as the access control token. This paper discusses the need for information distribution and automated access control, potential approaches for solving the need, and smart card work at the Hanford Site.

  3. EVALUATING NATURAL BIODEGRADATION OF MTBE AT MULTIPLE UST SITES

    EPA Science Inventory

    Until very recently, methyl t-butyl ether (MTBE) was considered non-biodegradable in the subsurface. This has been an impediment in applying remediation by natural attenuation (RNA) as a remedial strategy at MTBE-impacted sites. Although a number of recent studies have demonst...

  4. Idiopathic Multiple Eruptive Milia Occurred in Unusual Sites

    PubMed Central

    Cho, Eujin; Cho, Sang Hyun

    2010-01-01

    Milia are small, white, benign keratinous cysts that are frequently encountered. Multiple eruptive milia are rare, and are characterized by the development of milia that are more extensive in number and distribution than would be expected in primary milia. We report a case of a 19-year-old girl with tiny, white papules in her axillae and on her abdomen with a review of the relevant literature. PMID:21165223

  5. Multiple sites of extinction for a single learned response

    PubMed Central

    Mauk, Michael D.

    2012-01-01

    Most learned responses can be diminished by extinction, a process that can be engaged when a conditioned stimulus (CS) is presented but not reinforced. We present evidence that plasticity in at least two brain regions can mediate extinction of responses produced by trace eyelid conditioning, where the CS and the reinforcing stimulus are separated by a stimulus-free interval. We observed individual differences in the effects of blocking extinction mechanisms in the cerebellum, the structure that, along with several forebrain structures, mediates acquisition of trace eyelid responses; in some rabbits extinction was prevented, whereas in others it was largely unaffected. We also show that cerebellar mechanisms can mediate extinction when noncerebellar mechanisms are bypassed. Together, these observations indicate that trace eyelid responses can be extinguished via processes operating at more than one site, one in the cerebellum and one upstream in forebrain. The relative contributions of these sites may vary from animal to animal and situation to situation. PMID:21940608

  6. Multiple missions: The 300 Area in Hanford Site history

    SciTech Connect

    Gerber, M.S.

    1993-09-01

    This report provides an historical overview of the role of the 300 Area buildings at the Hanford Reservation. Topics covered are: Early fuel fabrication at the Hanford site (313 and 314 Buildings); N reactor fuel fabrication in the 300 Area; 305 test pile was Hanford`s first operating reactor; Early process improvement chemical research (321 and 3706 Buildings); Major 1952 and 1953 expansions in the 300 area (325 and 329 Buildings); Early 300 area facilities constructed to support reactor development (326 and 327 Buildings); Hanford site ventures with the peaceful atom (309, 308 and 318 Buildings); Modern 300 Area Buildings; Significant miscellaneous buildings in the 300 area; 300 Area process waste handling and disposal.

  7. Reaching site closure for groundwater under multiple regulatory agencies

    SciTech Connect

    Glucksberg, N.; Couture, B.

    2007-07-01

    Groundwater at the Connecticut Yankee Atomic Power Company (CYAPCO) Haddam Neck Plant (HNP) has been impacted by both radionuclides and chemical constituents. Furthermore, the cleanup standards and closure requirements for HNP are regulated both by federal and state agencies. The only consistent requirement is the development of a site conceptual model and an understanding of the hydrogeologic conditions that will govern contaminant transport and identify potential receptors. The cleanup criteria to reach site closure for radionuclides is regulated by both the Nuclear Regulatory Commission (NRC) and the Connecticut Department of Environmental Protection (CTDEP) Bureau of Air Management, Radiological Division. For license termination under the NRC, the total effective dose equivalent (TEDE) for all media can not exceed 25 milli-Rem per year (mRem/yr) plus As Low as Reasonably Achievable (ALARA). The CTDEP has a similar requirement with the TEDE not to exceed 19 mRem/yr plus ALARA. To reach these criteria, derived concentration guideline levels (DCGLs) were developed for radiological exposures from three (3) media components; soil, existing groundwater and future groundwater from left-in place foundations or footings. Based on current conditions, the target dose contribution from existing and future groundwater is not to exceed 2 mRem/yr TEDE. After source (soil) remediation is complete, the NRC requires two (2) years of quarterly monitoring to demonstrate that groundwater quality meets the DCGLs and does not show an upward trend. CYAPCO's NRC License Termination Plan (LTP) specifies a minimum 18-month period of groundwater monitoring, as long as samples are collected during two spring/high water seasons, to verify the efficacy of remedial actions at HNP. In addition to the 19 mRem/yr criteria, the CTDEP also requires groundwater to be in compliance with the Remediation Standards Regulation (RSRs). There are no published criteria for radionuclides in the RSRs

  8. Chuckwalla Valley multiple-well monitoring site, Chuckwalla Valley, Riverside County

    USGS Publications Warehouse

    Everett, Rhett

    2013-01-01

    The U.S. Geological Survey (USGS), in cooperation with the Bureau of Land Management, is evaluating the geohydrology and water availability of the Chuckwalla Valley, California. As part of this evaluation, the USGS installed the Chuckwalla Valley multiple-well monitoring site (CWV1) in the southeastern portion of the Chuckwalla Basin. Data collected at this site provide information about the geology, hydrology, geophysics, and geochemistry of the local aquifer system, thus enhancing the understanding of the geohydrologic framework of the Chuckwalla Valley. This report presents construction information for the CWV1 multiple-well monitoring site and initial geohydrologic data collected from the site.

  9. Reducing job coach assistance for supported workers with severe multiple disabilities: an alternative off-site/on-site model.

    PubMed

    Parsons, M B; Reid, D H; Green, C W; Browning, L B

    2001-01-01

    Adults with severe multiple disabilities constitute a very small percentage of individuals in supported work. When these persons do obtain community jobs, considerable assistance is usually required. We evaluated an off-site/on-site program for reducing job coach assistance provided for three adults with severe multiple disabilities in a part-time community job. Following observations of the supported workers' job performance in a publishing company, the job support reduction program was implemented while the individuals received more traditional day services when not at work. The program involved assessing the amount and type of assistance provided for each step in a worker's job tasks, and then reducing the assistance through environmental adaptations and instruction. After implementation in the nonwork setting, the adaptations and instruction were extended to the work site. Immediate reductions occurred in the amount of assistance provided by job coaches for each supported worker while on the job. No adverse effects on productivity were observed. These results suggest that an off-site/on-site approach to reducing work assistance represents a viable alternative to current supported work models. Social validity observations in 10 job sites highlighted the need to demonstrate ways to reduce work assistance provided for workers with severe multiple disabilities. Future research areas are noted, focusing on evaluating other models for enhancing supported work opportunities for people with highly significant disabilities.

  10. Reducing job coach assistance for supported workers with severe multiple disabilities: an alternative off-site/on-site model.

    PubMed

    Parsons, M B; Reid, D H; Green, C W; Browning, L B

    2001-01-01

    Adults with severe multiple disabilities constitute a very small percentage of individuals in supported work. When these persons do obtain community jobs, considerable assistance is usually required. We evaluated an off-site/on-site program for reducing job coach assistance provided for three adults with severe multiple disabilities in a part-time community job. Following observations of the supported workers' job performance in a publishing company, the job support reduction program was implemented while the individuals received more traditional day services when not at work. The program involved assessing the amount and type of assistance provided for each step in a worker's job tasks, and then reducing the assistance through environmental adaptations and instruction. After implementation in the nonwork setting, the adaptations and instruction were extended to the work site. Immediate reductions occurred in the amount of assistance provided by job coaches for each supported worker while on the job. No adverse effects on productivity were observed. These results suggest that an off-site/on-site approach to reducing work assistance represents a viable alternative to current supported work models. Social validity observations in 10 job sites highlighted the need to demonstrate ways to reduce work assistance provided for workers with severe multiple disabilities. Future research areas are noted, focusing on evaluating other models for enhancing supported work opportunities for people with highly significant disabilities. PMID:11325162

  11. Melatonin site and mechanism of action: single or multiple?

    PubMed

    Cardinali, D P; Golombek, D A; Rosenstein, R E; Cutrera, R A; Esquifino, A I

    1997-08-01

    By affecting the entrainment pathways of the biologic clock, melatonin has a major influence on the circadian and seasonal organization of vertebrates. In addition, a number of versatile functions that far transcend melatonin actions on photoperiodic time measurement and circadian entrainment have emerged. Melatonin is a free radical scavenger and antioxidant and it has a significant immunomodulatory activity, being presumably a major factor in an organism's defense toxic agents and invading organisms. Besides affecting specific receptors in cell membranes to exert its effects, the interaction of melatonin with nuclear receptor sites and with intracellular proteins, like calmodulin or tubulin-associated proteins, as well as the direct antioxidant effects of melatonin, may explain many general functions of the pineal hormone. PMID:9379344

  12. Characterization of nicotine binding to the rat brain P/sub 2/ preparation: the identification of multiple binding sites which include specific up-regulatory site(s)

    SciTech Connect

    Sloan, J.W.

    1984-01-01

    These studies show that nicotine binds to the rat brain P/sub 2/ preparation by saturable and reversible processes. Multiple binding sites were revealed by the configuration of saturation, kinetic and Scatchard plots. A least squares best fit of Scatchard data using nonlinear curve fitting programs confirmed the presence of a very high affinity site, an up-regulatory site, a high affinity site and one or two low affinity sites. Stereospecificity was demonstrated for the up-regulatory site where (+)-nicotine was more effective and for the high affinity site where (-)-nicotine had a higher affinity. Drugs which selectively up-regulate nicotine binding site(s) have been identified. Further, separate very high and high affinity sites were identified for (-)- and (+)-(/sup 3/H)nicotine, based on evidence that the site density for the (-)-isomer is 10 times greater than that for the (+)-isomer at these sites. Enhanced nicotine binding has been shown to be a statistically significant phenomenon which appears to be a consequence of drugs binding to specific site(s) which up-regulate binding at other site(s). Although Scatchard and Hill plots indicate positive cooperatively, up-regulation more adequately describes the function of these site(s). A separate up-regulatory site is suggested by the following: (1) Drugs vary markedly in their ability to up-regulate binding. (2) Both the affinity and the degree of up-regulation can be altered by structural changes in ligands. (3) Drugs with specificity for up-regulation have been identified. (4) Some drugs enhance binding in a dose-related manner. (5) Competition studies employing cold (-)- and (+)-nicotine against (-)- and (+)-(/sup 3/H)nicotine show that the isomers bind to separate sites which up-regulate binding at the (-)- and (+)-nicotine high affinity sites and in this regard (+)-nicotine is more specific and efficacious than (-)-nicotine.

  13. Multiple-site physician practices and their effect on service distribution.

    PubMed Central

    Cromley, E K; Albertsen, P C

    1993-01-01

    OBJECTIVE. This study explores the impact of multiple-site practices on the distribution of physician services within a medical service region. DATA SOURCES AND STUDY SETTING. A questionnaire was mailed to all urologists (100 percent response rate) practicing in north central Connecticut (the Hartford medical service area) and adjacent communities in September 1990. Data on community characteristics were obtained from the 1990 U.S. census and state government documents. STUDY DESIGN. Descriptive statistics and maps were used to summarize the attributes of single- and multiple-site practices and the communities where they were located. Key practice and community variables were analyzed. DATA COLLECTION/EXTRACTION METHODS. The questionnaires were coded and entered into a digital database with the tabulated community data. Responses of individual physicians were grouped by practice. PRINCIPAL FINDINGS. Multiple-site practices were common. Second-order sites accounted for 23 percent of total appointment capacity and were located in communities with higher than average elderly populations and incomes and lower than average minority populations. CONCLUSIONS. Analysis of multiple-site practices is important for the accurate assessment of medical service availability. Further research is needed to document the functioning of multiple-site practices across other specialties and geographic areas. PMID:8407340

  14. Electric properties and carrier multiplication in breakdown sites in multi-crystalline silicon solar cells

    SciTech Connect

    Schneemann, Matthias; Carius, Reinhard; Rau, Uwe; Kirchartz, Thomas

    2015-05-28

    This paper studies the effective electrical size and carrier multiplication of breakdown sites in multi-crystalline silicon solar cells. The local series resistance limits the current of each breakdown site and is thereby linearizing the current-voltage characteristic. This fact allows the estimation of the effective electrical diameters to be as low as 100 nm. Using a laser beam induced current (LBIC) measurement with a high spatial resolution, we find carrier multiplication factors on the order of 30 (Zener-type breakdown) and 100 (avalanche breakdown) as new lower limits. Hence, we prove that also the so-called Zener-type breakdown is followed by avalanche multiplication. We explain that previous measurements of the carrier multiplication using thermography yield results higher than unity, only if the spatial defect density is high enough, and the illumination intensity is lower than what was used for the LBIC method. The individual series resistances of the breakdown sites limit the current through these breakdown sites. Therefore, the measured multiplication factors depend on the applied voltage as well as on the injected photocurrent. Both dependencies are successfully simulated using a series-resistance-limited diode model.

  15. Decomposition of the factors that govern binding site preference in a multiple rotaxane.

    PubMed

    Angelo, Joseph P; Sohlberg, Karl

    2009-06-18

    A particularly interesting class of multiple rotaxanes consists of complexes where one long shaft threads two rings. If the shaft contains three or more potential binding sites for the rings, multiple co-conformations are possible. Such a complex is a molecular topological analogue to an abacus. Here we address the question, how does strength of ring binding to the shaft vary with respect to position on the shaft? Previous studies have found that a shaft with three binding sites exhibits strongest ring binding at the center site. Here a five-binding-site shaft is studied. We employ a novel method to partition the total energy of the system into contributions from intercomponent binding and intracomponent distortion. The method uses the output of quantum mechanical electronic structure calculations to determine fitting parameters in a set of coupled equations. The solution of the equations yields the energy partitioning and reveals the influence of long-range intercomponent interactions.

  16. Multiple base-recognition sites in a biological nanopore – two heads are better than one

    PubMed Central

    Stoddart, David; Maglia, Giovanni; Mikhailova, Ellina; Heron, Andrew J.; Bayley, Hagan

    2011-01-01

    Ultra-rapid sequencing of DNA strands with nanopores is under intense investigation. The αHL protein nanopore is a leading candidate sensor for this approach. Multiple base-recognition sites have been identified in engineered αHL pores. By using immobilized synthetic oligonucleotides, we show here that additional sequence information can be gained when two recognition sites, rather than one, are employed within a single nanopore. PMID:20014084

  17. Analysis and prediction of Multiple-Site Damage (MSD) fatigue crack growth

    NASA Technical Reports Server (NTRS)

    Dawicke, D. S.; Newman, J. C., Jr.

    1992-01-01

    A technique was developed to calculate the stress intensity factor for multiple interacting cracks. The analysis was verified through comparison with accepted methods of calculating stress intensity factors. The technique was incorporated into a fatigue crack growth prediction model and used to predict the fatigue crack growth life for multiple-site damage (MSD). The analysis was verified through comparison with experiments conducted on uniaxially loaded flat panels with multiple cracks. Configuration with nearly equal and unequal crack distribution were examined. The fatigue crack growth predictions agreed within 20 percent of the experimental lives for all crack configurations considered.

  18. Localisation of C reactive protein in infarcted tissue sites of multiple organs during sepsis.

    PubMed

    Baidoshvili, A; Nijmeijer, R; Lagrand, W K; Hack, C E; Niessen, H W M

    2002-02-01

    This report hypothesises an active role for the acute phase protein, C reactive protein (CRP), in local inflammatory reactions. This was studied in infarction sites from liver and kidney in a patient who died as a result of multiple complications after cholecystectomy. In this patient, a general acute phase protein reaction was induced, with an increase in plasma CRP. In infarction sites of kidney and liver, colocalisation of CRP and activated complement were found, whereas non-infarct sites were negative for CRP and complement. These results suggest that CRP directly participates in local inflammatory processes, possibly via complement activation, after binding of a suitable ligand.

  19. 24 CFR 1710.15 - Regulatory exemption-multiple site subdivision-determination required.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION General Requirements § 1710.15 Regulatory exemption—multiple site subdivision... prepared pursuant to the rules and regulations of the Interstate Land Sales Registration Division,...

  20. 24 CFR 1710.15 - Regulatory exemption-multiple site subdivision-determination required.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION General Requirements § 1710.15 Regulatory exemption—multiple site subdivision... prepared pursuant to the rules and regulations of the Interstate Land Sales Registration Division,...

  1. Traffic Management Advisor: Iterative Field Development and Assessment at Multiple Sites

    NASA Technical Reports Server (NTRS)

    Sanford, Beverly D.; Lee, Katharine K.; Harwood, Kelly; Denery, Dallas G. (Technical Monitor)

    1995-01-01

    Previous studies have demonstrated the necessity of involving users in the development of automation aids, especially for complex domains such as air traffic control (ATC). Traditional development only demanded a single field test to validate a completed system, but a more iterative combination of development and assessment ensures that the technology meets the requirements of its application domain. Exposure across an adequate spectrum of field users is also required during development, and the use of multiple development sites provides an opportunity to consider individual facility cultures as they relate to implementation strategies. The development of the Center/TRACON Automation System (CTAS) Traffic Management Advisor (TMA) at the Denver and Dallas ATC facilities demonstrates successful iterative development and assessment at multiple field sites. The use of field development changes the nature of assessment. As development progresses, periodic assessments are required to validate that system development is progressing along an appropriate track. In the development of the TMA, assessments were performed based on software in the field, and input from traffic managers was analyzed and incorporated into subsequent releases of the TMA, to be reassessed in the field. This has led to a tool with operational suitability and broad user acceptance. Assessment at multiple sites provides a more generalizable perspective that allows the production of a system that is both generic enough to be used at different sites and tailored enough to be of use at any site. In addition to providing a better understanding of specific facility requirements, the use of multiple assessment sites in the development of TMA has provided an opportunity to consider individual facility operations, procedures and cultures as they relate to development and implementation strategies.

  2. Multiple-regression equations for estimating low flows at ungaged stream sites in Ohio

    USGS Publications Warehouse

    Koltun, G.F.; Schwartz, R.R.

    1987-01-01

    This report presents multiple-regression equations for estimating selected low-flow characteristics for most unregulated Ohio streams at sites where little or no discharge data are available. The equations relate combinations of drainage area, main-channel length, main-channel slope, average basin elevation, forested area, average annual precipitation, and an index of infiltration to low flows with durations of 7 and 30 days and average recurrence intervals of 2 and 10 years. Data from 132 long-term continuous-record gaging stations and partial-record sites in Ohio were used in the analyses. Multiple-regression analyses were first performed by using data from all 132 sites in an attempt to develop equations that would be applicable statewide. Standard errors for the statewide equations were too high (111 to 189 percent) for them to be of practical use in estimating low streamflows. Data for the state were then subdivided into five regions, and multiple-regression equations were developed for each region. Standard errors for four of the five regions improved, and raged from 43 to 106 percent. Standard errors for region 5 remained high (74 to 129 percent). The multiple-regression equations presented in this report are not applicable to streams with significant low-flow regulation. The equations also are not applicable if (1) the site has been gaged and low-flow estimates have been developed from gaging-station records, (2) low flow can be estimated by the drainage-area transference method from data for a nearby gaged site, or (3) a sufficient number of partial-record measurements made at the site can be adquately correlated with concurrent base flows at a suitable index station.

  3. Residential exposure summary methodology for a reproductive health study of multiple hazardous waste sites.

    PubMed

    Marshall, E G; Geary, N S; Cayo, M R; Lauridsen, P A

    1993-01-01

    Evaluation of associations between residence near hazardous waste sites and rare outcomes requires the consideration of large geographic areas and multiple sources of contamination. For a case-control study of birth defects and solvents, metals and pesticide exposure, the authors rely on previously collected data to rate possible residential exposure from hazardous waste sites. Four pathways of exposure are evaluated: air vapor, air particulates, groundwater ingestion, and groundwater inhalation. Areas within one mile of each site are classified according to 1) the probability of exposure to solvents, metals, and pesticides, and, if available, 2) the relative concentration of contaminants. The probability of exposure (low, medium, or high) for air vapor and particulates depends on the evaporation and soil retention potential of the contaminants, degree of containment, predominant wind direction, and size of the contaminated area. The probability of exposure for groundwater ingestion and inhalation depends on whether there are water supply wells or affected basements within one mile, solubility of the contaminants, direction of groundwater flow, and groundwater sampling results. Relative concentration is based on sampling results for the most commonly sampled media. Exposures are shown on a standard template that defines 25 sectors within a 1 mile radius of each site. The method cannot provide exact estimates of residential exposure, because it relies on data of variable quality. It does provide a basis for evaluating health effects at multiple sites by identifying susceptible residential areas.

  4. PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing

    PubMed Central

    Malina, Abba; Cameron, Christopher J. F.; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

    2015-01-01

    In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification. PMID:26644285

  5. Molecular Communication Model for Targeted Drug Delivery in Multiple Disease Sites With Diversely Expressed Enzymes.

    PubMed

    Chude-Okonkwo, Uche A K; Malekian, Reza; Maharaj, B T Sunil

    2016-04-01

    Targeted drug delivery (TDD) for disease therapy using liposomes as nanocarriers has received extensive attention in the literature. The liposome's ability to incorporate capabilities such as long circulation, stimuli responsiveness, and targeting characteristics, makes it a versatile nanocarrier. Timely drug release at the targeted site requires that trigger stimuli such as pH, light, and enzymes be uniquely overexpressed at the targeted site. However, in some cases, the targeted sites may not express trigger stimuli significantly, hence, achieving effective TDD at those sites is challenging. In this paper, we present a molecular communication-based TDD model for the delivery of therapeutic drugs to multiple sites that may or may not express trigger stimuli. The nanotransmitter and nanoreceiver models for the molecular communication system are presented. Here, the nanotransmitter and nanoreceiver are injected into the targeted body system's blood network. The compartmental pharmacokinetics model is employed to model the transportation of these therapeutic nanocarriers to the targeted sites where they are meant to anchor before the delivery process commences. We also provide analytical expressions for the delivered drug concentration. The effectiveness of the proposed model is investigated for drug delivery on tissue surfaces. Results show that the effectiveness of the proposed molecular communication-based TDD depends on parameters such as the total transmitter volume capacity, the receiver radius, the diffusion characteristic of the microenvironment of the targeted sites, and the concentration of the enzymes associated with the nanotransmitter and the nanoreceiver designs.

  6. RF1 Knockout Allows Ribosomal Incorporation of Unnatural Amino Acids at Multiple Sites

    PubMed Central

    Johnson, David B.F.; Xu, Jianfeng; Shen, Zhouxin; Takimoto, Jeffrey K.; Schultz, Matthew D.; Schmitz, Robert J.; Ecker, Joseph R.; Briggs, Steven P.; Wang, Lei

    2011-01-01

    Stop codons have been exploited for genetic incorporation of unnatural amino acids (Uaas) in live cells, but the efficiency is low possibly due to competition from release factors, limiting the power and scope of this technology. Here we show that the reportedly essential release factor 1 can be knocked out from Escherichia coli by fixing release factor 2. The resultant strain JX33 is stable and independent, and reassigns UAG from a stop signal to an amino acid when a UAG-decoding tRNA/synthetase pair is introduced. Uaas were efficiently incorporated at multiple UAG sites in the same gene without translational termination in JX33. We also found that amino acid incorporation at endogenous UAG codons is dependent on RF1 and mRNA context, which explains why E. coli tolerates apparent global suppression of UAG. JX33 affords a unique autonomous host for synthesizing and evolving novel protein functions by enabling Uaa incorporation at multiple sites. PMID:21926996

  7. Calculating the habitable zones of multiple star systems with a new interactive Web site

    SciTech Connect

    Müller, Tobias W. A.; Haghighipour, Nader

    2014-02-10

    We have developed a comprehensive methodology and an interactive Web site for calculating the habitable zone (HZ) of multiple star systems. Using the concept of spectral weight factor, as introduced in our previous studies of the calculations of HZ in and around binary star systems, we calculate the contribution of each star (based on its spectral energy distribution) to the total flux received at the top of the atmosphere of an Earth-like planet, and use the models of the HZ of the Sun to determine the boundaries of the HZ in multiple star systems. Our interactive Web site for carrying out these calculations is publicly available at http://astro.twam.info/hz. We discuss the details of our methodology and present its application to some of the multiple star systems detected by the Kepler space telescope. We also present the instructions for using our interactive Web site, and demonstrate its capabilities by calculating the HZ for two interesting analytical solutions of the three-body problem.

  8. Characterizing multiple metal ion binding sites within a ribozyme by cadmium-induced EPR silencing

    PubMed Central

    Kisseleva, Natalia; Kraut, Stefanie; Jäschke, Andres; Schiemann, Olav

    2007-01-01

    In ribozyme catalysis, metal ions are generally known to make structural and∕or mechanistic contributions. The catalytic activity of a previously described Diels-Alderase ribozyme was found to depend on the concentration of divalent metal ions, and crystallographic data revealed multiple binding sites. Here, we elucidate the interactions of this ribozyme with divalent metal ions in solution using electron paramagnetic resonance (EPR) spectroscopy. Manganese ion titrations revealed five high-affinity Mn2+ binding sites with an upper Kd of 0.6±0.2 μM. In order to characterize each binding site individually, EPR-silent Cd2+ ions were used to saturate the other binding sites. This cadmium-induced EPR silencing showed that the Mn2+ binding sites possess different affinities. In addition, these binding sites could be assigned to three different types, including innersphere, outersphere, and a Mn2+ dimer. Based on simulations, the Mn2+-Mn2+ distance within the dimer was found to be ∼6 Å, which is in good agreement with crystallographic data. The EPR-spectroscopic characterization reveals no structural changes upon addition of a Diels-Alder product, supporting the concept of a preorganized catalytic pocket in the Diels-Alder ribozyme and the structural role of these ions. PMID:19404418

  9. Can the Site-Frequency Spectrum Distinguish Exponential Population Growth from Multiple-Merger Coalescents?

    PubMed Central

    Eldon, Bjarki; Birkner, Matthias; Blath, Jochen; Freund, Fabian

    2015-01-01

    The ability of the site-frequency spectrum (SFS) to reflect the particularities of gene genealogies exhibiting multiple mergers of ancestral lines as opposed to those obtained in the presence of population growth is our focus. An excess of singletons is a well-known characteristic of both population growth and multiple mergers. Other aspects of the SFS, in particular, the weight of the right tail, are, however, affected in specific ways by the two model classes. Using an approximate likelihood method and minimum-distance statistics, our estimates of statistical power indicate that exponential and algebraic growth can indeed be distinguished from multiple-merger coalescents, even for moderate sample sizes, if the number of segregating sites is high enough. A normalized version of the SFS (nSFS) is also used as a summary statistic in an approximate Bayesian computation (ABC) approach. The results give further positive evidence as to the general eligibility of the SFS to distinguish between the different histories. PMID:25575536

  10. Multiple, Ligand-Dependent Routes from the Active Site of Cytochrome P450 2C9

    SciTech Connect

    Cojocaru, Vlad; Winn, Peter J.; Wade, Rebecca C.

    2012-02-13

    The active site of liver-specific, drug-metabolizing cytochrome P450 (CYP) monooxygenases is deeply buried in the protein and is connected to the protein surface through multiple tunnels, many of which were found open in different CYP crystal structures. It has been shown that different tunnels could serve as ligand passage routes in different CYPs. However, it is not understood whether one CYP uses multiple routes for substrate access and product release and whether these routes depend on ligand properties. From 300 ns of molecular dynamics simulations of CYP2C9, the second most abundant CYP in the human liver we found four main ligand exit routes, the occurrence of each depending on the ligand type and the conformation of the F-G loop, which is likely to be affected by the CYP-membrane interaction. A non-helical F-G loop favored exit towards the putative membrane-embedded region. Important protein features that direct ligand exit include aromatic residues that divide the active site and whose motions control access to two pathways. The ligands interacted with positively charged residues on the protein surface through hydrogen bonds that appear to select for acidic substrates. The observation of multiple, ligand-dependent routes in a CYP aids understanding of how CYP mutations affect drug metabolism and provides new possibilities for CYP inhibition.

  11. Multiple sites of methylation in the methyl accepting chemotaxis proteins of Escherichia coli

    SciTech Connect

    Chelsky, D.; Dahlquist, F.W.

    1981-01-01

    The methyl-accepting chemotaxis proteins (MCP) of E coli show at least five bands when subjected to SDS-gel electrophoresis. The intensity of the individual bands varies depending on the environment of the cells before solubilization. The faster migrating bands are enhanced following attractant stimulation, whereas the slower migrating bands are enhanced following attractant dilution or repellent increase. The time scale of these intensity changes is similar to that for adaptation of the behavioral response in these cells suggesting that methylation of the MCP is involved in producing these bands. Peptide mapping experiments show three methylated peptides in both MCP I and MCP II. These results suggest multiple sites of methylation, which are responsible, at least in part, for the observed multiple bands of the MCPs.

  12. Simultaneous observation of VHF radio wave transmission anomaly propagated beyond line of site prior to earthquakes in multiple sites

    NASA Astrophysics Data System (ADS)

    Yamashita, H.; Mogi, T.; Moriya, T.; Takada, M.; Morisada, M.

    2010-12-01

    The VHF radio wave transmission anomalies propagated beyond line of site prior to earthquakes (M>4), (hereafter termed EQ-echo) have been observed more than 20 times from 2004 at the Erimo observatory (ERM) in Hokkaido, Northern Japan. A statistical relationship between magnitude of preceding earthquake and total duration time of the EQ-echo has been proposed (Moriya et al.2009). To confirm a region where the EQ-echo simultaneously observed for each earthquake, we installed another 3 observatory with approximately 5 km spacing in the surroundings of ERM. The EQ-echoes have been observed simultaneously at two observatories prior to four earthquakes since 2008. The initial time and duration of each EQ echo were same time in several cases but different at some minutes each other in other cases. The wave forms of the EQ-echoes were similar in both records. In the Fuyushima observatory (FYS, 10km away from ERM) , three-way antennas were installed at every 120 degree to detect an arrival direction of EQ-echoes. Simultaneous observations of EQ-echoes at ERM and FYS for the preceding EQ (M=4.7) that occurred in the Hidaka mountains revealed that this EQ-echo came from direction of the epicenter based on the FYS observation and this direction was consistent with that of EQ-echo observed simultaneously in ERM. Although some of simultaneous observed EQ-echoes were observed in same time completely at both observatories, but some of them were with time rag of duration of each EQ-echo between multiple observed sites. We discussed what these time rags mean by considering possibilities of moving of scattering objects, generation of a radio duct, and so on, as in response to this fact.

  13. Zinc-induced oligomerization of zinc α2 glycoprotein reveals multiple fatty acid-binding sites.

    PubMed

    Zahid, Henna; Miah, Layeque; Lau, Andy M; Brochard, Lea; Hati, Debolina; Bui, Tam T T; Drake, Alex F; Gor, Jayesh; Perkins, Stephen J; McDermott, Lindsay C

    2016-01-01

    Zinc α2 glycoprotein (ZAG) is an adipokine with a class I MHC protein fold and is associated with obesity and diabetes. Although its intrinsic ligand remains unknown, ZAG binds the dansylated C11 fatty acid 11-(dansylamino)undecanoic acid (DAUDA) in the groove between the α1 and α2 domains. The surface of ZAG has approximately 15 weak zinc-binding sites deemed responsible for precipitation from human plasma. In the present study the functional significance of these metal sites was investigated. Analytical ultracentrifugation (AUC) and CD showed that zinc, but not other divalent metals, causes ZAG to oligomerize in solution. Thus ZAG dimers and trimers were observed in the presence of 1 and 2 mM zinc. Molecular modelling of X-ray scattering curves and sedimentation coefficients indicated a progressive stacking of ZAG monomers, suggesting that the ZAG groove may be occluded in these. Using fluorescence-detected sedimentation velocity, these ZAG-zinc oligomers were again observed in the presence of the fluorescent boron dipyrromethene fatty acid C16-BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-hexadecanoic acid). Fluorescence spectroscopy confirmed that ZAG binds C16-BODIPY. ZAG binding to C16-BODIPY, but not to DAUDA, was reduced by increased zinc concentrations. We conclude that the lipid-binding groove in ZAG contains at least two distinct fatty acid-binding sites for DAUDA and C16-BODIPY, similar to the multiple lipid binding seen in the structurally related immune protein CD1c. In addition, because high concentrations of zinc occur in the pancreas, the perturbation of these multiple lipid-binding sites by zinc may be significant in Type 2 diabetes where dysregulation of ZAG and zinc homoeostasis occurs.

  14. Seeing the forest through the trees: Considering roost-site selection at multiple spatial scales

    USGS Publications Warehouse

    Jachowski, David S.; Rota, Christopher T.; Dobony, Christopher A.; Ford, W. Mark; Edwards, John W.

    2016-01-01

    Conservation of bat species is one of the most daunting wildlife conservation challenges in North America, requiring detailed knowledge about their ecology to guide conservation efforts. Outside of the hibernating season, bats in temperate forest environments spend their diurnal time in day-roosts. In addition to simple shelter, summer roost availability is as critical as maternity sites and maintaining social group contact. To date, a major focus of bat conservation has concentrated on conserving individual roost sites, with comparatively less focus on the role that broader habitat conditions contribute towards roost-site selection. We evaluated roost-site selection by a northern population of federally-endangered Indiana bats (Myotis sodalis) at Fort Drum Military Installation in New York, USA at three different spatial scales: landscape, forest stand, and individual tree level. During 2007–2011, we radiotracked 33 Indiana bats (10 males, 23 females) and located 348 roosting events in 116 unique roost trees. At the landscape scale, bat roost-site selection was positively associated with northern mixed forest, increased slope, and greater distance from human development. At the stand scale, we observed subtle differences in roost site selection based on sex and season, but roost selection was generally positively associated with larger stands with a higher basal area, larger tree diameter, and a greater sugar maple (Acer saccharum) component. We observed no distinct trends of roosts being near high-quality foraging areas of water and forest edges. At the tree scale, roosts were typically in American elm (Ulmus americana) or sugar maple of large diameter (>30 cm) of moderate decay with loose bark. Collectively, our results highlight the importance of considering day roost needs simultaneously across multiple spatial scales. Size and decay class of individual roosts are key ecological attributes for the Indiana bat, however, larger-scale stand structural

  15. Site-specific updating and aggregation of Bayesian belief network models for multiple experts.

    PubMed

    Stiber, Neil A; Small, Mitchell J; Pantazidou, Marina

    2004-12-01

    A method for combining multiple expert opinions that are encoded in a Bayesian Belief Network (BBN) model is presented and applied to a problem involving the cleanup of hazardous chemicals at a site with contaminated groundwater. The method uses Bayes Rule to update each expert model with the observed evidence, then uses it again to compute posterior probability weights for each model. The weights reflect the consistency of each model with the observed evidence, allowing the aggregate model to be tailored to the particular conditions observed in the site-specific application of the risk model. The Bayesian update is easy to implement, since the likelihood for the set of evidence (observations for selected nodes of the BBN model) is readily computed by sequential execution of the BBN model. The method is demonstrated using a simple pedagogical example and subsequently applied to a groundwater contamination problem using an expert-knowledge BBN model. The BBN model in this application predicts the probability that reductive dechlorination of the contaminant trichlorethene (TCE) is occurring at a site--a critical step in the demonstration of the feasibility of monitored natural attenuation for site cleanup--given information on 14 measurable antecedent and descendant conditions. The predictions for the BBN models for 21 experts are weighted and aggregated using examples of hypothetical and actual site data. The method allows more weight for those expert models that are more reflective of the site conditions, and is shown to yield an aggregate prediction that differs from that of simple model averaging in a potentially significant manner.

  16. Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting

    PubMed Central

    Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

    2016-01-01

    Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency. PMID:27432161

  17. Multiple binding sites in the nicotinic acetylcholine receptors: An opportunity for polypharmacolgy.

    PubMed

    Iturriaga-Vásquez, Patricio; Alzate-Morales, Jans; Bermudez, Isabel; Varas, Rodrigo; Reyes-Parada, Miguel

    2015-11-01

    For decades, the development of selective compounds has been the main goal for chemists and biologists involved in drug discovery. However, diverse lines of evidence indicate that polypharmacological agents, i.e. those that act simultaneously at various protein targets, might show better profiles than selective ligands, regarding both efficacy and side effects. On the other hand, the availability of the crystal structure of different receptors allows a detailed analysis of the main interactions between drugs and receptors in a specific binding site. Neuronal nicotinic acetylcholine receptors (nAChRs) constitute a large and diverse family of ligand-gated ion channels (LGICs) that, as a product of its modulation, regulate neurotransmitter release, which in turns produce a global neuromodulation of the central nervous system. nAChRs are pentameric protein complexes in such a way that expression of compatible subunits can lead to various receptor assemblies or subtypes. The agonist binding site, located at the extracellular region, exhibits different properties depending on the subunits that conform the receptor. In the last years, it has been recognized that nAChRs could also contain one or more allosteric sites which could bind non-classical nicotinic ligands including several therapeutically useful drugs. The presence of multiple binding sites in nAChRs offers an interesting possibility for the development of novel polypharmacological agents with a wide spectrum of actions. PMID:26318763

  18. RF1 knockout allows ribosomal incorporation of unnatural amino acids at multiple sites.

    PubMed

    Johnson, David B F; Xu, Jianfeng; Shen, Zhouxin; Takimoto, Jeffrey K; Schultz, Matthew D; Schmitz, Robert J; Xiang, Zheng; Ecker, Joseph R; Briggs, Steven P; Wang, Lei

    2011-11-01

    Stop codons have been exploited for genetic incorporation of unnatural amino acids (Uaas) in live cells, but their low incorporation efficiency, which is possibly due to competition from release factors, limits the power and scope of this technology. Here we show that the reportedly essential release factor 1 (RF1) can be knocked out from Escherichia coli by 'fixing' release factor 2 (RF2). The resultant strain JX33 is stable and independent, and it allows UAG to be reassigned from a stop signal to an amino acid when a UAG-decoding tRNA-synthetase pair is introduced. Uaas were efficiently incorporated at multiple UAG sites in the same gene without translational termination in JX33. We also found that amino acid incorporation at endogenous UAG codons is dependent on RF1 and mRNA context, which explains why E. coli tolerates apparent global suppression of UAG. JX33 affords a unique autonomous host for synthesizing and evolving new protein functions by enabling Uaa incorporation at multiple sites. PMID:21926996

  19. Somitogenesis clock-wave initiation requires differential decay and multiple binding sites for clock protein.

    PubMed

    Campanelli, Mark; Gedeon, Tomás

    2010-04-01

    Somitogenesis is a process common to all vertebrate embryos in which repeated blocks of cells arise from the presomitic mesoderm (PSM) to lay a foundational pattern for trunk and tail development. Somites form in the wake of passing waves of periodic gene expression that originate in the tailbud and sweep posteriorly across the PSM. Previous work has suggested that the waves result from a spatiotemporally graded control protein that affects the oscillation rate of clock-gene expression. With a minimally constructed mathematical model, we study the contribution of two control mechanisms to the initial formation of this gene-expression wave. We test four biologically motivated model scenarios with either one or two clock protein transcription binding sites, and with or without differential decay rates for clock protein monomers and dimers. We examine the sensitivity of wave formation with respect to multiple model parameters and robustness to heterogeneity in cell population. We find that only a model with both multiple binding sites and differential decay rates is able to reproduce experimentally observed waveforms. Our results show that the experimentally observed characteristics of somitogenesis wave initiation constrain the underlying genetic control mechanisms.

  20. Amyloid tracers detect multiple binding sites in Alzheimer's disease brain tissue.

    PubMed

    Ni, Ruiqing; Gillberg, Per-Göran; Bergfors, Assar; Marutle, Amelia; Nordberg, Agneta

    2013-07-01

    -1 (Ki: 0.2 nM, 70 nM), florbetapir (1.8 nM, 53 nM) and florbetaben (1.0 nM, 65 nM). BF-227 displaced 83% of (3)H-Pittsburgh compound B binding, mainly at a low-affinity site (311 nM), whereas FDDNP only partly displaced (40%). We propose a multiple binding site model for the amyloid tracers (binding sites 1, 2 and 3), where AV-45 (florbetapir), AV-1 (florbetaben), and Pittsburgh compound B, all show nanomolar affinity for the high-affinity site (binding site 1), as visualized by positron emission tomography. BF-227 shows mainly binding to site 3 and FDDNP shows only some binding to site 2. Different amyloid tracers may provide new insight into the pathophysiological mechanisms in the progression of Alzheimer's disease.

  1. Uncertainty analysis of the Operational Simplified Surface Energy Balance (SSEBop) model at multiple flux tower sites

    NASA Astrophysics Data System (ADS)

    Chen, Mingshi; Senay, Gabriel B.; Singh, Ramesh K.; Verdin, James P.

    2016-05-01

    Evapotranspiration (ET) is an important component of the water cycle - ET from the land surface returns approximately 60% of the global precipitation back to the atmosphere. ET also plays an important role in energy transport among the biosphere, atmosphere, and hydrosphere. Current regional to global and daily to annual ET estimation relies mainly on surface energy balance (SEB) ET models or statistical and empirical methods driven by remote sensing data and various climatological databases. These models have uncertainties due to inevitable input errors, poorly defined parameters, and inadequate model structures. The eddy covariance measurements on water, energy, and carbon fluxes at the AmeriFlux tower sites provide an opportunity to assess the ET modeling uncertainties. In this study, we focused on uncertainty analysis of the Operational Simplified Surface Energy Balance (SSEBop) model for ET estimation at multiple AmeriFlux tower sites with diverse land cover characteristics and climatic conditions. The 8-day composite 1-km MODerate resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) was used as input land surface temperature for the SSEBop algorithms. The other input data were taken from the AmeriFlux database. Results of statistical analysis indicated that the SSEBop model performed well in estimating ET with an R2 of 0.86 between estimated ET and eddy covariance measurements at 42 AmeriFlux tower sites during 2001-2007. It was encouraging to see that the best performance was observed for croplands, where R2 was 0.92 with a root mean square error of 13 mm/month. The uncertainties or random errors from input variables and parameters of the SSEBop model led to monthly ET estimates with relative errors less than 20% across multiple flux tower sites distributed across different biomes. This uncertainty of the SSEBop model lies within the error range of other SEB models, suggesting systematic error or bias of the SSEBop model is within the

  2. Uncertainty analysis of the Operational Simplified Surface Energy Balance (SSEBop) model at multiple flux tower sites

    USGS Publications Warehouse

    Chen, Mingshi; Senay, Gabriel B.; Singh, Ramesh K.; Verdin, James P.

    2016-01-01

    Evapotranspiration (ET) is an important component of the water cycle – ET from the land surface returns approximately 60% of the global precipitation back to the atmosphere. ET also plays an important role in energy transport among the biosphere, atmosphere, and hydrosphere. Current regional to global and daily to annual ET estimation relies mainly on surface energy balance (SEB) ET models or statistical and empirical methods driven by remote sensing data and various climatological databases. These models have uncertainties due to inevitable input errors, poorly defined parameters, and inadequate model structures. The eddy covariance measurements on water, energy, and carbon fluxes at the AmeriFlux tower sites provide an opportunity to assess the ET modeling uncertainties. In this study, we focused on uncertainty analysis of the Operational Simplified Surface Energy Balance (SSEBop) model for ET estimation at multiple AmeriFlux tower sites with diverse land cover characteristics and climatic conditions. The 8-day composite 1-km MODerate resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) was used as input land surface temperature for the SSEBop algorithms. The other input data were taken from the AmeriFlux database. Results of statistical analysis indicated that the SSEBop model performed well in estimating ET with an R2 of 0.86 between estimated ET and eddy covariance measurements at 42 AmeriFlux tower sites during 2001–2007. It was encouraging to see that the best performance was observed for croplands, where R2 was 0.92 with a root mean square error of 13 mm/month. The uncertainties or random errors from input variables and parameters of the SSEBop model led to monthly ET estimates with relative errors less than 20% across multiple flux tower sites distributed across different biomes. This uncertainty of the SSEBop model lies within the error range of other SEB models, suggesting systematic error or bias of the SSEBop model is within

  3. Seeing the Forest through the Trees: Considering Roost-Site Selection at Multiple Spatial Scales.

    PubMed

    Jachowski, David S; Rota, Christopher T; Dobony, Christopher A; Ford, W Mark; Edwards, John W

    2016-01-01

    Conservation of bat species is one of the most daunting wildlife conservation challenges in North America, requiring detailed knowledge about their ecology to guide conservation efforts. Outside of the hibernating season, bats in temperate forest environments spend their diurnal time in day-roosts. In addition to simple shelter, summer roost availability is as critical as maternity sites and maintaining social group contact. To date, a major focus of bat conservation has concentrated on conserving individual roost sites, with comparatively less focus on the role that broader habitat conditions contribute towards roost-site selection. We evaluated roost-site selection by a northern population of federally-endangered Indiana bats (Myotis sodalis) at Fort Drum Military Installation in New York, USA at three different spatial scales: landscape, forest stand, and individual tree level. During 2007-2011, we radiotracked 33 Indiana bats (10 males, 23 females) and located 348 roosting events in 116 unique roost trees. At the landscape scale, bat roost-site selection was positively associated with northern mixed forest, increased slope, and greater distance from human development. At the stand scale, we observed subtle differences in roost site selection based on sex and season, but roost selection was generally positively associated with larger stands with a higher basal area, larger tree diameter, and a greater sugar maple (Acer saccharum) component. We observed no distinct trends of roosts being near high-quality foraging areas of water and forest edges. At the tree scale, roosts were typically in American elm (Ulmus americana) or sugar maple of large diameter (>30 cm) of moderate decay with loose bark. Collectively, our results highlight the importance of considering day roost needs simultaneously across multiple spatial scales. Size and decay class of individual roosts are key ecological attributes for the Indiana bat, however, larger-scale stand structural components

  4. Seeing the Forest through the Trees: Considering Roost-Site Selection at Multiple Spatial Scales

    PubMed Central

    Jachowski, David S.; Rota, Christopher T.; Dobony, Christopher A.; Ford, W. Mark; Edwards, John W.

    2016-01-01

    Conservation of bat species is one of the most daunting wildlife conservation challenges in North America, requiring detailed knowledge about their ecology to guide conservation efforts. Outside of the hibernating season, bats in temperate forest environments spend their diurnal time in day-roosts. In addition to simple shelter, summer roost availability is as critical as maternity sites and maintaining social group contact. To date, a major focus of bat conservation has concentrated on conserving individual roost sites, with comparatively less focus on the role that broader habitat conditions contribute towards roost-site selection. We evaluated roost-site selection by a northern population of federally-endangered Indiana bats (Myotis sodalis) at Fort Drum Military Installation in New York, USA at three different spatial scales: landscape, forest stand, and individual tree level. During 2007–2011, we radiotracked 33 Indiana bats (10 males, 23 females) and located 348 roosting events in 116 unique roost trees. At the landscape scale, bat roost-site selection was positively associated with northern mixed forest, increased slope, and greater distance from human development. At the stand scale, we observed subtle differences in roost site selection based on sex and season, but roost selection was generally positively associated with larger stands with a higher basal area, larger tree diameter, and a greater sugar maple (Acer saccharum) component. We observed no distinct trends of roosts being near high-quality foraging areas of water and forest edges. At the tree scale, roosts were typically in American elm (Ulmus americana) or sugar maple of large diameter (>30 cm) of moderate decay with loose bark. Collectively, our results highlight the importance of considering day roost needs simultaneously across multiple spatial scales. Size and decay class of individual roosts are key ecological attributes for the Indiana bat, however, larger-scale stand structural

  5. An efficient method for multiple site-directed mutagenesis using type IIs restriction enzymes.

    PubMed

    Zhang, Zhiqiang; Xu, Kun; Xin, Ying; Zhang, Zhiying

    2015-05-01

    Site-directed mutagenesis (SDM) methods are very important in modern molecular biology, biochemistry, and protein engineering. Here, we present a novel SDM method that can be used for multiple mutation generation using type IIs restriction enzymes. This approach is faster and more convenient than the overlap polymerase chain reaction (PCR) method due to its having fewer reaction steps and being cheaper than, but as convenient as, enzymatic assembly. We illustrate the usefulness of our method by introducing three mutations into the bacterial Streptococcus thermophilus Cas9 (bStCas9) gene, converting the humanized S. thermophilus Cas9 (hStCas9) gene into nuclease dead or H847A nickase mutants and generating sunnyTALEN mutagenesis from a wild-type TALEN backbone.

  6. Necrotising sialometaplasia at multiple sites: a therapeutic challenge to oral physicians.

    PubMed

    Bijai Kumar, Laliytha; Muthukrishnan, Arvind; Gopalakrishnan, Shanmughapriya

    2016-01-01

    Necrotising sialometaplasia is a rare, benign and self-limiting inflammatory lesion that commonly involves minor salivary glands. Its clinical appearance, signs and symptoms very often mimic a carcinomatous lesion, thus creating a diagnostic dilemma for the clinician. Necrotising sialometaplasia being an important differential for an apparent carcinoma should be excluded histologically prior to radical therapy. It commonly occurs on the palatal mucosa following a palatal infiltration anaesthesia. The patient reports to the dentist with a sudden onset of painful ulcerations that rapidly increase in size. This case report describes the occurrence of necrotising sialometaplasia in a 46-year-old man with an unusual clinical presentation at multiple sites in the oral cavity. The importance of history taking, thorough clinical examination and careful histopathological examination in diagnosing necrotising sialometaplasia is highlighted in this paper. PMID:27581235

  7. Multiple sites of adaptation lead to contrast encoding in the Drosophila olfactory system.

    PubMed

    Cafaro, Jon

    2016-04-01

    Animals often encounter large increases in odor intensity that can persist for many seconds. These increases in the background odor are often accompanied by increases in the variance of the odor stimulus. Previous studies have shown that a persistent odor stimulus (odor background) results in a decrease in the response to brief odor pulses in the olfactory receptor neurons (ORNs). However, the contribution of adapting mechanisms beyond theORNs is not clear. Thus, it is unclear how adaptive mechanisms are distributed within the olfactory circuit and what impact downstream adaptation may have on the encoding of odor stimuli. In this study, adaptation to the same odor stimulus is examined at multiple levels in the well studied and accessibleDrosophilaolfactory system. The responses of theORNs are compared to the responses of the second order, projection neurons (PNs), directly connected to them. Adaptation inPNspike rate was found to be much greater than adaptation in theORNspike rate. This greater adaptation allowsPNs to encode odor contrast (ratio of pulse intensity to background intensity) with little ambiguity. Moreover, distinct neural mechanisms contribute to different aspects of adaptation; adaptation to the background odor is dominated by adaptation in spike generation in bothORNs andPNs, while adaptation to the odor pulse is dominated by changes within olfactory transduction and the glomerulus. These observations suggest that the olfactory system adapts at multiple sites to better match its response gain to stimulus statistics. PMID:27053295

  8. Multiple sites of adaptation lead to contrast encoding in the Drosophila olfactory system.

    PubMed

    Cafaro, Jon

    2016-04-01

    Animals often encounter large increases in odor intensity that can persist for many seconds. These increases in the background odor are often accompanied by increases in the variance of the odor stimulus. Previous studies have shown that a persistent odor stimulus (odor background) results in a decrease in the response to brief odor pulses in the olfactory receptor neurons (ORNs). However, the contribution of adapting mechanisms beyond theORNs is not clear. Thus, it is unclear how adaptive mechanisms are distributed within the olfactory circuit and what impact downstream adaptation may have on the encoding of odor stimuli. In this study, adaptation to the same odor stimulus is examined at multiple levels in the well studied and accessibleDrosophilaolfactory system. The responses of theORNs are compared to the responses of the second order, projection neurons (PNs), directly connected to them. Adaptation inPNspike rate was found to be much greater than adaptation in theORNspike rate. This greater adaptation allowsPNs to encode odor contrast (ratio of pulse intensity to background intensity) with little ambiguity. Moreover, distinct neural mechanisms contribute to different aspects of adaptation; adaptation to the background odor is dominated by adaptation in spike generation in bothORNs andPNs, while adaptation to the odor pulse is dominated by changes within olfactory transduction and the glomerulus. These observations suggest that the olfactory system adapts at multiple sites to better match its response gain to stimulus statistics.

  9. Remote observing with the Keck Telescopes from multiple sites in California

    NASA Astrophysics Data System (ADS)

    Kibrick, Robert I.; Hayes, Brian; Allen, Steven L.; Conrad, Albert

    2002-11-01

    Remote observing is now the dominant mode of operation for both Keck telescopesand their associated instruments. Over 90% of all Keck observations arecarried out remotely from the Keck Headquarters in Waimea, Hawaii. The majority of Keck observers, however, are affiliated with research institutions located on the U.S. mainland, primarily in California. To observe with the Keck telescopes, most of these astronomers currently travel several thousand kilometers in order to sit in a Keck remote control room located tens of kilometers from the telescopes. Given recent improvements in network infrastructure and facilities, many of these observations can now be conducted directly from California. This report describes the operation of a Keck telescope remote observing facility located at the UCO/Lick Observatory headquarters on the Santa Cruz campus of the University of California (UCSC). This facility currently enables remote operation and engineering of Keck optical instruments via Internet-2. The facility was initially located in temporaryquarters and became operational on a trial basis in September 2001. In June 2002, the facility moved to permanent quarters and became fully operational in July 2002. We examine in detail isssues of Internet network bandwidth and reliability, and describe the design, routing implementation, and operation of an automated fall-back network utilizing dialed ISDN telephone circuits and routers. This report also briefly describes the status of efforts to establish Keck remote observing facilities at other California sites, and how the fall-back network design could be expanded to support multiple sites.

  10. Multiple well-shutdown tests and site-scale flow simulation in fractured rocks.

    PubMed

    Tiedeman, Claire R; Lacombe, Pierre J; Goode, Daniel J

    2010-01-01

    A new method was developed for conducting aquifer tests in fractured-rock flow systems that have a pump-and-treat (P&T) operation for containing and removing groundwater contaminants. The method involves temporary shutdown of individual pumps in wells of the P&T system. Conducting aquifer tests in this manner has several advantages, including (1) no additional contaminated water is withdrawn, and (2) hydraulic containment of contaminants remains largely intact because pumping continues at most wells. The well-shutdown test method was applied at the former Naval Air Warfare Center (NAWC), West Trenton, New Jersey, where a P&T operation is designed to contain and remove trichloroethene and its daughter products in the dipping fractured sedimentary rocks underlying the site. The detailed site-scale subsurface geologic stratigraphy, a three-dimensional MODFLOW model, and inverse methods in UCODE_2005 were used to analyze the shutdown tests. In the model, a deterministic method was used for representing the highly heterogeneous hydraulic conductivity distribution and simulations were conducted using an equivalent porous media method. This approach was very successful for simulating the shutdown tests, contrary to a common perception that flow in fractured rocks must be simulated using a stochastic or discrete fracture representation of heterogeneity. Use of inverse methods to simultaneously calibrate the model to the multiple shutdown tests was integral to the effectiveness of the approach.

  11. Multiple-methods investigation of recharge at a humid-region fractured rock site, Pennsylvania, USA

    USGS Publications Warehouse

    Heppner, C.S.; Nimmo, J.R.; Folmar, G.J.; Gburek, W.J.; Risser, D.W.

    2007-01-01

    Lysimeter-percolate and well-hydrograph analyses were combined to evaluate recharge for the Masser Recharge Site (central Pennsylvania, USA). In humid regions, aquifer recharge through an unconfined low-porosity fractured-rock aquifer can cause large magnitude water-table fluctuations over short time scales. The unsaturated hydraulic characteristics of the subsurface porous media control the magnitude and timing of these fluctuations. Data from multiple sets of lysimeters at the site show a highly seasonal pattern of percolate and exhibit variability due to both installation factors and hydraulic property heterogeneity. Individual event analysis of well hydrograph data reveals the primary influences on water-table response, namely rainfall depth, rainfall intensity, and initial water-table depth. Spatial and seasonal variability in well response is also evident. A new approach for calculating recharge from continuous water-table elevation records using a master recession curve (MRC) is demonstrated. The recharge estimated by the MRC approach when assuming a constant specific yield is seasonal to a lesser degree than the recharge estimate resulting from the lysimeter analysis. Partial reconciliation of the two recharge estimates is achieved by considering a conceptual model of flow processes in the highly-heterogeneous underlying fractured porous medium. ?? Springer-Verlag 2007.

  12. A rigorous multiple independent binding site model for determining cell-based equilibrium dissociation constants.

    PubMed

    Drake, Andrew W; Klakamp, Scott L

    2007-01-10

    A new 4-parameter nonlinear equation based on the standard multiple independent binding site model (MIBS) is presented for fitting cell-based ligand titration data in order to calculate the ligand/cell receptor equilibrium dissociation constant and the number of receptors/cell. The most commonly used linear (Scatchard Plot) or nonlinear 2-parameter model (a single binding site model found in commercial programs like Prism(R)) used for analysis of ligand/receptor binding data assumes only the K(D) influences the shape of the titration curve. We demonstrate using simulated data sets that, depending upon the cell surface receptor expression level, the number of cells titrated, and the magnitude of the K(D) being measured, this assumption of always being under K(D)-controlled conditions can be erroneous and can lead to unreliable estimates for the binding parameters. We also compare and contrast the fitting of simulated data sets to the commonly used cell-based binding equation versus our more rigorous 4-parameter nonlinear MIBS model. It is shown through these simulations that the new 4-parameter MIBS model, when used for cell-based titrations under optimal conditions, yields highly accurate estimates of all binding parameters and hence should be the preferred model to fit cell-based experimental nonlinear titration data. PMID:17141800

  13. Fine-needle aspiration cytology of hematopoietic lesions from multiple sites.

    PubMed

    Silverman, J F; McLeod, D L; Park, H K

    1990-01-01

    We reviewed 130 fine-needle aspiration (FNA) biopsies from 118 patients with a variety of benign and malignant hematopoietic lesions. There were 74 (57%) malignant, 45 (35%) benign, and 11 (8%) atypical diagnoses. Immunocytochemistry of the aspirated material was performed in 47 (36%) and electron microscopy in 4 (3%) of the cases. FNA cytology was utilized to make a primary hematopoietic malignant diagnosis in approximately half of the cases and to confirm recurrence in the remainder. The malignant cases included non-Hodgkin's lymphoma. Hodgkin's disease, medullary and extramedullary plasmacytoma, and granulocytic sarcoma. Forty-two malignant cases had either previous or follow-up surgical biopsy with no false-positive diagnoses. Of the 11 atypical cases, seven had surgical confirmation with five malignant and two benign diagnoses. The benign hematopoietic lesions correctly identified included acute and chronic lymphadenitis, granulomatous processes, and eosinophilic granuloma. Only 5 of the 45 benign FNA biopsies had surgical pathology follow-up, with no false-negative diagnoses. The most commonly aspirated sites were lymph nodes (71%), although hematopoietic lesions were correctly identified in a number of extranodal locations, including soft tissue (8%), abdominal viscera (6%), lungs (5%), mediastinum (2.5%), bone (3%), and thyroid, salivary gland, and breast (1.5% each). This study demonstrates the clinical utility and diagnostic accuracy of FNA cytology in the evaluation of benign and malignant hematopoietic disorders from multiple sites. Ancillary studies performed on the aspirated material aided in making a specific and accurate diagnosis.

  14. Forced Ambiguity of the Leucine Codons for Multiple-Site-Specific Incorporation of a Noncanonical Amino Acid

    PubMed Central

    Kwon, Inchan; Choi, Eun Sil

    2016-01-01

    Multiple-site-specific incorporation of a noncanonical amino acid into a recombinant protein would be a very useful technique to generate multiple chemical handles for bioconjugation and multivalent binding sites for the enhanced interaction. Previously combination of a mutant yeast phenylalanyl-tRNA synthetase variant and the yeast phenylalanyl-tRNA containing the AAA anticodon was used to incorporate a noncanonical amino acid into multiple UUU phenylalanine (Phe) codons in a site-specific manner. However, due to the less selective codon recognition of the AAA anticodon, there was significant misincorporation of a noncanonical amino acid into unwanted UUC Phe codons. To enhance codon selectivity, we explored degenerate leucine (Leu) codons instead of Phe degenerate codons. Combined use of the mutant yeast phenylalanyl-tRNA containing the CAA anticodon and the yPheRS_naph variant allowed incorporation of a phenylalanine analog, 2-naphthylalanine, into murine dihydrofolate reductase in response to multiple UUG Leu codons, but not to other Leu codon sites. Despite the moderate UUG codon occupancy by 2-naphthylalaine, these results successfully demonstrated that the concept of forced ambiguity of the genetic code can be achieved for the Leu codons, available for multiple-site-specific incorporation. PMID:27028506

  15. Are sites with multiple single nucleotide variants in cancer genomes a consequence of drivers, hypermutable sites or sequencing errors?

    PubMed Central

    Carr, Antony M.

    2016-01-01

    Across independent cancer genomes it has been observed that some sites have been recurrently hit by single nucleotide variants (SNVs). Such recurrently hit sites might be either (i) drivers of cancer that are postively selected during oncogenesis, (ii) due to mutation rate variation, or (iii) due to sequencing and assembly errors. We have investigated the cause of recurrently hit sites in a dataset of >3 million SNVs from 507 complete cancer genome sequences. We find evidence that many sites have been hit significantly more often than one would expect by chance, even taking into account the effect of the adjacent nucleotides on the rate of mutation. We find that the density of these recurrently hit sites is higher in non-coding than coding DNA and hence conclude that most of them are unlikely to be drivers. We also find that most of them are found in parts of the genome that are not uniquely mappable and hence are likely to be due to mapping errors. In support of the error hypothesis, we find that recurently hit sites are not randomly distributed across sequences from different laboratories. We fit a model to the data in which the rate of mutation is constant across sites but the rate of error varies. This model suggests that ∼4% of all SNVs are errors in this dataset, but that the rate of error varies by thousands-of-fold between sites. PMID:27688957

  16. Are sites with multiple single nucleotide variants in cancer genomes a consequence of drivers, hypermutable sites or sequencing errors?

    PubMed Central

    Carr, Antony M.

    2016-01-01

    Across independent cancer genomes it has been observed that some sites have been recurrently hit by single nucleotide variants (SNVs). Such recurrently hit sites might be either (i) drivers of cancer that are postively selected during oncogenesis, (ii) due to mutation rate variation, or (iii) due to sequencing and assembly errors. We have investigated the cause of recurrently hit sites in a dataset of >3 million SNVs from 507 complete cancer genome sequences. We find evidence that many sites have been hit significantly more often than one would expect by chance, even taking into account the effect of the adjacent nucleotides on the rate of mutation. We find that the density of these recurrently hit sites is higher in non-coding than coding DNA and hence conclude that most of them are unlikely to be drivers. We also find that most of them are found in parts of the genome that are not uniquely mappable and hence are likely to be due to mapping errors. In support of the error hypothesis, we find that recurently hit sites are not randomly distributed across sequences from different laboratories. We fit a model to the data in which the rate of mutation is constant across sites but the rate of error varies. This model suggests that ∼4% of all SNVs are errors in this dataset, but that the rate of error varies by thousands-of-fold between sites.

  17. O-glucose trisaccharide is present at high but variable stoichiometry at multiple sites on mouse Notch1.

    PubMed

    Rana, Nadia A; Nita-Lazar, Aleksandra; Takeuchi, Hideyuki; Kakuda, Shinako; Luther, Kelvin B; Haltiwanger, Robert S

    2011-09-01

    Notch activity is regulated by both O-fucosylation and O-glucosylation, and Notch receptors contain multiple predicted sites for both. Here we examine the occupancy of the predicted O-glucose sites on mouse Notch1 (mN1) using the consensus sequence C(1)XSXPC(2). We show that all of the predicted sites are modified, although the efficiency of modifying O-glucose sites is site- and cell type-dependent. For instance, although most sites are modified at high stoichiometries, the site at EGF 27 is only partially glucosylated, and the occupancy of the site at EGF 4 varies with cell type. O-Glucose is also found at a novel, non-traditional consensus site at EGF 9. Based on this finding, we propose a revision of the consensus sequence for O-glucosylation to allow alanine N-terminal to cysteine 2: C(1)XSX(A/P)C(2). We also show through biochemical and mass spectral analyses that serine is the only hydroxyamino acid that is modified with O-glucose on EGF repeats. The O-glucose at all sites is efficiently elongated to the trisaccharide Xyl-Xyl-Glc. To establish the functional importance of individual O-glucose sites in mN1, we used a cell-based signaling assay. Elimination of most individual sites shows little or no effect on mN1 activation, suggesting that the major effects of O-glucose are mediated by modification of multiple sites. Interestingly, elimination of the site in EGF 28, found in the Abruptex region of Notch, does significantly reduce activity. These results demonstrate that, like O-fucose, the O-glucose modifications of EGF repeats occur extensively on mN1, and they play important roles in Notch function.

  18. Inclusion of multiple fragment types in the Site Identification by Ligand Competitive Saturation (SILCS) approach

    PubMed Central

    Raman, E. Prabhu; Yu, Wenbo; Lakkaraju, Sirish K.; MacKerell, Alexander D.

    2014-01-01

    The Site Identification by Ligand Competitive Saturation (SILCS) method identifies the location and approximate affinities of small molecular fragments on a target macromolecular surface by performing Molecular Dynamics (MD) simulations of the target in an aqueous solution of small molecules representative of different chemical functional groups. In this study, we introduce a set of small molecules to map potential interactions made by neutral hydrogen bond donors and acceptors, and charged donor and acceptor fragments in addition to nonpolar fragments. The affinity pattern is obtained in the form of discretized probability or, equivalently, free energy maps, called FragMaps, which can be visualized with the target surface. We performed SILCS simulations for four proteins for which structural and thermodynamic data is available for multiple, diverse ligands. Good overlap is shown between high affinity regions identified by the FragMaps and the crystallographic positions of ligand functional groups with similar chemical functionality, thus demonstrating the validity of the qualitative information obtained from the simulations. To test the ability of FragMaps in providing quantitative predictions, we calculate the previously introduced Ligand Grid Free Energy (LGFE) metric and observe its correspondence with experimentally measured binding affinity. LGFE is computed for different conformational ensembles and improvement in prediction is shown with increasing ligand conformational sampling. Ensemble generation includes a Monte Carlo sampling approach that uses the GFE FragMaps directly as the energy function. The results show some, but not all experimental trends are predicted, and warrant improvements in the scoring methodology. In addition, the potential utility of atom-based free energy contributions to the LGFE scores and the use of multiple ligands in SILCS to identify displaceable water molecules during ligand design are discussed. PMID:24245913

  19. The controlled relay of multiple protons required at the active site of nitrogenase.

    PubMed

    Dance, Ian

    2012-07-01

    The enzyme nitrogenase, when reducing natural and unnatural substrates, requires large numbers of protons per chemical catalytic cycle. The active face of the catalytic site (the FeMo-cofactor, FeMo-co) is situated in a protein domain which is largely hydrophobic and anhydrous, and incapable of serial provision of multiple protons. Through detailed analysis of the high quality protein crystal structures available the characteristics of a chain of water molecules leading from the protein surface to a key sulfur atom (S3B) of FeMo-co are described. The first half of the water chain from the surface inwards is branched, slightly variable, and able to accommodate exogenous small molecules: this is dubbed the proton bay. The second half, from the proton bay to S3B, is comprised of a single chain of eight hydrogen bonded water molecules. This section is strictly conserved, and is intimately involved in hydrogen bonds with homocitrate, an essential component that chelates Mo. This is the proton wire, and a detailed Grotthuss mechanism for serial translocation of protons through this proton wire to S3B is proposed. This controlled serial proton relay from the protein surface to S3B is an essential component of the intramolecular hydrogenation paradigm for the complete chemical mechanisms of nitrogenase. Each proton reaching S3B, instigated by electron transfer to FeMo-co, becomes a hydrogen atom that migrates to other components of the active face of FeMo-co and to bound substrates and intermediates, allowing subsequent multiple proton transfers along the proton wire. Experiments to test the proposed mechanism of proton supply are suggested. The water chain in nitrogenase is comparable with the purported proton pumping pathway of cytochrome c oxidase.

  20. Multiple cryptic splice sites can be activated by IDS point mutations generating misspliced transcripts.

    PubMed

    Lualdi, Susanna; Pittis, Maria G; Regis, Stefano; Parini, Rossella; Allegri, Anna E; Furlan, Francesca; Bembi, Bruno; Filocamo, Mirella

    2006-08-01

    Mutations in the gene encoding the enzyme iduronate-2-sulfatase (IDS) were reported as the cause of the X-linked recessive lysosomal disease, mucopolysaccharidosis II (MPS II). Amongst the different mutations, it emerges that nearly 10% are nucleotide substitutions causing splicing mutations. We now report the molecular characterisation of three MPS II patients with multiple aberrant transcripts due to three different point mutations. The c.418+1G>C that occurred in the invariant splice-site motif, produced only aberrantly spliced transcripts. Whilst the mutations affecting variant motifs (c.419G>T) or coding regions (c.245C>T) led to aberrantly spliced transcripts in addition to correctly spliced transcripts with the respective predicted missense mutation, p.G140V or p.A82V. A combination of experimental tests and computational approaches were used to understand the molecular basis underlying the altered transcription patterns. In addition, by using real-time reverse transcriptase polymerase chain reaction, the reduction of mRNA amount in two patients observed was likely due to nonsense-mediated mRNA decay pathway. Overall, our results further emphasised the importance of cloning and sequencing independent transcripts to reveal less abundant, aberrant products, which often could not be detected by direct sequencing. Moreover, the different splicing patterns observed in the three patients as a consequence of point mutations show how sensitive the balance is between constitutive and cryptic splice sites in the IDS gene. The generation of such diverse transcripts, together with their level of expression, could contribute to the profound phenotypic variability reported in MPS II.

  1. Import pathways of precursor proteins into mitochondria: multiple receptor sites are followed by a common membrane insertion site

    PubMed Central

    1988-01-01

    The precursor of porin, a mitochondrial outer membrane protein, competes for the import of precursors destined for the three other mitochondrial compartments, including the Fe/S protein of the bc1- complex (intermembrane space), the ADP/ATP carrier (inner membrane), subunit 9 of the F0-ATPase (inner membrane), and subunit beta of the F1- ATPase (matrix). Competition occurs at the level of a common site at which precursors are inserted into the outer membrane. Protease- sensitive binding sites, which act before the common insertion site, appear to be responsible for the specificity and selectivity of mitochondrial protein uptake. We suggest that distinct receptor proteins on the mitochondrial surface specifically recognize precursor proteins and transfer them to a general insertion protein component (GIP) in the outer membrane. Beyond GIP, the import pathways diverge, either to the outer membrane or to translocation contact-sites, and then subsequently to the other mitochondrial compartments. PMID:2974457

  2. Multiple-Site Hemodynamic Analysis of Doppler Ultrasound with an Adaptive Color Relation Classifier for Arteriovenous Access Occlusion Evaluation

    PubMed Central

    Wu, Jian-Xing; Du, Yi-Chun; Wu, Ming-Jui; Li, Chien-Ming; Lin, Chia-Hung; Chen, Tainsong

    2014-01-01

    This study proposes multiple-site hemodynamic analysis of Doppler ultrasound with an adaptive color relation classifier for arteriovenous access occlusion evaluation in routine examinations. The hemodynamic analysis is used to express the properties of blood flow through a vital access or a tube, using dimensionless numbers. An acoustic measurement is carried out to detect the peak-systolic and peak-diastolic velocities of blood flow from the arterial anastomosis sites (A) to the venous anastomosis sites (V). The ratio of the supracritical Reynolds (Resupra) number and the resistive (Res) index quantitates the degrees of stenosis (DOS) at multiple measurement sites. Then, an adaptive color relation classifier is designed as a nonlinear estimate model to survey the occlusion level in monthly examinations. For 30 long-term follow-up patients, the experimental results show the proposed screening model efficiently evaluates access occlusion. PMID:24892039

  3. Fatigue analysis of multiple site damage at a row of holes in a wide panel

    NASA Technical Reports Server (NTRS)

    Buhler, Kimberley; Grandt, Alten F., Jr.; Moukawsher, E. J.

    1994-01-01

    This paper is concerned with predicting the fatigue life of unstiffened panels which contain multiple site damage (MSD). The initial damage consists of through-the-thickness cracks emanating from a row of holes in the center of a finite width panel. A fracture mechanics analysis has been developed to predict the growth, interaction, and coalescence of the various cracks which propagate in the panel. A strain-life analysis incorporating Neuber's rule for notches, and Miner's rule for cumulative damage, is also employed to predict crack initiation for holes without initial cracking. This analysis is compared with the results of a series of fatigue tests on 2024-T3 aluminum panels, and is shown to do an excellent job of predicting the influence of MSD on the fatigue life of nine inch wide specimens. Having established confidence in the ability to analyze the influence of MSD on fatigue life, a parametric study is conducted to examine the influence of various MSD scenarios in an unstiffened panel. The numerical study considered 135 cases in all, with the parametric variables being the applied cyclic stress level, the lead crack geometry, and the number and location of MSD cracks. The numerical analysis provides details for the manner in which lead cracks and MSD cracks grow and coalesce leading to final failure. The results indicate that MSD located adjacent to lead cracks is the most damaging configuration, while for cases without lead cracks, MSD clusters which are not separated by uncracked holes are most damaging.

  4. Using level data to estimate inflow hydrographs in ungauged sites of multiple reach systems

    NASA Astrophysics Data System (ADS)

    D'Oria, M.; Mignosa, P.; Tanda, M.

    2013-12-01

    Considering a natural river system, usually only few sites are monitored and equipped to measure discharge over time. However, the knowledge of the discharge hydrograph in a specific station is important for many purposes: calibration of rainfall-runoff model, building of new structures, flood frequency analysis, water resource management, etc.. In addition, continuous direct measurement of discharges in open channels can be impossible and in any way difficult to assess. Therefore, most frequently, only level gauges are used for monitoring the system. In this work we propose a methodology to estimate a flow hydrograph in completely ungauged upstream sites of multiple reach systems by means of level data available at monitored stations downstream. In particular, a Bayesian approach is proposed to solve this kind of inverse problem. Prior information, in terms of geostatistical models and tools, is used to represent the structure of the unknowns and to regularize the solution. The methodology requires a forward hydraulic model of the considered river system able to reproduce the routing process and to account for all the reach characteristics: roughness, bed slope, cross sections, confluences, structures, etc.. In this work, the forward model is the widely known HEC-RAS river analysis system. The methodology has been tested through synthetic examples of river confluences, that differ in the available water level data, in the boundary conditions and in the number of the estimated inflow time series. Known inflow time-series were routed downstream by means of HEC-RAS to obtain the downstream stage hydrographs used as observations to test the reverse procedure. In almost all cases, the observed water levels were corrupted with random errors to highlight the reliability of the methodology in preventing instabilities and overfitting. The procedure has been also tested on a real case study of a river confluence located at the city of Parma (Italy) to assess the tributary

  5. Site and size of multiple sclerosis lesions predict enhanced or decreased female orgasmic function.

    PubMed

    Winder, Klemens; Seifert, Frank; Koehn, Julia; Deutsch, Martina; Engelhorn, Tobias; Dörfler, Arnd; Lee, De-Hyung; Linker, Ralf A; Hilz, Max J

    2015-12-01

    Neuroimaging identified brain areas involved in female orgasm. In women with multiple sclerosis (MS), associations between orgasmic function and the site and size of MS-related magnetic resonance imaging (MRI) changes are undetermined. This study intended to correlate MS-associated cerebral lesion load and location with clinical scores of female orgasmic function. In 50 women with MS (mean age 37.0 ± 9.9 years), we assessed Female Sexual Function Index (FSFI) scores for orgasmic frequency, difficulty and satisfaction. We determined disease duration, Expanded Disability Status Scale (EDSS) scores, and cerebral MS-lesion load and location using T2-weighed 1.5 T MRIs. We correlated FSFI scores for orgasm with patient age, disease duration, EDSS scores, and cerebral MS-lesion load (Spearman rank correlation; significance: p < 0.05). FSFI scores for orgasm correlated inversely with MS-lesion load in the left temporal periventricular white matter and right middle-inferior occipital area, but directly with MS-lesion load in the right frontal primary motor cortex, left prefrontal/inferior frontal cortex, right amygdala, left temporal middle-inferior and fusiform areas, and midbrain. FSFI scores for orgasm did not correlate with patient age, disease duration and EDSS scores (p > 0.05). In conclusion, our results indicate that MS-lesions in left temporal periventricular and right visual association areas deteriorate orgasmic function. In contrast, direct correlations between frontotemporal or midbrain lesions and higher FSFI scores, indicating enhanced or disinhibited orgasmic function, suggest that these brain regions normally buffer orgasmic responses. Moreover, our results indicate that orgasmic dysfunction in women with MS evolves independently of disease duration and physical disability. PMID:26459094

  6. Disabled-1 is a large common fragile site gene, inactivated in multiple cancers.

    PubMed

    McAvoy, Sarah; Zhu, Yu; Perez, Damon S; James, C David; Smith, David I

    2008-02-01

    Common fragile sites (CFS) are large, genomically unstable regions, which are hot-spots for deletions and other alterations, especially in cancer cells. Several have been shown to contain genes that span large genomic regions, such as FHIT (1.5 Mb), WWOX (1.0 Mb), GRID2 (1.36 Mb), PARK2 (1.3 Mb), and RORA (730 kb). These genes are frequently inactivated in multiple different cancers, and FHIT and WWOX are shown to function as tumor suppressors. The disabled-1 gene (DAB1) is one of the human homologs of the Drosophila disabled locus, which in mammals is involved in neuronal migration and lamination in the developing cerebral cortex. Mice DAB1 inactivation results in the neurological mutant Scrambler, having similarities to mice with the inactivation of PARK2 (Quaker), GRID2 (Lurcher), and RORA (Staggerer). We were interested in whether DAB1 was another large CFS gene that could have cancer development importance. We demonstrated here that the human DAB1 gene (spanning 1.25 Mb) mapped within FRA1B CFS region on chromosomal band 1p32.2. Real-time RT-PCR analysis revealed that the expression level of DAB1 was decreased in many human cancer samples, including primary tumor tissues and cancer-derived cell lines, from several different cancers, especially in brain and endometrial cancer. Additionally, the introduction of an over-expression DAB1 plasmid into two different cell lines, having insignificant endogenous DAB1 expression, resulted in decreased cell growth. In summary, DAB1 is another gene that resides within an unstable CFS region and might play a role in human tumorigenesis. These data may provide further linkage between neurological development and cancer.

  7. Site-directed alkylation of multiple opioid receptors. I. Binding selectivity

    SciTech Connect

    James, I.F.; Goldstein, A.

    1984-05-01

    A method for measuring and expressing the binding selectivity of ligands for mu, delta, and kappa opioid binding sites is reported. Radioligands are used that are partially selective for these sites in combination with membrane preparations enriched in each site. Enrichment was obtained by treatment of membranes with the alkylating agent beta-chlornaltrexamine in the presence of appropriate protecting ligands. After enrichment for mu receptors, (/sup 3/H) dihydromorphine bound to a single type of site as judged by the slope of competition binding curves. After enrichment for delta or kappa receptors, binding sites for (/sup 3/H) (D-Ala2, D-Leu5)enkephalin and (3H)ethylketocyclazocine, respectively, were still not homogeneous. There were residual mu sites in delta-enriched membranes but no evidence for residual mu or delta sites in kappa-enriched membranes were found. This method was used to identify ligands that are highly selective for each of the three types of sites.

  8. New Site(s) of Methylglyoxal-Modified Human Serum Albumin, Identified by Multiple Reaction Monitoring, Alter Warfarin Binding and Prostaglandin Metabolism

    PubMed Central

    Kimzey, Michael J.; Yassine, Hussein N.; Riepel, Brent M.; Tsaprailis, George; Monks, Terrence J.; Lau, Serrine S.

    2010-01-01

    Methylglyoxal (MG) is a biologically reactive byproduct of glucose metabolism levels of which increase in diabetes. MG modification of protein generates neutral hydroimidazolone adducts on arginine residues which can alter functional active sites. We investigated the site-specificity of MG adduction to human serum albumin (HSA) using multiple reaction monitoring (MRM) of 13 MG modified tryptic peptides, each containing an internal arginine. Seven new sites for MG modification (R257 >R209 >R222 >R81 >R485 >R472 >R10) are described. Analysis of MG-treated HSA showed substantial R257 and R410 modification, with MG-modified R257 (at 100 μM MG) in drug site I causing significant inhibition of prostaglandin catalysis. The MG hydroimidazolone (MG-H1) adduct was modeled at R257, and molecular dynamics simulations and affinity docking revealed a decrease of 12.8–16.5 kcal/mol (S and R isomers, respectively) for warfarin binding in drug site I. Taken together, these results suggest that R257 is a likely site for MG modification in vivo, which may have functional consequences for prostaglandin metabolism and drug bioavailability. PMID:20934417

  9. Correlation between reticle- and wafer-CD difference of multiple 28nm reticle-sites

    NASA Astrophysics Data System (ADS)

    Ning, Guoxiang; Richter, Frank; Thamm, Thomas; Ackmann, Paul; Staples, Marc; Weisbuch, Francois; Kurth, Karin; Schenker, Joerg; Leschok, Andre; GN, Fang Hong

    2012-11-01

    Reticle critical dimension uniformity (CDU) is an important criterion for the qualification of mask layer processes. Normally, the smaller the three sigma value of reticle CDU is, the better is the reticle CDU performance. For qualification of mask processes, the mask layers to be qualified should have a comparable reticle CDU compared to the process of record (POR) mask layers. Because the reticle critical dimension (CD) measurement is based on algorithms like "middle side lobe measurement", evaluation of the reticle CD-values can not reflect aspects like the sidewall angle of the reticle and variation in corner rounding which may be critical for 45nm technology nodes (and below). All involved tools and processes contribute to the wafer intra-field CDU (scanner, track, reticle, metrology). Normally, the reticle contribution to the wafer CDU should be as small as possible. In order to reduce the process contributions to the wafer intra-field CDU during the mask qualification process, the same toolset (exposure tool, metrology tool) should be applied as for the POR. Out of the results of these investigations the correlation between wafer measurement to target (MTT) and reticle MTT can be obtained in order to accurately qualify the CDU performance of the mask processes. We will demonstrate the correlation between reticle MTT and wafer MTT by use of multiple mask processes and alternative mask blank materials. We will investigate the results of four process-layers looking at advanced binary maskblank material from two different suppliers (moreover the results of a 2X-via layer as an example for a phase-shift maskblank is discussed). Objective of this article is to demonstrate the distribution between reticle MTT and wafer MTT as a qualification criterion for mask processes. The correlation between wafer CD-difference and reticle CD-difference of these mask processes are demonstrated by having performed investigations of dense features of different 28nmtechnology

  10. Success of multiple endosseous dental implant designs to second-stage surgery across study sites.

    PubMed

    Morris, H F; Manz, M C; Tarolli, J H

    1997-12-01

    A multicenter clinical study of dental implants is being conducted by the Dental Implant Clinical Research Group to investigate the influence of implant design, application, and site on clinical performance and crestal bone. This article reports on the percentage of success up to implant uncovering for different implant designs and the distribution of failures across study sites. Data from 2,847 implants placed at 32 study sites were analyzed. Percentages of success up to implant uncovering were calculated for study implants overall, by implant design, by implant design within study strata, and according to individual study sites and quartile groupings of sites based on success. Comparisons were made, with chi-square and exact tests employed where appropriate. Differences were found between the different implant designs for the study overall, and between implant designs within the different study strata. Although some implant designs were found to have generally high success across study sites, some study sites designated as having surgeons with less experience tended to have higher failure levels, and one implant design failed at higher rates in a subset of study sites. The percentage and distribution of implant failures varied across study sites and by implant design. These differences appeared to be in part related to the level of experience of the surgeons. Further investigation should focus on identification of factors that contribute to higher success in implant placement with different implant designs.

  11. Methicillin-resistant Staphylococcus aureus multiple sites surveillance: a systemic review of the literature

    PubMed Central

    Chipolombwe, John; Török, Mili Estee; Mbelle, Nontombi; Nyasulu, Peter

    2016-01-01

    Purpose The objective of this study was to evaluate the optimal number of sampling sites for detection of methicillin-resistant Staphylococcus aureus (MRSA) colonization. Methods We performed a Medline search from January 1966 to February 2014 for articles that reported the prevalence of MRSA at different body sites. Studies were characterized by study design, country and period of the study, number of patients and/or isolates of MRSA, specimen type, sites of MRSA isolation, study population sampled, diagnostic testing method, and percentage of the MRSA isolates at each site in relation to the total number of sites. Results We reviewed 3,211 abstracts and 177 manuscripts, of which 17 met the criteria for analysis (n=52,642 patients). MRSA colonization prevalence varied from 8% to 99% at different body sites. The nasal cavity as a single site had MRSA detection sensitivity of 68% (34%–91%). The throat and nares gave the highest detection rates as single sites. A combination of two swabs improved MRSA detection rates with the best combination being groin/throat (89.6%; 62.5%–100%). A combination of three swab sites improved MRSA detection rate to 94.2% (81%–100%) with the best combination being groin/nose/throat. Certain combinations were associated with low detection rates. MRSA detection rates also varied with different culture methods. Conclusion A combination of three swabs from different body sites resulted in the highest detection rate for MRSA colonization. The use of three swab sites would likely improve the recognition and treatment of MRSA colonization, which may in turn reduce infection and transmission of MRSA to other patients. PMID:26929653

  12. NATURAL ATTENUATION OF CHLORINATED SOLVENTS AT MULTIPLE AIR FORCE BASE DEMONSTRATION SITES

    EPA Science Inventory

    Natural attenuation treatability studies(TSs) were conducted at 14 US Air Force bases. Only sites where biodegradation of CAHs was suspected were selected for the study. The major initiative was to evaluate the effectiveness of monitored natural attenuation(MNA) at sites contam...

  13. National Register of Historic Places multiple property documentation form -- Historic, archaeological, and traditional cultural properties of the Hanford Site, Washington

    SciTech Connect

    Nickens, P.R.

    1997-08-01

    The US Department of Energy`s Hanford Site encompasses an area of 560 square miles on the Columbia River in southeastern Washington. Since 1943, the Hanford Site has existed as a protected area for activities primarily related to the production of radioactive materials for national defense uses. For cultural resources on the Hanford Site, establishment of the nuclear reservation as a high security area, with public access restricted, has resulted in a well-protected status, although no deliberate resource protection measures were in effect to mitigate effects of facilities construction and associated activities. Thus, the Hanford Site contains an extensive record of aboriginal archaeological sites and Native American cultural properties, along with pre-Hanford Euro-American sites (primarily archaeological in nature with the removal of most pre-1943 structures), and a considerable number of Manhattan Project/Cold War era buildings and structures. The recent mission change from production to clean up and disposal of DOE lands created a critical need for development and implementation of new and different cultural resource management strategies. DOE-RL has undertaken a preservation planning effort for the Hanford Site. The intent of this Plan is to enable DOE-RL to organize data and develop goals, objectives, and priorities for the identification, evaluation, registration, protection, preservation, and enhancement of the Site`s historical and cultural properties. Decisions made about the identification, evaluation, registration and treatment of historic properties are most aptly made when relationships between individual properties and other similar properties are considered. The historic context and the multiple property documentation (NTD) process provides DOE-RL the organizational framework for these decisions. Once significant patterns are identified, contexts developed, and expected properties are defined, the NTD process provides the foundation for future

  14. Multiple sites on prostaglandin cyclooxygenase are determinants in the action of nonsteroidal antiinflammatory agents.

    PubMed

    Humes, J L; Winter, C A; Sadowski, S J; Kuehl, F A

    1981-04-01

    Evidence is presented to show that nonsteroidal antiinflammatory drugs react with two sites on the cyclooxygenase (8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1). Although the degree of interaction with the catalytic site determines the potency of such compounds, interaction with the supplementary site is also obligatory for efficacy as cyclooxygenase inhibitors and may explain the selectivity of such drugs in inhibiting the cyclooxygenase but not the lipoxygenase pathway. Drugs that interact more effectively with the supplementary site than with the catalytic site--i.e., those of weak to moderate activity as cyclooxygenase inhibitors--are shown to prevent inhibition of the enzyme by indomethacin. Compounds in this class are also capable of blocking the ulcerogenic action of indomethacin, which suggests that this antiulcerogenic property stems from a direct action at the level of the cyclooxygenase in the stomach. PMID:6787598

  15. Analytical reduction of combinatorial complexity arising from multiple protein modification sites

    PubMed Central

    Birtwistle, Marc R.

    2015-01-01

    Combinatorial complexity is a major obstacle to ordinary differential equation (ODE) modelling of biochemical networks. For example, a protein with 10 sites that can each be unphosphorylated, phosphorylated or bound to adaptor protein requires 310 ODEs. This problem is often dealt with by making ad hoc assumptions which have unclear validity and disallow modelling of site-specific dynamics. Such site-specific dynamics, however, are important in many biological systems. We show here that for a common biological situation where adaptors bind modified sites, binding is slow relative to modification/demodification, and binding to one modified site hinders binding to other sites, for a protein with n modification sites and m adaptor proteins the number of ODEs needed to simulate the site-specific dynamics of biologically relevant, lumped bound adaptor states is independent of the number of modification sites and equal to m + 1, giving a significant reduction in system size. These considerations can be relaxed considerably while retaining reasonably accurate descriptions of the true system dynamics. We apply the theory to model, using only 11 ODEs, the dynamics of ligand-induced phosphorylation of nine tyrosines on epidermal growth factor receptor (EGFR) and primary recruitment of six signalling proteins (Grb2, PI3K, PLCγ1, SHP2, RasA1 and Shc1). The model quantitatively accounts for experimentally determined site-specific phosphorylation and dephosphorylation rates, differential affinities of binding proteins for the phosphorylated sites and binding protein expression levels. Analysis suggests that local concentration of site-specific phosphatases such as SHP2 in membrane subdomains by a factor of approximately 107 is critical for effective site-specific regulation. We further show how our framework can be extended with minimal effort to consider binding cooperativity between Grb2 and c-Cbl, which is important for receptor trafficking. Our theory has potentially broad

  16. Maintenance of high-frequency transmission at purkinje to cerebellar nuclear synapses by spillover from boutons with multiple release sites.

    PubMed

    Telgkamp, Petra; Padgett, Daniel E; Ledoux, Veronica A; Woolley, Catherine S; Raman, Indira M

    2004-01-01

    Cerebellar Purkinje neurons maintain high firing rates but their synaptic terminals depress only moderately, raising the question of how vesicle depletion is minimized. To identify mechanisms that limit synaptic depression, we evoked 100 Hz trains of GABAergic inhibitory postsynaptic currents (IPSCs) in cerebellar nuclear neurons by stimulating Purkinje axons in mouse brain slices. The paired-pulse ratio (IPSC(2)/IPSC(1)) of the total IPSC was approximately 1 and the steady-state ratio (IPSC(20)/IPSC(1)) was approximately 0.5, suggesting a high response probability of postsynaptic receptors, without an unusually high release probability. Three-dimensional electron microscopic reconstructions of Purkinje boutons revealed multiple active zones without intervening transporters, suggestive of "spillover"-mediated transmission. Simulations of boutons with 10-16 release sites, in which transmitter from any site can reach all receptors opposite the bouton, replicated multiple-pulse depression during normal, high, and low presynaptic Ca influx. These results suggest that release from multiple-site boutons limits depletion-based depression, permitting prolonged, high-frequency inhibition at corticonuclear synapses. PMID:14715139

  17. Multiple octamer binding sites in the promoter region of the bovine alpha s2-casein gene.

    PubMed Central

    Groenen, M A; Dijkhof, R J; van der Poel, J J; van Diggelen, R; Verstege, E

    1992-01-01

    Using a set of overlapping oligonucleotides from the promoter region of the bovine alpha s2-casein gene we have identified two nuclear factors which probably are involved in expression of this gene and the related calcium sensitive alpha s1- and beta-casein genes. One of these factors which was present in extracts of all tissues that have been tested including Hela cells turned out to be the octamer binding protein OCT-1. Oct-1 binds with different affinity to 4 sites at positions centred around -480, -260, -210 and -50. The strongest of these 4 binding sites, the one around position -50, is highly conserved in all calcium sensitive caseins of mouse, rat, rabbit and cattle. The other nuclear factor (MGF, mammary gland factor) which is specifically expressed in the mammary gland, binds to a site around position -90. This binding site is also highly conserved in all calcium sensitive caseins of mouse, rat, rabbit and cattle. Images PMID:1508722

  18. Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases.

    PubMed

    Guo, Rey-Ting; Cao, Rong; Liang, Po-Huang; Ko, Tzu-Ping; Chang, Tao-Hsin; Hudock, Michael P; Jeng, Wen-Yih; Chen, Cammy K-M; Zhang, Yonghui; Song, Yongcheng; Kuo, Chih-Jung; Yin, Fenglin; Oldfield, Eric; Wang, Andrew H-J

    2007-06-12

    Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in decreased prenylation of small GTPases. Here, we show that some bisphosphonates can also inhibit geranylgeranyl diphosphate synthase (GGPPS), as well as undecaprenyl diphosphate synthase (UPPS), a cis-prenyltransferase of interest as a target for antibacterial therapy. Our results on GGPPS (10 structures) show that there are three bisphosphonate-binding sites, consisting of FPP or isopentenyl diphosphate substrate-binding sites together with a GGPP product- or inhibitor-binding site. In UPPS, there are a total of four binding sites (in five structures). These results are of general interest because they provide the first structures of GGPPS- and UPPS-inhibitor complexes, potentially important drug targets, in addition to revealing a remarkably broad spectrum of binding modes not seen in FPPS inhibition.

  19. Characterization and autoradiographic localization of multiple tachykinin binding sites in gastrointestinal tract and bladder

    SciTech Connect

    Burcher, E.; Buck, S.H.; Lovenberg, W.; O'Donohue, T.L.

    1986-03-01

    Binding sites for the (125I)Bolton-Hunter-labeled tachykinins substance K (BHSK), eledoisin (BHE) and substance P (BHSP) were investigated using crude membrane suspensions and autoradiography. In smooth muscle membranes from guinea-pig small intestine and rat duodenum, specific binding of BHSK was saturable and reversible, showing a single class of sites with a KD of 1 to 3 nM and maximum number of specific binding sites of 1 to 2 fmol/mg of wet weight tissue. Pharmacological characterization of this binding revealed a novel receptor site (K) with affinity for substance K greater than kassinin greater than or equal to eledoisin greater than neuromedin K greater than substance P greater than physalaemin. Inhibition of the binding of BHSK in membranes from mouse urinary bladder exhibited a similar K-type pattern. In rat duodenum and mouse bladder membranes, the binding of BHE was inhibited by substance K greater than kassinin greater than eledoisin greater than neuromedin K greater than substance P greater than physalaemin indicating the same receptor site as for BHSK. In rat cerebral cortex membranes BHE binding was inhibited by neuromedin K = kassinin = eledoisin greater than physalaemin greater than substance K greater than substance P indicating a definitive tachykinin E receptor site. The same displacement pattern of BHE binding was also detected in longitudinal muscle membranes from the guinea-pig small intestine. In mouse bladder membranes and in rat and guinea-pig intestine, the binding of BHSP was inhibited by substance P greater than physalaemin greater than substance K greater than or equal to eledoisin = kassinin greater than neuromedin K indicating a definitive tachykinin P receptor site. Autoradiographic binding sites for both BHSK and BHSP were seen in circular muscle of the rat stomach, small intestine and colon and in circular and longitudinal muscle of the guinea-pig small intestine and colon.

  20. Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase

    PubMed Central

    Jacobs, Dave; Glossip, Danielle; Xing, Heming; Muslin, Anthony J.; Kornfeld, Kerry

    1999-01-01

    MAP kinases phosphorylate specific groups of substrate proteins. Here we show that the amino acid sequence FXFP is an evolutionarily conserved docking site that mediates ERK MAP kinase binding to substrates in multiple protein families. FXFP and the D box, a different docking site, form a modular recognition system, as they can function independently or in combination. FXFP is specific for ERK, whereas the D box mediates binding to ERK and JNK MAP kinase, suggesting that the partially overlapping substrate specificities of ERK and JNK result from recognition of shared and unique docking sites. These findings enabled us to predict new ERK substrates and design peptide inhibitors of ERK that functioned in vitro and in vivo. PMID:9925641

  1. Simultaneous fast measurement of circuit dynamics at multiple sites across the mammalian brain.

    PubMed

    Kim, Christina K; Yang, Samuel J; Pichamoorthy, Nandini; Young, Noah P; Kauvar, Isaac; Jennings, Joshua H; Lerner, Talia N; Berndt, Andre; Lee, Soo Yeun; Ramakrishnan, Charu; Davidson, Thomas J; Inoue, Masatoshi; Bito, Haruhiko; Deisseroth, Karl

    2016-04-01

    Real-time activity measurements from multiple specific cell populations and projections are likely to be important for understanding the brain as a dynamical system. Here we developed frame-projected independent-fiber photometry (FIP), which we used to record fluorescence activity signals from many brain regions simultaneously in freely behaving mice. We explored the versatility of the FIP microscope by quantifying real-time activity relationships among many brain regions during social behavior, simultaneously recording activity along multiple axonal pathways during sensory experience, performing simultaneous two-color activity recording, and applying optical perturbation tuned to elicit dynamics that match naturally occurring patterns observed during behavior.

  2. Biochemical View: A Web Site Providing Material for Teaching Biochemistry Using Multiple Approaches

    NASA Astrophysics Data System (ADS)

    Dórea, Fernanda C.; Rodrigues, Higor S.; Lapouble, Oscar M. M.; Pereira, Márcio R.; Castro, Mariana S.; Fontes, Wagner

    2007-11-01

    Computational resources are valuable tools for teaching biochemistry. Often, however, the necessary information is dispersed throughout several Web sites and many of the biochemistry software programs are only available commercially. Considering the difficulties of understanding abstract biochemical concepts, a Web site, Biochemical View (accessed Aug 2007) has been developed at the University of Brasília (UnB), Brazil. Its main goals are to complement course instruction and materials already in use, provide material to teachers preparing conventional and online courses, and—because free, full access is allowed—popularize the use of these resources in undergraduate courses. The contents, which include the usual metabolic pathways explaining the metabolism of carbohydrates, amino acids, lipids, and nucleic acids, are presented in two and three-dimensional formats, complemented with objective texts, schematics, and a description of regulation points. In this work, a new approach to metabolic pathways is employed, namely metabolic participation diagrams. In addition, experimental protocols for laboratory classes, study material, and detailed information about each molecule taking part in a specific metabolic pathway have been also made available in the Web site. The process of constructing the site is described and the results of students using this Web site are evaluated based on exam scores and survey forms, which show a significant improvement in students' success in learning biochemistry.

  3. Neural networks for determining protein specificity and multiple alignment of binding sites

    SciTech Connect

    Heumann, J.M.; Lapedes, A.S.; Stormo, G.D.

    1994-12-31

    We use a quantitative definition of specificity to develop a neural network for the identification of common protein binding sites in a collection of unaligned DNA fragments. We demonstrate the equivalence of the method to maximizing Information Content of the aligned sites when simple models of the binding energy and the genome are employed. The network method subsumes those simple models and is capable of working with more complicated ones. This is demonstrated using a Markov model of the E. coli genome and a sampling method to approximate the partition function. A variation of Gibbs sampling aids in avoiding local minima.

  4. Detection of multiple stresses in Scots pine growing at post-mining sites using visible to near-infrared spectroscopy.

    PubMed

    Zuzana, Lhotáková; Lukáš, Brodský; Lucie, Kupková; Veronika, Kopačková; Markéta, Potůčková; Jan, Mišurec; Aleš, Klement; Monika, Kovářová; Jana, Albrechtová

    2013-10-01

    Heavy metal contamination, low pH and high substrate heterogeneity are multiple stress factors that often occur at the post-mining sites and make difficult the biological reclamation. Efficient tools for detection of the status of reclaimed vegetation at post-mining sites are needed. We tested the potential of visible to near-infrared (VNIR) spectroscopy to detect multiple stresses in Scots pine (Pinus sylvestris L.) at acidic substrates rich in As. The needle chemical traits (chlorophyll a + b - Cab; carotenoids - Car; Car/Cab; relative water content - RWC; soluble phenolics; lignin contents) were tested for sensitivity to different soil conditions of post-mining sites. For Scots pine growing on degraded substrates, at least three non-specific stress indicators (RWC, photosynthetic pigments and phenolics) are required to achieve good site separability corresponding to the stress load. We constructed and validated empirical models of selected needle chemical traits using VNIR spectroscopy: calibration of Cab (R(2) = 0.97, RMSE = 0.17 mg g(-1)), RWC (R(2) = 0.88, RMSE = 1.41 mg g(-1)), Car (R(2) = 0.66, RMSE = 0.08 mg g(-1)), phenolics (R(2) = 0.64, RMSE = 23.01 mg g(-1)) and lignin (R(2) = 0.45, RMSE = 3.32 mg g(-1)). The reflectance data yielded comparable site separability with the separability calculated from the laboratory data. The presented approach has potential for large-scale monitoring of Scots pine status, thus, assessment of reclamation quality in post-mining regions using air-born or satellite hyperspectral data. PMID:24108147

  5. Crosstalk between signaling pathways provided by single and multiple protein phosphorylation sites.

    PubMed

    Nishi, Hafumi; Demir, Emek; Panchenko, Anna R

    2015-01-30

    Cellular fate depends on the spatiotemporal separation and integration of signaling processes that can be provided by phosphorylation events. In this study, we identify the crucial points in signaling crosstalk that can be triggered by discrete phosphorylation events on a single target protein. We integrated the data on individual human phosphosites with the evidence on their corresponding kinases, the functional consequences of phosphorylation on activity of the target protein and corresponding pathways. Our results show that there is a substantial fraction of phosphosites that can play critical roles in crosstalk between alternative and redundant pathways and regulatory outcome of phosphorylation can be linked to a type of phosphorylated residue. These regulatory phosphosites can serve as hubs in the signal flow and their functional roles are directly connected to their specific properties. Namely, phosphosites with similar regulatory functions are phosphorylated by the same kinases and participate in regulation of similar biochemical pathways. Such sites are more likely to cluster in sequence and space unlike sites with antagonistic outcomes of their phosphorylation on a target protein. In addition, we found that in silico phosphorylation of sites with similar functional consequences has comparable outcomes on a target protein stability. An important role of phosphorylation sites in biological crosstalk is evident from the analysis of their evolutionary conservation.

  6. Biochemical study of multiple drug recognition sites on central benzodiazepine receptors

    SciTech Connect

    Trifiletti, R.R.

    1986-01-01

    The benzodiazepine receptor complex of mammalian brain possesses recognition sites which mediate (at least in part) the pharmacologic actions of the 1,4-benzodiazepines and barbiturates. Evidence is provided suggesting the existence of least seven distinct drug recognition sites on this complex. Interactions between the various recognition sites have been explored using radioligand binding techniques. This information is utilized to provide a comprehensive scheme for characterizing receptor-active drugs on an anxiolytic-anticonvulsant/proconvulsant continuum using radioligand binding techniques, as well as a comprehensive program for identifying potential endogenous receptor-active substances. Further evidence is provided here supporting the notion of benzodiazepine recognition site heterogeneity. Classical 1,4-benzodiazepines do not appear to differentiate two populations of benzodiazepine receptors in an equilibrium sense, but appear to do so in a kinetic sense. An apparent physical separation of the two receptor subtypes can be achieved by differential solubilization. The benzodiazepine binding subunit can be identified by photoaffinity labeling with the benzodiazepine agonist (/sup 3/H)flunitrazepan. Conditions for reproducible partial proteolytic mapping of (/sup 3/H)flunitrazepam photoaffinity labeled receptors are established. From these maps, it is concluded that there are probably no major differences in the primary sequence of the benzodiazepine binding subunit in various regions of the rat central nervous system.

  7. Multiple transcription start sites for FOXP2 with varying cellular specificities.

    PubMed

    Schroeder, Diane I; Myers, Richard M

    2008-04-30

    FOXP2 is a forkhead transcription factor implicated in developmental verbal dyspraxia, a human speech and language disorder. FOXP2 is expressed in complex patterns during brain, lung, heart, and gut development and on into adulthood. Both the protein sequence and brain expression patterns are highly conserved through much of vertebrate evolution. FOXP2 also contains six ultraconserved regions in its introns, consistent with the idea that FOXP2 is tightly regulated. Previous evidence suggested the presence of three transcription start sites for FOXP2, and we sought to characterize them and determine their cell and tissue specificity. We used 5' RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) and RT-PCR to identify four transcription start sites for human FOXP2, the fourth being in a novel exon. Two of the transcription start sites, including the one in the novel exon, appear to be more cell line specific and lie in an area of remarkably high conservation. We propose that these two transcription start sites may be of great interest in future studies of FOXP2 regulation.

  8. Siting multiple conservation practices in a tile-drained watershed using LiDAR topographic data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Improving the effectiveness of conservation practices for achieving water quality goals will require a conservation planning with a watershed context. Conservation planning has traditionally been field or farm specific, and is usually aided by site specific information that includes topographic data...

  9. NATURAL ATTENUATION OF FUEL HYDROCARBONS AT MULTIPLE AIR FORCE BASE DEMONSTRATION SITES

    EPA Science Inventory

    A major initiative to evaluate monitored natural attenuation(MNA) of ground water contaminated with fuel hydrocarbons began in June 1993 and continued through October 2000. During this time site characterization studies, both initial and follow-up, were conducted at 28 Air Forc...

  10. Heisenberg antiferromagnetic chain with multiple spin 1/2 particles of different flavors per site

    NASA Astrophysics Data System (ADS)

    Duki, Solomon F.; Yu, Yi-Kuo

    Motivated by the discoveries of quasi-1D magnetic systems, we studied a quantum mechanical spin lattice system consisting of a one-dimensional antiferromagnetic Heisenberg chain. In this system we considered M spin 1/2 particles of different flavors per site, and the low-lying states, ground state included, of the Hamiltonian was solved numerically using the exact diagonalization method for finite cluster sizes. We have also obtained the corresponding solutions for systems of the same chain length but with one spin M/2 particle per site. The low energy spectra of both systems are then compared. For M = 2 and M =3, our result shows that the two spin chain systems (one spin M/2 per site vs. M spin 1/2 of different flavors per site) have the same excitation spectra at low energy and the number of overlapped states increases as the size of the cluster increases. The observed overlap also indicates that low energy excitations of the M flavored spin 1/2 chain system selects the high spin states, effectively satisfying the Hund's Rule even though the system does not possess the orbital angular momentum. This work was supported by the Intramural Research Program of the National Library of Medicine at the National Institutes of Health.

  11. Crosstalk between signaling pathways provided by single and multiple protein phosphorylation sites

    PubMed Central

    Nishi, Hafumi; Demir, Emek; Panchenko, Anna R.

    2014-01-01

    Cellular fate depends on the spatio-temporal separation and integration of signaling processes which can be provided by phosphorylation events. In this study we identify the crucial points in signaling crosstalk which can be triggered by discrete phosphorylation events on a single target protein. We integrated the data on individual human phosphosites with the evidence on their corresponding kinases, the functional consequences on phosphorylation on activity of the target protein and corresponding pathways. Our results show that there is a substantial fraction of phosphosites that can play critical roles in crosstalk between alternative or redundant pathways and regulatory outcome of phosphorylation can be linked to a type of phosphorylated residue. These regulatory phosphosites can serve as hubs in the signal flow and their functional roles are directly connected to their specific properties. Namely, phosphosites with similar regulatory functions are phosphorylated by the same kinases and participate in regulation of similar biochemical pathways. Such sites are more likely to cluster in sequence and space unlike sites with antagonistic outcomes of their phosphorylation on a target protein. In addition we found that in silico phosphorylation of sites with similar functional consequences have comparable outcomes on a target protein stability. An important role of phosphorylation sites in biological crosstalk is evident from the analysis of their evolutionary conservation. PMID:25451034

  12. Self-assembled nanospheres with multiple endohedral binding sites pre-organize catalysts and substrates for highly efficient reactions

    NASA Astrophysics Data System (ADS)

    Wang, Qi-Qiang; Gonell, Sergio; Leenders, Stefan H. A. M.; Dürr, Maximilian; Ivanović-Burmazović, Ivana; Reek, Joost N. H.

    2016-03-01

    Tuning reagent and catalyst concentrations is crucial in the development of efficient catalytic transformations. In enzyme-catalysed reactions the substrate is bound—often by multiple non-covalent interactions—in a well-defined pocket close to the active site of the enzyme; this pre-organization facilitates highly efficient transformations. Here we report an artificial system that co-encapsulates multiple catalysts and substrates within the confined space defined by an M12L24 nanosphere that contains 24 endohedral guanidinium-binding sites. Cooperative binding means that sulfonate guests are bound much more strongly than carboxylates. This difference has been used to fix gold-based catalysts firmly, with the remaining binding sites left to pre-organize substrates. This strategy was applied to a Au(I)-catalysed cyclization of acetylenic acid to enol lactone in which the pre-organization resulted in much higher reaction rates. We also found that the encapsulated sulfonate-containing Au(I) catalysts did not convert neutral (acid) substrates, and so could have potential in the development of substrate-selective catalysis and base-triggered on/off switching of catalysis.

  13. Self-assembled nanospheres with multiple endohedral binding sites pre-organize catalysts and substrates for highly efficient reactions.

    PubMed

    Wang, Qi-Qiang; Gonell, Sergio; Leenders, Stefan H A M; Dürr, Maximilian; Ivanović-Burmazović, Ivana; Reek, Joost N H

    2016-03-01

    Tuning reagent and catalyst concentrations is crucial in the development of efficient catalytic transformations. In enzyme-catalysed reactions the substrate is bound-often by multiple non-covalent interactions-in a well-defined pocket close to the active site of the enzyme; this pre-organization facilitates highly efficient transformations. Here we report an artificial system that co-encapsulates multiple catalysts and substrates within the confined space defined by an M12L24 nanosphere that contains 24 endohedral guanidinium-binding sites. Cooperative binding means that sulfonate guests are bound much more strongly than carboxylates. This difference has been used to fix gold-based catalysts firmly, with the remaining binding sites left to pre-organize substrates. This strategy was applied to a Au(I)-catalysed cyclization of acetylenic acid to enol lactone in which the pre-organization resulted in much higher reaction rates. We also found that the encapsulated sulfonate-containing Au(I) catalysts did not convert neutral (acid) substrates, and so could have potential in the development of substrate-selective catalysis and base-triggered on/off switching of catalysis. PMID:26892553

  14. Pacemaker activity in a sensory ending with multiple encoding sites: the cat muscle spindle primary ending.

    PubMed Central

    Banks, R W; Hulliger, M; Scheepstra, K A; Otten, E

    1997-01-01

    1. A combined physiological, histological and computer modelling study was carried out on muscle spindles of the cat tenuissimus muscle to examine whether there was any correlation between the functional interaction of putative encoding sites, operated separately by static and dynamic fusimotor neurones, and the topological structure of the preterminal branches of the primary sensory ending. 2. Spindles, whose I a responses to stretch and separate and combined static and dynamic fusimotor stimulation were recorded in physiological experiments, were located in situ. Subsequently the ramifications of the sensory ending were reconstructed histologically, and the topology of the branch tree was used in computer simulations of I a responses to examine the effect of the electronic separation of encoding sites on the static-dynamic interaction pattern. 3. Interactions between separate static and dynamic inputs, manifest in responses to combineed stimulation, were quantified by a coefficient of interaction (Ci) which, by definition, was 1 for strictly linear summation of separate inputs and zero for maximum occlusion between inputs. 4. For the majority of spindles static-dynamic interactions were characterized by pronounced occlusion (C1 < 0.35). In these spindles putative encoding sites (the peripheral heminodes of the branches supplying the intrafusal fibres activated by individual fusimotor efferents) were separated by a minimum conduction path of between three and ten myelinated segments (2-9 nodes of Ranvier). In contrast, significant summation (C1, approximately 0.7) was found in only one spindle. In this case putative encoding sites were separated by a single node. 5. Occlusion was not due to encoder saturation and it could not be accounted for by any other known physiological mechanisms (intrafusal fatigue or unloading). It is therefore attributed to competitive pacemaker interaction between encoding sites which are largely selectively operated by static and

  15. Screening Mixtures of Small Molecules for Binding to Multiple Sites on the Surface Tetanus Toxin C Fragment by Bioaffinity NMR

    SciTech Connect

    Cosman, M; Zeller, L; Lightstone, F C; Krishnan, V V; Balhorn, R

    2002-01-01

    also contains 3-sialyllactose (another predicted site 1 binder) and bisbenzimide 33342 (non-binder). A series of five predicted Site-2 binders were then screened sequentially in the presence of the Site-1 binder doxorubicin. These experiments showed that the compounds lavendustin A and naphthofluorescein-di-({beta}-D-galactopyranoside) binds along with doxorubicin to TetC. Further experiments indicate that doxorubicin and lavendustin are potential candidates to use in preparing a bidendate inhibitor specific for TetC. The simultaneous binding of two different predicted Site-2 ligands to TetC suggests that they may bind multiple sites. Another possibility is that the conformations of the binding sites are dynamic and can bind multiple diverse ligands at a single site depending on the pre-existing conformation of the protein, especially when doxorubicin is already bound.

  16. Dendrochemistry of multiple releases of chlorinated solvents at a former industrial site

    USGS Publications Warehouse

    Balouet, Jean Christophe; Burken, Joel G.; Karg, Frank; Vroblesky, Don; Smith, Kevin T.; Grudd, Hakan; Rindby, Anders; Beaujard, Francois; Chalot, Michel

    2012-01-01

    Trees can take up and assimilate contaminants from the soil, subsurface, and groundwater. Contaminants in the transpiration stream can become bound or incorporated into the annual rings formed in trees of the temperate zones. The chemical analysis of precisely dated tree rings, called dendrochemistry, can be used to interpret past plant interactions with contaminants. This investigation demonstrates that dendrochemistry can be used to generate historical scenarios of past contamination of groundwater by chlorinated solvents at a site in Verl, Germany. Increment cores from trees at the Verl site were collected and analyzed by energy-dispersive X-ray fluorescence (EDXRF) line scanning. The EDXRF profiles showed four to six time periods where tree rings had anomalously high concentrations of chlorine (Cl) as an indicator of potential contamination by chlorinated solvents.

  17. Dendrochemistry of multiple releases of chlorinated solvents at a former industrial site.

    PubMed

    Balouet, Jean Christophe; Burken, Joel G; Karg, Frank; Vroblesky, Don; Smith, Kevin T; Grudd, Håkan; Rindby, Anders; Beaujard, François; Chalot, Michel

    2012-09-01

    Trees can take up and assimilate contaminants from the soil, subsurface, and groundwater. Contaminants in the transpiration stream can become bound or incorporated into the annual rings formed in trees of the temperate zones. The chemical analysis of precisely dated tree rings, called dendrochemistry, can be used to interpret past plant interactions with contaminants. This investigation demonstrates that dendrochemistry can be used to generate historical scenarios of past contamination of groundwater by chlorinated solvents at a site in Verl, Germany. Increment cores from trees at the Verl site were collected and analyzed by energy-dispersive X-ray fluorescence (EDXRF) line scanning. The EDXRF profiles showed four to six time periods where tree rings had anomalously high concentrations of chlorine (Cl) as an indicator of potential contamination by chlorinated solvents.

  18. Multiple sup 3 H-oxytocin binding sites in rat myometrial plasma membranes

    SciTech Connect

    Crankshaw, D.; Gaspar, V.; Pliska, V. )

    1990-01-01

    The affinity spectrum method has been used to analyse binding isotherms for {sup 3}H-oxytocin to rat myometrial plasma membranes. Three populations of binding sites with dissociation constants (Kd) of 0.6-1.5 x 10(-9), 0.4-1.0 x 10(-7) and 7 x 10(-6) mol/l were identified and their existence verified by cluster analysis based on similarities between Kd, binding capacity and Hill coefficient. When experimental values were compared to theoretical curves constructed using the estimated binding parameters, good fits were obtained. Binding parameters obtained by this method were not influenced by the presence of GTP gamma S (guanosine-5'-O-3-thiotriphosphate) in the incubation medium. The binding parameters agree reasonably well with those found in uterine cells, they support the existence of a medium affinity site and may allow for an explanation of some of the discrepancies between binding and response in this system.

  19. Site specific monitoring of multiple information systems - the HappyFace Project

    NASA Astrophysics Data System (ADS)

    Büge, Volker; Mauch, Viktor; Quast, Günter; Scheurer, Armin; Trunov, Artem

    2010-04-01

    An efficient administration of computing centres requires sophisticated tools for the monitoring of the local infrastructure. Sharing such resources in a grid infrastructure, like the Worldwide LHC Computing Grid (WLCG), goes ahead with a large number of external monitoring systems, offering information on the status of the services and user jobs at a grid site. This huge flood of information from many different sources retards the identification of problems and complicates the local administration. In addition, the web interfaces for the access to the site specific information are often very slow and uncomfortable to use. A meta-monitoring system which automatically queries the different relevant monitoring systems could provide a fast and comfortable access to all important information for the local administration. It becomes also feasible to easily correlate information from different sources and provides an easy access also for non-expert users. In this paper, we describe the HappyFace Project, a modular software framework for such purpose. It queries existing monitoring sources and processes the results to provide a single point of entrance for information on a grid site and its specific services.

  20. Multiple sites of adaptive plasticity in the owl's auditory localization pathway.

    PubMed

    DeBello, William M; Knudsen, Eric I

    2004-08-01

    In the midbrain auditory localization pathway of the barn owl, a map of auditory space is relayed from the external nucleus of the inferior colliculus (ICX) to the deep and intermediate layers of the optic tectum (OT) and from these layers to the superficial layers. Within the OT, the auditory space map aligns with a visual map of space. Raising young barn owls with a prismatic displacement of the visual field leads to progressive changes in auditory tuning in the OT that tend to realign the auditory space map with the prismatically displaced visual space map. The only known site of this adaptive plasticity is in the ICX, in which the auditory system first creates a map of space. In this study, we identified an additional site of plasticity in the OT. In owls that experienced prisms beginning late in the juvenile period, adaptive shifts in auditory tuning in the superficial layers of the OT exceeded the adaptive shifts that occurred in the deep layers of the OT or in the ICX. Anatomical results from these owls demonstrated that the topography of intrinsic OT connections was systematically altered in the adaptive direction. In juvenile owls, plasticity in the OT increased as plasticity in the ICX decreased. Because plasticity at both sites has been shown to decline substantially in adults, these results suggest that an age-dependent decrease in auditory map plasticity occurs first in the ICX and later at the higher level, in the OT. PMID:15295019

  1. Possible multiple binding sites for o-aminophenol on uridine diphosphate glucuronyltransferase.

    PubMed Central

    Howland, R D; Bohm, L D

    1977-01-01

    1. Hepatic microsomal UDP-glucuronyltransferase (EC 2.4.1.17) derived from either weanling or adult rats exhibits three pH optima, at pH 5.4, 7.2 and 9.2, when o-aminophenol is the acceptor substrate, whereas p-nitrophenol is the acceptor substrate only on pH optimum is observed, at pH 5.4.2. Prior treatment of rats of either age with 3-methylcholanthrene results in a 2-3-fold increase in o-aminophenol conjugation at pH 5.4 and a 6-9-fold increase at pH 9.2. At pH 7.2, the induced enzyme is 2 to 3 times more active towards o-aminophenol than the control enzyme, but no pH optimum is demonstrable. 3. o-Aminophenol conjugation at pH 5.4 and 9.2 is inhibited competitively by both p-nitrophenol and p-nitrophenyl glucuronide, suggesting that the two phenolic aglycones share the same binding site. At pH 7.2, however, p-nitrophenyl glucuronide does not inhibit o-aminophenol conjugation, suggesting that the binding site at this pH is not shared by the two phenols. These data are consistent with the existence of more than one binding site for o-aminophenol on UDP-glucuronyltransferase. PMID:17389

  2. Evolution of the Florida Launch Site Architecture: Embracing Multiple Customers, Enhancing Launch Opportunities

    NASA Technical Reports Server (NTRS)

    Colloredo, Scott; Gray, James A.

    2011-01-01

    The impending conclusion of the Space Shuttle Program and the Constellation Program cancellation unveiled in the FY2011 President's budget created a large void for human spaceflight capability and specifically launch activity from the Florida launch Site (FlS). This void created an opportunity to re-architect the launch site to be more accommodating to the future NASA heavy lift and commercial space industry. The goal is to evolve the heritage capabilities into a more affordable and flexible launch complex. This case study will discuss the FlS architecture evolution from the trade studies to select primary launch site locations for future customers, to improving infrastructure; promoting environmental remediation/compliance; improving offline processing, manufacturing, & recovery; developing range interface and control services with the US Air Force, and developing modernization efforts for the launch Pad, Vehicle Assembly Building, Mobile launcher, and supporting infrastructure. The architecture studies will steer how to best invest limited modernization funding from initiatives like the 21 st elSe and other potential funding.

  3. Rrp5 Binding at Multiple Sites Coordinates Pre-rRNA Processing and Assembly

    PubMed Central

    Lebaron, Simon; Segerstolpe, Åsa; French, Sarah L.; Dudnakova, Tatiana; de lima Alves, Flavia; Granneman, Sander; Rappsilber, Juri; Beyer, Ann L.; Wieslander, Lars; Tollervey, David

    2013-01-01

    Summary In vivo UV crosslinking identified numerous preribosomal RNA (pre-rRNA) binding sites for the large, highly conserved ribosome synthesis factor Rrp5. Intramolecular complementation has shown that the C-terminal domain (CTD) of Rrp5 is required for pre-rRNA cleavage at sites A0–A2 on the pathway of 18S rRNA synthesis, whereas the N-terminal domain (NTD) is required for A3 cleavage on the pathway of 5.8S/25S rRNA synthesis. The CTD was crosslinked to sequences flanking A2 and to the snoRNAs U3, U14, snR30, and snR10, which are required for cleavage at A0–A2. The NTD was crosslinked to sequences flanking A3 and to the RNA component of ribonuclease MRP, which cleaves site A3. Rrp5 could also be directly crosslinked to several large structural proteins and nucleoside triphosphatases. A key role in coordinating preribosomal assembly and processing was confirmed by chromatin spreads. Following depletion of Rrp5, cotranscriptional cleavage was lost and preribosome compaction greatly reduced. PMID:24239293

  4. Radiometric calibration of multiple Earth observation sensors using airborne hyperspectral data at the Newell County rangeland test site

    NASA Astrophysics Data System (ADS)

    Teillet, Phil M.; Fedosejevs, Gunar; Gauthier, Robert P.; Shin, Raymond T.; O'Neill, Norman T.; Thome, Kurtis J.; Biggar, Stuart F.; Ripley, Herb T.; Meygret, Aime

    1999-09-01

    A single data set of spatially extensive hyperspectral imagery is used to carry out vicarious calibrations for multiple Earth observation sensors. Results are presented based on a data acquisition campaign at the newell County rangeland test site in Alberta in October 1998, which included ground-based measurements, satellite imagery, and airborne casi hyperspectral data. This paper present new calibration monitoring obtained for NOAA-14 AVHRR, OrbView-2 SeaWiFS, SPOT-4 VGT, Landsat-5 TM, and SPOT-2 HRV.

  5. Advanced source apportionment of size-resolved trace elements at multiple sites in London during winter

    NASA Astrophysics Data System (ADS)

    Visser, S.; Slowik, J. G.; Furger, M.; Zotter, P.; Bukowiecki, N.; Canonaco, F.; Flechsig, U.; Appel, K.; Green, D. C.; Tremper, A. H.; Young, D. E.; Williams, P. I.; Allan, J. D.; Coe, H.; Williams, L. R.; Mohr, C.; Xu, L.; Ng, N. L.; Nemitz, E.; Barlow, J. F.; Halios, C. H.; Fleming, Z. L.; Baltensperger, U.; Prévôt, A. S. H.

    2015-10-01

    Trace element measurements in PM10-2.5, PM2.5-1.0 and PM1.0-0.3 aerosol were performed with 2 h time resolution at kerbside, urban background and rural sites during the ClearfLo winter 2012 campaign in London. The environment-dependent variability of emissions was characterized using the Multilinear Engine implementation of the positive matrix factorization model, conducted on data sets comprising all three sites but segregated by size. Combining the sites enabled separation of sources with high temporal covariance but significant spatial variability. Separation of sizes improved source resolution by preventing sources occurring in only a single size fraction from having too small a contribution for the model to resolve. Anchor profiles were retrieved internally by analysing data subsets, and these profiles were used in the analyses of the complete data sets of all sites for enhanced source apportionment. A total of nine different factors were resolved (notable elements in brackets): in PM10-2.5, brake wear (Cu, Zr, Sb, Ba), other traffic-related (Fe), resuspended dust (Si, Ca), sea/road salt (Cl), aged sea salt (Na, Mg) and industrial (Cr, Ni); in PM2.5-1.0, brake wear, other traffic-related, resuspended dust, sea/road salt, aged sea salt and S-rich (S); and in PM1.0-0.3, traffic-related (Fe, Cu, Zr, Sb, Ba), resuspended dust, sea/road salt, aged sea salt, reacted Cl (Cl), S-rich and solid fuel (K, Pb). Human activities enhance the kerb-to-rural concentration gradients of coarse aged sea salt, typically considered to have a natural source, by 1.7-2.2. These site-dependent concentration differences reflect the effect of local resuspension processes in London. The anthropogenically influenced factors traffic (brake wear and other traffic-related processes), dust and sea/road salt provide further kerb-to-rural concentration enhancements by direct source emissions by a factor of 3.5-12.7. The traffic and dust factors are mainly emitted in PM10-2.5 and show strong

  6. Genome-Wide Assessment of Efficiency and Specificity in CRISPR/Cas9 Mediated Multiple Site Targeting in Arabidopsis.

    PubMed

    Peterson, Brenda A; Haak, David C; Nishimura, Marc T; Teixeira, Paulo J P L; James, Sean R; Dangl, Jeffery L; Nimchuk, Zachary L

    2016-01-01

    Simultaneous multiplex mutation of large gene families using Cas9 has the potential to revolutionize agriculture and plant sciences. The targeting of multiple genomic sites at once raises concerns about the efficiency and specificity in targeting. The model Arabidopsis thaliana is widely used in basic plant research. Previous work has suggested that the Cas9 off-target rate in Arabidopsis is undetectable. Here we use deep sequencing on pooled plants simultaneously targeting 14 distinct genomic loci to demonstrate that multiplex targeting in Arabidopsis is highly specific to on-target sites with no detectable off-target events. In addition, chromosomal translocations are extremely rare. The high specificity of Cas9 in Arabidopsis makes this a reliable method for clean mutant generation with no need to enhance specificity or adopt alternate Cas9 variants. PMID:27622539

  7. Use of multiple-site performance-contingent SEMG reward programming in pediatric rehabilitation: a retrospective review.

    PubMed

    Bolek, Jeffrey E

    2006-09-01

    We completed a retrospective review of the effectiveness of multi-site, performance-contingent reward programming on functional change in motor performance of 16 treatment resistant children. Patients were previously treated in physical or occupational therapy for head control, standing balance training, sitting and upper extremity use (brachial plexus injury). They then participated in a program that utilized multiple surface electromyography sites the use of which was rewarded with videos for performing the correct constellation of recruitment pattern (e.g., contracting some muscles while relaxing others). Onset of reward was calibrated for each patient and transfer of skill to outside the clinic was encouraged by linking a verbal cue to the correct motor plan. Fourteen of the 16 patients improved. The implications of the use of this technique in the treatment of motor dysfunction is discussed.

  8. Genome-Wide Assessment of Efficiency and Specificity in CRISPR/Cas9 Mediated Multiple Site Targeting in Arabidopsis

    PubMed Central

    Peterson, Brenda A.; Haak, David C.; Nishimura, Marc T.; Teixeira, Paulo J. P. L.; James, Sean R.; Dangl, Jeffery L.; Nimchuk, Zachary L.

    2016-01-01

    Simultaneous multiplex mutation of large gene families using Cas9 has the potential to revolutionize agriculture and plant sciences. The targeting of multiple genomic sites at once raises concerns about the efficiency and specificity in targeting. The model Arabidopsis thaliana is widely used in basic plant research. Previous work has suggested that the Cas9 off-target rate in Arabidopsis is undetectable. Here we use deep sequencing on pooled plants simultaneously targeting 14 distinct genomic loci to demonstrate that multiplex targeting in Arabidopsis is highly specific to on-target sites with no detectable off-target events. In addition, chromosomal translocations are extremely rare. The high specificity of Cas9 in Arabidopsis makes this a reliable method for clean mutant generation with no need to enhance specificity or adopt alternate Cas9 variants. PMID:27622539

  9. Expression and purification of histone H3 proteins containing multiple sites of lysine acetylation using nonsense suppression.

    PubMed

    Young, Isaac A; Mittal, Chitvan; Shogren-Knaak, Michael A

    2016-02-01

    Lysine acetylation is a common post-translational modification, which is especially prevalent in histone proteins in chromatin. A number of strategies exist for generating histone proteins containing lysine acetylation, but an especially attractive approach is to genetically encode acetyl-lysine residues using nonsense suppression. This strategy has been successfully applied to single sites of histone acetylation. However, because histone acetylation can often occur at multiple sites simultaneously, we were interested in determining whether this approach could be extended. Here we show that we can express histone H3 proteins that incorporate up to four sites of lysine acetylation on the histone tail. Because the amount of expressed multi-acetylated histone is reduced relative to the wild type, a purification strategy involving affinity purification and ion exchange chromatography was optimized. This expression and purification strategy ultimately generates H3 histone uniformly acetylated at the desired position at levels and purity sufficient to assemble histone octamers. Histone octamers containing four sites of lysine acetylation were assembled into mononucleosomes and enzymatic assays confirmed that this acetylation largely blocks further acetylation by the yeast SAGA acetyltransferase complex.

  10. The heterodimeric sweet taste receptor has multiple potential ligand binding sites.

    PubMed

    Cui, Meng; Jiang, Peihua; Maillet, Emeline; Max, Marianna; Margolskee, Robert F; Osman, Roman

    2006-01-01

    The sweet taste receptor is a heterodimer of two G protein coupled receptors, T1R2 and T1R3. This discovery has increased our understanding at the molecular level of the mechanisms underlying sweet taste. Previous experimental studies using sweet receptor chimeras and mutants show that there are at least three potential binding sites in this heterodimeric receptor. Receptor activity toward the artificial sweeteners aspartame and neotame depends on residues in the amino terminal domain of human T1R2. In contrast, receptor activity toward the sweetener cyclamate and the sweet taste inhibitor lactisole depends on residues within the transmembrane domain of human T1R3. Furthermore, receptor activity toward the sweet protein brazzein depends on the cysteine rich domain of human T1R3. Although crystal structures are not available for the sweet taste receptor, useful homology models can be developed based on appropriate templates. The amino terminal domain, cysteine rich domain and transmembrane helix domain of T1R2 and T1R3 have been modeled based on the crystal structures of metabotropic glutamate receptor type 1, tumor necrosis factor receptor, and bovine rhodopsin, respectively. We have used homology models of the sweet taste receptors, molecular docking of sweet ligands to the receptors, and site-directed mutagenesis of the receptors to identify potential ligand binding sites of the sweet taste receptor. These studies have led to a better understanding of the structure and function of this heterodimeric receptor, and can act as a guide for rational structure-based design of novel non-caloric sweeteners, which can be used in the fighting against obesity and diabetes. PMID:17168764

  11. HPV Prevalence in Multiple Anatomical Sites among Men Who Have Sex with Men in Peru

    PubMed Central

    Blas, Magaly M.; Brown, Brandon; Menacho, Luis; Alva, Isaac E.; Silva-Santisteban, Alfonso; Carcamo, Cesar

    2015-01-01

    Background Human Papilloma Virus (HPV) infection is the most common sexually transmitted viral infection worldwide. HPV is highly prevalent in sexually active men who have sex with men (MSM) and has been associated with anal cancer, penile cancer, and oropharyngeal cancer. Methods From March to September 2011, we conducted a cross-sectional study of HPV prevalence among MSM above age 18 years. Participants were recruited using respondent driven sampling at Clinica Cayetano Heredia. All participants provided anal, genital, and oral samples for HPV DNA testing, and blood for HIV and HPV antibody testing. Results A total of 200 MSM were recruited in the study. The mean age was 34 years (range 18–59 years, SD = 9.4) and101 participants were HIV negative (99 HIV positive). HPV 6/11/16/18 or quadrivalent HPV vaccine (HPV4) genotype seroprevalence among HIV negative and positive MSM was 64.3% (55%-75.9%) and 93.8% (87.6%-99.2%) respectively (p<0.001). HIV positivity was associated with a higher prevalence of HPV4 and HPV 16/18 DNA at external genital sites and the anal canal. HPV4 DNA prevalence at external genital sites among HIV negative and positive MSM was 14.9% and 28.7% (p = 0.02) respectively, at anal canal was 50.9% and 79.0% (p = 0.001), and at the oral cavity was 9.9% and 8.5% (p = 0.6). Conclusions HPV4 seroprevalence was high in our study among both HIV positives and negatives, with HPV DNA prevalence much lower, and the anal canal being the anatomical site with the highest HPV DNA prevalence. HPV prevention interventions are needed among MSM at high-risk for HIV infection. PMID:26437318

  12. The heterodimeric sweet taste receptor has multiple potential ligand binding sites.

    PubMed

    Cui, Meng; Jiang, Peihua; Maillet, Emeline; Max, Marianna; Margolskee, Robert F; Osman, Roman

    2006-01-01

    The sweet taste receptor is a heterodimer of two G protein coupled receptors, T1R2 and T1R3. This discovery has increased our understanding at the molecular level of the mechanisms underlying sweet taste. Previous experimental studies using sweet receptor chimeras and mutants show that there are at least three potential binding sites in this heterodimeric receptor. Receptor activity toward the artificial sweeteners aspartame and neotame depends on residues in the amino terminal domain of human T1R2. In contrast, receptor activity toward the sweetener cyclamate and the sweet taste inhibitor lactisole depends on residues within the transmembrane domain of human T1R3. Furthermore, receptor activity toward the sweet protein brazzein depends on the cysteine rich domain of human T1R3. Although crystal structures are not available for the sweet taste receptor, useful homology models can be developed based on appropriate templates. The amino terminal domain, cysteine rich domain and transmembrane helix domain of T1R2 and T1R3 have been modeled based on the crystal structures of metabotropic glutamate receptor type 1, tumor necrosis factor receptor, and bovine rhodopsin, respectively. We have used homology models of the sweet taste receptors, molecular docking of sweet ligands to the receptors, and site-directed mutagenesis of the receptors to identify potential ligand binding sites of the sweet taste receptor. These studies have led to a better understanding of the structure and function of this heterodimeric receptor, and can act as a guide for rational structure-based design of novel non-caloric sweeteners, which can be used in the fighting against obesity and diabetes.

  13. Communication: Active space decomposition with multiple sites: Density matrix renormalization group algorithm

    SciTech Connect

    Parker, Shane M.; Shiozaki, Toru

    2014-12-07

    We extend the active space decomposition method, recently developed by us, to more than two active sites using the density matrix renormalization group algorithm. The fragment wave functions are described by complete or restricted active-space wave functions. Numerical results are shown on a benzene pentamer and a perylene diimide trimer. It is found that the truncation errors in our method decrease almost exponentially with respect to the number of renormalization states M, allowing for numerically exact calculations (to a few μE{sub h} or less) with M = 128 in both cases. This rapid convergence is because the renormalization steps are used only for the interfragment electron correlation.

  14. The Transcription Factor Bach2 Is Phosphorylated at Multiple Sites in Murine B Cells but a Single Site Prevents Its Nuclear Localization.

    PubMed

    Ando, Ryo; Shima, Hiroki; Tamahara, Toru; Sato, Yoshihiro; Watanabe-Matsui, Miki; Kato, Hiroki; Sax, Nicolas; Motohashi, Hozumi; Taguchi, Keiko; Yamamoto, Masayuki; Nio, Masaki; Maeda, Tatsuya; Ochiai, Kyoko; Muto, Akihiko; Igarashi, Kazuhiko

    2016-01-22

    The transcription factor Bach2 regulates the immune system at multiple points, including class switch recombination (CSR) in activated B cells and the function of T cells in part by restricting their terminal differentiation. However, the regulation of Bach2 expression and its activity in the immune cells are still unclear. Here, we demonstrated that Bach2 mRNA expression decreased in Pten-deficient primary B cells. Bach2 was phosphorylated in primary B cells, which was increased upon the activation of the B cell receptor by an anti-immunoglobulin M (IgM) antibody or CD40 ligand. Using specific inhibitors of kinases, the phosphorylation of Bach2 in activated B cells was shown to depend on the phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway. The complex of mTOR and Raptor phosphorylated Bach2 in vitro. We identified multiple new phosphorylation sites of Bach2 by mass spectrometry analysis of epitope-tagged Bach2 expressed in the mature B cell line BAL17. Among the sites identified, serine 535 (Ser-535) was critical for the regulation of Bach2 because a single mutation of Ser-535 abolished cytoplasmic accumulation of Bach2, promoting its nuclear accumulation in pre-B cells, whereas Ser-509 played an auxiliary role. Bach2 repressor activity was enhanced by the Ser-535 mutation in B cells. These results suggest that the PI3K-Akt-mTOR pathway inhibits Bach2 by both repressing its expression and inducing its phosphorylation in B cells. PMID:26620562

  15. Partitioning of ferrocenium ions between multiple redox sites on spinacch plastocyanin

    SciTech Connect

    Pladziewicz, J.R.; Brenner, M.S.

    1987-10-21

    Kinetic measurements of the oxidation of plastocyanin (spinach) by ferrocenium, (hydroxymethyl)ferrocenium, and (chloromercurio)ferrocenium in the presence of the redox-inactive inhibitors ((NH/sub 3/)/sub 5/CoNH/sub 2/Co(NH/sub 3/)/sub 5/)/sup 5 +/, (Co(NH/sub 3/)/sub 6/)/sup 3 +/, and (Zr-(C/sub 2/O/sub 4/)/sub 4/)/sup 4 -/ as a function of pH at 25/sup 0/C and ..mu.. = 0.10 are reported. These results support a mechanism in which electrons are transferred from two locations on plastocyanin's surface; one site being the hydrophobic pocket near His-87 where copper is closest to the surface of the protein; the second being the hydrophilic, negatively charged region surrounding Tyr-83. The oxidizing agent's charge and ligand hydrophobicity and the solution pH are found to control the partitioning of the oxidizing agent between the two active sites, and the relative importance of oxidizing agent charge and hydrophobicity in this partitioning is assessed. Electron transfer from reduced plastocyanin is found to be markedly dependent on pH (pK/sub a/ = 5.03 +- 0.06), with the protonated protein being redox inactive.

  16. The mouse lymph node as an ectopic transplantation site for multiple tissues

    PubMed Central

    Komori, Junji; Boone, Lindsey; DeWard, Aaron; Hoppo, Toshitaka; Lagasse, Eric

    2012-01-01

    Cell-based therapy has been viewed as a promising alternative to organ transplantation, but cell transplantation aimed at organ repair is not always possible. Here, we show that the mouse lymph node can support the engraftment and growth of healthy cells from multiple tissues. Direct injection of hepatocytes into a single mouse lymph node generated enough ectopic liver mass to rescue survival of mice with lethal metabolic disease. Furthermore, thymuses transplanted into a lymph node of athymic nude mice generate a functional immune system capable of rejecting allogeneic and xenogeneic grafts. Finally, pancreatic islets injected into the lymph node of diabetic mice restore normal glucose control. Collectively, these results suggest the practical approach of targeting lymph nodes to restore, maintain or improve tissue and organ functions. PMID:23000933

  17. A Compact Microelectrode Array Chip with Multiple Measuring Sites for Electrochemical Applications

    PubMed Central

    Dimaki, Maria; Vergani, Marco; Heiskanen, Arto; Kwasny, Dorota; Sasso, Luigi; Carminati, Marco; Gerrard, Juliet A.; Emneus, Jenny; Svendsen, Winnie E.

    2014-01-01

    In this paper we demonstrate the fabrication and electrochemical characterization of a microchip with 12 identical but individually addressable electrochemical measuring sites, each consisting of a set of interdigitated electrodes acting as a working electrode as well as two circular electrodes functioning as a counter and reference electrode in close proximity. The electrodes are made of gold on a silicon oxide substrate and are passivated by a silicon nitride membrane. A method for avoiding the creation of high edges at the electrodes (known as lift-off ears) is presented. The microchip design is highly symmetric to accommodate easy electronic integration and provides space for microfluidic inlets and outlets for integrated custom-made microfluidic systems on top. PMID:24878592

  18. HPLC-purified 2-(/sup 125/I)iodomelatonin labels multiple binding sites in hamster brain

    SciTech Connect

    Niles, L.P.; Pickering, D.S.; Sayer, B.G.

    1987-09-30

    Binding of 2-(/sup 125/I)iodomelatonin in hamster brain synaptosomal membranes at 0 degrees C is rapid, saturable, reversible and sensitive to heat and trypsin treatment. Computer resolution of curvilinear Scatchard plots yielded high- and low-affinity components as follows: Kd1 = 0.32 +/- 0.14 nM, Bmax1 = 5.6 +/- 1.7 fmol/mg protein and Kd2 = 10.5 +/- 3.2 nM, Bmax2 = 123 +/- 33 fmol/mg protein (n = 3). Competition experiments indicated that 2-iodomelatonin and prazosin are the most potent inhibitors of high-affinity binding. Unlike prazosin, several alpha-adrenergic agents and various neurotransmitters were ineffective. These findings suggest that prazosin may be a potent antagonist at a unique, non-alpha-adrenergic, high-affinity binding site for melatonin.

  19. Multifocal extramammary Paget's disease-associated adenocarcinoma: a rare condition of flexoral skin of multiple sites.

    PubMed

    Wolf, Kristin; Stewart, Larissa; Rapini, Ronald; Mutyambizi, Kudakwashe

    2016-01-01

    Extramammary Paget disease (EMPD) is a rare malignant neoplasm of apocrine sweat glands that is morphologically and histologically identical to Paget disease of the breast. The primary lesion is usually a solitary, well-demarcated, erythematous, scaly plaque that may contain crust, erosions, or ulcerations. The vulva is the most common site, but any area containing apocrine sweat glands may be involved. We present a case of triple extramammary Paget disease of the groin and bilateral axillae in a diabetic patient whose axillary lesions appeared consistent with acanthosis nigricans. This case demonstrates the need to consider EMPD in the evaluation of acanthosis of the axilla given its ability to mimic more common conditions. PMID:26990474

  20. A challenging diagnosis: case report of extensive pyoderma gangrenosum at multiple sites

    PubMed Central

    Ye, Mingwei J; Ye, Joshua Mingsheng; Wu, Leonard; Keating, Cameron P; Choi, Wai-Ting

    2014-01-01

    Background Pyoderma gangrenosum (PG) is a rare dermatological condition characterized by the rapid progression of a painful, necrolytic ulcer with an irregular, undermined border and commonly affects the lower extremities, mainly in the pretibial area. The diagnosis of PG is not easy. Due to lack of diagnostic laboratory test and histopathological findings indicative of PG, it is often misdiagnosed as an infection. This results in delayed or inappropriate treatment of the condition, which leads to devastating consequences such as limb amputation and death. Main observations We report a rare case of a 51-year-old female who was initially diagnosed as having infected ulcers and underwent serial debridements, which resulted in extensive PG at three different sites (abdominal, left thigh, and sacral). Conclusion This case highlights the challenges in diagnosing PG, emphasizes the key clinical features to aid diagnosis, and the clinical consequences of delayed or misdiagnosis of this condition. PMID:24741322

  1. A Study on the Wind Power Generation Fluctuation of Multiple Sites

    NASA Astrophysics Data System (ADS)

    Yamagishi, Yoshio; Ueda, Tomoyuki; Kanao, Norikazu; Komami, Shintaro

    The use of renewable energy sources such as the sun and wind is increasing steadily. High penetration of wind power may affect electric power system frequency, because the fluctuations in wind power generation are much larger than that of conventional power plants. To evaluate wind power fluctuation and its effect on the power systems, it is important to acquire actual fluctuation data of wind farm power. In this paper, the authors report the results of an analysis of wind power fluctuation and smoothing effect from data measured at existing wind power sites in the Hokuriku region. A novel index is proposed to evaluate the smoothing effect, and impacts of high wind penetration are estimated using this index. This paper also proposes a control strategy of battery storage system for stabilizing wind farm output.

  2. The TRPV5/6 calcium channels contain multiple calmodulin binding sites with differential binding properties.

    PubMed

    Kovalevskaya, Nadezda V; Bokhovchuk, Fedir M; Vuister, Geerten W

    2012-06-01

    The epithelial Ca(2+) channels TRPV5/6 (transient receptor potential vanilloid 5/6) are thoroughly regulated in order to fine-tune the amount of Ca(2+) reabsorption. Calmodulin has been shown to be involved into calcium-dependent inactivation of TRPV5/6 channels by binding directly to the distal C-terminal fragment of the channels (de Groot et al. in Mol Cell Biol 31:2845-2853, 12). Here, we investigate this binding in detail and find significant differences between TRPV5 and TRPV6. We also identify and characterize in vitro four other CaM binding fragments of TRPV5/6, which likely are also involved in TRPV5/6 channel regulation. The five CaM binding sites display diversity in binding modes, binding stoichiometries and binding affinities, which may fine-tune the response of the channels to varying Ca(2+)-concentrations. PMID:22354706

  3. Uncertainty Analysis on an Operational Simplified Surface Energy Balance algorithm for Estimation of Evapotranspiration at Multiple Flux Tower Sites

    NASA Astrophysics Data System (ADS)

    Chen, M.; Senay, G. B.; Verdin, J. P.; Rowland, J.

    2014-12-01

    Current regional to global and daily to annual Evapotranspiration ( ET) estimation mainly relies on surface energy balance (SEB) ET models or statistical empirical methods driven by remote sensing data and various meteorology databases. However, these ET models face challenging issues—large uncertainties from inevitable input errors, poorly defined parameters, and inadequate model structures. The eddy covariance measurements on water, energy, and carbon fluxes at globally available FLUXNET tower sites provide a feasible opportunity to assess the ET modelling uncertainties. In this study, we focused on uncertainty analysis on an operational simplified surface energy balance (SSEBop) algorithm for ET estimation at multiple Ameriflux tower sites with diverse land cover characteristics and climatic conditions. The input land surface temperature (LST) data of the algorithm were adopted from the 8-day composite1-km Moderate Resolution Imaging Spectroradiometer (MODIS) land surface temperature. The other input data were taken from the Ameriflux database. Results of statistical analysis indicated that uncertainties or random errors from input variables and parameters of SSEBop led to daily and seasonal ET estimates with relative errors around 20% across multiple flux tower sites distributed across different biomes. This uncertainty of SSEBop lies in the error range of 20-30% of similar SEB-based ET algorithms, such as, Surface Energy Balance System and Surface Energy Balance Algorithm for Land. The R2 between daily and seasonal ET estimates by SSEBop and ET eddy covariance measurements at multiple Ameriflux tower sites exceed 0.7, and even up to 0.9 for croplands, grasslands, and forests, suggesting systematic error or bias of the SSEBop is acceptable. In summary, the uncertainty assessment verifies that the SSEBop is a reliable method for wide-area ET calculation and especially useful for detecting drought years and relative drought severity for agricultural production

  4. Localization of the Rsp5p Ubiquitin-Protein Ligase at Multiple Sites within the Endocytic Pathway

    PubMed Central

    Wang, Guangli; McCaffery, J. Michael; Wendland, Beverly; Dupré, Sophie; Haguenauer-Tsapis, Rosine; Huibregtse, Jon M.

    2001-01-01

    The Saccharomyces cerevisiae RSP5 gene encodes an essential HECT E3 ubiquitin-protein ligase. Rsp5p contains an N-terminal C2 domain, three WW domains in the central portion of the molecule, and a C-terminal catalytic HECT domain. A diverse group of substrates of Rsp5p and vertebrate C2 WW-domain-containing HECT E3s have been identified, including both nuclear and membrane-associated proteins. We determined the intracellular localization of Rsp5p and the determinants necessary for localization, in order to better understand how Rsp5p activities are coordinated. Using both green fluorescent protein fusions to Rsp5p and immunogold electron microscopy, we found that Rsp5p was distributed in a punctate pattern at the plasma membrane, corresponding to membrane invaginations that are likely sites of endosome formation, as well as at perivacuolar sites. The latter appeared to correspond to endocytic intermediates, as these structures were not seen in a sla2/end4-1 mutant, and double-immunogold labeling demonstrated colocalization of Rsp5p with the endosomal markers Pep12p and Vps32p. The C2 domain was an important determinant of localization; however, mutations that disrupted HECT domain function also caused mislocalization of Rsp5p, indicating that enzymatic activity is linked to localization. Deletion of the C2 domain partially stabilized Fur4p, a protein previously shown to undergo Rsp5p- and ubiquitin-mediated endocytosis; however, Fur4p was still ubiquitinated at the plasma membrane when the C2 domain was deleted from the protein. Together, these results indicate that Rsp5p is located at multiple sites within the endocytic pathway and suggest that Rsp5p may function at multiple steps in the ubiquitin-mediated endocytosis pathway. PMID:11313482

  5. Initial success of native grasses is contingent on multiple interactions among exotic grass competition, temporal priority, rainfall and site effects

    PubMed Central

    Young, Truman P.; Zefferman, Emily P.; Vaughn, Kurt J.; Fick, Stephen

    2015-01-01

    Ecological communities are increasingly being recognized as the products of contemporary drivers and historical legacies that are both biotic and abiotic. In an attempt to unravel multiple layers of ecological contingency, we manipulated (i) competition with exotic annual grasses, (ii) the timing of this competition (temporal priority in arrival/seeding times) and (iii) watering (simulated rainfall) in a restoration-style planting of native perennial grasses. In addition, we replicated this experiment simultaneously at three sites in north-central California. Native perennial grasses had 73–99 % less cover when planted with exotic annuals than when planted alone, but this reduction was greatly ameliorated by planting the natives 2 weeks prior to the exotics. In a drought year, irrigation significantly reduced benefits of early planting so that these benefits resembled those observed in a non-drought year. There were significant differences across the three sites (site effects and interactions) in (i) overall native cover, (ii) the response of natives to competition, (iii) the strength of the temporal priority effect and (iv) the degree to which supplemental watering reduced priority effects. These results reveal the strong multi-layered contingency that underlies even relatively simple communities. PMID:25480888

  6. SET7/9 Catalytic Mutants Reveal the Role of Active Site Water Molecules in Lysine Multiple Methylation*

    PubMed Central

    Del Rizzo, Paul A.; Couture, Jean-François; Dirk, Lynnette M. A.; Strunk, Bethany S.; Roiko, Marijo S.; Brunzelle, Joseph S.; Houtz, Robert L.; Trievel, Raymond C.

    2010-01-01

    SET domain lysine methyltransferases (KMTs) methylate specific lysine residues in histone and non-histone substrates. These enzymes also display product specificity by catalyzing distinct degrees of methylation of the lysine ϵ-amino group. To elucidate the molecular mechanism underlying this specificity, we have characterized the Y245A and Y305F mutants of the human KMT SET7/9 (also known as KMT7) that alter its product specificity from a monomethyltransferase to a di- and a trimethyltransferase, respectively. Crystal structures of these mutants in complex with peptides bearing unmodified, mono-, di-, and trimethylated lysines illustrate the roles of active site water molecules in aligning the lysine ϵ-amino group for methyl transfer with S-adenosylmethionine. Displacement or dissociation of these solvent molecules enlarges the diameter of the active site, accommodating the increasing size of the methylated ϵ-amino group during successive methyl transfer reactions. Together, these results furnish new insights into the roles of active site water molecules in modulating lysine multiple methylation by SET domain KMTs and provide the first molecular snapshots of the mono-, di-, and trimethyl transfer reactions catalyzed by these enzymes. PMID:20675860

  7. Initial success of native grasses is contingent on multiple interactions among exotic grass competition, temporal priority, rainfall and site effects.

    PubMed

    Young, Truman P; Zefferman, Emily P; Vaughn, Kurt J; Fick, Stephen

    2014-12-05

    Ecological communities are increasingly being recognized as the products of contemporary drivers and historical legacies that are both biotic and abiotic. In an attempt to unravel multiple layers of ecological contingency, we manipulated (i) competition with exotic annual grasses, (ii) the timing of this competition (temporal priority in arrival/seeding times) and (iii) watering (simulated rainfall) in a restoration-style planting of native perennial grasses. In addition, we replicated this experiment simultaneously at three sites in north-central California. Native perennial grasses had 73-99 % less cover when planted with exotic annuals than when planted alone, but this reduction was greatly ameliorated by planting the natives 2 weeks prior to the exotics. In a drought year, irrigation significantly reduced benefits of early planting so that these benefits resembled those observed in a non-drought year. There were significant differences across the three sites (site effects and interactions) in (i) overall native cover, (ii) the response of natives to competition, (iii) the strength of the temporal priority effect and (iv) the degree to which supplemental watering reduced priority effects. These results reveal the strong multi-layered contingency that underlies even relatively simple communities.

  8. Identification of multiple binding sites for the THAP domain of the Galileo transposase in the long terminal inverted-repeats.

    PubMed

    Marzo, Mar; Liu, Danxu; Ruiz, Alfredo; Chalmers, Ronald

    2013-08-01

    Galileo is a DNA transposon responsible for the generation of several chromosomal inversions in Drosophila. In contrast to other members of the P-element superfamily, it has unusually long terminal inverted-repeats (TIRs) that resemble those of Foldback elements. To investigate the function of the long TIRs we derived consensus and ancestral sequences for the Galileo transposase in three species of Drosophilids. Following gene synthesis, we expressed and purified their constituent THAP domains and tested their binding activity towards the respective Galileo TIRs. DNase I footprinting located the most proximal DNA binding site about 70 bp from the transposon end. Using this sequence we identified further binding sites in the tandem repeats that are found within the long TIRs. This suggests that the synaptic complex between Galileo ends may be a complicated structure containing higher-order multimers of the transposase. We also attempted to reconstitute Galileo transposition in Drosophila embryos but no events were detected. Thus, although the limited numbers of Galileo copies in each genome were sufficient to provide functional consensus sequences for the THAP domains, they do not specify a fully active transposase. Since the THAP recognition sequence is short, and will occur many times in a large genome, it seems likely that the multiple binding sites within the long, internally repetitive, TIRs of Galileo and other Foldback-like elements may provide the transposase with its binding specificity.

  9. Splice junctions in adenovirus 2 early region 4 mRNAs: multiple splice sites produce 18 to 24 RNAs.

    PubMed Central

    Tigges, M A; Raskas, H J

    1984-01-01

    We localized the splice junctions in adenovirus 2 early region 4 (E4) mRNAs. Processing of the E4 precursor RNA positioned the donor splice site of the 5' leader sequence adjacent to acceptor sites near the 5' ends of five of the six open reading regions in the E4 transcription unit. Of particular interest among the E4 mRNAs is an extensively spliced class which includes multiple species with sizes ranging from 1.1 to 0.75 kilobases (kb). Purified 1.1- to 0.75-kb mRNAs specified at least 10 polypeptides in vitro. We detected eight acceptor and two donor splice sites utilized in the deletion of the intron from the 3' portion of these mRNAs. E4 RNAs were isolated from the cytoplasm of infected cells at 5, 9, 12, and 18 h after infection. The E4 mRNAs were present throughout infection, but different members of the 1.1- to 0.7-kb class were predominant at each time assayed. Alternate splicing of the 3.0-kb E4 precursor RNA can generate as many as 25 mRNAs that encode at least 16 polypeptides. Images PMID:6336328

  10. Nonparametric statistical methods for comparing two sites based on data with multiple non-detect limits

    NASA Astrophysics Data System (ADS)

    Millard, Steven P.; Deverel, Steven J.

    1988-12-01

    As concern over the effects of trace amounts of pollutants has increased, so has the need for statistical methods that deal appropriately with data that include values reported as "less than" the detection limit. It has become increasingly common for water quality data to include censored values that reflect more than one detection limit for a single analyte. For such multiply censored data sets, standard statistical methods (for example, to compare analyte concentration in two areas) are not valid. In such cases, methods from the biostatistical field of survival analysis are applicable. Several common two-sample censored data rank tests are explained, and their behaviors are studied via a Monte Carlo simulation in which sample sizes and censoring mechanisms are varied under an assumed lognormal distribution. These tests are applied to shallow groundwater chemistry data from two sites in the San Joaquin Valley, California. The best overall test, in terms of maintained α level, is the normal scores test based on a permutation variance. In cases where the α level is maintained, however, the Peto-Prentice statistic based on an asymptotic variance performs as well or better.

  11. Using multiple ecological assessment techniques to screen for a wetlands reference site

    SciTech Connect

    Smith, B.M.; McNaughton, E.E.; Wagner, A.; Vig, A.; Zinky, L.; McCormick, S.

    1995-12-31

    Previous investigation of the landfill on the Concord Naval Weapons Station, located in a diked wetland, showed that the sediments exhibited elevated levels of inorganic analytes, as compared to national benchmarks, such as the NOAA ER-Ls. The need to identify a reference marsh was recognized because of the likelihood that these levels of inorganics were representative of ambient conditions, rather than associated with releases to the environment. A marsh location was selected that was upgradient of the landfill, and distant from sources of known contamination, such as roadways and railroad tracks. Sediment samples were analyzed for bulk sediment chemistry, toxicity, and benthic community structure. Bulk sediment chemistry results showed elevated concentrations of lead and petroleum-related organic compounds, perhaps associated with a historic pipeline break. Pore water was prepared from sediment collocated with the bulk chemistry samples and tested with the sea urchin development bioassay. Compared to the control, three of four sediment pore water samples were highly inhibitory of normal development. However, the benthic community survey from the same sampling stations showed a health assemblage of organisms, although one station that exhibited visible petroleum contamination also showed reduced abundance. The conflicting results demonstrate the necessity for taking more than one measure in developing the ecological assessment of a site.

  12. HWY-289, a novel semi-synthetic protoberberine derivative with multiple target sites in Candida albicans.

    PubMed

    Park, K S; Kang, K C; Kim, K Y; Jeong, P Y; Kim, J H; Adams, D J; Kim, J H; Paik, Y K

    2001-05-01

    The antifungal properties of 515 synthetic and semi-synthetic protoberberines were investigated. HWY-289 was chosen for further study because it exhibited the most significant anti-Candida activity (MICs were 1.56 mg/L for Candida albicans and Candida krusei; 6.25 mg/L for Candida guilliermondii) but did not demonstrate toxicity in rats. HWY-289 inhibited the incorporation of L-[methyl-(14)C]methionine into the C-24 of ergosterol in whole cells of C. albicans (IC(50) 20 microM). However, HWY-289 (100 microM) had no effect on mammalian cholesterol biosynthesis in rat microsomes while miconazole (100 microM) was a potent inhibitor of cholesterol biosynthesis under identical assay conditions. A second major target site for HWY-289 was identified that involves cell wall biosynthesis in C. albicans. HWY-289 was a potent inhibitor of the chitin synthase isozymes CaCHS1 and CaCHS2, with IC(50) values of 22 microM for each enzyme. The effect was highly specific in that HWY-289 had no significant effect on C. albicans CaCHS3 (IC(50) > 200 microM). Thus, HWY-289 compared favourably with well-established antifungal agents as an inhibitor of the growth of Candida species in vitro, and may have considerable potential as a new class of antifungal agent that lacks toxic side effects in the human host.

  13. Testing congruence among multiple grazing indicators: a multi-site study across the Tibetan plateau

    NASA Astrophysics Data System (ADS)

    Wang, Yun; Lehnert, Lukas; Holzapfel, Maika; Schultz, Roland; Heberling, Gwendolyn; Görzen, Eugen; Meyer, Hanna; Seeber, Elke; Pinkert, Stefan; Ritz, Markus; Ansorge, Hermann; Bendix, Jörg; Seifert, Bernhard; Miehe, Georg; Long, Ruijun; Yang, Yongping; Wesche, Karsten

    2015-04-01

    Aim Animal husbandry is one of the most widespread land use types, and grazing is a key topic in grassland management. A wide range of indicators are employed in grazing assessments and they often yield widely differing estimates on the associated level of degradation threat. Covering Tibet as a large grassland region with long history of pastoralism, we selected representative indicators to test: (1) how grazing responses change along large-scale climatic gradients, and (2) whether their responses to both grazing intensities and local abiotic conditions are congruent. Location Tibetan Plateau Methods Biotic indicators including species and growth form compositions of vascular plants, richness and abundance of small mammals and ants, together with soil nutrients and field spectra were compared in pairs of high and low grazing intensity at 18 sites across large climatic gradients. Altitude, temperature, and precipitation were considered as potentially influential abiotic factors. Responses of indicators to grazing intensity and environmental gradients were explored by multivariate and univariate analyses. Results All indicators responded strongly to environmental changes, but the response patterns and the most influential abiotic factors varied among indicators. Grazing responses showed low overall congruence. Only vegetation cover, soil nutrient concentrations, and spectral indices were sensitive to grazing across large spatial scales. Grazing effects were significant only when local abiotic factors were taken into account. Main conclusions The results imply that grazing assessments require both appropriate indicators and local calibration. Overall, the threat of grassland degradation across the Tibetan Plateau is not as severe as is commonly assumed.

  14. Probabilistic Inference on Multiple Normalized Signal Profiles from Next Generation Sequencing: Transcription Factor Binding Sites.

    PubMed

    Wong, Ka-Chun; Peng, Chengbin; Li, Yue

    2015-01-01

    With the prevalence of chromatin immunoprecipitation (ChIP) with sequencing (ChIP-Seq) technology, massive ChIP-Seq data has been accumulated. The ChIP-Seq technology measures the genome-wide occupancy of DNA-binding proteins in vivo. It is well-known that different DNA-binding protein occupancies may result in a gene being regulated in different conditions (e.g. different cell types). To fully understand a gene's function, it is essential to develop probabilistic models on multiple ChIP-Seq profiles for deciphering the gene transcription causalities. In this work, we propose and describe two probabilistic models. Assuming the conditional independence of different DNA-binding proteins' occupancies, the first method (SignalRanker) is developed as an intuitive method for ChIP-Seq genome-wide signal profile inference. Unfortunately, such an assumption may not always hold in some gene regulation cases. Thus, we propose and describe another method (FullSignalRanker) which does not make the conditional independence assumption. The proposed methods are compared with other existing methods on ENCODE ChIP-Seq datasets, demonstrating its regression and classification ability. The results suggest that FullSignalRanker is the best-performing method for recovering the signal ranks on the promoter and enhancer regions. In addition, FullSignalRanker is also the best-performing method for peak sequence classification. We envision that SignalRanker and FullSignalRanker will become important in the era of next generation sequencing. FullSignalRanker program is available on the following website: http://www.cs.toronto.edu/~wkc/FullSignalRanker/.

  15. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

    PubMed

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus

    2011-10-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

  16. Probabilistic Inference on Multiple Normalized Signal Profiles from Next Generation Sequencing: Transcription Factor Binding Sites.

    PubMed

    Wong, Ka-Chun; Peng, Chengbin; Li, Yue

    2015-01-01

    With the prevalence of chromatin immunoprecipitation (ChIP) with sequencing (ChIP-Seq) technology, massive ChIP-Seq data has been accumulated. The ChIP-Seq technology measures the genome-wide occupancy of DNA-binding proteins in vivo. It is well-known that different DNA-binding protein occupancies may result in a gene being regulated in different conditions (e.g. different cell types). To fully understand a gene's function, it is essential to develop probabilistic models on multiple ChIP-Seq profiles for deciphering the gene transcription causalities. In this work, we propose and describe two probabilistic models. Assuming the conditional independence of different DNA-binding proteins' occupancies, the first method (SignalRanker) is developed as an intuitive method for ChIP-Seq genome-wide signal profile inference. Unfortunately, such an assumption may not always hold in some gene regulation cases. Thus, we propose and describe another method (FullSignalRanker) which does not make the conditional independence assumption. The proposed methods are compared with other existing methods on ENCODE ChIP-Seq datasets, demonstrating its regression and classification ability. The results suggest that FullSignalRanker is the best-performing method for recovering the signal ranks on the promoter and enhancer regions. In addition, FullSignalRanker is also the best-performing method for peak sequence classification. We envision that SignalRanker and FullSignalRanker will become important in the era of next generation sequencing. FullSignalRanker program is available on the following website: http://www.cs.toronto.edu/~wkc/FullSignalRanker/. PMID:26671811

  17. Pharmacophore modeling using Site-Identification by Ligand Competitive Saturation (SILCS) with multiple probe molecules

    PubMed Central

    Yu, Wenbo; Lakkaraju, Sirish Kaushik; Raman, E. Prabhu; Fang, Lei; MacKerell, Alexander D.

    2015-01-01

    Receptor-based pharmacophore modeling is an efficient computer-aided drug design technique that uses the structure of the target protein to identify novel leads. However, most methods consider protein flexibility and desolvation effects in a very approximate way, which may limit their use in practice. The Site-Identification by Ligand Competitive Saturation (SILCS) assisted pharmacophore modeling protocol (SILCS-Pharm) was introduced recently to address these issues as SILCS naturally takes both protein flexibility and desolvation effects into account by using full MD simulations to determine 3D maps of the functional group-affinity patterns on a target receptor. In the present work, the SILCS-Pharm protocol is extended to use a wider range of probe molecules including benzene, propane, methanol, formamide, acetaldehyde, methylammonium, acetate and water. This approach removes the previous ambiguity brought by using water as both the hydrogen-bond donor and acceptor probe molecule. The new SILCS-Pharm protocol is shown to yield improved screening results as compared to the previous approach based on three target proteins. Further validation of the new protocol using five additional protein targets showed improved screening compared to those using common docking methods, further indicating improvements brought by the explicit inclusion of additional feature types associated with the wider collection of probe molecules in the SILCS simulations. The advantage of using complementary features and volume constraints, based on exclusion maps of the protein defined from the SILCS simulations, is presented. In addition, re-ranking using SILCS-based ligand grid free energies is shown to enhance the diversity of identified ligands for the majority of targets. These results suggest that the SILCS-Pharm protocol will be of utility in rational drug design. PMID:25622696

  18. Multiple-site replacement analogs of glucagon. A molecular basis for antagonist design.

    PubMed

    Unson, C G; Wu, C R; Fitzpatrick, K J; Merrifield, R B

    1994-04-29

    Extensive structure activity analysis has allowed us to identify specific residues in the glucagon sequence that are responsible for either receptor recognition or signal transduction. For instance, we have demonstrated that aspartic acid 9 and histidine 1 are essential for activation, and that an ionic interaction between the negative carboxylate and the protonated imidazole may contribute to the activation reaction at the molecular level. In the absence of the carboxylic group at position 9, aspartic 21 or aspartic 15 might furnish distal electrostatic effects to maintain partial agonism. Further investigation established that each of the 4 serine residues in the hormone play distinct roles. Serine 8 provides an important determinant of binding. Whereas neither serines 2, 11, nor 16 are required for receptor recognition. We have shown that serine 16 is essential for signal transduction and thus have identified it to be the third residue in glucagon to participate in a putative catalytic triad together with aspartic 9 and histidine 1, in the transduction of the glucagon response. In this work, we utilized insights into the functional significance of particular residues in the peptide appropriated from our structure-function assignments, as the basis of a molecular approach for the design of active-site directed antagonists of glucagon. The importance as well as the accuracy of our findings are confirmed by the synthesis of a series of improved glucagon antagonists based on replacements at positions 1, 9, 11, 16, and 21. The inhibition index, (I/A)50, of our best antagonist des-His1-[Nle9-Ala11-Ala16]glucagon amide, has been improved 10-fold over the previous best glucagon inhibitor. PMID:8175663

  19. Replication initiates at multiple dispersed sites in the ribosomal DNA plasmid of the protozoan parasite Entamoeba histolytica.

    PubMed

    Dhar, S K; Choudhury, N R; Mittal, V; Bhattacharya, A; Bhattacharya, S

    1996-05-01

    In the protozoan parasite Entamoeba histolytica (which causes amoebiasis in humans), the rRNA genes (rDNA) in the nucleus are carried on an extrachromosomal circular plasmid. For strain HM-1:IMSS, the size of the rDNA plasmid is 24.5 kb, and 200 copies per genome are present. Each circle contains two rRNA transcription units as inverted repeats separated by upstream and downstream spacers. We have studied the replication of this molecule by neutral/neutral two-dimensional gel electrophoresis and by electron microscopy. All restriction fragments analyzed by two-dimensional gel electrophoresis gave signals corresponding to simple Y's and bubbles. This showed that replication initiated in this plasmid at multiple, dispersed locations spread throughout the plasmid. On the basis of the intensity of the bubble arcs, initiations from the rRNA transcription units seemed to occur more frequently than those from intergenic spacers. Multiple, dispersed initiation sites were also seen in the rDNA plasmid of strain HK-9 when it was analyzed by two-dimensional gel electrophoresis. Electron microscopic visualization of replicating plasmid molecules in strain HM-1:IMISS showed multiple replication bubbles in the same molecule. The location of bubbles on the rDNA circle was mapped by digesting with PvuI or BsaHI, which linearize the molecule, and with SacII, which cuts the circle twice. The distance of the bubbles from one end of the molecule was measured by electron microscopy. The data corroborated those from two-dimensional gels and showed that replication bubbles were distributed throughout the molecule and that they appeared more frequently in rRNA transcription units. The same interpretation was drawn from electron microscopic analysis of the HK-9 plasmid. Direct demonstration of more than one bubble in the same molecule is clear evidence that replication of this plasmid initiates at multiple sites. Potential replication origins are distributed throughout the plasmid. Such a

  20. Myc-Max heterodimers activate a DEAD box gene and interact with multiple E box-related sites in vivo.

    PubMed

    Grandori, C; Mac, J; Siëbelt, F; Ayer, D E; Eisenman, R N

    1996-08-15

    The c-Myc protein is involved in cell proliferation, differentiation and apoptosis though heterodimerization with Max to form a transcriptionally active sequence-specific DNA binding complex. By means of sequential immunoprecipitation of chromatin using anti-Max and anti-Myc antibodies, we have identified a Myc-regulated gene and genomic sites occupied by Myc-Max in vivo. Four of 27 sites recovered by this procedure corresponded to the highest affinity 'canonical' CACGTG sequence. However, the most common in vivo binding sites belonged to the group of 'non-canonical' E box-related binding sites previously identified by in vitro selection. Several of the genomic fragments isolated contained transcribed sequences, including one, MrDb, encoding an evolutionarily conserved RNA helicase of the DEAD box family. The corresponding mRNA was induced following activation of a Myc-estrogen receptor fusion protein (Myc-ER) in the presence of a protein synthesis inhibitor, consistent with this helicase gene being a direct target of Myc-Max. In addition, as for c-Myc, the expression of MrDb is induced upon proliferative stimulation of primary human fibroblasts as well as B cells and down-regulated during terminal differentiation of HL60 leukemia cells. Our results indicate that Myc-Max heterodimers interact in vivo with a specific set of E box-related DNA sequences and that Myc is likely to activate multiple target genes including a highly conserved DEAD box protein. Therefore, Myc may exert its effects on cell behavior through proteins that affect RNA structure and metabolism.

  1. Multiple Scattering X-Ray Absorption Studies of Zn2+ Binding Sites in Bacterial Photosynthetic Reaction Centers

    PubMed Central

    Giachini, Lisa; Francia, Francesco; Mallardi, Antonia; Palazzo, Gerardo; Carpenè, Emilio; Boscherini, Federico; Venturoli, Giovanni

    2005-01-01

    Binding of transition metal ions to the reaction center (RC) protein of the photosynthetic bacterium Rhodobacter sphaeroides has been previously shown to slow light-induced electron and proton transfer to the secondary quinone acceptor molecule, QB. On the basis of x-ray diffraction at 2.5 Å resolution a site, formed by AspH124, HisH126, and HisH128, has been identified at the protein surface which binds Cd2+ or Zn2+. Using Zn K-edge x-ray absorption fine structure spectroscopy we report here on the local structure of Zn2+ ions bound to purified RC complexes embedded into polyvinyl alcohol films. X-ray absorption fine structure data were analyzed by combining ab initio simulations and multiparameter fitting; structural contributions up to the fourth coordination shell and multiple scattering paths (involving three atoms) have been included. Results for complexes characterized by a Zn to RC stoichiometry close to one indicate that Zn2+ binds two O and two N atoms in the first coordination shell. Higher shell contributions are consistent with a binding cluster formed by two His, one Asp residue, and a water molecule. Analysis of complexes characterized by ∼2 Zn ions per RC reveals a second structurally distinct binding site, involving one O and three N atoms, not belonging to a His residue. The local structure obtained for the higher affinity site nicely fits the coordination geometry proposed on the basis of x-ray diffraction data, but detects a significant contraction of the first shell. Two possible locations of the second new binding site at the cytoplasmic surface of the RC are proposed. PMID:15613631

  2. Interaction between CME and surrounding magnetic fields producing multiple flaring sites

    NASA Astrophysics Data System (ADS)

    van Driel-Gesztelyi, Lidia M.

    2015-08-01

    L. van Driel-Gesztelyi (1,2,3), D. Baker (1), T. Török (4), E. Pariat (2), L.M. Green (1),D.R. Williams (1), J. Carlyle (1,5) G. Valori (1, 2), P. Démoulin (2), B. Kliem (1,7,8),D. Long (1), S.A. Matthews (1), J.-M. Malherbe (2)(1) UCL/MSSL, UK, (2) Paris Observatory, LESIA, CNRS, France, (3) Konkoly Observatory, Hungary, (4) Predictive Science, Dan Diego, USA, (5) Max Planck Inst., Göttingen, Germany, (6) INAF, Obs. Roma, Italy, (7) Potsdam Univ., Germany, (8) Yunnan Observatories, Kunming, ChinaAnalyzing Solar Dynamics Observatory (SDO) observations of the spectacular Coronal Mass Ejection eruption on 7 June 2011, we present evidence of coronal magnetic reconnection between the expanding magnetic structure of the CME and the magnetic fields of an adjacent active region (AR). The onset of reconnection first became apparent in the SDO/AIA images when filament plasma, originally contained within the erupting flux rope, was re-directed towards remote areas in the neighboring AR, tracing the change of large-scale magnetic connectivity. The observations are presented jointly with a topological analysis of the pre-eruption magnetic configuration, and a data-constrained numerical simulation of the three-AR complex, demonstrating the formation/intensification of current sheets along a pre-existing hyperbolic flux tube (HFT) at the interface between the CME and the neighboring AR, where a secondary flare ribbon was created. Reconnection across this current sheet resulted in the formation of new magnetic connections between the erupting magnetic structure and a neighboring AR about 200 Mm from the eruption site, in strong qualitative agreement with the observations. In addition, the CME temporarily created unusually dense plasma conditions around a reconnection region at high coronal altitudes, enabling us to observe emission resulting from it. We argue that this exceptional observation of a coronal brightening was directly observable at SDO/AIA wavelengths owing to the

  3. Activation of multiple sites by adenosine analogues in the rat isolated aorta.

    PubMed Central

    Prentice, D. J.; Hourani, S. M.

    1996-01-01

    microM) E/[A] curves to NECA and CPA were right-shifted. However, no further shift of the CPA E/[A] curve was obtained when 8-SPT (50 microM) was administered concomitantly. The locations of curves to R-PIA and adenosine were unaffected by L-NAME (100 microM). 6. In the presence of PD 115,199 (0.1 microM) a parallel rightward shift of NECA E/[A] curves was observed (pA2 = 7.50 +/- 0.19). PD 115,199 (0.1 and 1 microM) gave smaller rightward shifts of E/[A] curves to R-PIA and CPA, but E/[A] curves to adenosine were not significantly shifted in the presence of PD 115,199 (0.1 or 1 microM). 7. The presence of ZM 241385 (3 nM-0.3 microM) caused parallel rightwad shifts of NECA E/[A] curves (pKB = 8.73 +/- 0.11). No significant shifts of E/[A] curves to adenosine, CPA or R-PIA were observed in the presence of 0.1 microM ZM 241385. 8. CGS 21680 (1 microM) elicited a relaxant response equivalent to approximately 40% of the NECA maximum response. In the presence of this concentration of CGS 21680, E/[A] curves to NECA were right-shifted in excess of 2-log units, whereas E/[A] curves to R-PIA were not significantly shifted. 9. BWA1433 (100 microM) caused a small but significant right-shift of the E/[A] curve to R-PIA yielding a pA2 estimate of 4.1 IB-MECA (N6-(3-iodo-benzyl)adenosine-5(1)-N-methyl uronamide) elicited relaxant responses which were resistant to blockade by 8-SPT (p[A]50 = 5.26 +/- 0.13). 10. The results suggest that whereas relaxations to NECA (10 nM-1 microM) are mediated via adenosine A2a receptors, which are located at least in part on the endothelium, R-PIA and CPA may activate A2b receptors on the endothelium and an additional, as yet undefined site, which is likely to be located on the smooth muscle and which is not susceptible to blockade by 8-SPT, PD 115,199 or ZM 241385. This site is unlikely to be an A3 receptor since the very small shift obtained in the presence of BWA1433 (100 microM), and the low potency of IB-MECA is not consistent with the affin

  4. Observation of multiple, identical binding sites in the exchange of carboxylic acid ligands with CdS nanocrystals.

    PubMed

    Li, Xin; Nichols, Valerie M; Zhou, Dapeng; Lim, Cynthia; Pau, George Shu Heng; Bardeen, Christopher J; Tang, Ming L

    2014-06-11

    We study ligand exchange between the carboxylic acid group and 5.0 nm oleic-acid capped CdS nanocrystals (NCs) using fluorescence resonance energy transfer (FRET). This is the first measurement of the initial binding events between cadmium chalcogenide NCs and carboxylic acid groups. The binding behavior can be described as an interaction between a ligand with single binding group and a substrate with multiple, identical binding sites. Assuming Poissonian binding statistics, our model fits both steady-state and time-resolved photoluminescence (SSPL and TRPL, respectively) data well. A modified Langmuir isotherm reveals that a CdS nanoparticle has an average of 3.0 new carboxylic acid ligands and binding constant, Ka, of 3.4 × 10(5) M(-1).

  5. An internal ribosome entry site (IRES) mutant library for tuning expression level of multiple genes in mammalian cells.

    PubMed

    Koh, Esther Y C; Ho, Steven C L; Mariati; Song, Zhiwei; Bi, Xuezhi; Bardor, Muriel; Yang, Yuansheng

    2013-01-01

    A set of mutated Encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) elements with varying strengths is generated by mutating the translation initiation codons of 10(th), 11(th), and 12(th) AUG to non-AUG triplets. They are able to control the relative expression of multiple genes over a wide range in mammalian cells in both transient and stable transfections. The relative strength of each IRES mutant remains similar in different mammalian cell lines and is not gene specific. The expressed proteins have correct molecular weights. Optimization of light chain over heavy chain expression by these IRES mutants enhances monoclonal antibody expression level and quality in stable transfections. Uses of this set of IRES mutants can be extended to other applications such as synthetic biology, investigating interactions between proteins and its complexes, cell engineering, multi-subunit protein production, gene therapy, and reprogramming of somatic cells into stem cells. PMID:24349195

  6. Bivalent Compound 17MN Exerts Neuroprotection through Interaction at Multiple Sites in a Cellular Model of Alzheimer's Disease.

    PubMed

    Liu, Kai; Chojnacki, Jeremy E; Wade, Emily E; Saathoff, John M; Lesnefsky, Edward J; Chen, Qun; Zhang, Shijun

    2015-01-01

    Multiple pathogenic factors have been suggested to play a role in the development of Alzheimer's disease (AD). The multifactorial nature of AD also suggests the potential use of compounds with polypharmacology as effective disease-modifying agents. Recently, we have developed a bivalent strategy to include cell membrane anchorage into the molecular design. Our results demonstrated that the bivalent compounds exhibited multifunctional properties and potent neuroprotection in a cellular AD model. Herein, we report the mechanistic exploration of one of the representative bivalent compounds, 17MN, in MC65 cells. Our results established that MC65 cells die through a necroptotic mechanism upon the removal of tetracycline (TC). Furthermore, we have shown that mitochondrial membrane potential and cytosolic Ca2+ levels are increased upon removal of TC. Our bivalent compound 17MN can reverse such changes and protect MC65 cells from TC removal induced cytotoxicity. The results also suggest that 17MN may function between the Aβ species and RIPK1 in producing its neuroprotection. Colocalization studies employing a fluorescent analog of 17MN and confocal microscopy demonstrated the interactions of 17MN with both mitochondria and endoplasmic reticulum, thus suggesting that 17MN exerts its neuroprotection via a multiple-site mechanism in MC65 cells. Collectively, these results strongly support our original design rationale of bivalent compounds and encourage further optimization of this bivalent strategy to develop more potent analogs as novel disease-modifying agents for AD. PMID:26401780

  7. Bivalent compound 17MN exerts neuroprotection through interaction at multiple sites in a cellular model of Alzheimer’s disease

    PubMed Central

    Liu, Kai; Chojnacki, Jeremy E.; Wade, Emily E.; Saathoff, John M.; Lesnefsky, Edward J.; Chen, Qun; Zhang, Shijun

    2016-01-01

    Multiple pathogenic factors have been suggested in playing a role in the development of Alzheimer’s disease (AD). The multifactorial nature of AD also suggests the potential use of compounds with polypharmacology as effective disease-modifying agents. Recently, we have developed a bivalent strategy to include cell membrane anchorage into the molecular design. Our results demonstrated that the bivalent compounds exhibited multifunctional properties and potent neuroprotection in a cellular AD model. Herein, we report the mechanistic exploration of one of the representative bivalent compounds, 17MN, in MC65 cells. Our results established that MC65 cells die through a necroptotic mechanism upon the removal of tetracycline (TC). Furthermore, we have shown that mitochondrial membrane potential (MMP) and cytosolic Ca2+ levels are increased upon removal of TC. Our bivalent compound 17MN can reverse such changes and protect MC65 cells from TC removal induced cytotoxicity. The results also suggest that 17MN may function between the Aβ species and RIPK1 in producing its neuroprotection. Colocalization studies employing a fluorescent analog of 17MN and confocal microscopy demonstrated the interactions of 17MN with both mitochondria and endoplasmic reticulum (ER), thus suggesting that 17MN exerts its neuroprotection via a multiple-site mechanism in MC65 cells. Collectively, these results strongly support our original design rationale of bivalent compounds and encourage further optimization of this bivalent strategy to develop more potent analogs as novel disease-modifying agents for AD. PMID:26401780

  8. Source apportionment of PM2.5 at multiple sites in Venice (Italy): Spatial variability and the role of weather

    NASA Astrophysics Data System (ADS)

    Masiol, Mauro; Squizzato, Stefania; Rampazzo, Giancarlo; Pavoni, Bruno

    2014-12-01

    This study investigates the chemical speciation of fine particulate matter (PM2.5) collected at three sites in the Venice area, eastern Po Valley (Italy). This area is one of the few hot spots left in Europe where levels of PM2.5 frequently breach EU target values and cause a serious risk for public health. Elemental composition, inorganic ions and polycyclic aromatic hydrocarbon concentrations were quantified in 448 PM2.5 samples and the multiple-site PMF receptor model was based on the elemental and inorganic ion data. Six factors associated with potential sources were quantified, namely, secondary sulfate, ammonium nitrate and combustions, fossil fuels, traffic, industrial and glassmaking. Source apportionment results were further processed using a series of chemometric tools for returning additional information about the seasonal and spatial changes of factors extracted by the PMF analysis. In addition, PMF results were also studied in combination with weather conditions and PAH concentrations revealing that sources of secondary nitrate and sulfate are homogeneously distributed throughout the area, while remaining pollutant sources may have a distinct origin. PMF results were cluster analyzed to sort out samples with similar source profiles and then the wind roses of grouped samples were examined to assess the role of wind speed and direction on PM2.5 pollution and chemistry. The tested tools and the results obtained can be used for air quality assessment studies and air pollution reduction strategies.

  9. Binding site multiplicity with fatty acid ligands: implications for the regulation of PKR kinase autophosphorylation with palmitate.

    PubMed

    Fang, Liang; Cho, Hyun Ju; Chan, Christina; Feig, Michael

    2014-10-01

    Saturated long chain-free fatty acids (FFAs), especially palmitate, have been implicated in apoptosis by inhibiting the activity of PKR (double-stranded RNA-dependent protein kinase). We recently found evidence that palmitate interacts directly with the kinase domain of PKR, subsequently inhibiting the autophosphorylation of PKR. To investigate the interactions of palmitate with PKR and its effects on PKR autophosphorylation, we performed extensive unbiased MD simulations combined with biochemical and biophysical experiments. The simulations predict multiple putative binding sites of palmitate on both the phosphorylated and unphosphorylated PKR with similar binding affinities. Ligand-protein interactions involving a large variety of different binding modes challenge the conventional view of highly specific, single binding sites. Key interactions of palmitate involve the αC-helix of PKR, especially near residue R307. Experimental mutation of R307 was found to affect palmitate binding and reduce its inhibitory effect. Based on this study a new allosteric mechanism is proposed where palmitate binding to the αC-helix prevents the inactive-to-active transition of PKR and subsequently reduces its ability to autophosphorylate.

  10. The N-terminal domain of the tomato immune protein Prf contains multiple homotypic and Pto kinase interaction sites.

    PubMed

    Saur, Isabel Marie-Luise; Conlan, Brendon Francis; Rathjen, John Paul

    2015-05-01

    Resistance to Pseudomonas syringae bacteria in tomato (Solanum lycopersicum) is conferred by the Prf recognition complex, composed of the nucleotide-binding leucine-rich repeats protein Prf and the protein kinase Pto. The complex is activated by recognition of the P. syringae effectors AvrPto and AvrPtoB. The N-terminal domain is responsible for Prf homodimerization, which brings two Pto kinases into close proximity and holds them in inactive conformation in the absence of either effector. Negative regulation is lost by effector binding to the catalytic cleft of Pto, leading to disruption of its P+1 loop within the activation segment. This change is translated through Prf to a second Pto molecule in the complex. Here we describe a schematic model of the unique Prf N-terminal domain dimer and its interaction with the effector binding determinant Pto. Using heterologous expression in Nicotiana benthamiana, we define multiple sites of N domain homotypic interaction and infer that it forms a parallel dimer folded centrally to enable contact between the N and C termini. Furthermore, we found independent binding sites for Pto at either end of the N-terminal domain. Using the constitutively active mutant ptoL205D, we identify a potential repression site for Pto in the first ∼100 amino acids of Prf. Finally, we find that the Prf leucine-rich repeats domain also binds the N-terminal region, highlighting a possible mechanism for transfer of the effector binding signal to the NB-LRR regulatory unit (consisting of a central nucleotide binding and C-terminal leucine-rich repeats). PMID:25792750

  11. The N-terminal domain of the tomato immune protein Prf contains multiple homotypic and Pto kinase interaction sites.

    PubMed

    Saur, Isabel Marie-Luise; Conlan, Brendon Francis; Rathjen, John Paul

    2015-05-01

    Resistance to Pseudomonas syringae bacteria in tomato (Solanum lycopersicum) is conferred by the Prf recognition complex, composed of the nucleotide-binding leucine-rich repeats protein Prf and the protein kinase Pto. The complex is activated by recognition of the P. syringae effectors AvrPto and AvrPtoB. The N-terminal domain is responsible for Prf homodimerization, which brings two Pto kinases into close proximity and holds them in inactive conformation in the absence of either effector. Negative regulation is lost by effector binding to the catalytic cleft of Pto, leading to disruption of its P+1 loop within the activation segment. This change is translated through Prf to a second Pto molecule in the complex. Here we describe a schematic model of the unique Prf N-terminal domain dimer and its interaction with the effector binding determinant Pto. Using heterologous expression in Nicotiana benthamiana, we define multiple sites of N domain homotypic interaction and infer that it forms a parallel dimer folded centrally to enable contact between the N and C termini. Furthermore, we found independent binding sites for Pto at either end of the N-terminal domain. Using the constitutively active mutant ptoL205D, we identify a potential repression site for Pto in the first ∼100 amino acids of Prf. Finally, we find that the Prf leucine-rich repeats domain also binds the N-terminal region, highlighting a possible mechanism for transfer of the effector binding signal to the NB-LRR regulatory unit (consisting of a central nucleotide binding and C-terminal leucine-rich repeats).

  12. Progression of a Fracture Site Impaction as a Prognostic Indicator of Impacted Femoral Neck Fracture Treated with Multiple Pinning

    PubMed Central

    Yoon, Pil Whan; Shin, Young Ho; Yoo, Jeong Joon; Yoon, Kang Sup

    2012-01-01

    Background We evaluated the clinical and radiologic results of impacted femoral neck fractures treated with multiple pinning and determined the influence of the progression of impaction at the fracture site on clinical outcome. Methods There were 34 patients with a mean age of 65.5 years. The mean follow-up period was 3.4 years. Progression of fracture site impaction was measured using an articulo-trochanteric distance index and the percentage decrease in the articulo-trochanteric distance index between follow-up intervals. The failure of treatment was clarified as non-union and avascular necrosis. Other characteristics of the patients, including mean waiting time for surgery, preoperative Singh index score, and body mass index, were also measured to evaluate the influence on the clinical outcome of surgery. Results There were 6 fractures which were not treated successfully (3 non-union, 8.8% and 3 avascular necrosis, 8.8%). The mean percentage decrease of the articulo-trochanteric distance index within the first 6 weeks after surgery was 4.5% in the successful group and 25.1% in the failure group (p < 0.001). There was also a significant mean percentage decrease in the articulo-trochanteric distance index between 6 weeks and 3 months (p < 0.001). Conclusions Primary stabilization with Knowles pins for impacted femoral neck fractures had a reasonable clinical outcome with low morbidity. Despite a significant difference of a mean percentage decrease in the articulo-trochanteric distance index between the successful group and the failure group, we could not verify it as a risk factor for failure of treatment because the odds ratio was not statistically significant. PMID:22379557

  13. Multiple techniques for mineral identification on Mars:. a study of hydrothermal rocks as potential analogues for astrobiology sites on Mars

    NASA Astrophysics Data System (ADS)

    Bishop, Janice L.; Murad, Enver; Lane, Melissa D.; Mancinelli, Rocco L.

    2004-06-01

    Spectroscopic studies of Mars analog materials combining multiple spectral ranges and techniques are necessary in order to obtain ground truth information for interpretation of rocks and soils on Mars. Two hydrothermal rocks from Yellowstone National Park, Wyoming, were characterized here because they contain minerals requiring water for formation and they provide a possible niche for some of the earliest organisms on Earth. If related rocks formed in hydrothermal sites on Mars, identification of these would be important for understanding the geology of the planet and potential habitability for life. XRD, thermal properties, VNIR, mid-IR, and Raman spectroscopy were employed to identify the mineralogy of the samples in this study. The rocks studied here include a travertine from Mammoth Formation that contains primarily calcite with some aragonite and gypsum and a siliceous sinter from Octopus Spring that contains a variety of poorly crystalline to amorphous silicate minerals. Calcite was detected readily in the travertine rock using any one of the techniques studied. The small amount of gypsum was uniquely identified using XRD, VNIR, and mid-IR, while the aragonite was uniquely identified using XRD and Raman. The siliceous sinter sample was more difficult to characterize using each of these techniques and a combination of all techniques was more useful than any single technique. Although XRD is the historical standard for mineral identification, it presents some challenges for remote investigations. Thermal properties are most useful for minerals with discrete thermal transitions. Raman spectroscopy is most effective for detecting polarized species such as CO 3, OH, and CH, and exhibits sharp bands for most highly crystalline minerals when abundant. Mid-IR spectroscopy is most useful in characterizing Si-O (and metal-O) bonds and also has the advantage that remote information about sample texture (e.g., particle size) can be determined. Mid-IR spectroscopy is also

  14. Compact Solar Spectrometer Column CO2, and CH4 Observations: Performance Evaluation at Multiple North American TCCON Sites

    NASA Astrophysics Data System (ADS)

    Parker, H. A.; Hedelius, J.; Viatte, C.; Wunch, D.; Wennberg, P. O.; Chen, J.; Wofsy, S.; Jones, T.; Franklin, J.; Dubey, M. K.; Roehl, C. M.; Podolske, J. R.; Hillyard, P. W.; Iraci, L. T.

    2015-12-01

    Measurement, reporting and verification (MRV) of anthropogenic emissions and natural sources and sinks of carbon dioxide (CO2) and methane (CH4) are crucial to predict climate change and develop transparent accounting policies to contain climate forcing. Remote sensing technologies are monitoring column averaged dry air mole fractions of CO2 and CH4 (XCO2 & XCH4) from ground and space (OCO-2 and GOSAT) with solar spectroscopy enabling direct MRV. However, current ground based coverage is sparse due to the need for large and expensive high-resolution spectrometers that are part of the Total Column Carbon Observing Network (TCCON, Bruker 125HR). This limits our MRV and satellite validation abilities, both regionally and globally. There are striking monitoring gaps in Asia, South America and Africa where the CO2 emissions are growing and there is a large uncertainty in fluxes from land use change, biomass burning and rainforest vulnerability. To fill this gap we evaluate the precision, accuracy and stability of compact, affordable and easy to use low-resolution spectrometers (Bruker EM27/SUN) by comparing with XCO2 and XCH4 retrieved from much larger high-resolution TCCON instruments. As these instruments will be used in a variety of locations, we evaluate their performance by comparing with 2 previous and 4 current United States TCCON sites in different regions up to 2700 km apart. These sites range from polluted to unpolluted, latitudes of 32 to 46°N, and altitudes of 230 to 2241 masl. Comparisons with some of these sites cover multiple years allowing assessment of the EM27/SUN performance not only in various regions, but also over an extended period of time and with different seasonal influences. Results show that our 2 EM27/SUN instruments capture the diurnal variability of the aforementioned constituents very well, but with offsets from TCCON and long-term variability which may be due in part to the extensive movement these spectrometers were subjected to. These

  15. Multiple active site histidine protonation states in Acetobacter aceti N5-carboxyaminoimidazole ribonucleotide mutase detected by REDOR NMR.

    PubMed

    Schaefer, Jacob; Jiang, Hong; Ransome, Aaron E; Kappock, T Joseph

    2007-08-21

    Class I PurE (N5-carboxyaminoimidazole mutase) catalyzes a chemically unique mutase reaction. A working mechanistic hypothesis involves a histidine (His45 in Escherichia coli PurE) functioning as a general acid, but no evidence for multiple protonation states has been obtained. Solution NMR is a peerless tool for this task but has had limited application to enzymes, most of which are larger than its effective molecular size limit. Solid-state NMR is not subject to this limit. REDOR NMR studies of a 151 kDa complex of uniformly 15N-labeled Acetobacter aceti PurE (AaPurE) and the active site ligand [6-13C]citrate probed a single ionization equilibrium associated with the key histidine (AaPurE His59). In the AaPurE complex, the citrate central carboxylate C6 13C peak moves upfield, indicating diminution of negative charge, and broadens, indicating heterogeneity. Histidine 15N chemical shifts indicate His59 exists in approximately equimolar amounts of an Ndelta-unprotonated (pyridine-like) form and an Ndelta-protonated (pyrrole-like) form, each of which is approximately 4 A from citrate C6. The spectroscopic data are consistent with proton transfers involving His59 Ndelta that are invoked in the class I PurE mechanism.

  16. Structural and Functional Characterization of CRM1-Nup214 Interactions Reveals Multiple FG-Binding Sites Involved in Nuclear Export.

    PubMed

    Port, Sarah A; Monecke, Thomas; Dickmanns, Achim; Spillner, Christiane; Hofele, Romina; Urlaub, Henning; Ficner, Ralf; Kehlenbach, Ralph H

    2015-10-27

    CRM1 is the major nuclear export receptor. During translocation through the nuclear pore, transport complexes transiently interact with phenylalanine-glycine (FG) repeats of multiple nucleoporins. On the cytoplasmic side of the nuclear pore, CRM1 tightly interacts with the nucleoporin Nup214. Here, we present the crystal structure of a 117-amino-acid FG-repeat-containing fragment of Nup214, in complex with CRM1, Snurportin 1, and RanGTP at 2.85 Å resolution. The structure reveals eight binding sites for Nup214 FG motifs on CRM1, with intervening stretches that are loosely attached to the transport receptor. Nup214 binds to N- and C-terminal regions of CRM1, thereby clamping CRM1 in a closed conformation and stabilizing the export complex. The role of conserved hydrophobic pockets for the recognition of FG motifs was analyzed in biochemical and cell-based assays. Comparative studies with RanBP3 and Nup62 shed light on specificities of CRM1-nucleoporin binding, which serves as a paradigm for transport receptor-nucleoporin interactions.

  17. Multiple co-morbidities and interest in research participation among clients of a nonprofit food distribution site

    PubMed Central

    Higashi, Robin T.; Craddock Lee, Simon J.; Leonard, Tammy; Cuate, Erica L.; Cole, Jay; Pruitt, Sandi L.

    2015-01-01

    Background Persons accessing food from nonprofit distribution sites face numerous challenges and typically have significant unmet health needs. However, given limited and intermittent healthcare system engagement, this vulnerable population is under-represented in clinical research. We sought to better understand the health needs of a non-clinical population to inform future research and interventions. Methods Focus groups were conducted in English (n=4) and Spanish (n=4) with clients of Crossroads Community Services (CCS), the largest distributor of North Texas Food Bank. Discussions probed participants' health status, healthcare utilization, understanding and utilization of mammography, and attitudes toward participation in research. Results Participants included 42 CCS clients, primarily Hispanic or African-American women. Participants reported multiple co-morbid conditions among household members, yet utilization of health services was often limited by cost. The majority expressed interest in participating in research to communicate their health concerns and obtain emotional support. Conclusion CCS clients represent a high-need, under-reached population willing to engage in health-related research that affords them opportunity to connect with peers in group settings and obtain information to improve management of daily life challenges. The Community Assistance Research (CARe) Initiative, a community-academic collaboration, establishes a much-needed opportunity for ongoing clinical research and intervention among this underserved population. PMID:26277918

  18. Multiple Glycogen-binding Sites in Eukaryotic Glycogen Synthase Are Required for High Catalytic Efficiency toward Glycogen

    SciTech Connect

    Baskaran, Sulochanadevi; Chikwana, Vimbai M.; Contreras, Christopher J.; Davis, Keri D.; Wilson, Wayne A.; DePaoli-Roach, Anna A.; Roach, Peter J.; Hurley, Thomas D.

    2012-12-10

    Glycogen synthase is a rate-limiting enzyme in the biosynthesis of glycogen and has an essential role in glucose homeostasis. The three-dimensional structures of yeast glycogen synthase (Gsy2p) complexed with maltooctaose identified four conserved maltodextrin-binding sites distributed across the surface of the enzyme. Site-1 is positioned on the N-terminal domain, site-2 and site-3 are present on the C-terminal domain, and site-4 is located in an interdomain cleft adjacent to the active site. Mutation of these surface sites decreased glycogen binding and catalytic efficiency toward glycogen. Mutations within site-1 and site-2 reduced the V{sub max}/S{sub 0.5} for glycogen by 40- and 70-fold, respectively. Combined mutation of site-1 and site-2 decreased the V{sub max}/S{sub 0.5} for glycogen by >3000-fold. Consistent with the in vitro data, glycogen accumulation in glycogen synthase-deficient yeast cells ({Delta}gsy1-gsy2) transformed with the site-1, site-2, combined site-1/site-2, or site-4 mutant form of Gsy2p was decreased by up to 40-fold. In contrast to the glycogen results, the ability to utilize maltooctaose as an in vitro substrate was unaffected in the site-2 mutant, moderately affected in the site-1 mutant, and almost completely abolished in the site-4 mutant. These data show that the ability to utilize maltooctaose as a substrate can be independent of the ability to utilize glycogen. Our data support the hypothesis that site-1 and site-2 provide a 'toehold mechanism,' keeping glycogen synthase tightly associated with the glycogen particle, whereas site-4 is more closely associated with positioning of the nonreducing end during catalysis.

  19. Integrating ecosystems measurements from multiple eddy-covariance sites to a simple model of ecosystem process - Are there possibilities for a uniform model calibration?

    NASA Astrophysics Data System (ADS)

    Minunno, Francesco; Peltoniemi, Mikko; Launiainen, Samuli; Mäkelä, Annikki

    2014-05-01

    Biogeochemical models quantify the material and energy flux exchanges between biosphere, atmosphere and soil, however there is still considerable uncertainty underpinning model structure and parametrization. The increasing availability of data from of multiple sources provides useful information for model calibration and validation at different space and time scales. We calibrated a simplified ecosystem process model PRELES to data from multiple sites. In this work we had the following objective: to compare a multi-site calibration and site-specific calibrations, in order to test if PRELES is a model of general applicability, and to test how well one parameterization can predict ecosystem fluxes. Model calibration and evaluation were carried out by the means of the Bayesian method; Bayesian calibration (BC) and Bayesian model comparison (BMC) were used to quantify the uncertainty in model parameters and model structure. Evapotranspiration (ET) and gross primary production (GPP) measurements collected in 9 sites of Finland and Sweden were used in the study; half dataset was used for model calibrations and half for the comparative analyses. 10 BCs were performed; the model was independently calibrated for each of the nine sites (site-specific calibrations) and a multi-site calibration was achieved using the data from all the sites in one BC. Then 9 BMCs were carried out, one for each site, using output from the multi-site and the site-specific versions of PRELES. Similar estimates were obtained for the parameters at which model outputs are most sensitive. Not surprisingly, the joint posterior distribution achieved through the multi-site calibration was characterized by lower uncertainty, because more data were involved in the calibration process. No significant differences were encountered in the prediction of the multi-site and site-specific versions of PRELES, and after BMC, we concluded that the model can be reliably used at regional scale to simulate carbon and

  20. The streptomyces genome contains multiple pseudo-attB sites for the (phi)C31-encoded site-specific recombination system.

    PubMed

    Combes, Patricia; Till, Rob; Bee, Sally; Smith, Margaret C M

    2002-10-01

    The integrase from the Streptomyces phage (phi)C31 is a member of the serine recombinase family of site-specific recombinases and is fundamentally different from that of lambda or its relatives. Moreover, (phi)C31 int/attP is used widely as an essential component of integration vectors (such as pSET152) employed in the genetic analysis of Streptomyces species. phiC31 or integrating plasmids containing int/attP have been shown previously to integrate at a locus, attB, in the chromosome. The DNA sequences of the attB sites of various Streptomyces species revealed nonconserved positions. In particular, the crossover site was narrowed to the sequence 5'TT present in both attP and attB. Strains of Streptomyces coelicolor and S. lividans were constructed with a deletion of the attB site ((Delta)attB), and pSET152 was introduced into these strains by conjugation. Thus, secondary or pseudo-attB sites were identified by Southern blotting and after rescue of plasmids containing DNA flanking the insertion sites from the chromosome. The sequences of the integration sites had similarity to those of attB. Analysis of the insertions of pSET152 into both attB(+) and (Delta)attB strains indicated that this plasmid can integrate at several loci via independent recombination events within a transconjugant.

  1. MONKEY: Identifying conserved transcription-factor binding sitesin multiple alignments using a binding site-specific evolutionarymodel

    SciTech Connect

    Moses, Alan M.; Chiang, Derek Y.; Pollard, Daniel A.; Iyer, VenkyN.; Eisen, Michael B.

    2004-10-28

    We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.

  2. Development of a regression model to predict copper toxicity to Daphnia magna and site-specific copper criteria across multiple surface-water drainages in an arid landscape.

    PubMed

    Fulton, Barry A; Meyer, Joseph S

    2014-08-01

    The water effect ratio (WER) procedure developed by the US Environmental Protection Agency is commonly used to derive site-specific criteria for point-source metal discharges into perennial waters. However, experience is limited with this method in the ephemeral and intermittent systems typical of arid climates. The present study presents a regression model to develop WER-based site-specific criteria for a network of ephemeral and intermittent streams influenced by nonpoint sources of Cu in the southwestern United States. Acute (48-h) Cu toxicity tests were performed concurrently with Daphnia magna in site water samples and hardness-matched laboratory waters. Median effect concentrations (EC50s) for Cu in site water samples (n=17) varied by more than 12-fold, and the range of calculated WER values was similar. Statistically significant (α=0.05) univariate predictors of site-specific Cu toxicity included (in sequence of decreasing significance) dissolved organic carbon (DOC), hardness/alkalinity ratio, alkalinity, K, and total dissolved solids. A multiple-regression model developed from a combination of DOC and alkalinity explained 85% of the toxicity variability in site water samples, providing a strong predictive tool that can be used in the WER framework when site-specific criteria values are derived. The biotic ligand model (BLM) underpredicted toxicity in site waters by more than 2-fold. Adjustments to the default BLM parameters improved the model's performance but did not provide a better predictive tool compared with the regression model developed from DOC and alkalinity.

  3. Geologic, hydrologic, and water-quality data from multiple-well monitoring sites in the Central and West Coast basins, Los Angeles County, California, 1995-2000

    USGS Publications Warehouse

    Land, Michael; Everett, R.R.; Crawford, S.M.

    2002-01-01

    In 1995, the U.S. Geological Survey (USGS), in cooperation with the HYPERLINK 'http://wrd.org' Water Replenishment District of Southern California (WRDSC), began a study to examine ground-water resources in the Central and West Coast Basins in Los Angeles County, California. The study characterizes the geohydrology and geochemistry of the regional ground-water flow system and provides extensive data for evaluating ground-water management issues. This report is a compilation of geologic, hydrologic, and water-quality data collected from 24 recently constructed multiple-well monitoring sites for the period 1995?2000. Descriptions of the collected drill cuttings were compiled into lithologic logs, which are summarized along with geophysical logs?including gamma-ray, spontaneous potential, resistivity, electromagnetic induction, and temperature tool logs?for each monitoring site. At selected sites, cores were analyzed for magnetic orientation, physical and thermal properties, and mineralogy. Field and laboratory estimates of hydraulic conductivity are presented for most multiple-well monitoring sites. Periodic water-level measurements are also reported. Water-quality information for major ions, nutrients, trace elements, deuterium and oxygen-18, and tritium is presented for the multiple-well monitoring locations, and for selected existing production and observation wells. In addition, boron-11, carbon-13, carbon-14, sulfur-34, and strontium-87/86 data are presented for selected wells.

  4. A novel carboxyl-terminal protease derived from Paenibacillus lautus CHN26 exhibiting high activities at multiple sites of substrates

    PubMed Central

    2013-01-01

    Background Carboxyl-terminal protease (CtpA) plays essential functions in posttranslational protein processing in prokaryotic and eukaryotic cells. To date, only a few bacterial ctpA genes have been characterized. Here we cloned and characterized a novel CtpA. The encoding gene, ctpAp (ctpA of Paenibacillus lautus), was derived from P. lautus CHN26, a Gram-positive bacterium isolated by functional screening. Recombinant protein was obtained from protein over-expression in Escherichia coli and the biochemical properties of the enzyme were investigated. Results Screening of environmental sediment samples with a skim milk-containing medium led to the isolation of a P. lautus CHN26 strain that exhibited a high proteolytic activity. A gene encoding a carboxyl-terminal protease (ctpAp) was cloned from the isolate and characterized. The deduced mature protein contains 466 aa with a calculated molecular mass of 51.94 kDa, displaying 29-38% amino acid sequence identity to characterized bacterial CtpA enzymes. CtpAp contains an unusual catalytic dyad (Ser309-Lys334) and a PDZ substrate-binding motif, characteristic for carboxyl-terminal proteases. CtpAp was expressed as a recombinant protein and characterized. The purified enzyme showed an endopeptidase activity, which effectively cleaved α S1- and β- casein substrates at carboxyl-terminus as well as at multiple internal sites. Furthermore, CtpAp exhibited a high activity at room temperature and strong tolerance to conventional protease inhibitors, demonstrating that CtpAp is a novel endopeptidase. Conclusions Our work on CtpA represents the first investigation of a member of Family II CtpA enzymes. The gene was derived from a newly isolated P. lautus CHN26 strain exhibiting a high protease activity in the skim milk assay. We have demonstrated that CtpAp is a novel endopeptidase with distinct cleavage specificities, showing a strong potential in biotechnology and industry applications. PMID:24161150

  5. Quantitative determination of occupation sites of trace Co substituted for multiple Fe sites in M-type hexagonal ferrite using statistical beam-rocking TEM-EDXS analysis.

    PubMed

    Ohtsuka, Masahiro; Muto, Shunsuke; Tatsumi, Kazuyoshi; Kobayashi, Yoshinori; Kawata, Tsunehiro

    2016-04-01

    The occupation sites and the occupancies of trace dopants in La/Co co-doped Sr-M-type ferrite, SrFe12O19, were quantitatively and precisely determined by beam-rocking energy-dispersive X-ray spectroscopy (EDXS) on the basis of electron-channeling effects. Because the Co atoms, in particular, should be partially substituted for the five crystallographically inequivalent sites, which could be key parameters in improving the magneto-crystalline anisotropy, it is difficult yet intriguing to discover their occupation sites and occupancies without using the methods of large-scale facilities, such as neutron diffraction and synchrotron radiation. In the present study, we tackled this problem by applying an extended statistical atom location by channeling enhanced microanalysis method, using conventional transmission electron microscopy, EDXS and dynamical electron elastic/inelastic scattering theories. The results show that the key occupation sites of Co were the 2a, 4f1 and 12k sites. The quantified occupancies of Co were consistent with those of the previous study, which involved a combination of neutron diffraction and extended X-ray absorption fine structure analysis, as well as energetics considerations based on by first-principles calculations.

  6. Quantitative determination of occupation sites of trace Co substituted for multiple Fe sites in M-type hexagonal ferrite using statistical beam-rocking TEM-EDXS analysis.

    PubMed

    Ohtsuka, Masahiro; Muto, Shunsuke; Tatsumi, Kazuyoshi; Kobayashi, Yoshinori; Kawata, Tsunehiro

    2016-04-01

    The occupation sites and the occupancies of trace dopants in La/Co co-doped Sr-M-type ferrite, SrFe12O19, were quantitatively and precisely determined by beam-rocking energy-dispersive X-ray spectroscopy (EDXS) on the basis of electron-channeling effects. Because the Co atoms, in particular, should be partially substituted for the five crystallographically inequivalent sites, which could be key parameters in improving the magneto-crystalline anisotropy, it is difficult yet intriguing to discover their occupation sites and occupancies without using the methods of large-scale facilities, such as neutron diffraction and synchrotron radiation. In the present study, we tackled this problem by applying an extended statistical atom location by channeling enhanced microanalysis method, using conventional transmission electron microscopy, EDXS and dynamical electron elastic/inelastic scattering theories. The results show that the key occupation sites of Co were the 2a, 4f1 and 12k sites. The quantified occupancies of Co were consistent with those of the previous study, which involved a combination of neutron diffraction and extended X-ray absorption fine structure analysis, as well as energetics considerations based on by first-principles calculations. PMID:26520786

  7. Source apportionment of PM2.5 at multiple Northwest U.S. sites: Assessing regional winter wood smoke impacts from residential wood combustion

    NASA Astrophysics Data System (ADS)

    Kotchenruther, Robert A.

    2016-10-01

    Wood smoke from residential wood combustion is a significant source of elevated PM2.5 in many communities across the Northwest U.S. Accurate representation of residential wood combustion in source-oriented regional scale air quality models is challenging because of multiple uncertainties. As an alternative to source-oriented source apportionment, this work provides, through receptor-oriented source apportionment, an assessment of winter residential wood combustion impacts at multiple Northwest U.S. locations. Source apportionment was performed on chemically speciated PM2.5 from 19 monitoring sites using the Positive Matrix Factorization (PMF) receptor model. Each site was modeled independently, but a common data preparation and modeling protocol was used so that results were as comparable as possible across sites. Model solutions had from 4 to 8 PMF factors, depending on the site. PMF factors at each site were associated with a source classification (e.g., primary wood smoke), a dominant chemical composition (e.g., ammonium nitrate), or were some mixture. 15 different sources or chemical compositions were identified as contributing to PM2.5 across the 19 sites. The 6 most common were; aged wood smoke and secondary organic carbon, motor vehicles, primary wood smoke, ammonium nitrate, ammonium sulfate, and fugitive dust. Wood smoke was identified at every site, with both aged and primary wood smoke identified at most sites. Wood smoke contributions to PM2.5 were averaged for the two winter months of December and January, the months when wood smoke in the Northwest U.S. is mainly from residential wood combustion. The total contribution of residential wood combustion, that from primary plus aged smoke, ranged from 11.4% to 92.7% of average December and January PM2.5 depending on the site, with the highest percent contributions occurring in smaller towns that have fewer expected sources of winter PM2.5. Receptor modeling at multiple sites, such as that conducted in this

  8. Selective labeling of serotonin uptake sites in rat brain by (/sup 3/H)citalopram contrasted to labeling of multiple sites by (/sup 3/H)imipramine

    SciTech Connect

    D'Amato, R.J.; Largent, B.L.; Snowman, A.M.; Snyder, S.H.

    1987-07-01

    Citalopram is a potent and selective inhibitor of neuronal serotonin uptake. In rat brain membranes (/sup 3/H)citalopram demonstrates saturable and reversible binding with a KD of 0.8 nM and a maximal number of binding sites (Bmax) of 570 fmol/mg of protein. The drug specificity for (/sup 3/H)citalopram binding and synaptosomal serotonin uptake are closely correlated. Inhibition of (/sup 3/H)citalopram binding by both serotonin and imipramine is consistent with a competitive interaction in both equilibrium and kinetic analyses. The autoradiographic pattern of (/sup 3/H)citalopram binding sites closely resembles the distribution of serotonin. By contrast, detailed equilibrium-saturation analysis of (/sup 3/H)imipramine binding reveals two binding components, i.e., high affinity (KD = 9 nM, Bmax = 420 fmol/mg of protein) and low affinity (KD = 553 nM, Bmax = 8560 fmol/mg of protein) sites. Specific (/sup 3/H)imipramine binding, defined as the binding inhibited by 100 microM desipramine, is displaced only partially by serotonin. Various studies reveal that the serotonin-sensitive portion of binding corresponds to the high affinity sites of (/sup 3/H)imipramine binding whereas the serotonin-insensitive binding corresponds to the low affinity sites. Lesioning of serotonin neurons with p-chloroamphetamine causes a large decrease in (/sup 3/H)citalopram and serotonin-sensitive (/sup 3/H)imipramine binding with only a small effect on serotonin-insensitive (/sup 3/H)imipramine binding. The dissociation rate of (/sup 3/H)imipramine or (/sup 3/H)citalopram is not altered by citalopram, imipramine or serotonin up to concentrations of 10 microM. The regional distribution of serotonin sensitive (/sup 3/H)imipramine high affinity binding sites closely resembles that of (/sup 3/H)citalopram binding.

  9. Studies of the biogenic amine transporters. IV. Demonstration of a multiplicity of binding sites in rat caudate membranes for the cocaine analog [125I]RTI-55.

    PubMed

    Rothman, R B; Cadet, J L; Akunne, H C; Silverthorn, M L; Baumann, M H; Carroll, F I; Rice, K C; de Costa, B R; Partilla, J S; Wang, J B

    1994-07-01

    membranes prepared from rat caudate or COS cells that transiently expressed the cloned cocaine-sensitive DA transporter complementary DNA. Similar experiments also resolved two components of the caudate 5-HT transporter. Viewed collectively, these data provide evidence that [125I]RTI-55 labels multiple binding sites associated with the DA and 5-HT transporters.

  10. High-risk human papillomavirus infection involving multiple anatomic sites of the female lower genital tract: a multiplex real-time polymerase chain reaction-based study.

    PubMed

    Hui, Yiang; Manna, Pradip; Ou, Joyce J; Kerley, Spencer; Zhang, Cunxian; Sung, C James; Lawrence, W Dwayne; Quddus, M Ruhul

    2015-09-01

    High-risk human papillomavirus infection usually is seen at one anatomic site in an individual. Rarely, infection at multiple anatomic sites of the female lower genital tract in the same individual is encountered either simultaneously and/or at a later date. The current study identifies the various subtypes of high-risk human papillomavirus infection in these scenarios and analyzes the potential significance of these findings. High-risk human papillomavirus infection involving 22 anatomic sites from 7 individuals was identified after institutional review board approval. Residual paraffin-embedded tissue samples were retrieved, and all 15 high-risk human papillomavirus were identified and viral load quantified using multiplex real-time polymerase chain reaction-based method. Multiple high-risk human papillomavirus subtypes were identified in 32% of the samples and as many as 5 different subtypes of high-risk human papillomavirus infection in a single anatomic site. In general, each anatomic site has unique combination of viral subtypes, although one individual showed overlapping subtypes in the vagina, cervix, and vulvar samples. Higher viral load and rare subtypes are more frequent in younger patients and in dysplasia compared with carcinoma. Follow-up ranging from 3 to 84 months revealed persistent high-risk human papillomavirus infection in 60% of cases.

  11. Scheduling the Remediation of Port Hope: Logistical and Regulatory Challenges of a Multiple Site Urban Remediation Project - 13119

    SciTech Connect

    Ferguson Jones, Andrea; Lee, Angela; Palmeter, Tim

    2013-07-01

    The Port Hope Project is part of the larger CAN$1.28 billion Port Hope Area Initiative (PHAI), a community-based program for the development and implementation of a safe, local, long-term management solution for historic Low-Level Radioactive Waste (LLRW) in the Municipalities of Port Hope and Clarington, Ontario, Canada. Atomic Energy of Canada (AECL) is the Project Proponent, Public Works and Government Services (PWGSC) is managing the procurement of services and the MMM Group Limited - Conestoga Rovers and Associates Joint Venture (MMM-CRA Joint Venture) is providing detailed design and construction oversight and administration services for the Project. The Port Hope Project includes the construction of a long-term waste management facility (LTWMF) in the Municipality of Port Hope and the remediation of 18 (eighteen) large-scale LLRW, numerous small-scale sites still being identified and industrial sites within the Municipality. The total volume to be remediated is over one million cubic metres and will come from sites that include temporary storage sites, ravines, beaches, parks, private commercial and residential properties and vacant industrial sites all within the urban area of Port Hope. Challenges that will need to be overcome during this 10 year project include: - Requirements stipulated by the Environmental Assessment (EA) that affect Project logistics and schedule. - Coordination of site remediation with the construction schedule at the LTWMF. - Physical constraints on transport routes and at sites affecting production rates. - Despite being an urban undertaking, seasonal constrains for birds and fish (i.e., nesting and spawning seasons). - Municipal considerations. - Site-specific constraints. - Site interdependencies exist requiring consideration in the schedule. Several sites require the use of an adjacent site for staging. (authors)

  12. SigniSite: Identification of residue-level genotype-phenotype correlations in protein multiple sequence alignments.

    PubMed

    Jessen, Leon Eyrich; Hoof, Ilka; Lund, Ole; Nielsen, Morten

    2013-07-01

    Identifying which mutation(s) within a given genotype is responsible for an observable phenotype is important in many aspects of molecular biology. Here, we present SigniSite, an online application for subgroup-free residue-level genotype-phenotype correlation. In contrast to similar methods, SigniSite does not require any pre-definition of subgroups or binary classification. Input is a set of protein sequences where each sequence has an associated real number, quantifying a given phenotype. SigniSite will then identify which amino acid residues are significantly associated with the data set phenotype. As output, SigniSite displays a sequence logo, depicting the strength of the phenotype association of each residue and a heat-map identifying 'hot' or 'cold' regions. SigniSite was benchmarked against SPEER, a state-of-the-art method for the prediction of specificity determining positions (SDP) using a set of human immunodeficiency virus protease-inhibitor genotype-phenotype data and corresponding resistance mutation scores from the Stanford University HIV Drug Resistance Database, and a data set of protein families with experimentally annotated SDPs. For both data sets, SigniSite was found to outperform SPEER. SigniSite is available at: http://www.cbs.dtu.dk/services/SigniSite/. PMID:23761454

  13. [[superscript 3]H]-Flunitrazepam-Labeled Benzodiazepine Binding Sites in the Hippocampal Formation in Autism: A Multiple Concentration Autoradiographic Study

    ERIC Educational Resources Information Center

    Guptill, Jeffrey T.; Booker, Anne B.; Gibbs, Terrell T.; Kemper, Thomas L.; Bauman, Margaret L.; Blatt, Gene J.

    2007-01-01

    Increasing evidence indicates that the GABAergic system in cerebellar and limbic structures is affected in autism. We extended our previous study that found reduced [[superscript 3]H] flunitrazepam-labeled benzodiazepine sites in the autistic hippocampus to determine whether this reduction was due to a decrease in binding site number (B [subscript…

  14. Patterns and plasticity in RNA-protein interactions enable recruitment of multiple proteins through a single site

    SciTech Connect

    Valley, Cary T.; Porter, Douglas F.; Qiu, Chen; Campbell, Zachary T.; Tanaka Hall, Traci M.; Wickens, Marvin

    2012-06-28

    mRNA control hinges on the specificity and affinity of proteins for their RNA binding sites. Regulatory proteins must bind their own sites and reject even closely related noncognate sites. In the PUF [Pumilio and fem-3 binding factor (FBF)] family of RNA binding proteins, individual proteins discriminate differences in the length and sequence of binding sites, allowing each PUF to bind a distinct battery of mRNAs. Here, we show that despite these differences, the pattern of RNA interactions is conserved among PUF proteins: the two ends of the PUF protein make critical contacts with the two ends of the RNA sites. Despite this conserved 'two-handed' pattern of recognition, the RNA sequence is flexible. Among the binding sites of yeast Puf4p, RNA sequence dictates the pattern in which RNA bases are flipped away from the binding surface of the protein. Small differences in RNA sequence allow new modes of control, recruiting Puf5p in addition to Puf4p to a single site. This embedded information adds a new layer of biological meaning to the connections between RNA targets and PUF proteins.

  15. Soil-water movement under natural-site and waste-site conditions: A multiple-year field study in the Mojave Desert, Nevada

    USGS Publications Warehouse

    Andraski, B.J.

    1997-01-01

    Soil-water movement under natural-site and simulated waste-site conditions were compared by monitoring four experimental sites in the Mojave Desert, Nevada, during a 5-year period: one vegetated soil profile, one soil profile where vegetation was removed, and two nonvegetated test trenches. Precipitation ranged from 14 to 162 mm/yr. Temporal changes in water content measured by neutron probe were limited to the upper 0.5-1 m; values ranged from 0.01 to 0.19 m3/m3. Water potential and temperature were measured by thermocouple psychrometers; 77% remained operable for ???4.5 years. For vegetated soil, precipitation that accumulated in the upper 0.75 m of soil was removed by evapotranspiration: water potentials decreased seasonally by 4 to >8 MPa. During 2 years with below-average precipitation, water potentials below the apparent root zone decreased by 2.3 (1.2-m depth) to 0.4 MPa (5-m depth), and the gradients became predominantly upward. Water potentials then rebounded during 2 years with near-and above-average precipitation, and seasonally variant water: potential gradients were reestablished above the 4.2-m depth. Under nonvegetated Waste-site conditions, data indicated the long-term accumulation and shallow, but continued, penetration of precipitation: water potentials showed moisture penetration to depths of 0.75-1.85 m. The method of simulated-waste drum placement (stacked versus random) and the associated differences m subsidence showed no measurable influence on the water balance of the trenches: subsidence totaled ???13 mm during the study. Water potentials below the trenches and below the 2-m depth ???13 the nonvegetated soil remained low (???-5.5 to -7.5 MPa) and indicated the persistence of typically upward driving forces for isothermal water flow. Water fluxes estimated from water potential and temperature data suggested that isothermal liquid, isothermal vapor, and nonisothermal vapor flow need to be considered in the conceptualization of unsaturated

  16. Integration of paleoseismic data from multiple sites to develop an objective earthquake chronology: Application to the Weber segment of the Wasatch fault zone, Utah

    USGS Publications Warehouse

    DuRoss, Christopher B.; Personius, Stephen F.; Crone, Anthony J.; Olig, Susan S.; Lund, William R.

    2011-01-01

    We present a method to evaluate and integrate paleoseismic data from multiple sites into a single, objective measure of earthquake timing and recurrence on discrete segments of active faults. We apply this method to the Weber segment (WS) of the Wasatch fault zone using data from four fault-trench studies completed between 1981 and 2009. After systematically reevaluating the stratigraphic and chronologic data from each trench site, we constructed time-stratigraphic OxCal models that yield site probability density functions (PDFs) of the times of individual earthquakes. We next qualitatively correlated the site PDFs into a segment-wide earthquake chronology, which is supported by overlapping site PDFs, large per-event displacements, and prominent segment boundaries. For each segment-wide earthquake, we computed the product of the site PDF probabilities in common time bins, which emphasizes the overlap in the site earthquake times, and gives more weight to the narrowest, best-defined PDFs. The product method yields smaller earthquake-timing uncertainties compared to taking the mean of the site PDFs, but is best suited to earthquakes constrained by broad, overlapping site PDFs. We calculated segment-wide earthquake recurrence intervals and uncertainties using a Monte Carlo model. Five surface-faulting earthquakes occurred on the WS at about 5.9, 4.5, 3.1, 1.1, and 0.6 ka. With the exception of the 1.1-ka event, we used the product method to define the earthquake times. The revised WS chronology yields a mean recurrence interval of 1.3 kyr (0.7–1.9-kyr estimated two-sigma [2δ] range based on interevent recurrence). These data help clarify the paleoearthquake history of the WS, including the important question of the timing and rupture extent of the most recent earthquake, and are essential to the improvement of earthquake-probability assessments for the Wasatch Front region.

  17. Integration of paleoseismic data from multiple sites to develop an objective earthquake chronology: Application to the Weber segment of the Wasatch fault zone, Utah

    USGS Publications Warehouse

    DuRoss, C.B.; Personius, S.F.; Crone, A.J.; Olig, S.S.; Lund, W.R.

    2011-01-01

    We present a method to evaluate and integrate paleoseismic data from multiple sites into a single, objective measure of earthquake timing and recurrence on discrete segments of active faults. We apply this method to the Weber segment (WS) of the Wasatch fault zone using data from four fault-trench studies completed between 1981 and 2009. After systematically reevaluating the stratigraphic and chronologic data from each trench site, we constructed time-stratigraphic OxCal models that yield site probability density functions (PDFs) of the times of individual earthquakes. We next qualitatively correlated the site PDFs into a segment-wide earthquake chronology, which is supported by overlapping site PDFs, large per-event displacements, and prominent segment boundaries. For each segment-wide earthquake, we computed the product of the site PDF probabilities in common time bins, which emphasizes the overlap in the site earthquake times, and gives more weight to the narrowest, best-defined PDFs. The product method yields smaller earthquake-timing uncertainties compared to taking the mean of the site PDFs, but is best suited to earthquakes constrained by broad, overlapping site PDFs. We calculated segment-wide earthquake recurrence intervals and uncertainties using a Monte Carlo model. Five surface-faulting earthquakes occurred on the WS at about 5.9, 4.5, 3.1, 1.1, and 0.6 ka. With the exception of the 1.1-ka event, we used the product method to define the earthquake times. The revised WS chronology yields a mean recurrence interval of 1.3 kyr (0.7-1.9-kyr estimated two-sigma [2??] range based on interevent recurrence). These data help clarify the paleoearthquake history of the WS, including the important question of the timing and rupture extent of the most recent earthquake, and are essential to the improvement of earthquake-probability assessments for the Wasatch Front region.

  18. Analysis and apportionment of organic carbon and fine particulate matter sources at multiple sites in the midwestern United States.

    PubMed

    Buzcu-Guven, Birnur; Brown, Steven G; Frankel, Anna; Hafner, Hilary R; Roberts, Paul T

    2007-05-01

    Speciated fine particulate matter (PM2.5) data collected as part of the Speciation Trends Network at four sites in the Midwest (Detroit, MI; Cincinnati, OH; Indianapolis, IN; and Northbrook, IL) and as part of the Interagency Monitoring of Protected Visual Environments program at the rural Bondville, IL, site were analyzed to understand sources contributing to organic carbon (OC) and PM2.5 mass. Positive matrix factorization (PMF) was applied to available data collected from January 2002 through March 2005, and seven to nine factors were identified at each site. Common factors at all of the sites included mobile (gasoline)/secondary organic aerosols with high OC, diesel with a high elemental carbon/OC ratio (only at the urban sites), secondary sulfate, secondary nitrate, soil, and biomass burning. Identified industrial factors included copper smelting (Northbrook, Indianapolis, and Bondville), steel/manufacturing with iron (Northbrook), industrial zinc (Northbrook, Cincinnati, Indianapolis, and Detroit), metal plating with chromium and nickel (Detroit, Indianapolis, and Bondville), mixed industrial with copper and iron (Cincinnati), and limestone with calcium and iron (Bondville). PMF results, on average, accounted for 96% of the measured PM2.5 mass at each site; residuals were consistently within tolerance (+/-3), and goodness-of-fit (Q) was acceptable. Potential source contribution function analysis helped identify regional and local impacts of the identified source types. Secondary sulfate and soil factors showed regional characteristics at each site, whereas industrial sources typically appeared to be locally influenced. These regional factors contributed approximately one third of the total PM2.5 mass, on average, whereas local mobile and industrial sources contributed to the remaining mass. Mobile sources were a major contributor (55-76% at the urban sites) to OC mass, generally with at least twice as much mass from nondiesel sources as from diesel. Regional

  19. Analysis and apportionment of organic carbon and fine particulate matter sources at multiple sites in the midwestern United States.

    PubMed

    Buzcu-Guven, Birnur; Brown, Steven G; Frankel, Anna; Hafner, Hilary R; Roberts, Paul T

    2007-05-01

    Speciated fine particulate matter (PM2.5) data collected as part of the Speciation Trends Network at four sites in the Midwest (Detroit, MI; Cincinnati, OH; Indianapolis, IN; and Northbrook, IL) and as part of the Interagency Monitoring of Protected Visual Environments program at the rural Bondville, IL, site were analyzed to understand sources contributing to organic carbon (OC) and PM2.5 mass. Positive matrix factorization (PMF) was applied to available data collected from January 2002 through March 2005, and seven to nine factors were identified at each site. Common factors at all of the sites included mobile (gasoline)/secondary organic aerosols with high OC, diesel with a high elemental carbon/OC ratio (only at the urban sites), secondary sulfate, secondary nitrate, soil, and biomass burning. Identified industrial factors included copper smelting (Northbrook, Indianapolis, and Bondville), steel/manufacturing with iron (Northbrook), industrial zinc (Northbrook, Cincinnati, Indianapolis, and Detroit), metal plating with chromium and nickel (Detroit, Indianapolis, and Bondville), mixed industrial with copper and iron (Cincinnati), and limestone with calcium and iron (Bondville). PMF results, on average, accounted for 96% of the measured PM2.5 mass at each site; residuals were consistently within tolerance (+/-3), and goodness-of-fit (Q) was acceptable. Potential source contribution function analysis helped identify regional and local impacts of the identified source types. Secondary sulfate and soil factors showed regional characteristics at each site, whereas industrial sources typically appeared to be locally influenced. These regional factors contributed approximately one third of the total PM2.5 mass, on average, whereas local mobile and industrial sources contributed to the remaining mass. Mobile sources were a major contributor (55-76% at the urban sites) to OC mass, generally with at least twice as much mass from nondiesel sources as from diesel. Regional

  20. Assigning Quantitative Function to Post-Translational Modifications Reveals Multiple Sites of Phosphorylation That Tune Yeast Pheromone Signaling Output

    SciTech Connect

    Pincus, David; Ryan, Christopher J.; Smith, Richard D.; Brent, Roger; Resnekov, Orna; Hakimi, Mohamed Ali

    2013-03-12

    Cell signaling systems transmit information by post-­translationally modifying signaling proteins, often via phosphorylation. While thousands of sites of phosphorylation have been identified in proteomic studies, the vast majority of sites have no known function. Assigning functional roles to the catalog of uncharacterized phosphorylation sites is a key research challenge. Here we present a general approach to address this challenge and apply it to a prototypical signaling pathway, the pheromone response pathway in Saccharomyces cerevisiae. The pheromone pathway includes a mitogen activated protein kinase (MAPK) cascade activated by a G-­protein coupled receptor (GPCR). We used mass spectrometry-based proteomics to identify sites whose phosphorylation changed when the system was active, and evolutionary conservation to assign priority to a list of candidate MAPK regulatory sites. We made targeted alterations in those sites, and measured the effects of the mutations on pheromone pathway output in single cells. Our work identified six new sites that quantitatively tuned system output. We developed simple computational models to find system architectures that recapitulated the quantitative phenotypes of the mutants. Our results identify a number of regulated phosphorylation events that contribute to adjust the input-­output relationship of this model eukaryotic signaling system. We believe this combined approach constitutes a general means not only to reveal modification sites required to turn a pathway on and off, but also those required for more subtle quantitative effects that tune pathway output. Our results further suggest that relatively small quantitative influences from individual regulatory phosphorylation events endow signaling systems with plasticity that evolution may exploit to quantitatively tailor signaling outcomes.

  1. The Impact of Multiple-Site Interactions on the Energy Resolution of a High-Pressure Xenon Gamma-Ray Spectrometer

    SciTech Connect

    Kiff, Scott D.; He, Zhong

    2007-11-30

    High-pressure xenon (HPXe) ionization chambers have generated interest as a radiation detection medium for purposes requiring good energy resolution, high detection efficiency, and uniform response over a broad temperature range, such as homeland security and well logging applications. These chambers generally exhibit a substantial degradation of the measured energy resolution relative to theoretical limits. This investigation studies the impact of the number of interaction sites in an event sequence on the measured energy resolution using a benchmarked simulation package. The prominence of single and multiple-site interactions is investigated in addition to the photopeak broadening due to each event class. A radial position-sensing technique developed for coplanar-anode HPXe chambers is shown to have benefit for only single-site events.

  2. Multiple Transport-Active Binding Sites Are Available for a Single Substrate on Human P-Glycoprotein (ABCB1)

    PubMed Central

    Chufan, Eduardo E.; Kapoor, Khyati; Sim, Hong-May; Singh, Satyakam; Talele, Tanaji T.; Durell, Stewart R.; Ambudkar, Suresh V.

    2013-01-01

    P-glycoprotein (Pgp, ABCB1) is an ATP-Binding Cassette (ABC) transporter that is associated with the development of multidrug resistance in cancer cells. Pgp transports a variety of chemically dissimilar amphipathic compounds using the energy from ATP hydrolysis. In the present study, to elucidate the binding sites on Pgp for substrates and modulators, we employed site-directed mutagenesis, cell- and membrane-based assays, molecular modeling and docking. We generated single, double and triple mutants with substitutions of the Y307, F343, Q725, F728, F978 and V982 residues at the proposed drug-binding site with cys in a cysless Pgp, and expressed them in insect and mammalian cells using a baculovirus expression system. All the mutant proteins were expressed at the cell surface to the same extent as the cysless wild-type Pgp. With substitution of three residues of the pocket (Y307, Q725 and V982) with cysteine in a cysless Pgp, QZ59S-SSS, cyclosporine A, tariquidar, valinomycin and FSBA lose the ability to inhibit the labeling of Pgp with a transport substrate, [125I]-Iodoarylazidoprazosin, indicating these drugs cannot bind at their primary binding sites. However, the drugs can modulate the ATP hydrolysis of the mutant Pgps, demonstrating that they bind at secondary sites. In addition, the transport of six fluorescent substrates in HeLa cells expressing triple mutant (Y307C/Q725C/V982C) Pgp is also not significantly altered, showing that substrates bound at secondary sites are still transported. The homology modeling of human Pgp and substrate and modulator docking studies support the biochemical and transport data. In aggregate, our results demonstrate that a large flexible pocket in the Pgp transmembrane domains is able to bind chemically diverse compounds. When residues of the primary drug-binding site are mutated, substrates and modulators bind to secondary sites on the transporter and more than one transport-active binding site is available for each substrate

  3. Exposure to bleached kraft pulp mill effluent disrupts the pituitary-gonadal axis of white sucker at multiple sites

    SciTech Connect

    Van Der Kraak, G.J.; Munkittrick, K.R.; McMaster, M.E.; Portt, C.B.; Chang, J.P. )

    1992-08-01

    Recent studies have demonstrated reproductive problems in white sucker (Catostomus commersoni) exposed to bleached kraft pulp mill effluent (BKME) at Jackfish Bay on Lake Superior. These fish exhibit delayed sexual maturity, reduced gonadal size, reduced secondary sexual characteristics, and circulating steroid levels depressed relative to those of reference populations. The present studies were designed to evaluate sites in the pituitary-gonadal axis of prespawning white sucker affected by BKME exposure. At the time of entry to the spawning stream, plasma levels of immunoreactive gonadotropin (GtH)-II (LH-type GtH) in male and female white sucker were 30- and 50-fold lower, respectively, than the levels in fish from a reference site. A single intraperitoneal injection of D-Arg6, Pro9N-Et sGnRH (sGnRH-A, 0.1 mg/kg) increased plasma GtH levels in male and female fish at both sites, although the magnitude of the response was greatly reduced in BKME-exposed fish. Fish at the BKME site did not ovulate in response to sGnRH-A, while 10 of 10 fish from the reference site ovulated within 6 hr. Plasma 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) levels were depressed in BKME-exposed fish and unlike fish at the reference site, failed to increase in response to sGnRH-A. Testosterone levels in both sexes and 11-ketostestosterone levels in males were elevated in fish from the reference site but were not further increased by GnRH treatment. In contrast, BKME-exposed fish exhibit a transitory increase in testosterone levels in response to the GnRH analog. In vitro incubations of ovarian follicles obtained from fish at the BKME site revealed depressed basal secretion of testosterone and 17,20 beta-P and reduced responsiveness to the GtH analog human chorionic gonadotropin and to forskolin, a direct activator of adenylate cyclase.

  4. Optimising geological storage of CO2 by development of multiple injection sites in regionally extensive storage sandstones

    NASA Astrophysics Data System (ADS)

    Akhurst, Maxine; McDermott, Christopher; Williams, John; Mackay, Eric; Jin, Min; Tucker, Owain; Mallows, Tom; Hannis, Sarah; Pearce, Jonathan

    2016-04-01

    Carbon capture, transport and storage (CCS) is considered a key technology to provide secure, low-carbon energy supply and industrial processes to reduce the greenhouse gas emissions that contribute to the adverse effects of climatic change. Geological storage of carbon dioxide (CO2), captured during hydrocarbon production at the Sleipner Field, in strata beneath the Norwegian sector of the North Sea has been in operation since 1996. Projects to store CO2 captured at power plants in strata underlying the North Sea are currently in design. Storage of the CO2 is planned in depleted hydrocarbon fields or regionally extensive sandstones containing brine (saline aquifer sandstones). The vast majority of the UK potential storage resource is within brine-saturated sandstone formations. The sandstone formations are each hundreds to thousands of square kilometres in extent and underlie all sectors of the North Sea. The immense potential to store CO2 in these rocks can only be fully achieved by the operation of more than one injection site within each formation. Here we report an investigation into the operation of more than one injection site within a storage formation using a UK North Sea case study of the Captain Sandstone and the included Goldeneye Field, which is part of the mature hydrocarbon province offshore Scotland. Research by the CO2MultiStore project was targeted to increase understanding and confidence in the operation of two sites within the Captain Sandstone. Methods were implemented to reduce the effort and resources needed to characterise the sandstone, and increase understanding of its stability and performance during operation of more than one injection site. Generic learning was captured throughout the research relevant to the characterisation of extensive storage sandstones, management of the planned injection operations and monitoring of CO2 injection at two (or more) sites within any connected sandstone formation. The storage of CO2 can be optimised

  5. 15 CFR 921.33 - Boundary changes, amendments to the management plan, and addition of multiple-site components.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Reserve, may be made only after written approval by NOAA. NOAA may require public notice, including notice... statement may be required. NOAA will place a notice in the Federal Register of any proposed changes in... made. NOAA will publish notice of the proposed new site including an invitation for comments from...

  6. 15 CFR 921.33 - Boundary changes, amendments to the management plan, and addition of multiple-site components.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Reserve, may be made only after written approval by NOAA. NOAA may require public notice, including notice... statement may be required. NOAA will place a notice in the Federal Register of any proposed changes in... made. NOAA will publish notice of the proposed new site including an invitation for comments from...

  7. Correcting for Incomplete Saturation and Off-Resonance Effects in Multiple-Site Saturation-Transfer Kinetic Measurements

    NASA Astrophysics Data System (ADS)

    Kingsley, Peter B.; Monahan, W. Gordon

    2000-09-01

    The effects of incomplete saturation and off-resonance irradiation on nuclear magnetic resonance saturation-transfer measurements of three-site chemical-exchange rates are discussed. A new method that uses double-saturation measurements is compared with two published methods, one that uses single-saturation measurements and one that uses a single-saturation measurement and a double-saturation measurement. Several formulas are compared for measuring the exchange rate constant kDE for exchange from a detected spin D to an exchanging spin E in the presence of exchange from spin D to a competing spin C. For each method, formulas are derived with corrections for incomplete saturation or off-resonance effects, with both corrections, and with neither correction. Exact formulas are available for three exchanging sites with incomplete saturation if there are no off-resonance effects. Off-resonance corrections are imperfect even with complete saturation.

  8. Exploring multiple binding sites of an indoloquinoline in triple-helical DNA: a paradigm for DNA triplex-selective intercalators.

    PubMed

    Dickerhoff, Jonathan; Riechert-Krause, Fanny; Seifert, Jenny; Weisz, Klaus

    2014-12-01

    Employing NMR spectroscopic methods preferred binding sites of a triplex-selective indoloquinoline drug were examined with three DNA triplex targets. To directly derive and evaluate number and type of the different sites of interaction, studies were performed on short triple-helical constructs specifically labeled with 3-(15)N thymidine probes. The detection and assignment of several coexisting species was enabled through the observation of slow exchange on the chemical shift timescale between complexes and free triplex. In general, the 5'-triplex-duplex junction constitutes the most favorable intercalation site, in particular when flanked by a TAT base triad. NMR data also revealed two different orientations for the intercalating indoloquinoline drug. Binding affinity significantly decreases with a C(+)GC triad bordering the junction but junction binding is still preferred over intercalation between TAT base triads within the triplex stem. In addition to the intercalation between two uncharged TAT triplets, intercalation between a TAT and a 3'-terminal C(+)GC triplet was also observed, indicating a non-protonated third strand cytosine at the triplex end position.

  9. The SLO1 PPR protein is required for RNA editing at multiple sites with similar upstream sequences in Arabidopsis mitochondria.

    PubMed

    Sung, Tzu-Ying; Tseng, Ching-Chih; Hsieh, Ming-Hsiun

    2010-08-01

    In Arabidopsis, RNA editing changes more than 500 cytidines to uridines in mitochondrial transcripts. The editing enzyme and co-factors involved in these processes are largely unknown. We have identified a nuclear gene SLOW GROWTH1 (SLO1) encoding an E motif-containing pentatricopeptide repeat protein that is required for RNA editing of nad4 and nad9 in Arabidopsis mitochondria. The SLO1 protein is localized to the mitochondrion, and its absence gives rise to small plants with slow growth and delayed development. A survey of approximately 500 mitochondrial RNA editing sites in Arabidopsis reveals that the editing of two sites, nad4-449 and nad9-328, is abolished in the slo1 mutants. Sequence comparison in the upstream (from -1 to -15 bp) of nad4-449 and nad9-328 editing sites shows that nine of the 15 nucleotides are identical. In addition to RNA editing, we used RNA gel blot analysis to compare the abundance and banding patterns of mitochondrial transcripts between the wild type and slo1 mutants. Of the 79 genes and open reading frames examined, steady-state levels of 56 mitochondrial transcripts are increased in the slo1 mutants. These results suggest that the SLO1 protein may indirectly regulate plant growth and development via affecting mitochondrial RNA editing and gene expression.

  10. Closure Strategy for a Waste Disposal Facility with Multiple Waste Types and Regulatory Drivers at the Nevada Test Site

    SciTech Connect

    D. Wieland, V. Yucel, L. Desotell, G. Shott, J. Wrapp

    2008-04-01

    The U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) plans to close the waste and classified material storage cells in the southeast quadrant of the Area 5 Radioactive Waste Management Site (RWMS), informally known as the '92-Acre Area', by 2011. The 25 shallow trenches and pits and the 13 Greater Confinement Disposal (GCD) borings contain various waste streams including low-level waste (LLW), low-level mixed waste (LLMW), transuranic (TRU), mixed transuranic (MTRU), and high specific activity LLW. The cells are managed under several regulatory and permit programs by the U.S. Department of Energy (DOE) and the Nevada Division of Environmental Protection (NDEP). Although the specific closure requirements for each cell vary, 37 closely spaced cells will be closed under a single integrated monolayer evapotranspirative (ET) final cover. One cell will be closed under a separate cover concurrently. The site setting and climate constrain transport pathways and are factors in the technical approach to closure and performance assessment. Successful implementation of the integrated closure plan requires excellent communication and coordination between NNSA/NSO and the regulators.

  11. DEVELOPING SITE-SPECIFIC DERIVED CONCENTRATION GUIDELINE LEVELS FOR MULTIPLE MEDIA AT THE CONNECTICUT YANKEE HADDAM NECK PLANT

    SciTech Connect

    Taylor, S.W.; Smith, L.C.; Carr, R.K.; Carson, A.; Darois, E.

    2003-02-27

    As part of the license termination process, site-specific Derived Concentration Guideline Levels for the Haddam Neck Plant site are developed for soil, groundwater, concrete left standing, and concrete demolished that satisfy the radiological criteria for unrestricted use as defined in 10 CFR 20.1402. Background information on the license termination process and characteristics of the Haddam Neck Plant site are presented. The dose models and associated resident farmer and building occupancy scenarios, applicable pathways, and critical groups developed to establish the Derived Concentration Guideline Levels are described. A parameter assignment process is introduced wherein general population values are used to establish behavioral and metabolic parameters representative of an average member of the critical group, while the uncertainty associated with important physical parameters is considered. A key element of the parameter assignment process is the use of sensitivity analysis to identify the dose sensitive physical parameters and to ensure that such parameters are assigned conservative values. Structuring the parameter assignment process, completing the formal sensitivity analyses, and assigning conservative values to the sensitive physical parameters in a consistent way establishes a calculation framework that lead to Derived Concentration Guideline Levels with a uniform level of conservatism across all media and all radionuclides.

  12. Evaluating multiple indices of agricultural water use efficiency and productivity to improve comparisons between sites and trends

    NASA Astrophysics Data System (ADS)

    Levy, M. C.

    2012-12-01

    Approximately 70% of global available freshwater supplies are used in the agricultural sector. Increased demands for water to meet growing population food requirements, and expected changes in the reliability of freshwater supplies due to climate change, threaten the sustainability of water supplies worldwide - not only on farms, but in connected cities and industries. Researchers concerned with agricultural water use sustainability use a variety of theoretical and empirical measures of efficiency and productivity to gain insight into the sustainability of agricultural water use. However, definitions of measures, or indices, vary between different natural and political boundaries, across regions, states and nations and between their respective research, industry, and environmental groups. Index development responds to local data availability and local agendas, and there is debate about the validity of various indices. However, real differences in empirical index measures are not well-understood across the multiple disciplines that study agricultural water use, including engineering and hydrology, agronomy, climate and soil sciences, and economics. Nevertheless reliable, accessible, and generalizable indices are required for planners and policymakers to promote sustainable water use systems. This study synthesizes a set of water use efficiency and productivity indices based on academic, industry and government literature in California and Australia, two locations with similarly water-stressed and valuable agricultural industries under pressure to achieve optimal water use efficiency and productivity. Empirical data at the irrigation district level from the California San Joaquin Valley and Murray Darling Basin states of Victoria and New South Wales in Australia are used to compute indices that estimate efficiency, yield productivity, and economic productivity of agricultural water use. Multiple index estimates of same time-series data demonstrate historical spread

  13. Ferromanganese nodules from MANOP Sites H, S, and R-Control of mineralogical and chemical composition by multiple accretionary processes

    USGS Publications Warehouse

    Dymond, J.; Lyle, M.; Finney, B.; Piper, D.Z.; Murphy, K.; Conard, R.; Pisias, N.

    1984-01-01

    The chemical composition of ferromanganese nodules from the three nodule-bearing MANOP sites in the Pacific can be accounted for in a qualitative way by variable contributions of distinct accretionary processes. These accretionary modes are: 1. (1) hydrogenous, i.e., direct precipitation or accumulation of colloidal metal oxides in seawater, 2. (2) oxic diagenesis which refers to a variety of ferromanganese accretion processes occurring in oxic sediments; and 3. (3) suboxic diagenesis which results from reduction of Mn+4 by oxidation of organic matter in the sediments. Geochemical evidence suggests processes (1) and (2) occur at all three MANOP nodule-bearing sites, and process (3) occurs only at the hemipelagic site, H, which underlies the relatively productive waters of the eastern tropical Pacific. A normative model quantitatively accounts for the variability observed in nearly all elements. Zn and Na, however, are not well explained by the three end-member model, and we suggest that an additional accretionary process results in greater variability in the abundances of these elements. Variable contributions from the three accretionary processes result in distinct top-bottom compositional differences at the three sites. Nodule tops from H are enriched in Ni, Cu, and Zn, instead of the more typical enrichments of these elements in nodule bottoms. In addition, elemental correlations typical of most pelagic nodules are reversed at site H. The three accretionary processes result in distinct mineralogies. Hydrogenous precipitation produces ??MnO2. Oxic diagenesis, however, produces Cu-Ni-rich todorokite, and suboxic diagenesis results in an unstable todorokite which transforms to a 7 A?? phase ("birnessite") upon dehydration. The presence of Cu and Ni as charge-balancing cations influence the stability of the todorokite structure. In the bottoms of H nodules, which accrete dominantly by suboxic diagenesis, Na+ and possibly Mn+2 provide much of the charge balance for

  14. Closure Strategy for a Waste Disposal Facility with Multiple Waste Types and Regulatory Drivers at the Nevada Test Site

    SciTech Connect

    L. Desotell; D. Wieland; V. Yucel; G. Shott; J. Wrapp

    2008-03-01

    The U.S. Department of Energy, National Security Administration Nevada Site Office (NNSA/NSO) is planning to close the 92-Acre Area of the Area 5 Radioactive Waste Management Site (RWMS) at the Nevada Test Site (NTS), which is about 65 miles northwest of Las Vegas, Nevada. Closure planning for this facility must take into account the regulatory requirements for a diversity of waste streams, disposal and storage configurations, disposal history, and site conditions. This paper provides a brief background of the Area 5 RWMS, identifies key closure issues, and presents the closure strategy. Disposals have been made in 25 shallow excavated pits and trenches and 13 Greater Confinement Disposal (GCD) boreholes at the 92-Acre Area since 1961. The pits and trenches have been used to dispose unclassified low-level waste (LLW), low-level mixed waste (LLMW), and asbestiform waste, and to store classified low-level and low-level mixed materials. The GCD boreholes are intermediate-depth disposal units about 10 feet (ft) in diameter and 120 ft deep. Classified and unclassified high-specific activity LLW, transuranic (TRU), and mixed TRU are disposed in the GCD boreholes. TRU waste was also disposed inadvertently in trench T-04C. Except for three disposal units that are active, all pits and trenches are operationally covered with 8-ft thick alluvium. The 92-Acre Area also includes a Mixed Waste Disposal Unit (MWDU) operating under Resource Conservation and Recovery Act (RCRA) Interim Status, and an asbestiform waste unit operating under a state of Nevada Solid Waste Disposal Site Permit. A single final closure cover is envisioned over the 92-Acre Area. The cover is the evapotranspirative-type cover that has been successfully employed at the NTS. Closure, post-closure care, and monitoring must meet the requirements of the following regulations: U.S. Department of Energy Order 435.1, Title 40 Code of Federal Regulations (CFR) Part 191, Title 40 CFR Part 265, Nevada Administrative

  15. Cost reduction performance enhancements of multiple site cooling water systems, enabled by remote system monitoring/control and multifaceted data management

    SciTech Connect

    Cook, B.; Young, D.; Tari, K.

    1998-12-31

    An outsourced cooling water treatment automated control and data acquisition package, has been designed, installed, and commissioned in over 70 sites in North America and offshore. The standard package consists of a controller, sensors, human-machine interface software, data acquisition and management software, communications, and reporting. Significant challenges to applying this standard package in multiple sites arose from variations in cooling system design and makeup water quality as well as operations, environmental considerations, metrics, and language. A standard approach has met these challenges and overcome effects of downsizing through significant reduction in non-value-added, manual activities. Overall system reliability has been improved by migration to best practice throughout the organizations involved and immediate proactive response to out-of-specification conditions. This paper documents the evolution of a standard cooling water automation and data management package from its inception to current practice.

  16. Constraining the factor analytical solutions obtained from multiple-year receptor modeling of ambient PM2.5 data from five speciation sites in Ontario, Canada

    NASA Astrophysics Data System (ADS)

    Sofowote, Uwayemi M.; Su, Yushan; Dabek-Zlotorzynska, Ewa; Rastogi, Ankit K.; Brook, Jeff; Hopke, Philip K.

    2015-05-01

    Rotational ambiguity in factor analyses leads to solutions that are not always consistent with reality. The inherent non-negativity constraints in positive matrix factorization (PMF) help to prevent factor solutions from becoming overly unrealistic, but they are not sufficient to prevent unwanted rotations that could manifest in factors that should have similar compositions varying across multiple sites. The Canadian National Air Pollution Surveillance (NAPS) network operates five fine particulate matter (PM2.5) speciation sites in Ontario. Data from these sites from 2005 to 2010 were subjected to PMF to obtain factors representing sources of particulate matter. Eight factors were found to be common across these sites. These factors had profiles that varied greatly from one site to the other, suggesting that the PMF solutions were impacted by some rotational ambiguity. New features in the EPA PMF V5 program allow the use of a priori information to impose mathematical constraints that guide the evolution of the factor solutions. These constraints reduce the rotational space. In situations where major emissions sources are known and located in the neighborhood of receptors, or emissions inventories and literature source profiles exist, it is easy to use these profiles to force the factor solutions to conform to the expected signatures. In our case, reported source profiles were neither available nor applicable due to the large spatial span of potential sources and receptor sites. This work describes how such constraints can be generated and used in these complex situations. The fundamental principle explored in this work is the concept of 'stiffness' of PMF solutions to identify the desirable non-rotating factors.

  17. Variance Component Analysis of a Multi-Site Study for the Reproducibility of Multiple Reaction Monitoring Measurements of Peptides in Human Plasma

    PubMed Central

    Xia, Jessie Q.; Sedransk, Nell; Feng, Xingdong

    2011-01-01

    Background In the Addona et al. paper (Nature Biotechnology 2009), a large-scale multi-site study was performed to quantify Multiple Reaction Monitoring (MRM) measurements of proteins spiked in human plasma. The unlabeled signature peptides derived from the seven target proteins were measured at nine different concentration levels, and their isotopic counterparts were served as the internal standards. Methodology/Principal Findings In this paper, the sources of variation are analyzed by decomposing the variance into parts attributable to specific experimental factors: technical replicates, sites, peptides, transitions within each peptide, and higher-order interaction terms based on carefully built mixed effects models. The factors of peptides and transitions are shown to be major contributors to the variance of the measurements considering heavy (isotopic) peptides alone. For the light (12C) peptides alone, in addition to these factors, the factor of study*peptide also contributes significantly to the variance of the measurements. Heterogeneous peptide component models as well as influence analysis identify the outlier peptides in the study, which are then excluded from the analysis. Using a log-log scale transformation and subtracting the heavy/isotopic peptide [internal standard] measurement from the peptide measurements (i.e., taking the logarithm of the peak area ratio in the original scale establishes that), the MRM measurements are overall consistent across laboratories following the same standard operating procedures, and the variance components related to sites, transitions and higher-order interaction terms involving sites have greatly reduced impact. Thus the heavy peptides have been effective in reducing apparent inter-site variability. In addition, the estimates of intercepts and slopes of the calibration curves are calculated for the sub-studies. Conclusions/Significance The MRM measurements are overall consistent across laboratories following the same

  18. Chemical synthesis of idiotopes. Evidence that antisera to the same JH1 peptide detect multiple binding site-associated idiotopes

    PubMed Central

    1984-01-01

    In an attempt to better understand the molecular basis of idiotypy, we have generated several site-specific antisera through immunization of animals with synthetic peptides corresponding to the (JH1) heavy chain joining segment 1 of the mouse heavy chain variable (VH) region. These anti-peptide sera identify several idiotypic determinants present on intact hybridoma and myeloma immunoglobulins. Expression of at least three of these idiotopes is correlated with the antigen specificity of the family of immunoglobulins bearing the determinant. Use of synthetic peptides may prove a powerful technique in the generation of molecularly defined antiidiotypic reagents. PMID:6201582

  19. Multiple Conserved Heteroplasmic Sites in tRNA Genes in the Mitochondrial Genomes of Terrestrial Isopods (Oniscidea)

    PubMed Central

    Chandler, Christopher H.; Badawi, Myriam; Moumen, Bouziane; Grève, Pierre; Cordaux, Richard

    2015-01-01

    Mitochondrial genome structure and organization are relatively conserved among metazoans. However, in many isopods, especially the terrestrial isopods (Oniscidea), the mitochondrial genome consists of both ∼14-kb linear monomers and ∼28-kb circular dimers. This unusual organization is associated with an ancient and conserved constitutive heteroplasmic site. This heteroplasmy affects the anticodon of a tRNA gene, allowing this single locus to function as a “dual” tRNA gene for two different amino acids. Here, we further explore the evolution of these unusual mitochondrial genomes by assembling complete mitochondrial sequences for two additional Oniscidean species, Trachelipus rathkei and Cylisticus convexus. Strikingly, we find evidence of two additional heteroplasmic sites that also alter tRNA anticodons, creating additional dual tRNA genes, and that are conserved across both species. These results suggest that the unique linear/circular organization of isopods’ mitochondrial genomes may facilitate the evolution of stable mitochondrial heteroplasmies, and, conversely, once such heteroplasmies have evolved, they constrain the multimeric structure of the mitochondrial genome in these species. Finally, we outline some possible future research directions to identify the factors influencing mitochondrial genome evolution in this group. PMID:25911226

  20. Multiple Conserved Heteroplasmic Sites in tRNA Genes in the Mitochondrial Genomes of Terrestrial Isopods (Oniscidea).

    PubMed

    Chandler, Christopher H; Badawi, Myriam; Moumen, Bouziane; Grève, Pierre; Cordaux, Richard

    2015-04-24

    Mitochondrial genome structure and organization are relatively conserved among metazoans. However, in many isopods, especially the terrestrial isopods (Oniscidea), the mitochondrial genome consists of both ∼14-kb linear monomers and ∼28-kb circular dimers. This unusual organization is associated with an ancient and conserved constitutive heteroplasmic site. This heteroplasmy affects the anticodon of a tRNA gene, allowing this single locus to function as a "dual" tRNA gene for two different amino acids. Here, we further explore the evolution of these unusual mitochondrial genomes by assembling complete mitochondrial sequences for two additional Oniscidean species, Trachelipus rathkei and Cylisticus convexus. Strikingly, we find evidence of two additional heteroplasmic sites that also alter tRNA anticodons, creating additional dual tRNA genes, and that are conserved across both species. These results suggest that the unique linear/circular organization of isopods' mitochondrial genomes may facilitate the evolution of stable mitochondrial heteroplasmies, and, conversely, once such heteroplasmies have evolved, they constrain the multimeric structure of the mitochondrial genome in these species. Finally, we outline some possible future research directions to identify the factors influencing mitochondrial genome evolution in this group.

  1. A multiple-method approach to flood assessment at a low-level radioactive waste site in southern Nevada

    SciTech Connect

    Miller, J.J.; Gustafson, D.L.; Schmeltzer, J.S.

    1994-12-31

    Flood hazard analysis on alluvial fans using Federal Emergency Management Agency (FEMA) method are not limited to the FEMA Alluvial Fan Methodology (FEMA AFM). Flood hazard delineations using a combination of methods provide a more thorough assessment that using only the FEMA AFM. Other FEMA-accepted methods, such as the HEC-2 model for shallow concentrated flow and the Manning Equation for sheetflow, may be more appropriate. A flood assessment using a multiple-method approach was performed to determine the 100-year flood hazard in this arid region. Understanding the limitations and assumptions of these methods is important to determine which method is applicable and when a method can provide reasonable results.

  2. [Anesthetic Management of a Patient with Facioscapulohumeral Muscular Dystrophy: Importance of Monitoring Neuromuscular Function at Multiple Sites].

    PubMed

    Matsui, Shuhei; Tanaka, Satoshi; Kiyosawa, Kenkichi; Tanaka, Toshiyuki; Kawamata, Mikito

    2015-12-01

    A 39-year-old female with facioscapulohumeral muscular dystrophy (FSHD) was scheduled for thoracoscopic resection of an anterior mediastinal tumor. She had slowly progressive weakness and atrophy in the fascial and shoulder girdle muscles. General anesthesia was induced and maintained with propofol, remifentanil, and fentanyl combined with thoracic paravertebral block. Rocuronium-induced neuromuscular blockade was evaluated with acceleromyography at the corrugator supercilii, masseter, and adductor pollicis muscles. There was no reaction at the atrophic corrugator supercilii muscle in response to train-of-four (TOF) stimulation even before rocuronium administration. In contrast twitch responses at the masseter and adductor pollicis muscles to TOF stimulation could be evoked and the duration of action of rocuronium was found to be similar to that of the normal population. The perioperative course was uneventful. Neuromuscular monitoring sites should be carefully selected in FSHD patients because of possible inability to monitor neuromuscular function at the atrophic muscles. PMID:26790332

  3. Multiple repeats of Helicobacter pylori CagA EPIYA-C phosphorylation sites predict risk of gastric ulcer in Iran.

    PubMed

    Honarmand-Jahromy, Sahar; Siavoshi, Farideh; Malekzadeh, Reza; Sattari, Taher Nejad; Latifi-Navid, Saeid

    2015-12-01

    Biological activity of Helicobacter pylori oncoprotein CagA is determined by a diversity in the tyrosine phosphorylation motif sites. In the present study, the diversity and the type of the H. pylori CagA EPIYA motifs and their association with gastric ulcer (GU) and duodenal ulcer (DU) in Iranian dyspeptic patients were assessed. PCR amplification, sequencing, and bioinformatic analysis were performed to determine the pattern of CagA EPIYA motifs. Of 168 H. pylori cagA(+) strains, the frequency of ABC was 93.50%, ABCCC 5.40%, ABC + ABCCC 0.6% and ABCC 0.6%. There was no EPIYA-D segment. The ABCCC pattern of EPIYA motif was more frequent in the H. pylori isolates from GU (8/50, 16%) than in those from chronic gastritis (CG) (0/81, 0%) (P = 0). In contrast, The ABC pattern of EPIYA motif was less frequent in the H. pylori isolates from GU (41/50, 82%) than in those from CG (80/81, 98.80%) (Age-sex-adjusted odds ratio (OR) = 0.020, 95% CI = 0.002-0.259; P = 0.003). The distribution of the ABC motif was almost the same in H. pylori isolates from CG (98.80%) and DU diseases (97.30%). There was no significant association between the number of CagA EPIYA-C segment and DU (P > 0.05). We have proposed that CagA from Iranian H. pylori strains were Western type and all strains had active phosphorylation sites. The three EPIYA-C motifs of CagA were more frequently observed in the H. pylori strains from GU; thus it might be an important biomarker for predicting the GU risk in Iran. PMID:26408373

  4. Identification of multiple SNT-binding sites on NPM-ALK oncoprotein and their involvement in cell transformation.

    PubMed

    Chikamori, M; Fujimoto, J; Tokai-Nishizumi, N; Yamamoto, T

    2007-05-01

    The t(2;5) chromosomal translocation occurs in anaplastic large-cell lymphoma arising from activated T lymphocytes. This genomic rearrangement generates the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) oncoprotein that is a chimeric protein consisting of parts of the nuclear protein NPM and ALK receptor protein-tyrosine kinase. We used yeast two-hybrid screening to identify an adaptor protein Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target (SNT)-2 as a new partner that interacted with the cytoplasmic domain of ALK. Immunoprecipitation assay revealed that SNT-1 and SNT-2 interacted with NPM-ALK and kinase-negative NPM-ALK mutant. Y156, Y567 and a 19-amino-acid sequence (aa 631-649) of NPM-ALK were essential for this interaction. The interaction through Y156 and Y567 was dependent on phosphorylation of these tyrosines, whereas the interaction through the 19-amino-acid sequence was independent of phosphorylation. NPM-ALK mutant protein mutated at these three binding sites showed significantly reduced transforming activity. This transformation-defective NPM-ALK mutant still interacted with signal transducing proteins such as phospholipase C-gamma and phosphatidylinositol 3-kinase, which were previously reported to be relevant to NPM-ALK-dependent tumorigenesis. These observations indicate that the three SNT-binding sites of NPM-ALK are important for its transforming activity. This raises a possibility that SNT family proteins play significant roles in cellular transformation triggered by NPM-ALK, which though remains to be verified.

  5. Multiple repeats of Helicobacter pylori CagA EPIYA-C phosphorylation sites predict risk of gastric ulcer in Iran.

    PubMed

    Honarmand-Jahromy, Sahar; Siavoshi, Farideh; Malekzadeh, Reza; Sattari, Taher Nejad; Latifi-Navid, Saeid

    2015-12-01

    Biological activity of Helicobacter pylori oncoprotein CagA is determined by a diversity in the tyrosine phosphorylation motif sites. In the present study, the diversity and the type of the H. pylori CagA EPIYA motifs and their association with gastric ulcer (GU) and duodenal ulcer (DU) in Iranian dyspeptic patients were assessed. PCR amplification, sequencing, and bioinformatic analysis were performed to determine the pattern of CagA EPIYA motifs. Of 168 H. pylori cagA(+) strains, the frequency of ABC was 93.50%, ABCCC 5.40%, ABC + ABCCC 0.6% and ABCC 0.6%. There was no EPIYA-D segment. The ABCCC pattern of EPIYA motif was more frequent in the H. pylori isolates from GU (8/50, 16%) than in those from chronic gastritis (CG) (0/81, 0%) (P = 0). In contrast, The ABC pattern of EPIYA motif was less frequent in the H. pylori isolates from GU (41/50, 82%) than in those from CG (80/81, 98.80%) (Age-sex-adjusted odds ratio (OR) = 0.020, 95% CI = 0.002-0.259; P = 0.003). The distribution of the ABC motif was almost the same in H. pylori isolates from CG (98.80%) and DU diseases (97.30%). There was no significant association between the number of CagA EPIYA-C segment and DU (P > 0.05). We have proposed that CagA from Iranian H. pylori strains were Western type and all strains had active phosphorylation sites. The three EPIYA-C motifs of CagA were more frequently observed in the H. pylori strains from GU; thus it might be an important biomarker for predicting the GU risk in Iran.

  6. The Arabidopsis PR-1 promoter contains multiple integration sites for the coactivator NPR1 and the repressor SNI1.

    PubMed

    Pape, Sebastian; Thurow, Corinna; Gatz, Christiane

    2010-12-01

    Systemic acquired resistance is a broad-spectrum plant immune response involving massive transcriptional reprogramming. The Arabidopsis (Arabidopsis thaliana) PATHOGENESIS-RELATED-1 (PR-1) gene has been used in numerous studies to elucidate transcriptional control mechanisms regulating systemic acquired resistance. WRKY transcription factors and basic leucine zipper proteins of the TGA family regulate the PR-1 promoter by binding to specific cis-elements. In addition, the promoter is under the control of two proteins that do not directly contact the DNA: the positive regulator NONEXPRESSOR OF PR GENES1 (NPR1), which physically interacts with TGA factors, and the repressor SUPPRESSOR OF NPR1, INDUCIBLE1 (SNI1). In this study, we analyzed the importance of the TGA-binding sites LS5 and LS7 and the WKRY box LS4 for regulation by NPR1 and SNI1. In the absence of LS5 and LS7, NPR1 activates the PR-1 promoter through a mechanism that requires LS4. Since transcriptional activation of WRKY genes is under the control of NPR1 and since LS4 is not sufficient for the activation of a truncated PR-1 promoter by the effector protein NPR1-VP16 in transient assays, it is concluded that the LS4-dependent activation of the PR-1 promoter is indirect. In the case of NPR1 acting directly through TGA factors at its target promoters, two TGA-binding sites are necessary but not sufficient for NPR1 function in transgenic plants and in the NPR-VP16-based trans-activation assay in protoplasts. SNI1 exerts its negative effect in the noninduced state by targeting unknown proteins associated with sequences between bp -816 and -573. Under induced conditions, SNI1 negatively regulates the function of WRKY transcription factors binding to WKRY boxes between bp -550 and -510.

  7. The Arabidopsis PR-1 Promoter Contains Multiple Integration Sites for the Coactivator NPR1 and the Repressor SNI1[W

    PubMed Central

    Pape, Sebastian; Thurow, Corinna; Gatz, Christiane

    2010-01-01

    Systemic acquired resistance is a broad-spectrum plant immune response involving massive transcriptional reprogramming. The Arabidopsis (Arabidopsis thaliana) PATHOGENESIS-RELATED-1 (PR-1) gene has been used in numerous studies to elucidate transcriptional control mechanisms regulating systemic acquired resistance. WRKY transcription factors and basic leucine zipper proteins of the TGA family regulate the PR-1 promoter by binding to specific cis-elements. In addition, the promoter is under the control of two proteins that do not directly contact the DNA: the positive regulator NONEXPRESSOR OF PR GENES1 (NPR1), which physically interacts with TGA factors, and the repressor SUPPRESSOR OF NPR1, INDUCIBLE1 (SNI1). In this study, we analyzed the importance of the TGA-binding sites LS5 and LS7 and the WKRY box LS4 for regulation by NPR1 and SNI1. In the absence of LS5 and LS7, NPR1 activates the PR-1 promoter through a mechanism that requires LS4. Since transcriptional activation of WRKY genes is under the control of NPR1 and since LS4 is not sufficient for the activation of a truncated PR-1 promoter by the effector protein NPR1-VP16 in transient assays, it is concluded that the LS4-dependent activation of the PR-1 promoter is indirect. In the case of NPR1 acting directly through TGA factors at its target promoters, two TGA-binding sites are necessary but not sufficient for NPR1 function in transgenic plants and in the NPR-VP16-based trans-activation assay in protoplasts. SNI1 exerts its negative effect in the noninduced state by targeting unknown proteins associated with sequences between bp −816 and −573. Under induced conditions, SNI1 negatively regulates the function of WRKY transcription factors binding to WKRY boxes between bp −550 and −510. PMID:20935179

  8. Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt.

    PubMed

    Bisanz, Jordan E; Enos, Megan K; PrayGod, George; Seney, Shannon; Macklaim, Jean M; Chilton, Stephanie; Willner, Dana; Knight, Rob; Fusch, Christoph; Fusch, Gerhard; Gloor, Gregory B; Burton, Jeremy P; Reid, Gregor

    2015-08-01

    The nutritional status of pregnant women is vital for healthy outcomes and is a concern for a large proportion of the world's population. The role of the microbiota in pregnancy and nutrition is a promising new area of study with potential health ramifications. In many African countries, maternal and infant death and morbidity are associated with malnutrition. Here, we assess the influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1, supplemented with Moringa plant as a source of micronutrients, on the health and oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an open-label study design, 26 subjects received yogurt daily, and 30 were untreated during the last two trimesters and for 1 month after birth. Samples were analyzed using 16S rRNA gene sequencing, and dietary recalls were recorded. Women initially categorized as nourished or undernourished consumed similar calories and macronutrients, which may explain why there was no difference in the microbiota at any body site. Consumption of yogurt increased the relative abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn feces but had no effect on the mother's microbiota at any body site. The microbiota of the oral cavity and GI tract remained stable over pregnancy, but the vaginal microbiota showed a significant increase in diversity leading up to and after birth. In summary, daily micronutrient-supplemented probiotic yogurt provides a safe, affordable food for pregnant women in rural Tanzania, and the resultant improvement in the gut microbial profile of infants is worthy of further study. PMID:25979893

  9. Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt

    PubMed Central

    Bisanz, Jordan E.; Enos, Megan K.; PrayGod, George; Seney, Shannon; Macklaim, Jean M.; Chilton, Stephanie; Willner, Dana; Knight, Rob; Fusch, Christoph; Fusch, Gerhard; Gloor, Gregory B.; Burton, Jeremy P.

    2015-01-01

    The nutritional status of pregnant women is vital for healthy outcomes and is a concern for a large proportion of the world's population. The role of the microbiota in pregnancy and nutrition is a promising new area of study with potential health ramifications. In many African countries, maternal and infant death and morbidity are associated with malnutrition. Here, we assess the influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1, supplemented with Moringa plant as a source of micronutrients, on the health and oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an open-label study design, 26 subjects received yogurt daily, and 30 were untreated during the last two trimesters and for 1 month after birth. Samples were analyzed using 16S rRNA gene sequencing, and dietary recalls were recorded. Women initially categorized as nourished or undernourished consumed similar calories and macronutrients, which may explain why there was no difference in the microbiota at any body site. Consumption of yogurt increased the relative abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn feces but had no effect on the mother's microbiota at any body site. The microbiota of the oral cavity and GI tract remained stable over pregnancy, but the vaginal microbiota showed a significant increase in diversity leading up to and after birth. In summary, daily micronutrient-supplemented probiotic yogurt provides a safe, affordable food for pregnant women in rural Tanzania, and the resultant improvement in the gut microbial profile of infants is worthy of further study. PMID:25979893

  10. Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt.

    PubMed

    Bisanz, Jordan E; Enos, Megan K; PrayGod, George; Seney, Shannon; Macklaim, Jean M; Chilton, Stephanie; Willner, Dana; Knight, Rob; Fusch, Christoph; Fusch, Gerhard; Gloor, Gregory B; Burton, Jeremy P; Reid, Gregor

    2015-08-01

    The nutritional status of pregnant women is vital for healthy outcomes and is a concern for a large proportion of the world's population. The role of the microbiota in pregnancy and nutrition is a promising new area of study with potential health ramifications. In many African countries, maternal and infant death and morbidity are associated with malnutrition. Here, we assess the influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1, supplemented with Moringa plant as a source of micronutrients, on the health and oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an open-label study design, 26 subjects received yogurt daily, and 30 were untreated during the last two trimesters and for 1 month after birth. Samples were analyzed using 16S rRNA gene sequencing, and dietary recalls were recorded. Women initially categorized as nourished or undernourished consumed similar calories and macronutrients, which may explain why there was no difference in the microbiota at any body site. Consumption of yogurt increased the relative abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn feces but had no effect on the mother's microbiota at any body site. The microbiota of the oral cavity and GI tract remained stable over pregnancy, but the vaginal microbiota showed a significant increase in diversity leading up to and after birth. In summary, daily micronutrient-supplemented probiotic yogurt provides a safe, affordable food for pregnant women in rural Tanzania, and the resultant improvement in the gut microbial profile of infants is worthy of further study.

  11. Utility of multiple chemical techniques in archaeological residential mobility studies: case studies from Tiwanaku- and Chiribaya-affiliated sites in the Andes.

    PubMed

    Knudson, Kelly J; Price, T Douglas

    2007-01-01

    In the south central Andes, archaeologists have long debated the extent of Tiwanaku colonization during the Middle Horizon (AD 500-1000). We tested the hypotheses regarding the nature of Tiwanaku influence using strontium isotope, trace element concentration, and oxygen isotope data from archaeological human tooth enamel and bone from Tiwanaku- and Chiribaya-affiliated sites in the south central Andes. Strontium isotope analysis of 25 individuals buried at the Tiwanaku-affiliated Moquegua Valley site of Chen Chen demonstrates that it was likely a Tiwanaku colony. In contrast, no immigrants from the Lake Titicaca Basin were present in 27 individuals analyzed from the San Pedro de Atacama cemeteries of Coyo Oriental, Coyo-3, and Solcor-3; it is likely that these sites represent economic and religious alliances, but not colonies. However, strontium isotope analysis alone cannot distinguish movement between the Tiwanaku- and Chiribaya-affiliated sites in the Moquegua and Ilo Valleys of southern Peru. Analyzing oxygen isotope and trace element concentration data and comparing it with strontium isotope data from the same individuals provides a more detailed picture of residential mobility in the Tiwanaku and Chiribaya polities. In addition to monitoring diagenetic contamination, trace element concentration data identified movement during adulthood for certain individuals. However, these data could not distinguish movement between the Moquegua and Ilo Valleys. While oxygen isotope data could clearly distinguish the high-altitude sites from others, more data is needed to characterize the local oxygen isotope ratios of these regions. These data demonstrate the potential for archaeological reconstruction of residential mobility through multiple lines of evidence. PMID:17063464

  12. SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle

    PubMed Central

    Figueroa-Romero, Claudia; Iñiguez-Lluhí, Jorge A.; Stadler, Julia; Chang, Chuang-Rung; Arnoult, Damien; Keller, Peter J.; Hong, Yu; Blackstone, Craig; Feldman, Eva L.

    2009-01-01

    Dynamin-related protein (Drp) 1 is a key regulator of mitochondrial fission and is composed of GTP-binding, Middle, insert B, and C-terminal GTPase effector (GED) domains. Drp1 associates with mitochondrial fission sites and promotes membrane constriction through its intrinsic GTPase activity. The mechanisms that regulate Drp1 activity remain poorly understood but are likely to involve reversible post-translational modifications, such as conjugation of small ubiquitin-like modifier (SUMO) proteins. Through a detailed analysis, we find that Drp1 interacts with the SUMO-conjugating enzyme Ubc9 via multiple regions and demonstrate that Drp1 is a direct target of SUMO modification by all three SUMO isoforms. While Drp1 does not harbor consensus SUMOylation sequences, our analysis identified2 clusters of lysine residues within the B domain that serve as noncanonical conjugation sites. Although initial analysis indicates that mitochondrial recruitment of ectopically expressed Drp1 in response to staurosporine is unaffected by loss of SUMOylation, we find that Drp1 SUMOylation is enhanced in the context of the K38A mutation. This dominant-negative mutant, which is deficient in GTP binding and hydrolysis, does not associate with mitochondria and prevents normal mitochondrial fission. This finding suggests that SUMOylation of Drp1 is linked to its activity cycle and is influenced by Drp1 localization.—Figueroa-Romero, C., Iñiguez-Lluhí, J. A., Stadler, J., Chang, C.-R., Arnoult, D., Keller, P. J., Hong, Y., Blackstone, C., Feldman, E. L. SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle. PMID:19638400

  13. Geochemistry of ferromanganese nodules from DOMES site a, Northern Equatorial Pacific: Multiple diagenetic metal sources in the deep sea

    USGS Publications Warehouse

    Calvert, S.E.; Piper, D.Z.

    1984-01-01

    The major and minor element composition of ferromanganese nodules from DOMES Site A has been determined by X-ray fluorescence methods. Three phases appear to control the bulk compositions: Mn and Fe oxyhydroxides and aluminosilicates. Relatively wide compositional variations are evident throughout the area. Nodules with high Mn/Fe ratios, high Cu, Mg, Mo, Ni and Zn concentrations and high todorokite/??-MnO2 ratios have granular surface textures and are confined to an east-west trending depression with thin Quaternary sediment cover. Nodules with low Mn/Fe ratios, high concentrations of As, Ca, Ce, Co, La, P, Sr, Ti, V, Y and Zr and low todorokite/??-MnO2 ratios have smooth surfaces and are confined to shallower areas with relatively thick Quaternary sediment to the north and south of the depression. All nodules in the area have compositions which are influenced by diagenesis, but those with the most marked diagenetic signature (high Mn/Fe and Cu/Ni ratios, low Ce/La ratios and more todorokite) are found in areas of very slow or non-existent sedimentation; many of these nodules are actually in contact with outcropping Tertiary sediment. This paradox may be resolved by postulating, by analogy with some shallow-water occurrences, that the nodules accrete from bottom waters which have enhanced particulate and dissolved metal contents derived from diagenetic reaction in areas remote from the site of nodule formation. The metals are supplied in a bottom flow (probably Antarctic Bottom Water) which also erodes, or prevents modern sedimentation in, the depression. Nodules on the flanks of the depression are not evidently affected by this flow and derive at least pan of their constituent metals from diagenetic reaction in the underlying Quaternary sediment. Apparently, abyssal diagenetic nodules can have an immediate and a remote diagenetic metal source. Metal fluxes derived from pore water dissolved metal gradients may not be relevant to particular accreting nodules if a

  14. Tissue-specific expression of the bovine aromatase-encoding gene uses multiple transcriptional start sites and alternative first exons.

    PubMed

    Fürbass, R; Kalbe, C; Vanselow, J

    1997-07-01

    Here we report on the genomic structure of the bovine aromatase cytochrome P450-encoding gene (Cyp19) and its tissue-specific transcript variants. The gene comprises at least 14 exons (1.1, 1.2a, 1.2b, 1.3,1.4, and 2-10) spanning more than 56 kilobases of genomic DNA. The coding area is confined to exons 2-10. Transcriptional start sites of Cyp19 were examined in granulosa cells, placenta, testis, adrenal gland, and brain, employing 5'-RACE (rapid amplification of complementary DNA ends) and primer extension. The analysis of 5'-RACE clones revealed six Cyp19 transcript variants that were different within their 5'-untranslated regions (5'-UTR). Yet, the coding region was identical in all clones. Although two of these 5'-UTR (the first 152 nucleotides of exon 2 and exon 1.4) are conserved among different species, four others (exons 1.1, 1.2a, 1.2b, and 1.3) did not show sequence homology to any other species. Transcription from exons 1.1 and 2 starts at several adjacent sites. In granulosa cells and placenta, but not in brain, a fraction of transcripts starting with exon 1.2a contains an additional untranslated exon, 1.2b, due to alternative splicing. Transcript variants comprising exon 1.1, 1.2a, 1.2b, or 1.3 were mainly found in the placenta, those with the 5'-UTR of exon 2 were predominant in granulosa cells, and transcripts with exon 1.4 prevailed in the brain. Estimates of Cyp19 transcript concentrations in six different tissues revealed high levels in granulosa cells and placenta, intermediate levels in testis and brain, and low levels in adrenal gland and liver. Our experiments demonstrate that six transcript variants of the bovine Cyp19 gene, including 9-11 exons, are expressed with tissue-specific preferences. These transcripts are presumably generated using five different promoter regions and tissue-specific alternative splicing. PMID:9202222

  15. Effect of application sites and multiple doses on nicotine pharmacokinetics in healthy male Japanese smokers following application of the transdermal nicotine patch.

    PubMed

    Sobue, Satoshi; Sekiguchi, Kaneo; Kikkawa, Hironori; Irie, Shin

    2005-12-01

    The transdermal nicotine patch, which contains 25 mg nicotine per 30 cm(2), is designed to deliver approximately 15 mg nicotine to the blood circulation in 16 hours of application for the treatment of smoking cessation. It was applied to 3 different skin sites (upper arm, abdomen, and back) to examine regional variations in percutaneous nicotine absorption in a single-dose, 3-period, crossover study involving 9 healthy male Japanese smokers. Nicotine pharmacokinetics during once-daily application of the transdermal nicotine patch for 5 days was also investigated in 10 healthy smokers. There were statistically significant effects of application sites on percutaneous nicotine absorption. The ratios (90% confidence intervals) of AUC and C(max) for comparison to the upper arm were 102% (88, 117%) and 106% (95, 119%) for the back and 75% (65, 87%) and 75% (66, 84%) for the abdomen, respectively. These suggest that systemic exposure after application to the upper arm was greater compared with the abdomen but equivalent to the back. Following multiple doses, linear pharmacokinetics and no significant accumulation of nicotine concentrations were observed, and steady state was reached by day 2. Only mild itching and erythema were observed at the application sites. The transdermal nicotine patch was well tolerated in both studies.

  16. Wild leafy vegetable use and knowledge across multiple sites in Morocco: a case study for transmission of local knowledge?

    PubMed Central

    2014-01-01

    Background There are few publications on the use and diversity of wild leafy vegetables (WLVs) in Morocco. In order to address this gap, we conducted ethnobotanical field work in Taounate, Azilal and El House regions. Methods Ethnobotanical collections, free listing, qualitative interviews and a 7 day food frequency questionnaire. Results More than 30 species in 23 genera of WLV were identified. Of these 4 had not previously recorded as WLVs used in Morocco in the literature. WLVs were used by 84% of households surveyed in Taounate (N = 61, in March 2005), and were used up to 4 times a week. Qualitative data revealed both positive and negative perceptions of WLVs and detailed knowledge about preparation among women. The greatest diversity of WLV knowledge and use was in the Rif Mountains (Taounate). There was significant variation in nomenclature and salience of WLVs, not only between regions, but also between villages in the same region. Within the same region (or even village) different local names were used for a given species or genus, and different species were identified by the same local name (including species from different botanical families). Data showed greater overlap in knowledge among villages using the same market. Conclusion We believe the results suggest that markets are important sites for WLV knowledge transmission. PMID:24708730

  17. FAst MEtabolizer (FAME): A rapid and accurate predictor of sites of metabolism in multiple species by endogenous enzymes.

    PubMed

    Kirchmair, Johannes; Williamson, Mark J; Afzal, Avid M; Tyzack, Jonathan D; Choy, Alison P K; Howlett, Andrew; Rydberg, Patrik; Glen, Robert C

    2013-11-25

    FAst MEtabolizer (FAME) is a fast and accurate predictor of sites of metabolism (SoMs). It is based on a collection of random forest models trained on diverse chemical data sets of more than 20 000 molecules annotated with their experimentally determined SoMs. Using a comprehensive set of available data, FAME aims to assess metabolic processes from a holistic point of view. It is not limited to a specific enzyme family or species. Besides a global model, dedicated models are available for human, rat, and dog metabolism; specific prediction of phase I and II metabolism is also supported. FAME is able to identify at least one known SoM among the top-1, top-2, and top-3 highest ranked atom positions in up to 71%, 81%, and 87% of all cases tested, respectively. These prediction rates are comparable to or better than SoM predictors focused on specific enzyme families (such as cytochrome P450s), despite the fact that FAME uses only seven chemical descriptors. FAME covers a very broad chemical space, which together with its inter- and extrapolation power makes it applicable to a wide range of chemicals. Predictions take less than 2.5 s per molecule in batch mode on an Ultrabook. Results are visualized using Jmol, with the most likely SoMs highlighted. PMID:24219364

  18. Single Active Site Mutation Causes Serious Resistance of HIV Reverse Transcriptase to Lamivudine: Insight from Multiple Molecular Dynamics Simulations.

    PubMed

    Moonsamy, Suri; Bhakat, Soumendranath; Walker, Ross C; Soliman, Mahmoud E S

    2016-03-01

    Molecular dynamics simulations, binding free energy calculations, principle component analysis (PCA), and residue interaction network analysis were employed in order to investigate the molecular mechanism of M184I single mutation which played pivotal role in making the HIV-1 reverse transcriptase (RT) totally resistant to lamivudine. Results showed that single mutations at residue 184 of RT caused (1) distortion of the orientation of lamivudine in the active site due to the steric conflict between the oxathiolane ring of lamivudine and the side chain of beta-branched amino acids Ile at position 184 which, in turn, perturbs inhibitor binding, (2) decrease in the binding affinity by (~8 kcal/mol) when compared to the wild-type, (3) variation in the overall enzyme motion as evident from the PCA for both systems, and (4) distortion of the hydrogen bonding network and atomic interactions with the inhibitor. The comprehensive analysis presented in this report can provide useful information for understanding the drug resistance mechanism against lamivudine. The results can also provide some potential clues for further design of novel inhibitors that are less susceptible to drug resistance. PMID:26972300

  19. The Chondroitin Sulfate A-binding Site of the VAR2CSA Protein Involves Multiple N-terminal Domains*

    PubMed Central

    Dahlbäck, Madeleine; Jørgensen, Lars M.; Nielsen, Morten A.; Clausen, Thomas M.; Ditlev, Sisse B.; Resende, Mafalda; Pinto, Vera V.; Arnot, David E.; Theander, Thor G.; Salanti, Ali

    2011-01-01

    Malaria during pregnancy is a major health problem for African women. The disease is caused by Plasmodium falciparum malaria parasites, which accumulate in the placenta by adhering to chondroitin sulfate A (CSA). The interaction between infected erythrocytes and the placental receptor is mediated by a parasite expressed protein named VAR2CSA. A vaccine protecting pregnant women against placental malaria should induce antibodies inhibiting the interaction between VAR2CSA and CSA. Much effort has been put into defining the part of the 350 kDa VAR2CSA protein that is responsible for binding. It has been shown that full-length recombinant VAR2CSA binds specifically to CSA with high affinity, however to date no sub-fragment of VAR2CSA has been shown to interact with CSA with similar affinity or specificity. In this study, we used a biosensor technology to examine the binding properties of a panel of truncated VAR2CSA proteins. The experiments indicate that the core of the CSA-binding site is situated in three domains, DBL2X-CIDRPAM and a flanking domain, located in the N-terminal part of VAR2CSA. Furthermore, recombinant VAR2CSA subfragments containing this region elicit antibodies with high parasite adhesion blocking activity in animal immunization experiments. PMID:21398524

  20. Comparative Genomic Hybridization of Human Malignant Gliomas Reveals Multiple Amplification Sites and Nonrandom Chromosomal Gains and Losses

    PubMed Central

    Schròck, Evelin; Thiel, Gundula; Lozanova, Tanka; du Manoir, Stanislas; Meffert, Marie-Christine; Jauch, Anna; Speicher, Michael R.; Nürnberg, Peter; Vogel, Siegfried; Janisch, Werner; Donis-Keller, Helen; Ried, Thomas; Witkowski, Regine; Cremer, Thomas

    1994-01-01

    Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five cases. Loss of chromosome band 17p13 and gain of chromosome 20 were revealed each in three cases. The validity of the CGH data was confirmed using interphase cytogenetics with YAC clones, chromosome painting in tumor metaphase spreads, and DNA fingerprinting. A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue ImagesFigure 1Figure 4Figure 6 PMID:8203461

  1. Accumulation of multiple oxidative equivalents at a single site by cross-surface electron transfer on TiO2.

    PubMed

    Song, Wenjing; Ito, Akitaka; Binstead, Robert A; Hanson, Kenneth; Luo, Hanlin; Brennaman, M Kyle; Concepcion, Javier J; Meyer, Thomas J

    2013-08-01

    The photodriven accumulation of two oxidative equivalents at a single site was investigated on TiO2 coloaded with a ruthenium polypyridyl chromophore [Ru(bpy)2((4,4'-(OH)2PO)2bpy)](2+) (Ru(II)P(2+), bpy = 2,2'-bipyridine, ((OH)2PO)2-bpy = 2,2'-bipyridine-4,4'-diyldiphosphonic acid) and a water oxidation catalyst [Ru(Mebimpy) ((4,4'-(OH)2PO-CH2)2bpy)(OH2)](2+) (Ru(II)OH2(2+), Mebimpy = 2,6-bis(1-methylbenzimidazol-2-yl)pyridine, (4,4'-(OH)2PO-CH2)2bpy) = 4,4'-bis-methlylenephosphonato-2,2'-bipyridine). Electron injection from the metal-to-ligand charge transfer (MLCT) excited state of -Ru(II)P(2+) (-Ru(II)P(2+)*) to give -Ru(III)P(3+) and TiO2(e(-)) was followed by rapid (<20 ns) nearest-neighbor -Ru(II)OH2(2+) to -Ru(III)P(3+) electron transfer. On surfaces containing both -Ru(II)P(2+) and -Ru(III)OH2(3+) (or -Ru(III)OH(2+)), -Ru(II)OH2(2+) was formed by random migration of the injected electron inside the TiO2 nanoparticle and recombination with the preoxidized catalyst, followed by relatively slow (μs-ms) non-nearest neighbor cross-surface electron transfer from -Ru(II)OH2(2+) to -Ru(III)P(3+). Steady state illumination of coloaded TiO2 photoanodes in a dye sensitized photoelectrosynthesis cell (DSPEC) configuration resulted in the buildup of -Ru(III)P(3+), -Ru(III)OH(2+), and -Ru(IV)═O(2+), with -Ru(IV)═O(2+) formation favored at high chromophore to catalyst ratios. PMID:23848562

  2. The Tim8-Tim13 complex has multiple substrate binding sites and binds cooperatively to Tim23.

    PubMed

    Beverly, Kristen N; Sawaya, Michael R; Schmid, Einhard; Koehler, Carla M

    2008-10-24

    The Tim8-Tim13 complex, located in the mitochondrial intermembrane space, functions in the TIM22 import pathway that mediates the import of the mitochondrial carriers Tim23, Tim22, and Tim17 into the mitochondrial inner membrane. The Tim8-Tim13 complex assembles as a hexamer and binds to the substrate Tim23 to chaperone the hydrophobic Tim23 across the aqueous intermembrane space. However, both structural features of the Tim8-Tim13 complex and the binding interaction to Tim23 remain poorly defined. The crystal structure of the yeast Tim8-Tim13 complex, reported here at 2.6 A resolution, reveals that the architecture of the Tim8-Tim13 complex is similar to those of other chaperones such as Tim9-Tim10, prefoldin, and Skp, in which long helices extend from a central body like tentacles from a jellyfish. Surface plasmon resonance was applied to investigate interactions between the Tim8-Tim13 complex and Tim23. The Tim8-Tim13 complex contained approximately six binding sites and showed a complex binding interaction indicative of positive cooperativity rather than a simple bimolecular interaction. By combining results from the structural and binding studies, we provide a molecular model of the Tim8-Tim13 complex binding to Tim23. The regions where the tentacle helices attach to the body of the Tim8-Tim13 complex contain six hydrophobic pockets that likely interact with specific sequences of Tim23 and possibly other substrates. Smaller hydrophobic patches on the tentacles themselves likely interact nonspecifically with the substrate's transmembrane helices, shielding it from the aqueous intermembrane space. The central region of Tim23, which enters the intermembrane space first, may serve to nucleate the binding of the Tim8-Tim13 complex, thereby initiating the chaperoned translocation of Tim23 to the mitochondrial inner membrane. PMID:18706423

  3. Floating chip mounting system driven by repulsive force of permanent magnets for multiple on-site SPR immunoassay measurements.

    PubMed

    Horiuchi, Tsutomu; Tobita, Tatsuya; Miura, Toru; Iwasaki, Yuzuru; Seyama, Michiko; Inoue, Suzuyo; Takahashi, Jun-ichi; Haga, Tsuneyuki; Tamechika, Emi

    2012-10-17

    We have developed a measurement chip installation/removal mechanism for a surface plasmon resonance (SPR) immunoassay analysis instrument designed for frequent testing, which requires a rapid and easy technique for changing chips. The key components of the mechanism are refractive index matching gel coated on the rear of the SPR chip and a float that presses the chip down. The refractive index matching gel made it possible to optically couple the chip and the prism of the SPR instrument easily via elastic deformation with no air bubbles. The float has an autonomous attitude control function that keeps the chip parallel in relation to the SPR instrument by employing the repulsive force of permanent magnets between the float and a float guide located in the SPR instrument. This function is realized by balancing the upward elastic force of the gel and the downward force of the float, which experiences a leveling force from the float guide. This system makes it possible to start an SPR measurement immediately after chip installation and to remove the chip immediately after the measurement with a simple and easy method that does not require any fine adjustment. Our sensor chip, which we installed using this mounting system, successfully performed an immunoassay measurement on a model antigen (spiked human-IgG) in a model real sample (non-homogenized milk) that included many kinds of interfering foreign substances without any sample pre-treatment. The ease of the chip installation/removal operation and simple measurement procedure are suitable for frequent on-site agricultural, environmental and medical testing.

  4. Multiple initiators and C/EBP binding sites are involved in transcription from the TATA-less rat XDH/XO basal promoter.

    PubMed Central

    Chow, C W; Clark, M P; Rinaldo, J E; Chalkley, R

    1995-01-01

    In the present study, we have explored further the organization of the TATA-less rat xanthine dehydrogenase/oxidase gene (XDH/XO). A DNase I hypersensitive site has been identified which it colocalizes with the basal promoter reported previously [Chow et al. (1994) Nucleic Acids Res., 22, 1846-1854]. Gel mobility shift assays indicate the presence of multiple binding factors located in the promoter. At least six footprints were detected of which two have been shown to be C/EBP binding sites. Members of the C/EBP-alpha and C/EBP-beta, but not C/EBP-delta, family are able to bind to these two sites. Deletional and mutational studies revealed that C/EBP binding is not essential for the basal level of transcription initiation of this promoter. Much of the transcriptional activity resides in the -102 to -7 DNA fragment, which contains all initiator activity which acts unidirectionally. Within this fragment, four putative initiator elements could be identified; interestingly, the linear integrity of these initiators is important for efficient transcription of the XDH/XO gene. Separation of the initiators leads to a complete loss of transcription activity; however, this loss could be partially restored by the introduction of an Sp1 binding site upstream of the separated initiators. Despite a difference in usage/frequency of initiation at the various initiators, primer extension analyses reveal similar positions for transcription initiations in both XDH/XO reporter constructs and in the endogenous XDH/XO gene. The differential usage of initiators may imply a possible post-transcriptional regulation for the XDH/XO gene. Images PMID:7667089

  5. MODEL IMPLEMENTATION TO EVALUATE THE COLLECTIVE FUTURE RADIONUCLIDE RELEASES FROM MULTIPLE FACILITIES AT THE SAVANNAH RIVER SITE

    SciTech Connect

    Hiergesell, R.; Smith, F.; Hamm, L.; Phifer, M.; Swingle, R.

    2009-12-15

    A comprehensive Composite Analysis (CA) has been performed considering 152 sources of residual radioactive material at the Savannah River Site (SRS). As part of the CA a model was developed to perform deterministic base case calculations using the commercial GoldSim software. The model treated transport and decay of radionuclides as they are released at the source location and transported through the source region, vadose zone and aquifer to stream outcrops and from there to the Savannah River. A dose to the public was calculated assuming recreational use of stream water and residential use of river water. The specific results from the GoldSim modeling evaluation conducted as part of the CA indicate that the collective maximum dose resulting from the release of radionuclides from all 152 anticipated SRS End State sources of residual radionuclides demonstrate that maximum exposures expected to occur to any offsite MOP will not approach the 300 uSv/yr (30 mrem/yr) dose constraint, and in fact are currently estimated to be only 10% of this. For each of the POA's evaluated, the highest cumulative dose is realized at the Lower Three Runs POA and is calculated to be 29.7 uSv/yr (2.97 mrem/yr). The major dose contributing radionuclide for all of the POA's, with the exception of Upper Three Runs, was {sup 137}Cs in the contaminated streambed sediments. In Upper Three Runs {sup 237}Np from the H-Area Canyon Building was the major dose contributing radionuclide. The major exposure pathway for the SRS streams (where the Recreational Scenario was evaluated) was by the ingestion of fish. In the Savannah River, where the Residential Scenario was evaluated, ingestion of vegetation was the dominant exposure pathway. The uncertainty evaluation lends added assurance to the conclusion that the 30 mrem/yr dose constraint will not be exceeded, in that even at the 95th Percentile, this performance measure is not expected to be exceeded. It must also be added that these conclusions

  6. DNA replication during amplification of the C3 puff of Rhynchosciara americana initiates at multiple sites in a 6 kb region.

    PubMed

    Yokosawa, J; Soares, M A; Dijkwel, P A; Stocker, A J; Hamlin, J L; Lara, F J

    1999-09-01

    Two independent two-dimensional agarose gel electrophoresis methods have been used to map the origin of replication that directs amplification of the C3 DNA puff of Rhynchosciara americana. The results of neutral/neutral two-dimensional gel electrophoresis show that DNA replication initiates at multiple sites in a zone of at least 6 kb situated immediately upstream from the promoter of the main transcription unit of this puff. The complementary neutral/alkaline two-dimensional gel electrophoresis technique shows that, within the initiation zone, forks move in both directions. In contrast, unidirectional fork movement away from the initiation zone is observed at the ends of the region, implying that it is the only place in the amplified region of the C3 puff where initiations occur. Since the initiation zone coincides with the region that is most highly amplified, amplification of the C3 puff probably occurs by an onion skin-type mechanism. PMID:10525965

  7. Expression, characterization, and site-directed mutation of a multiple herbicide-resistant acetohydroxyacid synthase (rAHAS) from Pseudomonas sp. Lm10.

    PubMed

    Lang, Zhi-Fei; Shen, Jing-Jing; Cai, Shu; Zhang, Jun; He, Jian; Li, Shun-Peng

    2011-08-01

    A multiple herbicide-resistant acetohydroxyacid synthase (rAHAS) gene was cloned from Pseudomonas sp. Lm10. Sequence analysis showed that the rAHAS regulatory subunit was identical to that of Pseudomonas putida KT2440 (sensitive AHAS, sAHAS), whereas six different sites [H134→N (rAHAS→sAHAS), A135→P, S136→T, I210→V, F264→Y, and S486→W] were found in the catalytic subunit. The rAHAS and sAHAS were over expressed, purified and characterized. rAHAS showed higher resistance to four kinds of AHAS-inhibitor herbicides than sAHAS. The resistance factor of rAHAS was 56.0-fold, 12.6-fold, 6.5-fold, and 9.2-fold as compared with sAHAS when metsulfuron-methyl, imazethapyr, flumetsulam, and pyriminobac-methyl used as inhibitor, respectively. The specific activity of rAHAS was lower than that of sAHAS and the K (m) value of rAHAS for pyruvate was approximately onefold higher than the corresponding value for sAHAS. Data from site-directed mutagenesis demonstrated that alteration at A135, F264, and S486 resulted in resistance reduction, while the mutation at H134, S136, and I210 has little effect on the resistance. A135 was mainly responsible for resistance to imidazolinone; F264 conferred resistance to sulfonylurea and triazolopyrimidine sulfonamide; and S486 showed multiple herbicides resistance to the four herbicides. PMID:21638043

  8. Isoaspartic acid is present at specific sites in myelin basic protein from multiple sclerosis patients: could this represent a trigger for disease onset?

    PubMed

    Friedrich, Michael G; Hancock, Sarah E; Raftery, Mark J; Truscott, Roger J W

    2016-01-01

    Multiple sclerosis (MS) is associated with breakdown of the myelin sheath that coats neurons in the central nervous system. The cause of MS is not known, although the pathogenesis involves destruction of myelin by the immune system. It was the aim of this study to examine the abundant myelin protein, myelin basic protein (MBP), to determine if there are sites of modification that may be characteristic for MS. MBP from the cerebellum was examined from controls and MS patients across the age range using mass spectrometry and amino acid analysis. Amino acid racemization data indicated that myelin basic protein is long-lived and proteomic analysis of MBP showed it to be highly modified. A common modification of MBP was racemization of Asp and this was significantly greater in MS patients. In long-lived proteins, L-Asp and L-Asn can racemize to three other isomers, D-isoAsp, L-isoAsp and D-Asp and this is significant because isoAsp formation in peptides renders them immunogenic.Proteomic analysis revealed widespread modifications of MBP with two surface regions that are altered in MS. In particular, isoAsp was significantly elevated at these sites in MS patients. The generation of isoAsp could be responsible for eliciting an immune response to modified MBP and therefore be implicated in the etiology of MS. PMID:27519525

  9. Isoaspartic acid is present at specific sites in myelin basic protein from multiple sclerosis patients: could this represent a trigger for disease onset?

    PubMed

    Friedrich, Michael G; Hancock, Sarah E; Raftery, Mark J; Truscott, Roger J W

    2016-08-12

    Multiple sclerosis (MS) is associated with breakdown of the myelin sheath that coats neurons in the central nervous system. The cause of MS is not known, although the pathogenesis involves destruction of myelin by the immune system. It was the aim of this study to examine the abundant myelin protein, myelin basic protein (MBP), to determine if there are sites of modification that may be characteristic for MS. MBP from the cerebellum was examined from controls and MS patients across the age range using mass spectrometry and amino acid analysis. Amino acid racemization data indicated that myelin basic protein is long-lived and proteomic analysis of MBP showed it to be highly modified. A common modification of MBP was racemization of Asp and this was significantly greater in MS patients. In long-lived proteins, L-Asp and L-Asn can racemize to three other isomers, D-isoAsp, L-isoAsp and D-Asp and this is significant because isoAsp formation in peptides renders them immunogenic.Proteomic analysis revealed widespread modifications of MBP with two surface regions that are altered in MS. In particular, isoAsp was significantly elevated at these sites in MS patients. The generation of isoAsp could be responsible for eliciting an immune response to modified MBP and therefore be implicated in the etiology of MS.

  10. Assessment of BTEX-induced health risk under multiple uncertainties at a petroleum-contaminated site: An integrated fuzzy stochastic approach

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaodong; Huang, Guo H.

    2011-12-01

    Groundwater pollution has gathered more and more attention in the past decades. Conducting an assessment of groundwater contamination risk is desired to provide sound bases for supporting risk-based management decisions. Therefore, the objective of this study is to develop an integrated fuzzy stochastic approach to evaluate risks of BTEX-contaminated groundwater under multiple uncertainties. It consists of an integrated interval fuzzy subsurface modeling system (IIFMS) and an integrated fuzzy second-order stochastic risk assessment (IFSOSRA) model. The IIFMS is developed based on factorial design, interval analysis, and fuzzy sets approach to predict contaminant concentrations under hybrid uncertainties. Two input parameters (longitudinal dispersivity and porosity) are considered to be uncertain with known fuzzy membership functions, and intrinsic permeability is considered to be an interval number with unknown distribution information. A factorial design is conducted to evaluate interactive effects of the three uncertain factors on the modeling outputs through the developed IIFMS. The IFSOSRA model can systematically quantify variability and uncertainty, as well as their hybrids, presented as fuzzy, stochastic and second-order stochastic parameters in health risk assessment. The developed approach haw been applied to the management of a real-world petroleum-contaminated site within a western Canada context. The results indicate that multiple uncertainties, under a combination of information with various data-quality levels, can be effectively addressed to provide supports in identifying proper remedial efforts. A unique contribution of this research is the development of an integrated fuzzy stochastic approach for handling various forms of uncertainties associated with simulation and risk assessment efforts.

  11. Multiple Geophysical Observations by a newly developed multi-component borehole instrument at the Continental Deep Drilling Site of the CCSD, Donghai, China

    NASA Astrophysics Data System (ADS)

    Xu, J.; Zhao, Z.; Ishii, H.; Yamauchi, T.

    2004-12-01

    Multiple Geophysical Observations by a newly developed multi-component borehole instrument at the Continental Deep Drilling Site of the CCSD, Donghai, China Jiren Xu1 (+86-10-68992879; xujiren@ccsd.org.cn) Zhixin Zhao1 (+86-10-68999734; zhaozhixin@ccsd.org.cn) Hiroshi Ishii2 (+81-0572-67-3105; ishii@tries.gr.jp Tsuneo Yamauchi3 (+81-052-789-3045; yamauchi@seis.nagoya-u.ac.jp) 1 Institute of Geology, Chinese Academy of Geological Sciences, China 2 Tono Research Institute of Earthquake Science (TRIES), Japan 3 Graduate School of Environmental Studies, Nagoya University, Japan The Chinese Continental Scientific Drilling (CCSD) site is located in the Donghai area of the Dabie-Sulu belt, which is the largest UHPM belt in the world. The drilling of the main borehole with 5000m will finish in next year. Three satellite boreholes, PP1, PP2 and PP3 were drilled and various surveys have been performed in the Donghai area about 6 years ago. We are going to install a newly developed Multi-component Instrument for borehole observations in main hole near the large Tanlu fault, and establish a long-term underground observation laboratory, which is the first noiseless one in China. The seismic activity and various geophysical fields, viz. strain, geomagnetism, geothermy, tilt, pore pressure etc. will be investigated. Data from the underground laboratory will be open to scientific, engineering and public services. We will measure the initial stress in various depths of the borehole by overcoring method using a new developed wireless intelligent type strainmeter of in-situ stress. Establishing a long-term noiseless underground observation laboratory at deep borehole and investigating crustal movement in East China are important for observing the physical conditions of the earth¡_s interior and solving many social problems, such as resources, disasters and environment. Multiple geophysical observations and the study in deep borehole will speed up and develop the study on tectonics

  12. Mental stress and psychosocial factors at work in relation to multiple-site musculoskeletal pain: a longitudinal study of kitchen workers.

    PubMed

    Haukka, Eija; Leino-Arjas, Päivi; Ojajärvi, Anneli; Takala, Esa-Pekka; Viikari-Juntura, Eira; Riihimäki, Hilkka

    2011-04-01

    Among 385 female kitchen workers, we examined (1) whether mental stress and psychosocial factors at work (job control, skill discretion, supervisor support, co-worker relationships, and hurry) predict multiple-site musculoskeletal pain (MSP; defined as pain at ≥ 3 of seven sites) and (2) reversedly, whether MSP predicts these psychosocial factors. Data were collected by questionnaire at 3-month intervals during 2 years. Trajectory analysis was applied. Four trajectories of MSP prevalence emerged: Low, Descending, Ascending, and High. For the psychosocial factors, a two-trajectory model (Ascending or High vs. Low) yielded the best fit. In logistic regression analysis, with the Low MSP trajectory as reference, poor co-worker relationships (odds ratio [OR] 3.9), mental stress (3.1) and hurry (2.1) at baseline predicted belonging to the High MSP trajectory. Also MSP at baseline predicted the trajectories (Ascending vs. Low) of low job control (2.2) and mental stress (3.2). Adverse changes in most psychosocial factors were associated with belonging to the High (ORs between 2.3 and 8.6) and Ascending (2.7-5.5) MSP trajectories. In generalized estimating equations, time-lagged by 3 months, all psychosocial factors but two predicted MSP (1.4-2.1), allowing, e.g. for MSP at baseline, and vice versa, MSP predicted low job control, low supervisor support, and mental stress (1.4-2.0), after adjustment for e.g. the relevant psychosocial factor at baseline. In conclusion, we found that several psychosocial factors predicted MSP and that MSP predicted several psychosocial factors. The results suggest a cumulative process in which adverse psychosocial factors and MSP influence each other. PMID:20932789

  13. Kinetic isotope effects for concerted multiple proton transfer: a direct dynamics study of an active-site model of carbonic anhydrase II.

    PubMed

    Smedarchina, Zorka; Siebrand, Willem; Fernández-Ramos, Antonio; Cui, Qiang

    2003-01-01

    The rate constant of the reaction catalyzed by the enzyme carbonic anhydrase II, which removes carbon dioxide from body fluids, is calculated for a model of the active site. The rate-determining step is proton transfer from a zinc-bound water molecule to a histidine residue via a bridge of two or more water molecules. The structure of the active site is known from X-ray studies except for the number and location of the water molecules. Model calculations are reported for a system of 58 atoms including a four-coordinated zinc ion connected to a methylimidazole molecule by a chain of two waters, constrained to reproduce the size of the active site. The structure and vibrational force field are calculated by an approximate density functional treatment of the proton-transfer step at the Self-Consistent-Charge Density Functional Tight Binding (SCC-DFTB) level. A single transition state is found indicating concerted triple proton transfer. Direct-dynamics calculations for proton and deuteron transfer and combinations thereof, based on the Approximate Instanton Method and on Variational Transition State Theory with Tunneling Corrections, are in fair agreement and yield rates that are considerably higher and kinetic isotope effects (KIEs) that are somewhat higher than experiment. Classical rate constants obtained from Transition State Theory are smaller than the quantum values but the corresponding KIEs are five times larger. For multiple proton transfer along water bridges classical KIEs are shown to be generally larger than quantum KIEs, which invalidates the standard method to distinguish tunneling and over-barrier transfer. In the present case, a three-way comparison of classical and quantum results with the observed data is necessary to conclude that proton transfer along the bridge proceeds by tunneling. The results suggest that the two-water bridge is present in low concentrations but makes a substantial contribution to proton transport because of its high

  14. Modeling municipal solid waste collection: A generalized vehicle routing model with multiple transfer stations, gather sites and inhomogeneous vehicles in time windows.

    PubMed

    Son, Le Hoang; Louati, Amal

    2016-06-01

    Municipal Solid Waste (MSW) collection is a necessary process in any municipality resulting in the quality-of-life, economic aspects and urban structuralization. The intrinsic nature of MSW collection relates to the development of effective vehicle routing models that optimize the total traveling distances of vehicles, the environmental emission and the investment costs. In this article, we propose a generalized vehicle routing model including multiple transfer stations, gather sites and inhomogeneous vehicles in time windows for MSW collection. It takes into account traveling in one-way routes, the number of vehicles per m(2) and waiting time at traffic stops for reduction of operational time. The proposed model could be used for scenarios having similar node structures and vehicles' characteristics. A case study at Danang city, Vietnam is given to illustrate the applicability of this model. The experimental results have clearly shown that the new model reduces both total traveling distances and operational hours of vehicles in comparison with those of practical scenarios. Optimal routes of vehicles on streets and markets at Danang are given. Those results are significant to practitioners and local policy makers.

  15. Modeling municipal solid waste collection: A generalized vehicle routing model with multiple transfer stations, gather sites and inhomogeneous vehicles in time windows.

    PubMed

    Son, Le Hoang; Louati, Amal

    2016-06-01

    Municipal Solid Waste (MSW) collection is a necessary process in any municipality resulting in the quality-of-life, economic aspects and urban structuralization. The intrinsic nature of MSW collection relates to the development of effective vehicle routing models that optimize the total traveling distances of vehicles, the environmental emission and the investment costs. In this article, we propose a generalized vehicle routing model including multiple transfer stations, gather sites and inhomogeneous vehicles in time windows for MSW collection. It takes into account traveling in one-way routes, the number of vehicles per m(2) and waiting time at traffic stops for reduction of operational time. The proposed model could be used for scenarios having similar node structures and vehicles' characteristics. A case study at Danang city, Vietnam is given to illustrate the applicability of this model. The experimental results have clearly shown that the new model reduces both total traveling distances and operational hours of vehicles in comparison with those of practical scenarios. Optimal routes of vehicles on streets and markets at Danang are given. Those results are significant to practitioners and local policy makers. PMID:27036996

  16. Detection and site localization of phosphorylcholine-modified peptides by NanoLC-ESI-MS/MS using precursor ion scanning and multiple reaction monitoring experiments.

    PubMed

    Timm, Thomas; Lenz, Christof; Merkel, Dietrich; Sadiffo, Christian; Grabitzki, Julia; Klein, Jochen; Lochnit, Guenter

    2015-03-01

    Phosphorylcholine (PC)-modified biomolecules like lipopolysaccharides, glycosphingolipids, and (glyco)proteins are widespread, highly relevant antigens of parasites, since this small hapten shows potent immunomodulatory capacity, which allows the establishment of long-lasting infections of the host. Especially for PC-modified proteins, structural data is rare because of the zwitterionic nature of the PC substituent, resulting in low sensitivities and unusual but characteristic fragmentation patterns. We have developed a targeted mass spectrometric approach using hybrid triple quadrupole/linear ion trap (QTRAP) mass spectrometry coupled to nanoflow chromatography for the sensitive detection of PC-modified peptides from complex proteolytic digests, and the localization of the PC-modification within the peptide backbone. In a first step, proteolytic digests are screened using precursor ion scanning for the marker ions of choline (m/z 104.1) and phosphorylcholine (m/z 184.1) to establish the presence of PC-modified peptides. Potential PC-modified precursors are then subjected to a second analysis using multiple reaction monitoring (MRM)-triggered product ion spectra for the identification and site localization of the modified peptides. The approach was first established using synthetic PC-modified synthetic peptides and PC-modified model digests. Following the optimization of key parameters, we then successfully applied the method to the detection of PC-peptides in the background of a proteolytic digest of a whole proteome. This methodological invention will greatly facilitate the detection of PC-substituted biomolecules and their structural analysis.

  17. Detection and Site Localization of Phosphorylcholine-Modified Peptides by NanoLC-ESI-MS/MS Using Precursor Ion Scanning and Multiple Reaction Monitoring Experiments

    NASA Astrophysics Data System (ADS)

    Timm, Thomas; Lenz, Christof; Merkel, Dietrich; Sadiffo, Christian; Grabitzki, Julia; Klein, Jochen; Lochnit, Guenter

    2015-03-01

    Phosphorylcholine (PC)-modified biomolecules like lipopolysaccharides, glycosphingolipids, and (glyco)proteins are widespread, highly relevant antigens of parasites, since this small hapten shows potent immunomodulatory capacity, which allows the establishment of long-lasting infections of the host. Especially for PC-modified proteins, structural data is rare because of the zwitterionic nature of the PC substituent, resulting in low sensitivities and unusual but characteristic fragmentation patterns. We have developed a targeted mass spectrometric approach using hybrid triple quadrupole/linear ion trap (QTRAP) mass spectrometry coupled to nanoflow chromatography for the sensitive detection of PC-modified peptides from complex proteolytic digests, and the localization of the PC-modification within the peptide backbone. In a first step, proteolytic digests are screened using precursor ion scanning for the marker ions of choline ( m/z 104.1) and phosphorylcholine ( m/z 184.1) to establish the presence of PC-modified peptides. Potential PC-modified precursors are then subjected to a second analysis using multiple reaction monitoring (MRM)-triggered product ion spectra for the identification and site localization of the modified peptides. The approach was first established using synthetic PC-modified synthetic peptides and PC-modified model digests. Following the optimization of key parameters, we then successfully applied the method to the detection of PC-peptides in the background of a proteolytic digest of a whole proteome. This methodological invention will greatly facilitate the detection of PC-substituted biomolecules and their structural analysis.

  18. 3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

    NASA Astrophysics Data System (ADS)

    Cui, P. X.; Lian, F. L.; Wang, Y.; Wen, Yi; Chu, W. S.; Zhao, H. F.; Zhang, S.; Li, J.; Lin, D. H.; Wu, Z. Y.

    2014-02-01

    Prion-related protein (PrP), a cell-surface copper-binding glycoprotein, is considered to be responsible for a number of transmissible spongiform encephalopathies (TSEs). The structural conversion of PrP from the normal cellular isoform (PrPC) to the post-translationally modified form (PrPSc) is thought to be relevant to Cu2+ binding to histidine residues. Rabbits are one of the few mammalian species that appear to be resistant to TSEs, because of the structural characteristics of the rabbit prion protein (RaPrPC) itself. Here we determined the three-dimensional local structure around the C-terminal high-affinity copper-binding sites using X-ray absorption near-edge structure combined with ab initio calculations in the framework of the multiple-scattering (MS) theory. Result shows that two amino acid resides, Gln97 and Met108, and two histidine residues, His95 and His110, are involved in binding this copper(II) ion. It might help us understand the roles of copper in prion conformation conversions, and the molecular mechanisms of prion-involved diseases.

  19. The Autographa californica Multiple Nucleopolyhedrovirus ac54 Gene Is Crucial for Localization of the Major Capsid Protein VP39 at the Site of Nucleocapsid Assembly

    PubMed Central

    Guan, Zhanwen; Zhong, Ling; Li, Chunyan; Wu, Wenbi; Yuan, Meijin

    2016-01-01

    ABSTRACT Baculovirus DNAs are synthesized and inserted into preformed capsids to form nucleocapsids at a site in the infected cell nucleus, termed the virogenic stroma. Nucleocapsid assembly of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) requires the major capsid protein VP39 and nine minor capsid proteins, including VP1054. However, how VP1054 participates in nucleocapsid assembly remains elusive. In this study, the VP1054-encoding gene (ac54) was deleted to generate the ac54-knockout AcMNPV (vAc54KO). In vAc54KO-transfected cells, nucleocapsid assembly was disrupted, leading to the formation of abnormally elongated capsid structures. Interestingly, unlike cells transfected with AcMNPV mutants lacking other minor capsid proteins, in which capsid structures were distributed within the virogenic stroma, ac54 ablation resulted in a distinctive location of capsid structures and VP39 at the periphery of the nucleus. The altered distribution pattern of capsid structures was also observed in cells transfected with AcMNPV lacking BV/ODV-C42 or in cytochalasin d-treated AcMNPV-infected cells. BV/ODV-C42, along with PP78/83, has been shown to promote nuclear filamentous actin (F-actin) formation, which is another requisite for nucleocapsid assembly. Immunofluorescence using phalloidin indicated that the formation and distribution of nuclear F-actin were not affected by ac54 deletion. However, immunoelectron microscopy revealed that BV/ODV-C42, PP78/83, and 38K failed to integrate into capsid structures in the absence of VP1054, and immunoprecipitation further demonstrated that in transient expression assays, VP1054 interacted with BV/ODV-C42 and VP80 but not VP39. Our findings suggest that VP1054 plays an important role in the transport of capsid proteins to the nucleocapsid assembly site prior to the process of nucleocapsid assembly. IMPORTANCE Baculoviruses are large DNA viruses whose replication occurs within the host nucleus. The localization of

  20. Geologic, water-chemistry, and hydrologic data from multiple-well monitoring sites and selected water-supply wells in the Santa Clara Valley, California, 1999-2003

    USGS Publications Warehouse

    Newhouse, M.W.; Hanson, R.T.; Wentworth, C.M.; Everett, Rhett; Williams, C.F.; Tinsley, J.C.; Noce, T.E.; Carkin, B.A.

    2004-01-01

    To better identify the three-dimensional geohydrologic framework of the Santa Clara Valley, lithologic, geologic, geophysical, geomechanical, hydraulic, and water-chemistry data were collected from eight ground-water multiple-well monitoring sites constructed in Santa Clara County, California, as part of a series of cooperative studies between the U.S. Geological Survey and the Santa Clara Valley Water District. The data are being used to update and improve the three-dimensional geohydrologic framework of the basin and to address issues related to water supply, water chemistry, sequence stratigraphy, geology, and geological hazards. This report represents a compilation of data collected from 1999 to 2003, including location and design of the monitoring sites, cone penetrometer borings, geologic logs, lithologic logs, geophysical logs, core analysis, water-chemistry analysis, ground-water-level measurements, and hydraulic and geomechanical properties from wells and core samples. Exploratory cone penetrometer borings taken in the upper 17 to 130 feet at six of the monitoring sites identified the base of Holocene as no deeper than 75 feet in the central confined area and no deeper than 35 feet in the southern unconfined areas of the valley. Generalized lithologic characterization from the monitoring sites indicates about four to six different aquifer units separated by relatively fine-grained units occur within the alluvial deposits shallower than 860 feet deep. Analysis of geophysical logs indicates that coarse-grained units varied in thickness between 10 and 25 feet in the southeastern unconfined area of the valley and between 50 and 200 feet in the south-central and southwestern areas of the valley. Deviations from temperature-gradient logs indicate that the majority of horizontal ground-water flow occurs above a depth of 775 feet in the south central and above 510 feet in the southeastern areas of the valley. Bulk physical properties from more than 1,150 feet of

  1. Multiple microRNAs targeted to internal ribosome entry site against foot-and-mouth disease virus infection in vitro and in vivo

    PubMed Central

    2014-01-01

    Background Foot-and-mouth disease virus (FMDV) causes a severe vesicular disease in domestic and wild cloven-hoofed animals. Because of the limited early protection induced by current vaccines, emergency antiviral strategies to control the rapid spread of FMD outbreaks are needed. Here we constructed multiple microRNAs (miRNAs) targeting the internal ribosome entry site (IRES) element of FMDV and investigated the effect of IRES-specific miRNAs on FMDV replication in baby hamster kidney (BHK-21) cells and suckling mice. Results Four IRES-specific miRNAs significantly reduced enhanced green fluorescent protein (EGFP) expression from IRES-EGFP reporter plasmids, which were used with each miRNA expression plasmid in co-transfection of BHK-21 cells. Furthermore, treatment of BHK-21 cells with Bi-miRNA (a mixture of two miRNA expression plasmids) and Dual-miRNA (a co-cistronic expression plasmid containing two miRNA hairpin structures) induced more efficient and greater inhibition of EGFP expression than did plasmids carrying single miRNA sequences. Stably transformed BHK-21 cells and goat fibroblasts with an integrating IRES-specific Dual-miRNA were generated, and real-time quantitative RT-PCR showed that the Dual-miRNA was able to effectively inhibit the replication of FMDV (except for the Mya98 strain) in the stably transformed BHK-21 cells. The Dual-miRNA plasmid significantly delayed the deaths of suckling mice challenged with 50× and 100× the 50% lethal dose (LD50) of FMDV vaccine strains of three serotypes (O, A and Asia 1), and induced partial/complete protection against the prevalent PanAsia-1 and Mya98 strains of FMDV serotype O. Conclusion These data demonstrate that IRES-specific miRNAs can significantly inhibit FMDV infection in vitro and in vivo. PMID:24393133

  2. Multiple site optical recording of transmembrane voltage (MSORTV) in patterned growth heart cell cultures: assessing electrical behavior, with microsecond resolution, on a cellular and subcellular scale.

    PubMed Central

    Rohr, S; Salzberg, B M

    1994-01-01

    We have applied multiple site optical recording of transmembrane voltage (MSORTV) to patterned growth cultures of heart cells to analyze the effect of geometry per se on impulse propagation in excitable tissue, with cellular and subcellular resolution. Extensive dye screening led to the choice of di-8-ANEPPS as the most suitable voltage-sensitive dye for this application; it is internalized slowly and permits optical recording with signal-to-noise ratios as high as 40:1 (measured peak-to-peak) and average fractional fluorescence changes of 15% per 100 mV. Using a x 100 objective and a fast data acquisition system, we could resolve impulse propagation on a microscopic scale (15 microns) with high temporal resolution (uncertainty of +/- 5 microseconds). We could observe the decrease in conduction velocity of an impulse propagating along a narrow cell strand as it enters a region of abrupt expansion, and we could explain this phenomenon in terms of the micro-architecture of the tissue. In contrast with the elongated and aligned cells forming the narrow strands, the cells forming the expansions were aligned at random and presented 2.5 times as many cell-to-cell appositions per unit length. If the decrease in conduction velocity results entirely from this increased number of cell-to-cell boundaries per unit length, the mean activation delay introduced by each boundary can be estimated to be 70 microseconds. Using this novel experimental system, we could also demonstrate the electrical coupling of fibroblasts and endotheloid cells to myocytes in culture. Images FIGURE 1 FIGURE 2 FIGURE 4 FIGURE 5 FIGURE 7 FIGURE 8 PMID:7811945

  3. A genomic library-based amplification approach (GL-PCR) for the mapping of multiple IS6110 insertion sites and strain differentiation of Mycobacterium tuberculosis.

    PubMed

    Namouchi, Amine; Mardassi, Helmi

    2006-11-01

    Evidence suggests that insertion of the IS6110 element is not without consequence to the biology of Mycobacterium tuberculosis complex strains. Thus, mapping of multiple IS6110 insertion sites in the genome of biomedically relevant clinical isolates would result in a better understanding of the role of this mobile element, particularly with regard to transmission, adaptability and virulence. In the present paper, we describe a versatile strategy, referred to as GL-PCR, that amplifies IS6110-flanking sequences based on the construction of a genomic library. M. tuberculosis chromosomal DNA is fully digested with HincII and then ligated into a plasmid vector between T7 and T3 promoter sequences. The ligation reaction product is transformed into Escherichia coli and selective PCR amplification targeting both 5' and 3' IS6110-flanking sequences are performed on the plasmid library DNA. For this purpose, four separate PCR reactions are performed, each combining an outward primer specific for one IS6110 end with either T7 or T3 primer. Determination of the nucleotide sequence of the PCR products generated from a single ligation reaction allowed mapping of 21 out of the 24 IS6110 copies of two 12 banded M. tuberculosis strains, yielding an overall sensitivity of 87,5%. Furthermore, by simply comparing the migration pattern of GL-PCR-generated products, the strategy proved to be as valuable as IS6110 RFLP for molecular typing of M. tuberculosis complex strains. Importantly, GL-PCR was able to discriminate between strains differing by a single IS6110 band. PMID:16725220

  4. iLoc-Virus: a multi-label learning classifier for identifying the subcellular localization of virus proteins with both single and multiple sites.

    PubMed

    Xiao, Xuan; Wu, Zhi-Cheng; Chou, Kuo-Chen

    2011-09-01

    In the last two decades or so, although many computational methods were developed for predicting the subcellular locations of proteins according to their sequence information, it is still remains as a challenging problem, particularly when the system concerned contains both single- and multiple-location proteins. Also, among the existing methods, very few were developed specialized for dealing with viral proteins, those generated by viruses. Actually, knowledge of the subcellular localization of viral proteins in a host cell or virus-infected cell is very important because it is closely related to their destructive tendencies and consequences. In this paper, by introducing the "multi-label scale" and by hybridizing the gene ontology information with the sequential evolution information, a predictor called iLoc-Virus is developed. It can be utilized to identify viral proteins among the following six locations: (1) viral capsid, (2) host cell membrane, (3) host endoplasmic reticulum, (4) host cytoplasm, (5) host nucleus, and (6) secreted. The iLoc-Virus predictor not only can more accurately predict the location sites of viral proteins in a host cell, but also have the capacity to deal with virus proteins having more than one location. As a user-friendly web-server, iLoc-Virus is freely accessible to the public at http://icpr.jci.edu.cn/bioinfo/iLoc-Virus. Meanwhile, a step-by-step guide is provided on how to use the web-server to get the desired results. Furthermore, for the user's convenience, the iLoc-Virus web-server also has the function to accept the batch job submission. It is anticipated that iLoc-Virus may become a useful high throughput tool for both basic research and drug development.

  5. Initiation and growth of multiple-site damage in the riveted lap joint of a curved stiffened fuselage panel: An experimental and analytical study

    NASA Astrophysics Data System (ADS)

    Ahmed, Abubaker Ali

    As part of the structural integrity research of the National Aging Aircraft Research Program, a comprehensive study on multiple-site damage (MSD) initiation and growth in a pristine lap-joint fuselage panel has been conducted. The curved stiffened fuselage panel was tested at the Full-Scale Aircraft Structural Test Evaluation and Research (FASTER) facility located at the Federal Aviation Administration William J. Hughes Technical Center. A strain survey test was conducted to verify proper load application. The panel was then subjected to a fatigue test with constant-amplitude cyclic loading. The applied loading spectrum included underload marker cycles so that crack growth history could be reconstructed from post-test fractographic examinations. Crack formation and growth were monitored via nondestructive and high-magnification visual inspections. Strain gage measurements recorded during the strain survey tests indicated that the inner surface of the skin along the upper rivet row of the lap joint experienced high tensile stresses due to local bending. During the fatigue loading, cracks were detected by eddy-current inspections at multiple rivet holes along the upper rivet row. Through-thickness cracks were detected visually after about 80% of the fatigue life. Once MSD cracks from two adjacent rivet holes linked up, there was a quick deterioration in the structural integrity of the lap joint. The linkup resulted in a 2.87" (72.9-mm) lead fatigue crack that rapidly propagated across 12 rivet holes and crossed over into the next skin bay, at which stage the fatigue test was terminated. A post-fatigue residual strength test was then conducted by loading the panel quasi-statically up to final failure. The panel failed catastrophically when the crack extended instantaneously across three additional bays. Post-test fractographic examinations of the fracture surfaces in the lap joint of the fuselage panel were conducted to characterize subsurface crack initiation and

  6. A multi-label classifier for predicting the subcellular localization of gram-negative bacterial proteins with both single and multiple sites.

    PubMed

    Xiao, Xuan; Wu, Zhi-Cheng; Chou, Kuo-Chen

    2011-01-01

    Prediction of protein subcellular localization is a challenging problem, particularly when the system concerned contains both singleplex and multiplex proteins. In this paper, by introducing the "multi-label scale" and hybridizing the information of gene ontology with the sequential evolution information, a novel predictor called iLoc-Gneg is developed for predicting the subcellular localization of gram-positive bacterial proteins with both single-location and multiple-location sites. For facilitating comparison, the same stringent benchmark dataset used to estimate the accuracy of Gneg-mPLoc was adopted to demonstrate the power of iLoc-Gneg. The dataset contains 1,392 gram-negative bacterial proteins classified into the following eight locations: (1) cytoplasm, (2) extracellular, (3) fimbrium, (4) flagellum, (5) inner membrane, (6) nucleoid, (7) outer membrane, and (8) periplasm. Of the 1,392 proteins, 1,328 are each with only one subcellular location and the other 64 are each with two subcellular locations, but none of the proteins included has pairwise sequence identity to any other in a same subset (subcellular location). It was observed that the overall success rate by jackknife test on such a stringent benchmark dataset by iLoc-Gneg was over 91%, which is about 6% higher than that by Gneg-mPLoc. As a user-friendly web-server, iLoc-Gneg is freely accessible to the public at http://icpr.jci.edu.cn/bioinfo/iLoc-Gneg. Meanwhile, a step-by-step guide is provided on how to use the web-server to get the desired results. Furthermore, for the user's convenience, the iLoc-Gneg web-server also has the function to accept the batch job submission, which is not available in the existing version of Gneg-mPLoc web-server. It is anticipated that iLoc-Gneg may become a useful high throughput tool for Molecular Cell Biology, Proteomics, System Biology, and Drug Development.

  7. New 40Ar/39Ar age of the Bishop Tuff from multiple sites and sediment rate calibration for the Matuyama-Brunhes boundary

    USGS Publications Warehouse

    Sarna-Wojcicki, A. M.; Pringle, M.S.; Wijbrans, J.

    2000-01-01

    Precise dating of sanidine from proximal ash flow Bishop Tuff and air fall Bishop pumice and ash, California, can be used to derive an absolute age of the Matuyama Reversed-Brunhes Normal (M-B) paleomagnetic transition, identified stratigraphically close beneath the Bishop Tuff and ash at many sites in the western United States. An average age of 758.9 ?? 1.8 ka, standard error of the mean (SEM), was obtained for individual sanidine crystals or groups of several crystals, determined from ???70 individual analyses of sanidine separates from 11 sample groups obtained at five localities. The basal air fall pumice (757.7 ?? 1.8 ka) and overlying ash flow tuff (762.2 ?? 4.7 ka) from near the source yield essentially the same dates within errors of analysis, suggesting that the two units were emplaced close in time. A date on distal Bishop air fall ash bed at Friant, California, ???100 km to the west of the source area, is younger, 750.1 ?? 4.3 ka, but not significantly different within analytical error (??1 standard deviation). Previous dates of the Bishop Tuff, obtained by others using conventional K-Ar and the fission track method on zircons, ranged from ???650 ka to ???1.0 Ma. The most recent, generally accepted date by the K-Ar method on sanidine was 738 ?? 3 ka. We infer, as others before, that many K-Ar dates on sanidine feldspar are too young owing to incomplete degassing of radiogenic Ar during fusion in the K-Ar technique and that many older K-Ar dates are too old owing to detrital or xenocrystic contamination in the larger samples that are necessary for the technique. The new dates are similar to recent 40Ar/39Ar ages of the Bishop Tuff determined on individual samples by others but are derived from a larger proximal sample population and from multiple analysis of each sample. The results provide a definitive and precise age calibration of this widespread chronostratigraphic marker in the western United States and northeastern Pacific Ocean. We calculated the

  8. Developing Multiple-Site Kinetic Models in Catalysis Simulation: A Case Study of 02+2N0 ↔ 2 NO2 Oxidation-Reduction Chemistry on Pt(100) Catalyst Crystal Facets

    SciTech Connect

    Disselkamp, Robert S.; Tonkyn, Russell G.; Chin, Ya-Huei; Peden, Charles HF

    2006-02-15

    It is generally recognized that developing a kinetic model for a supported catalyst is difficult since multiple site types exist. These sites can arise from a distribution of crystal facets (e.g., (100), (110), etc.) each with their unique intrinsic site types (e.g., atop, bridge, hollow, etc.). Additional complexities arise from non-basel plane site types (defect, edge, corner, etc.), all whose differing lateral interaction energies may be coverage dependent for each site pairwise interaction. To demonstrate the complexities that develop even for a greatly simplified system, we examine a multiple site kinetic model of the reaction 2NO + O2 - 2NO2 on an ideal Pt(100) catalyst. A model of the Pt(100) surface is adopted where atop, bridge, and 4-fold hollow sites are responsible for O2, NO, and NO2 chemisorption to form Pt-O, Pt-NO, and Pt-NO2 species. In our kinetic scheme, equilibrium is assumed for O2, NO, and NO2 chemisorption due to their high sticking coefficients (all > 0.1). A single rate determining step of the Langmuir-Hinshelwood type was chosen to describe the oxidation of NO on platinum via the reaction PtH,A,B-O + PtH,A,B-NO - PtH,A,B + PtH,A,B-NO2, where H, A, and B represent 4-fold hollow, atop, and bridge sites. Equal kinetic parameters for all site combinations were assumed to exist and, in part, taken from the literature to be AH+=83 kJ/mol and AS+=20 J/K mol. The exercise here is largely hypothetical but offers insight into how more detailed kinetic models may be developed, such as through the use of reaction velocity matrices, a concept introduced here. Specifically for this system, the model yielded insight into NOx chemistry on Pt(100) in that it predicted that the greatest reaction velocities (forward and reverse) occurred via the reaction Pt-O(atop) + Pt-NO(bridge) A Pt(atop) + Pt-NO2(bridge). We believe the framework of a site-specific modeling scheme presented here is an important starting point for future site-specific microkinetic

  9. Assessing natural attenuation potential at a uranium (U) in situ recovery site (Rosita, TX, USA) using multiple redox-sensitive isotope systems

    NASA Astrophysics Data System (ADS)

    Basu, A.; Brown, S. T.; Christensen, J. N.; DePaolo, D. J.; Reimus, P. W.; Heikoop, J. M.; Simmons, A. M.; House, B.; Schilling, K.; Johnson, T. M.; Pelizza, M.

    2013-12-01

    The In Situ Recovery (ISR) U mining operation at Rosita, TX, USA, involved oxidative dissolution of U from roll front U deposits. This process mobilized U along with other characteristic elements (e.g., Se) from the roll fronts in their soluble and toxic oxidized forms (e.g., U(VI), Se(VI)). The dissolved U(VI) in groundwater poses significant ecological risk due to its chemical toxicity and must be restored below the existing regulatory limit to minimize the environmental impact of ISR mining. However, the undisturbed sediments downgradient to the roll front deposits are expected to remain reduced. Naturally occurring Fe-minerals (e.g., FeS, siderite, magnetite) and microorganisms in the sediments downgradient to ISR activity can reduce dissolved U(VI) to less toxic and insoluble U(IV) and promote natural attenuation. The reduction of oxyanions of U or Se induces measurable isotopic fractionation that can be used to monitor the natural attenuation by downgradient sediments. Here, we used multiple redox-sensitive isotope systems (U, Se, and S) to detect reducing conditions and natural attenuation of U(VI) at the ISR site. We collected groundwater samples from 26 wells located in the ore body, upgradient and downgradient to the ore body. The δ238U values measured in groundwater samples from 23 wells range from 0.48‰ to -1.66‰ (×0.12‰). A preliminary investigation of 6 groundwater samples shows a variation of δ82Se values from -1.44‰ to 5.24‰ (×0.15‰). The δ34SO4 measurements in groundwater vary from 11.8‰ to -19.9‰. The reduction of Se(VI) and SO42- fractionates the lighter isotopes (i.e., 32S and 76Se) in the reduced product phase rendering the remaining reactants in the groundwater enriched in heavier isotopes. Therefore, the high δ82Se and δ34SO4 values may suggest reduction of Se(VI) and SO42-, respectively. The highest δ238U values are observed in the wells located in the ore body or upgradient to the ore body whereas the downgradient

  10. Impact of vegetation cover and stand age on scaling carbon fluxes in the upper Midwest: a multiple eddy flux site study

    NASA Astrophysics Data System (ADS)

    Desai, A. R.; Normeets, A.; Bolstad, P. V.; Chen, J.; Cook, B. D.; Curtis, P. S.; Davis, K. J.; Euskirchen, E.; Gough, C.; Martin, J.; Ricciuto, D. M.; Schmid, H. P.; Tang, J.; Su, H.; Vogel, C.; Wang, W.

    2004-12-01

    Eight permanent and three roving eddy flux towers were used to observe the exchange of carbon dioxide between the ecosystem and atmosphere at fourteen different sites in northern Wisconsin and Michigan (USA) during the growing seasons (May-Sept) of 2002 and 2003. These towers were part of the Chequamegon Ecosystem-Atmosphere Study (ChEAS), the University of Michigan Biological Station (UMBS), and the Michigan Technical University. The sites spanned a range of vegetation types typical of the region (northern hardwood, hemlock-hardwood, mixed forest, red pine, jack pine, pine barrens and shrub wetland). The hardwood and red pine sites also spanned a range of forest stand age (young, intermediate, mature and old). All sites experienced roughly similar climate; thus, comparisons among the sites allow for an examination of the impact of heterogeneous vegetation cover and stand age across a regional landscape. Carbon fluxes at different sites generally reacted similarly in response to variability in climate. Results suggest that both cover type and stand age are important variables for modeling and predicting fluxes in this region. These results have implications for developing methods of scaling carbon dioxide fluxes from sites to regions. These results will be contrasted to a flux decomposition at the WLEF tall tower.

  11. The intergenic region between the divergently transcribed niiA and niaD genes of Aspergillus nidulans contains multiple NirA binding sites which act bidirectionally.

    PubMed Central

    Punt, P J; Strauss, J; Smit, R; Kinghorn, J R; van den Hondel, C A; Scazzocchio, C

    1995-01-01

    The niaD and niiA genes of Aspergillus nidulans, which code, respectively, for nitrate and nitrite reductases, are divergently transcribed, and their ATGs are separated by 1,200 bp. The genes are under the control of the positively acting NirA transcription factor, which mediates nitrate induction. The DNA binding domain of NirA was expressed as a fusion protein with the glutathione S-transferase of Schistosoma japonicum. Gel shift and footprint experiments have shown that in the intergenic region there are four binding sites for the NirA transcription factor. These sites can be represented by the nonpalindromic consensus 5'CTCCGHGG3'. Making use of a bidirectional expression vector, we have analyzed the role of each of the sites in niaD and niiA expression. The sites were numbered from the niiA side. It appeared that site 1 is necessary for the inducibility of niiA only, while sites 2, 3, and to a lesser extent 4 (which is nearer to and strongly affects niaD) act bidirectionally. The results also suggest that of the 10 binding sites for the AreA protein, which mediates nitrogen metabolite repression, those which are centrally located are physiologically important. The insertion of an unrelated upstream activating sequence into the intergenic region strongly affected the expression of both genes, irrespective of the orientation in which the element was inserted. PMID:7565720

  12. Multiple-trait analysis of fluctuating asymmetry levels in anthropogenically and naturally stressed sites: a case study using Chironomus riparius Meigen, 1804 larvae.

    PubMed

    Servia, M J; Cobo, F; González, M A

    2004-01-01

    Fluctuating asymmetry levels were measured in fourth-instar Chironomus riparius larvae collected from various sampling sites in Galicia (northwest Spain) subjected to different types and degrees of stress. Specifically, we selected sites with contamination of anthropogenic origin, ranging from urban and industrial sewages to organic wastes, as well as two sites without chemical contamination, but with marked diurnal variations in their physicochemical conditions. Fluctuating asymmetry levels were determined for various structures of the head capsule (antennal segment I length, antennal segment II length, mentum width, and number of pecten epipharyngis teeth). The results obtained group the sampling sites in a similar way to other measures of stress. In particular, grouping resulted to be similar to that obtained after analysis of head capsule deformities. Moreover, results of our work are consistent with the hypothesis that some characters may possibly be useful indicators of specific types of stress. PMID:15887366

  13. Site migration in seeking care services from multiple providers is associated with worse clinical outcomes among HIV-infected individuals in Washington, DC.

    PubMed

    Jia, Yujiang; Sengupta, Debapriya; Opoku, Jenevieve; Wu, Charles; Griffin, Angelique; West, Tiffany; Samala, Rowena; Shaikh, Irshad; Pappas, Gregory

    2014-01-01

    Washington, DC, is a metropolitan city with a severe HIV epidemic and faces challenges in retaining people living with HIV (PLWH) in quality care. This study assessed site migration in seeking care services and its correlates among PLWH in DC. PLWH diagnosed before 2008 and living through the end of 2010 were analyzed. Six scenarios of site migration were examined as patients visited =2, =3, and =4 different providers for their CD4 cell count and/or viral load (VL) tests in the past 3 years from 2008 to 2010 and 2 years from 2009 to 2010, respectively. Of 6480 patients analyzed from 2008 to 2010, 18.4% had CD4 < 200 cells/mm(3), 30.5% had VL > 400 copies/mL, and 76.6% were retained in same care sites; 23.4%, 5.0%, and 0.9% visited =2, =3, and =4 sites in the past 3 years from 2008 to 2010, respectively. Of 5954 patients analyzed from 2009 to 2010, 16.8% had CD4 < 200 cells/mm(3), 29.4% had VL > 400 copies/mL, and 81.9% were retained in same care sites; 18.1%, 3.1%, and 0.6% visited =2, =3, and =4 sites in the past 2 years from 2009 to 2010, respectively. Multivariable logistic regression analyses revealed that migration across six scenarios are consistently associated with CD4 < 200 cells/mm(3) and VL > 400 copies/mL. Site migration was common and associated with lower CD4 and higher VL among PLWH in DC. Frequent migration might be a factor in achieving optimal health outcomes for a subset of patients. Site migration might potentially limit effective delivery of high quality care and treatment services. The preliminary findings underscore the need for further research to assess the predictors of migration and its impact on stage of care. PMID:24797410

  14. Uptake of gamma-aminobutyric acid and L-glutamic acid by synaptosomes from postmortem human cerebral cortex: multiple sites, sodium dependence and effect of tissue preparation.

    PubMed

    Dodd, P R; Watson, W E; Morrison, M M; Johnston, G A; Bird, E D; Cowburn, R F; Hardy, J A

    1989-06-26

    The uptake of gamma-aminobutyric acid (GABA) and L-glutamic acid by synaptosomes prepared from frozen postmortem human brain was shown to be effected via distinct high and low affinity sites. At approximately 17 h postmortem delay, the kinetic parameters for GABA uptake were: high affinity site, Km 7.1 +/- 2.5 microM, Vmax 18.7 +/- 4.8 nmol.min-1 per 100 mg protein; low affinity site, Km 2 +/- 1 mM, Vmax 425 +/- 250 nmol.min-1 per 100 mg protein (means +/- S.E.M., n = 13). Kinetic parameters for L-glutamate uptake were: high affinity site, Km 7.5 +/- 1.0 microM, Vmax 85 +/- 8 nmol.min-1 per 100 mg protein; low affinity site, Km 1.8 +/- 1.2 mM. Vmax 780 +/- 175 nmol.min-1 per 100 mg protein (n = 11). A detailed kinetic analysis of high affinity GABA uptake was performed over a range of sodium ion concentrations. The results were consistent with a coupling ratio of one Na+ ion to one GABA molecule; a similar result was found with rat brain synaptosomes. However, rat and human synaptosomes differed in the degree to which the substrate affinity of the high affinity GABA uptake site varied with decreasing Na+ ion concentration. High affinity GABA uptake was markedly affected by the method used to freeze and divide the tissue, but did not vary greatly in different cortical regions. There was some decline of high affinity GABA uptake activity with postmortem delay, apparently due to a loss of sites rather than a change in site affinity.

  15. Validation of a radiosonde-based cloud layer detection method against a ground-based remote sensing method at multiple ARM sites

    NASA Astrophysics Data System (ADS)

    Zhang, Jinqiang; Li, Zhanqing; Chen, Hongbin; Cribb, Maureen

    2013-01-01

    Cloud vertical structure is a key quantity in meteorological and climate studies, but it is also among the most difficult quantities to observe. In this study, we develop a long-term (10 years) radiosonde-based cloud profile product for the U.S. Department of Energy's Atmospheric Radiation Measurement (ARM) program Southern Great Plains (SGP), Tropical Western Pacific (TWP), and North Slope of Alaska (NSA) sites and a shorter-term product for the ARM Mobile Facility (AMF) deployed in Shouxian, Anhui Province, China (AMF-China). The AMF-China site was in operation from 14 May to 28 December 2008; the ARM sites have been collecting data for over 15 years. The Active Remote Sensing of Cloud (ARSCL) value-added product (VAP), which combines data from the 95-GHz W-band ARM Cloud Radar (WACR) and/or the 35-GHz Millimeter Microwave Cloud Radar (MMCR), is used in this study to validate the radiosonde-based cloud layer retrieval method. The performance of the radiosonde-based cloud layer retrieval method applied to data from different climate regimes is evaluated. Overall, cloud layers derived from the ARSCL VAP and radiosonde data agree very well at the SGP and AMF-China sites. At the TWP and NSA sites, the radiosonde tends to detect more cloud layers in the upper troposphere.

  16. Ropizine concurrently enhances and inhibits ( sup 3 H) dextromethorpan binding to different structures of the guinea pig brain: Autoradiographic evidence for multiple binding sites

    SciTech Connect

    Canoll, P.D.; Smith, P.R.; and Musacchio, J.M. )

    1990-01-01

    Ropizine produces a simultaneous enhancement and inhibition of ({sup 3}H) dextromethorphan (DM) high-affinity binding to different areas of the guinea pig brain. These results imply that there are two distinct types of high-affinity ({sup 3}H)DM binding sites, which are present in variable proportions in different brain structures. The ropizine-enhances ({sup 3}H)DM binding type was preferentially inhibited by (+)-pentazocine. This is consistent with the presumption that the (+)-pentazocine-sensitive site is identical with the common site for DM and 3-(-3-Hydroxphenyl)-N-(1-propyl)piperidine ((+)-3-PPP). The second binding type, which is inhibited by ropizine and is not so sensitive to (+){minus} pentazocine, has not been fully characterized. This study demonstrates that the biphasic effects to ropizine are due, at least in part, to the effects of ropizine on two different types of ({sup 3}H)DM binding sites. However, this study does not rule out that the common DM/(+)-3-PPP site also might be inhibited by higher concentrations of ropizine.

  17. Modeling field-scale multiple tracer injection at a low-level waste disposal site in fractured rocks: effect of multiscale heterogeneity and source term uncertainty on conceptual understanding of mass transfer processes.

    PubMed

    Gwo, Jin-Ping; Jardine, Philip M; Sanford, William E

    2005-03-01

    Multiple factors may affect the scale-up of laboratory multi-tracer injection into structured porous media to the field. Under transient flow conditions and with multiscale heterogeneities in the field, previous attempts to scale-up laboratory experiments have not answered definitely the questions about the governing mechanisms and the spatial extent of the influence of small-scale mass transfer processes such as matrix diffusion. The objective of this research is to investigate the effects of multiscale heterogeneity, mechanistic and site model conceptualization, and source term density effect on elucidating and interpreting tracer movement in the field. Tracer release and monitoring information previously obtained in a field campaign of multiple, conservative tracer injection under natural hydraulic gradients at a low-level waste disposal site in eastern Tennessee, United States, is used for the research. A suite of two-pore-domain, or fracture-matrix, groundwater flow and transport models are calibrated and used to conduct model parameter and prediction uncertainty analyses. These efforts are facilitated by a novel nested Latin-hypercube sampling technique. Our results verify, at field scale, a multiple-pore-domain, multiscale mechanistic conceptual model that was used previously to interpret only laboratory observations. The results also suggest that, integrated over the entire field site, mass flux rates attributable to small-scale mass transfer are comparable to that of field-scale solute transport. The uncertainty analyses show that fracture spacing is the most important model parameter and model prediction uncertainty is relatively higher at the interface between the preferred flow path and its parent bedrock. The comparisons of site conceptual models indicate that the effect of matrix diffusion may be confined to the immediate neighborhood of the preferential flow path. Finally, because the relatively large amount of tracer needed for field studies, it is

  18. Identification of multiple integration sites for Stx-phage Phi24B in the Escherichia coli genome, description of a novel integrase and evidence for a functional anti-repressor.

    PubMed

    Fogg, Paul C M; Gossage, Sharon M; Smith, Darren L; Saunders, Jon R; McCarthy, Alan J; Allison, Heather E

    2007-12-01

    The key virulence factor in Shiga-toxigenic Escherichia coli is the expression of Shiga toxin (Stx), which is conferred by Stx-encoding temperate lambdoid phages (Stx-phages). It had been assumed that Stx-phages would behave similarly to lambda phage. However, contrary to the lambda superinfection immunity model, it has been demonstrated that double lysogens can be produced with the Stx-phage Phi24(B). Here, the Phi24(B) integrase gene is identified, and the preferred site of integration defined. Although an E. coli int gene was identified close to the Phi24(B) integration site, it was shown not to be involved in the phage integration event. An additional six potential integration sites were identified in the E. coli genome, and three of these were confirmed experimentally. Two of the other potential sites lie within genes predicted to be essential to E. coli and are therefore unlikely to support phage integration. A Phi24(B) gene, possessing similarity to the well-characterized P22 ant gene, was identified. RT-PCR was used to demonstrate that ant is transcribed in a Phi24(B) E. coli lysogen, and expression of an anti-repressor is the likely explanation for the absence of immunity to superinfection. Demonstration of the ability of Phi24(B) to form multiple lysogens has two potentially serious impacts. First, multiple integrated prophages will drive the evolution of bacterial pathogens as novel Stx-phages emerge following intracellular mutation/recombination events. Second, multiple copies of the stx gene may lead to an increase in toxin production and consequently increased virulence.

  19. Sorption of trivalent lanthanides and actinides onto montmorillonite: Macroscopic, thermodynamic and structural evidence for ternary hydroxo and carbonato surface complexes on multiple sorption sites.

    PubMed

    Fernandes, M Marques; Scheinost, A C; Baeyens, B

    2016-08-01

    The credibility of long-term safety assessments of radioactive waste repositories may be greatly enhanced by a molecular level understanding of the sorption processes onto individual minerals present in the near- and far-fields. In this study we couple macroscopic sorption experiments to surface complexation modelling and spectroscopic investigations, including extended X-ray absorption fine structure (EXAFS) and time-resolved laser fluorescence spectroscopies (TRLFS), to elucidate the uptake mechanism of trivalent lanthanides and actinides (Ln/An(III)) by montmorillonite in the absence and presence of dissolved carbonate. Based on the experimental sorption isotherms for the carbonate-free system, the previously developed 2 site protolysis non electrostatic surface complexation and cation exchange (2SPNE SC/CE) model needed to be complemented with an additional surface complexation reaction onto weak sites. The fitting of sorption isotherms in the presence of carbonate required refinement of the previously published model by reducing the strong site capacity and by adding the formation of Ln/An(III)-carbonato complexes both on strong and weak sites. EXAFS spectra of selected Am samples and TRLFS spectra of selected Cm samples corroborate the model assumptions by showing the existence of different surface complexation sites and evidencing the formation of Ln/An(III) carbonate surface complexes. In the absence of carbonate and at low loadings, Ln/An(III) form strong inner-sphere complexes through binding to three Al(O,OH)6 octahedra, most likely by occupying vacant sites in the octahedral layers of montmorillonite, which are exposed on {010} and {110} edge faces. At higher loadings, Ln/An(III) binds to only one Al octahedron, forming a weaker, edge-sharing surface complex. In the presence of carbonate, we identified a ternary mono- or dicarbonato Ln/An(III) complex binding directly to one Al(O,OH)6 octahedron, revealing that type-A ternary complexes form with the one

  20. Orally active 7-substituted (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as active-site inhibitors of sphingosine 1-phosphate lyase for the treatment of multiple sclerosis.

    PubMed

    Weiler, Sven; Braendlin, Nadine; Beerli, Christian; Bergsdorf, Christian; Schubart, Anna; Srinivas, Honnappa; Oberhauser, Berndt; Billich, Andreas

    2014-06-26

    Sphingosine 1-phosphate (S1P) lyase has recently been implicated as a therapeutic target for the treatment of multiple sclerosis (MS), based on studies in a genetic mouse model. Potent active site directed inhibitors of the enzyme are not known so far. Here we describe the discovery of (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrile 5 in a high-throughput screen using a biochemical assay, and its further optimization. This class of compounds was found to inhibit catalytic activity of S1PL by binding to the active site of the enzyme, as seen in the cocrystal structure of derivative 31 with the homodimeric human S1P lyase. 31 induces profound reduction of peripheral T cell numbers after oral dosage and confers pronounced protection in a rat model of multiple sclerosis. In conclusion, this novel class of direct S1P lyase inhibitors provides excellent tools to further explore the therapeutic potential of T cell-targeted therapies in multiple sclerosis and other autoimmune and inflammatory diseases.

  1. The zinc binuclear cluster activator AlcR is able to bind to single sites but requires multiple repeated sites for synergistic activation of the alcA gene in Aspergillus nidulans.

    PubMed

    Panozzo, C; Capuano, V; Fillinger, S; Felenbok, B

    1997-09-01

    The alcA gene which is part of the recently identified ethanol regulon, is one of the most strongly inducible genes in Aspergillus nidulans. Its transcriptional activation is mediated by the AlcR transactivator which contains a DNA-binding domain belonging to the C6 zinc binuclear cluster family. AlcR differs from the other members of this family by several features, the most striking characteristic being its binding to both symmetric and asymmetric DNA sites with the same apparent affinity. However, AlcR is also able to bind to a single site with high affinity, suggesting that unlike the other C6 proteins, AlcR binds as a monomer. In this report, we show that AlcR targets, to be functional in vivo, have to be organized as inverted or direct repeats. In addition, we show a strong synergistic activation of alcA transcription in which the number and the position of the AlcR-binding sites are crucial. The fact that the AlcR unit for in vitro binding is a single site whereas the in vivo functional unit is a repeat opens the question of the mechanism of the strong alcA transactivation. These results show that AlcR displays both in vitro and in vivo a new range of binding specificity and provides a novel example in the C6 zinc cluster protein family.

  2. Multiple stressors and complex life cycles: insights from a population-level assessment of breeding site contamination and terrestrial habitat loss in an amphibian.

    PubMed

    Salice, Christopher J; Rowe, Christopher L; Pechmann, Joseph H K; Hopkins, William A

    2011-12-01

    Understanding the effects of chemical contaminants on natural populations is challenging, as multiple anthropogenic and natural stressors may individually and interactively influence responses. Population models can be used to evaluate the impacts of multiple stressors and to provide insight into population-level effects and/or data gaps. For amphibians with complex life cycles, population models may be useful in understanding impacts of stressors that are unique to the habitat type (aquatic, terrestrial) and that operate at different times in the life cycle. We investigated the population-level effects of aquatic contaminants (coal combustion residues, CCR) and terrestrial habitat loss on the eastern narrowmouth toad, Gastrophryne carolinensis, using existing empirical data that demonstrated negative reproductive and developmental effects of CCR and a series of population models that incorporated density dependence and environmental stochasticity. Results of deterministic models indicated that when terrestrial habitat was abundant, CCR-exposed toads had a larger population size compared to the reference population as a result of reduced density-dependent effects on larval survival. However, when stochasticity in the form of catastrophic reproductive failure was included, CCR-exposed toads were more susceptible to decline and extinction compared to toads from the reference populations. The results highlight the complexities involved in assessing the effects of anthropogenic factors on natural populations, especially for species that are exposed to multiple biotic and abiotic stressors during different periods in the life cycle.

  3. Multiple sites of impingement of a tracheal tube as it is advanced over a fibreoptic bronchoscope or tracheal tube introducer in anaesthetized, paralysed patients.

    PubMed

    Jackson, A H; Orr, B; Yeo, C; Parker, C; Craven, R; Greenberg, S L

    2006-08-01

    Impingement of the tracheal tube on upper airway structures occurs commonly during advancement over a fibreoptic bronchoscope or introducer. In this descriptive study a fibrescope was used to assess the site and mechanism of tracheal tube impingement during advancement over a variety of fibreoptic bronchoscopes and introducers during orotracheal intubation in anaesthetized adults. The effect of the 90 degree counterclockwise rotation manoeuvre in overcoming impingement was also assessed. We recorded impingement at the right arytenoid, left arytenoid, epiglottis, interarytenoid tissue and the left pyriform fossa. Our study found a wider range of sites at which impingement may occur than in previous studies. We also found that when 90 degree counterclockwise rotation of the tip of the tracheal tube was achieved, the impingement was reliably overcome.

  4. The effects of the built environment, traffic patterns, and micrometeorology on street level ultrafine particle concentrations at a block scale: Results from multiple urban sites.

    PubMed

    Choi, Wonsik; Ranasinghe, Dilhara; Bunavage, Karen; DeShazo, J R; Wu, Lisa; Seguel, Rodrigo; Winer, Arthur M; Paulson, Suzanne E

    2016-05-15

    This study attempts to explain explicitly the direct and quantitative effects of complicated urban built-environment on near-road dispersion and levels of vehicular emissions at the scale of several city blocks, based on ultrafine particle concentrations ([UFP]). On short timescales, ultrafine particles are an excellent proxy for other roadway emissions. Five measurement sites in the greater Los Angeles with different built environments but similar mesoscale meteorology were explored. After controlling for traffic, for most sampling days and sites, morning [UFP] were higher than those in the afternoon due to limited dispersion capacity combined with a relatively stable surface layer. [UFP] at the intersection corners were also higher than those over the sampling sites, implying that accelerating vehicles around the intersections contributed to [UFP] elevation. In the calm morning, the areal aspect ratio (Ararea), developed in this study for real urban configurations, showed a strong relationship with block-scale [UFP]. Ararea includes the building area-weighted building height, the amount of open space, and the building footprint. In the afternoon, however, when wind speeds were generally higher and turbulence was stronger, vertical turbulence intensity σw was the most effective factor controlling [UFP]. The surrounding built environment appears to play an indirect role in observed [UFP], by affecting surface level micrometeorology. The effects are substantial; controlling for traffic, differences in Ararea and building heterogeneity were related to differences in [UFP] of factors of two to three among our five study sites. These results have significant implications for pedestrian exposure as well as transit-oriented urban planning.

  5. Phosphorylation of arylsulphatase A occurs through multiple interactions with the UDP-N-acetylglucosamine-1-phosphotransferase proximal and distal to its retrieval site by the KDEL receptor.

    PubMed Central

    Dittmer, F; von Figura, K

    1999-01-01

    Phosphorylation of oligosaccharides of the lysosomal enzyme arylsulphatase A (ASA), which accumulate in the secretions of cells that mis-sort most of the newly synthesized lysosomal enzymes due to a deficiency of mannose 6-phosphate receptors, was found to be site specific. ASA residing within the secretory route of these cells contains about one third of the incorporated [2-3H]mannose in phosphorylated oligosaccharides. Oligosaccharides carrying two phosphate groups are almost 2-fold less frequent than those with one phosphate group and only a few of the phosphate groups are uncovered. Addition of a KDEL (Lys-Asp-Glu-Leu) retention signal prolongs the residence time of ASA within the secretory route 6-fold, but does not result in more efficient phosphorylation. In contrast, more than 90% of the [2-3H]mannose incorporated into secreted ASA (with or without a KDEL retention signal) is present in phosphorylated oligosaccharides. Those with two phosphate groups are almost twice as frequent as those with one phosphate group and most of the phosphate groups are uncovered. Thus, ASA receives N-acetylglucosamine 1-phosphate groups in a sequential manner at two or more sites located within the secretory route proximal and distal to the site where ASA is retrieved by the KDEL receptor, i.e. proximal to the trans-Golgi. At each of these sites up to two N-acetylglucosamine 1-phosphate groups can be added to a single oligosaccharide. Of several drugs known to inhibit transit of ASA through the secretory route only the ionophore monensin had a major inhibitory effect on phosphorylation, uncovering and sialylation. PMID:10359658

  6. High resolution refinement of beta-galactosidase in a new crystal form reveals multiple metal-binding sites and provides a structural basis for alpha-complementation.

    PubMed Central

    Juers, D. H.; Jacobson, R. H.; Wigley, D.; Zhang, X. J.; Huber, R. E.; Tronrud, D. E.; Matthews, B. W.

    2000-01-01

    The unrefined fold of Escherichia coli beta-galactosidase based on a monoclinic crystal form with four independent tetramers has been reported previously. Here, we describe a new, orthorhombic form with one tetramer per asymmetric unit that has permitted refinement of the structure at 1.7 A resolution. This high-resolution analysis has confirmed the original description of the structure and revealed new details. An essential magnesium ion, identified at the active site in the monoclinic crystals, is also seen in the orthorhombic form. Additional putative magnesium binding sites are also seen. Sodium ions are also known to affect catalysis, and five putative binding sites have been identified, one close to the active site. In a crevice on the protein surface, five linked five-membered solvent rings form a partial clathrate-like structure. Some other unusual aspects of the structure include seven apparent cis-peptide bonds, four of which are proline, and several internal salt-bridge networks. Deep solvent-filled channels and tunnels extend across the surface of the molecule and pass through the center of the tetramer. Because of these departures from a compact globular shape, the molecule is not well characterized by prior empirical relationships between the mass and surface area of proteins. The 50 or so residues at the amino terminus have a largely extended conformation and mostly lie across the surface of the protein. At the same time, however, segment 13-21 contributes to a subunit interface, and residues 29-33 pass through a "tunnel" formed by a domain interface. Taken together, the overall arrangement provides a structural basis for the phenomenon of alpha-complementation. PMID:11045615

  7. The effects of the built environment, traffic patterns, and micrometeorology on street level ultrafine particle concentrations at a block scale: Results from multiple urban sites.

    PubMed

    Choi, Wonsik; Ranasinghe, Dilhara; Bunavage, Karen; DeShazo, J R; Wu, Lisa; Seguel, Rodrigo; Winer, Arthur M; Paulson, Suzanne E

    2016-05-15

    This study attempts to explain explicitly the direct and quantitative effects of complicated urban built-environment on near-road dispersion and levels of vehicular emissions at the scale of several city blocks, based on ultrafine particle concentrations ([UFP]). On short timescales, ultrafine particles are an excellent proxy for other roadway emissions. Five measurement sites in the greater Los Angeles with different built environments but similar mesoscale meteorology were explored. After controlling for traffic, for most sampling days and sites, morning [UFP] were higher than those in the afternoon due to limited dispersion capacity combined with a relatively stable surface layer. [UFP] at the intersection corners were also higher than those over the sampling sites, implying that accelerating vehicles around the intersections contributed to [UFP] elevation. In the calm morning, the areal aspect ratio (Ararea), developed in this study for real urban configurations, showed a strong relationship with block-scale [UFP]. Ararea includes the building area-weighted building height, the amount of open space, and the building footprint. In the afternoon, however, when wind speeds were generally higher and turbulence was stronger, vertical turbulence intensity σw was the most effective factor controlling [UFP]. The surrounding built environment appears to play an indirect role in observed [UFP], by affecting surface level micrometeorology. The effects are substantial; controlling for traffic, differences in Ararea and building heterogeneity were related to differences in [UFP] of factors of two to three among our five study sites. These results have significant implications for pedestrian exposure as well as transit-oriented urban planning. PMID:26938315

  8. Multiple Propofol-binding Sites in a γ-Aminobutyric Acid Type A Receptor (GABAAR) Identified Using a Photoreactive Propofol Analog*♦

    PubMed Central

    Jayakar, Selwyn S.; Zhou, Xiaojuan; Chiara, David C.; Dostalova, Zuzana; Savechenkov, Pavel Y.; Bruzik, Karol S.; Dailey, William P.; Miller, Keith W.; Eckenhoff, Roderic G.; Cohen, Jonathan B.

    2014-01-01

    Propofol acts as a positive allosteric modulator of γ-aminobutyric acid type A receptors (GABAARs), an interaction necessary for its anesthetic potency in vivo as a general anesthetic. Identifying the location of propofol-binding sites is necessary to understand its mechanism of GABAAR modulation. [3H]2-(3-Methyl-3H-diaziren-3-yl)ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate (azietomidate) and R-[3H]5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (mTFD-MPAB), photoreactive analogs of 2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate (etomidate) and mephobarbital, respectively, have identified two homologous but pharmacologically distinct classes of intersubunit-binding sites for general anesthetics in the GABAAR transmembrane domain. Here, we use a photoreactive analog of propofol (2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenol ([3H]AziPm)) to identify propofol-binding sites in heterologously expressed human α1β3 GABAARs. Propofol, AziPm, etomidate, and R-mTFD-MPAB each inhibited [3H]AziPm photoincorporation into GABAAR subunits maximally by ∼50%. When the amino acids photolabeled by [3H]AziPm were identified by protein microsequencing, we found propofol-inhibitable photolabeling of amino acids in the β3-α1 subunit interface (β3Met-286 in β3M3 and α1Met-236 in α1M1), previously photolabeled by [3H]azietomidate, and α1Ile-239, located one helical turn below α1Met-236. There was also propofol-inhibitable [3H]AziPm photolabeling of β3Met-227 in βM1, the amino acid in the α1-β3 subunit interface photolabeled by R-[3H]mTFD-MPAB. The propofol-inhibitable [3H]AziPm photolabeling in the GABAAR β3 subunit in conjunction with the concentration dependence of inhibition of that photolabeling by etomidate or R-mTFD-MPAB also establish that each anesthetic binds to the homologous site at the β3-β3 subunit interface. These results establish that AziPm as well as propofol bind to the homologous intersubunit sites in the

  9. Intercomparison and assessment of long-term (2004-2013) multiple satellite aerosol products over two contrasting sites in South Africa

    NASA Astrophysics Data System (ADS)

    Adesina, A. Joseph; Kumar, K. Raghavendra; Sivakumar, V.; Piketh, Stuart J.

    2016-10-01

    To build a long-term database and improve the accuracy of the satellite products used for aerosol studies, there is a need to carry out intercomparison and validation of these satellite observations with ground-based measurements. With this objective, we estimated the long-term inter-annual variations and percentage change in trends of aerosol optical depth (AOD) retrieved from MODerate resolution Imaging Spectroradiometer (MODIS) and Multi-angle Imaging Spectro-Radiometer (MISR) sensors for a 10-year period during 2004-2013 over two distinct sites namely, Skukuza (SKZ; 24.99°S, 31.58°E) and Richards Bay (RBAY; 28.8°S, 21.1°E) in South Africa. The validation performed over SKZ site shows that MISR was better correlated with AErosol RObotic NETwork (AERONET) when compared to Terra and Aqua satellites of MODIS. Later both the MODIS products (Terra and Aqua) were compared on the annual and seasonal basis to derive the relationship between them through scattering plot. The long-term regression analysis performed at these sites shows that the annual trends were decreasing, with the MODIS products underestimating MISR. This is due to difficulties of the MODIS algorithm when dealing with highly complex surface reflectance conditions and aerosol model assumptions. Also, the temporal variations of AOD derived from the two sensors noticed maximum in spring (September/October) and minimum in winter (June). Further, the Ultra-Violet Aerosol Index (UVAI) retrieved from the Ozone Monitoring Instrument (OMI) at the two locations for 9 years (2005-2013) showed a significant increasing trend with a high value of +0.009 yr-1 at SKZ than +0.006 yr-1 at RBAY during the study period, which is due to the transport of dust and smoke particles.

  10. Attenuation-difference radar tomography: results of a multiple-plane experiment at the U.S. Geological Survey Fractured-Rock Research Site, Mirror Lake, New Hampshire

    USGS Publications Warehouse

    Lane, J.W.; Day-Lewis, F. D.; Harris, J.M.; Haeni, F.P.; Gorelick, S.M.

    2000-01-01

    Attenuation-difference, borehole-radar tomography was used to monitor a series of sodium chloride tracer injection tests conducted within the FSE, wellfield at the U.S. Geological Survey Fractured-Rock Hydrology Research Site in Grafton County, New Hampshire, USA. Borehole-radar tomography surveys were conducted using the sequential-scanning and injection method in three boreholes that form a triangular prism of adjoining tomographic image planes. Results indicate that time-lapse tomography methods provide high-resolution images of tracer distribution in permeable zones.

  11. Multiple phosphorylation sites at the C-terminus regulate nuclear import of HCMV DNA polymerase processivity factor ppUL44

    SciTech Connect

    Alvisi, Gualtiero; Marin, Oriano; Pari, Gregory; Mancini, Manuela; Avanzi, Simone; Loregian, Arianna; Jans, David A.; Ripalti, Alessandro

    2011-09-01

    The processivity factor of human cytomegalovirus DNA polymerase, phosphoprotein ppUL44, is essential for viral replication. During viral infection ppUL44 is phosphorylated by the viral kinase pUL97, but neither the target residues on ppUL44 nor the effect of phosphorylation on ppUL44's activity are known. We report here that ppUL44 is phosphorylated when transiently expressed in mammalian cells and coimmunoprecipitates with cellular kinases. Of three potential phosphorylation sites (S413, S415, S418) located upstream of ppUL44's nuclear localization signal (NLS) and one (T427) within the NLS itself, protein kinase CK2 (CK2) specifically phosphorylates S413, to trigger a cascade of phosphorylation of S418 and S415 by CK1 and CK2, respectively. Negative charge at the CK2/CK1 target serine residues facilitates optimal nuclear accumulation of ppUL44, whereas negative charge on T427, a potential cyclin-dependent 1 phosphorylation site, strongly decreases nuclear accumulation. Thus, nuclear transport of ppUL44 is finely tuned during viral infection through complex phosphorylation events.

  12. The integration host factor of Escherichia coli binds to multiple sites at plasmid R6K gamma origin and is essential for replication.

    PubMed Central

    Filutowicz, M; Appelt, K

    1988-01-01

    Examination of the effect of the himA and himD mutants of E. coli on the maintenance of plasmid R6K has revealed that the gamma origin-containing replicons cannot be established in any of the mutants deficient in the production of E. coli Integration Host Factor (IHF). Contrary, the R6K derivatives containing other origins of the plasmid (alpha and/or beta) replicate in a host lacking functional IHF protein. We show that IHF protein binds specifically to a segment of the replication region which is essential for the activity of all three R6K origins. Mapping the IHF binding sequence with neocarzinostatin showed that the protein protects three segments of the origin: two strong binding sites reside within an AT-rich block, while the third, considerably weaker site is separated from the other two by a cluster of the seven 22 bp direct repeats. These seven repeats have been shown previously to bind the R6K-encoded initiator protein pi. We also demonstrate that the establishment of pi-origin complexes prior to IHF addition prevents the binding of the IHF protein to the gamma origin. The binding sequences of IHF and pi proteins do not overlap, therefore, we propose that the binding of pi protein alters the structure of the DNA and thereby prevents the subsequent binding of IHF protein. Images PMID:2967465

  13. [(3) H]-L685,458 binding sites are abundant in multiple peripheral organs in rats: implications for safety assessment of putative γ-secretase targeting drugs.

    PubMed

    Yang, Zhi-Ying; Li, Jian-Ming; Xiao, Ling; Mou, Lin; Cai, Yan; Huang, He; Luo, Xue-Gang; Yan, Xiao-Xin

    2014-12-01

    γ-Secretase is a multimeric enzyme complex that carries out proteolytic processing to a variety of cellular proteins. It is currently explored as a therapeutic target for Alzheimer's disease (AD) and cancer. Mechanism-based toxicity needs to be thoroughly evaluated for γ-secretase inhibitory and/or modulatory drugs. This study comparatively assessed putative γ-secretase catalytic sites in rat peripheral tissues relative to brain and explored an effort of its pharmacological inhibition on hair regeneration. Using [(3) H]-labelled L685,458, a potent γ-secretase inhibitor, as probe, we found more abundant presence of γ-secretase binding sites in the liver, gastrointestinal tract, hair follicle, pituitary gland, ovary and testis, as compared to the brain. Local application of L658,458 delayed vibrissal regrowth following whisker removal. These results suggest that γ-secretase may execute important biological functions in many peripheral systems, as in the brain. The development of γ-secretase inhibitors/modulators for AD and cancer therapy should include close monitoring of toxicological panels for hepatic, gastrointestinal, endocrinal and reproductive functions. PMID:24861611

  14. Reverse Monte Carlo Modeling of Pair Distribution Function Data as a Tool for Separating the Coordination Environments of Multiple Atoms Disordered Over a Single Site

    NASA Astrophysics Data System (ADS)

    King, Graham; Llobet, Anna; Ricciardo, Rebecca; Soliz, Jennifer; Woodward, Patrick; Ramezanipour, Farshid; Greedan, John

    2012-02-01

    The local structures of 8 perovskite compounds which contain equal concentrations of 2 transition metal cations disordered over the B-sites have been investigated using reverse Monte Carlo (RMC) modeling of neutron pair distribution function (PDF) data. Such compounds are known to display a number of interesting magnetic and electronic properties which, due to the cation disorder, cannot be correlated with the average long range structure and so remain poorly understood. In compounds with B=Mn/Ru there exists a valence degeneracy between Mn^3+/Ru^5+ and Mn^4+/Ru^4+. We demonstrate that the RMC method can be used as an effective tool to separate out the individual coordination environments of these cations and also to monitor the relative concentrations of the different oxidation states. We find that the valency ratio is governed by the size of the A-site cations. In a different series of Sr2FeMnO6-x perovskites we find that locally the structures are quite different from the average cubic structures, with the local coordination environments more closely resembling those of the brownmillerite structure. In all compounds the octahedra containing Mn^3+ are Jahn-Teller distorted, even if this distortion is not evident in the average structure.

  15. Diffusion magnetic resonance imaging study of schizophrenia in the context of abnormal neurodevelopment using multiple site data in a Chinese Han population.

    PubMed

    Li, Y; Xie, S; Liu, B; Song, M; Chen, Y; Li, P; Lu, L; Lv, L; Wang, H; Yan, H; Yan, J; Zhang, H; Zhang, D; Jiang, T

    2016-01-19

    Schizophrenia has increasingly been considered a neurodevelopmental disorder, and the advancement of neuroimaging techniques and associated computational methods has enabled quantitative re-examination of this important theory on the pathogenesis of the disease. Inspired by previous findings from neonatal brains, we proposed that an increase in diffusion magnetic resonance imaging (dMRI) mean diffusivity (MD) should be observed in the cerebral cortex of schizophrenia patients compared with healthy controls, corresponding to lower tissue complexity and potentially a failure to reach cortical maturation. We tested this hypothesis using dMRI data from a Chinese Han population comprising patients from four different hospital sites. Utilizing data-driven methods based on the state-of-the-art tensor-based registration algorithm, significantly increased MD measurements were consistently observed in the cortex of schizophrenia patients across all four sites, despite differences in psychopathology, exposure to antipsychotic medication and scanners used for image acquisition. Specifically, we found increased MD in the limbic system of the schizophrenic brain, mainly involving the bilateral insular and prefrontal cortices. In light of the existing literature, we speculate that this may represent a neuroanatomical signature of the disorder, reflecting microstructural deficits due to developmental abnormalities. Our findings not only provide strong support to the abnormal neurodevelopment theory of schizophrenia, but also highlight an important neuroimaging endophenotype for monitoring the developmental trajectory of high-risk subjects of the disease, thereby facilitating early detection and prevention.

  16. [(3) H]-L685,458 binding sites are abundant in multiple peripheral organs in rats: implications for safety assessment of putative γ-secretase targeting drugs.

    PubMed

    Yang, Zhi-Ying; Li, Jian-Ming; Xiao, Ling; Mou, Lin; Cai, Yan; Huang, He; Luo, Xue-Gang; Yan, Xiao-Xin

    2014-12-01

    γ-Secretase is a multimeric enzyme complex that carries out proteolytic processing to a variety of cellular proteins. It is currently explored as a therapeutic target for Alzheimer's disease (AD) and cancer. Mechanism-based toxicity needs to be thoroughly evaluated for γ-secretase inhibitory and/or modulatory drugs. This study comparatively assessed putative γ-secretase catalytic sites in rat peripheral tissues relative to brain and explored an effort of its pharmacological inhibition on hair regeneration. Using [(3) H]-labelled L685,458, a potent γ-secretase inhibitor, as probe, we found more abundant presence of γ-secretase binding sites in the liver, gastrointestinal tract, hair follicle, pituitary gland, ovary and testis, as compared to the brain. Local application of L658,458 delayed vibrissal regrowth following whisker removal. These results suggest that γ-secretase may execute important biological functions in many peripheral systems, as in the brain. The development of γ-secretase inhibitors/modulators for AD and cancer therapy should include close monitoring of toxicological panels for hepatic, gastrointestinal, endocrinal and reproductive functions.

  17. The counterreceptor binding site of human CD2 exhibits an extended surface patch with multiple conformations fluctuating with millisecond to microsecond motions.

    PubMed Central

    Wyss, D. F.; Dayie, K. T.; Wagner, G.

    1997-01-01

    We have used 15N NMR relaxation experiments to probe, for the glycosylated human CD2 adhesion domain, the overall molecular motion, as well as very fast nanosecond-picosecond (ns-ps) and slow millisecond-microsecond (ms-microsecond) internal motions. Using a novel analysis method that considers all residues, we obtained a correlation time for the overall motion of 9.5 +/- 0.3 ns. Surprisingly, we found a large contiguous patch of residues in the counterreceptor (CD58) binding site of human CD2 exhibiting slow conformational exchange motions (ms-microsecond). On the other hand, almost none of the residues of the CD58 binding side display fast (ns-ps) internal motions of amplitudes larger than what is seen for well-ordered regions of the structure. Residues close to the N-glycosylation site, and the first N-acetylglucosamine of the high mannose glycan are as rigid as the protein core. Residues conserved in the immunoglobulin superfamily V-set domain are generally very rigid. PMID:9070436

  18. Genome-Wide Mapping of Binding Sites Reveals Multiple Biological Functions of the Transcription Factor Cst6p in Saccharomyces cerevisiae

    PubMed Central

    Bergenholm, David

    2016-01-01

    ABSTRACT In the model eukaryote Saccharomyces cerevisiae, the transcription factor Cst6p has been reported to play important roles in several biological processes. However, the genome-wide targets of Cst6p and its physiological functions remain unknown. Here, we mapped the genome-wide binding sites of Cst6p at high resolution. Cst6p binds to the promoter regions of 59 genes with various biological functions when cells are grown on ethanol but hardly binds to the promoter at any gene when cells are grown on glucose. The retarded growth of the CST6 deletion mutant on ethanol is attributed to the markedly decreased expression of NCE103, encoding a carbonic anhydrase, which is a direct target of Cst6p. The target genes of Cst6p have a large overlap with those of stress-responsive transcription factors, such as Sko1p and Skn7p. In addition, a CST6 deletion mutant growing on ethanol shows hypersensitivity to oxidative stress and ethanol stress, assigning Cst6p as a new member of the stress-responsive transcriptional regulatory network. These results show that mapping of genome-wide binding sites can provide new insights into the function of transcription factors and highlight the highly connected and condition-dependent nature of the transcriptional regulatory network in S. cerevisiae. PMID:27143390

  19. Diffusion magnetic resonance imaging study of schizophrenia in the context of abnormal neurodevelopment using multiple site data in a Chinese Han population

    PubMed Central

    Li, Y; Xie, S; Liu, B; Song, M; Chen, Y; Li, P; Lu, L; Lv, L; Wang, H; Yan, H; Yan, J; Zhang, H; Zhang, D; Jiang, T

    2016-01-01

    Schizophrenia has increasingly been considered a neurodevelopmental disorder, and the advancement of neuroimaging techniques and associated computational methods has enabled quantitative re-examination of this important theory on the pathogenesis of the disease. Inspired by previous findings from neonatal brains, we proposed that an increase in diffusion magnetic resonance imaging (dMRI) mean diffusivity (MD) should be observed in the cerebral cortex of schizophrenia patients compared with healthy controls, corresponding to lower tissue complexity and potentially a failure to reach cortical maturation. We tested this hypothesis using dMRI data from a Chinese Han population comprising patients from four different hospital sites. Utilizing data-driven methods based on the state-of-the-art tensor-based registration algorithm, significantly increased MD measurements were consistently observed in the cortex of schizophrenia patients across all four sites, despite differences in psychopathology, exposure to antipsychotic medication and scanners used for image acquisition. Specifically, we found increased MD in the limbic system of the schizophrenic brain, mainly involving the bilateral insular and prefrontal cortices. In light of the existing literature, we speculate that this may represent a neuroanatomical signature of the disorder, reflecting microstructural deficits due to developmental abnormalities. Our findings not only provide strong support to the abnormal neurodevelopment theory of schizophrenia, but also highlight an important neuroimaging endophenotype for monitoring the developmental trajectory of high-risk subjects of the disease, thereby facilitating early detection and prevention. PMID:26784969

  20. Diffusion magnetic resonance imaging study of schizophrenia in the context of abnormal neurodevelopment using multiple site data in a Chinese Han population.

    PubMed

    Li, Y; Xie, S; Liu, B; Song, M; Chen, Y; Li, P; Lu, L; Lv, L; Wang, H; Yan, H; Yan, J; Zhang, H; Zhang, D; Jiang, T

    2016-01-01

    Schizophrenia has increasingly been considered a neurodevelopmental disorder, and the advancement of neuroimaging techniques and associated computational methods has enabled quantitative re-examination of this important theory on the pathogenesis of the disease. Inspired by previous findings from neonatal brains, we proposed that an increase in diffusion magnetic resonance imaging (dMRI) mean diffusivity (MD) should be observed in the cerebral cortex of schizophrenia patients compared with healthy controls, corresponding to lower tissue complexity and potentially a failure to reach cortical maturation. We tested this hypothesis using dMRI data from a Chinese Han population comprising patients from four different hospital sites. Utilizing data-driven methods based on the state-of-the-art tensor-based registration algorithm, significantly increased MD measurements were consistently observed in the cortex of schizophrenia patients across all four sites, despite differences in psychopathology, exposure to antipsychotic medication and scanners used for image acquisition. Specifically, we found increased MD in the limbic system of the schizophrenic brain, mainly involving the bilateral insular and prefrontal cortices. In light of the existing literature, we speculate that this may represent a neuroanatomical signature of the disorder, reflecting microstructural deficits due to developmental abnormalities. Our findings not only provide strong support to the abnormal neurodevelopment theory of schizophrenia, but also highlight an important neuroimaging endophenotype for monitoring the developmental trajectory of high-risk subjects of the disease, thereby facilitating early detection and prevention. PMID:26784969

  1. Membrane and Core Periplasmic Agrobacterium tumefaciens Virulence Type IV Secretion System Components Localize to Multiple Sites around the Bacterial Perimeter during Lateral Attachment to Plant Cells

    PubMed Central

    Aguilar, Julieta; Cameron, Todd A.; Zupan, John; Zambryski, Patricia

    2011-01-01

    ABSTRACT Type IV secretion systems (T4SS) transfer DNA and/or proteins into recipient cells. Here we performed immunofluorescence deconvolution microscopy to localize the assembled T4SS by detection of its native components VirB1, VirB2, VirB4, VirB5, VirB7, VirB8, VirB9, VirB10, and VirB11 in the C58 nopaline strain of Agrobacterium tumefaciens, following induction of virulence (vir) gene expression. These different proteins represent T4SS components spanning the inner membrane, periplasm, or outer membrane. Native VirB2, VirB5, VirB7, and VirB8 were also localized in the A. tumefaciens octopine strain A348. Quantitative analyses of the localization of all the above Vir proteins in nopaline and octopine strains revealed multiple foci in single optical sections in over 80% and 70% of the bacterial cells, respectively. Green fluorescent protein (GFP)-VirB8 expression following vir induction was used to monitor bacterial binding to live host plant cells; bacteria bind predominantly along their lengths, with few bacteria binding via their poles or subpoles. vir-induced attachment-defective bacteria or bacteria without the Ti plasmid do not bind to plant cells. These data support a model where multiple vir-T4SS around the perimeter of the bacterium maximize effective contact with the host to facilitate efficient transfer of DNA and protein substrates. PMID:22027007

  2. Multiple Insecticide Resistance in the Malaria Vector Anopheles funestus from Northern Cameroon Is Mediated by Metabolic Resistance Alongside Potential Target Site Insensitivity Mutations

    PubMed Central

    Menze, Benjamin D.; Riveron, Jacob M.; Ibrahim, Sulaiman S.; Irving, Helen; Antonio-Nkondjio, Christophe; Awono-Ambene, Parfait H.; Wondji, Charles S.

    2016-01-01

    Background Despite the recent progress in establishing the patterns of insecticide resistance in the major malaria vector Anopheles funestus, Central African populations of this species remain largely uncharacterised. To bridge this important gap and facilitate the implementation of suitable control strategies against this vector, we characterised the resistance patterns of An. funestus population from northern Cameroon. Methods and Findings Collection of indoor-resting female mosquitoes in Gounougou (northern Cameroon) in 2012 and 2015 revealed a predominance of An. funestus during dry season. WHO bioassays performed using F1 An. funestus revealed that the population was multiple resistant to several insecticide classes including pyrethroids (permethrin, deltamethrin, lambda-cyhalothrin and etofenprox), carbamates (bendiocarb) and organochlorines (DDT and dieldrin). However, a full susceptibility was observed against the organophosphate malathion. Bioassays performed with 2015 collection revealed that resistance against pyrethroids and DDT is increasing. PBO synergist assays revealed a significant recovery of susceptibility for all pyrethroids but less for DDT. Analysis of the polymorphism of a portion of the voltage-gated sodium channel gene (VGSC) revealed the absence of the L1014F/S kdr mutation but identified 3 novel amino acid changes I877L, V881L and A1007S. However, no association was established between VGSC polymorphism and pyrethroid/DDT resistance. The DDT resistant 119F-GSTe2 allele (52%) and the dieldrin resistant 296S-RDL allele (45%) were detected in Gounougou. Temporal analysis between 2006, 2012 and 2015 collections revealed that the 119F-GSTe2 allele was relatively stable whereas a significant decrease is observed for 296S-RDL allele. Conclusion This multiple resistance coupled with the temporal increased in resistance intensity highlights the need to take urgent measures to prolong the efficacy of current insecticide-based interventions against

  3. Remote engineering for a cheese whey biorefinery: an Internet-based application for process design, economic analysis, monitoring, and control of multiple plant sites.

    PubMed

    Pinto, Gilson A; Giordano, Raquel L C; Giordano, Roberto C

    2009-01-01

    The proteolysis of cheese whey with the aid of immobilized enzymes is an attractive alternative for this by-product of the dairy industry. Among some possible applications for whey protein hydrolysates, one may cite their use as protein source for individuals with reduced capacity of digestion, or with genetic metabolic disorders (phenylketonuria patients, for instance). The multipurpose plant that processes whey is named here as a cheese whey biorefinery. This work presents the remote control and monitoring of the whey biorefineries using the Internet. In an integrated environment, the web application also enables simulation and economic analyses of the process. This technology might allow small companies to access a remote "engineering centre", with know-how on plant design and advanced control techniques. The idea can also be extended to large dairy companies, providing the remote control of geographically spread sites of production. PMID:18431600

  4. Remote engineering for a cheese whey biorefinery: an Internet-based application for process design, economic analysis, monitoring, and control of multiple plant sites.

    PubMed

    Pinto, Gilson A; Giordano, Raquel L C; Giordano, Roberto C

    2009-01-01

    The proteolysis of cheese whey with the aid of immobilized enzymes is an attractive alternative for this by-product of the dairy industry. Among some possible applications for whey protein hydrolysates, one may cite their use as protein source for individuals with reduced capacity of digestion, or with genetic metabolic disorders (phenylketonuria patients, for instance). The multipurpose plant that processes whey is named here as a cheese whey biorefinery. This work presents the remote control and monitoring of the whey biorefineries using the Internet. In an integrated environment, the web application also enables simulation and economic analyses of the process. This technology might allow small companies to access a remote "engineering centre", with know-how on plant design and advanced control techniques. The idea can also be extended to large dairy companies, providing the remote control of geographically spread sites of production.

  5. Pain at multiple body sites and health-related quality of life in older adults: results from the North Staffordshire Osteoarthritis Project

    PubMed Central

    Belcher, John; Rathod, Trishna; Wilkie, Ross; Thomas, Elaine; McBeth, John

    2014-01-01

    Objectives. Number of pain sites (NPS) is a potentially important marker of health-related quality of life (HRQoL) but remains unexplored in older people. This cross-sectional study investigated whether, in older people including the oldest old, NPS was independently associated with poorer mental and physical HRQoL and if the association was moderated by age. Methods. A postal questionnaire sent to a population sample of adults aged ≥50 years in North Staffordshire, UK, included the 12-item Short Form Health Survey (SF-12) mental component summary (MCS) and physical component summary (PCS), a blank body pain manikin, socio-demographic, health behaviour and morbidity questions. Participants shaded sites of pain lasting ≥1 day in the past 4 weeks on the manikin. OA consultation data were obtained for participants consenting to medical records review. Results. A total of 13 986 individuals (adjusted response 70.6%) completed a questionnaire, of which 12 408 provided complete pain data. The median NPS reported was 4 [interquartile range (IQR) 0–8]. General linear models showed that an increasing NPS was significantly associated with poorer MCS (β = −0.43, 95% CI −0.46, −0.40) and PCS (β = −0.87, 95% CI −0.90, −0.84). Adjustment for covariates attenuated the associations but they remained significant (MCS: β = −0.28, 95% CI −0.31, −0.24; PCS: β = −0.63, 95% CI −0.66, −0.59). The association between NPS and MCS or PCS was moderated by age, but the strongest associations were not in the oldest old. Conclusion. NPS appears to be a potentially modifiable target for improving physical and mental HRQoL in older people. Future analyses should investigate the influence of NPS on HRQoL over time in older people. PMID:24925881

  6. Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites

    NASA Astrophysics Data System (ADS)

    Pothof, F.; Bonini, L.; Lanzilotto, M.; Livi, A.; Fogassi, L.; Orban, G. A.; Paul, O.; Ruther, P.

    2016-08-01

    Objective. Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localisation using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. Approach. Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are integrated with a minimal feature size of 5 μm. The polyimide foils are rolled into the cylindrical probe shape at a diameter of 0.8 mm. The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. Main results. Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. Significance. With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localisation in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the

  7. Osteopontin Is Cleaved at Multiple Sites Close to Its Integrin-binding Motifs in Milk and Is a Novel Substrate for Plasmin and Cathepsin D*

    PubMed Central

    Christensen, Brian; Schack, Lotte; Kläning, Eva; Sørensen, Esben S.

    2010-01-01

    Osteopontin (OPN) is a highly modified integrin-binding protein present in most tissues and body fluids where it has been implicated in numerous biological processes. A significant regulation of OPN function is mediated through phosphorylation and proteolytic processing. Proteolytic cleavage by thrombin and matrix metalloproteinases close to the integrin-binding Arg-Gly-Asp sequence modulates the function of OPN and its integrin binding properties. In this study, seven N-terminal OPN fragments originating from proteolytic cleavage have been characterized from human milk. Identification of the cleavage sites revealed that all fragments contained the Arg–Gly–Asp145 sequence and were generated by cleavage of the Leu151–Arg152, Arg152–Ser153, Ser153–Lys154, Lys154–Ser155, Ser155–Lys156, Lys156–Lys157, or Phe158–Arg159 peptide bonds. Six cleavages cannot be ascribed to thrombin or matrix metalloproteinase activity, whereas the cleavage at Arg152–Ser153 matches thrombin specificity for OPN. The principal protease in milk, plasmin, hydrolyzed the same peptide bond as thrombin, but its main cleavage site was identified to be Lys154–Ser155. Another endogenous milk protease, cathepsin D, cleaved the Leu151–Arg152 bond. OPN fragments corresponding to plasmin activity were also identified in urine showing that plasmin cleavage of OPN is not restricted to milk. Plasmin, but not cathepsin D, cleavage of OPN increased cell adhesion mediated by the αVβ3- or α5β1-integrins. Similar cellular adhesion was mediated by plasmin and thrombin-cleaved OPN showing that plasmin can be a potent regulator of OPN activity. These data show that OPN is highly susceptible to cleavage near its integrin-binding motifs, and the protein is a novel substrate for plasmin and cathepsin D. PMID:20071328

  8. Modeling field-scale multiple tracer injection at a low-level waste disposal site in fractured rocks: effect of multiscale heterogeneity and source term uncertainty on conceptual understanding of mass transfer processes.

    PubMed

    Gwo, Jin-Ping; Jardine, Philip M; Sanford, William E

    2005-03-01

    Multiple factors may affect the scale-up of laboratory multi-tracer injection into structured porous media to the field. Under transient flow conditions and with multiscale heterogeneities in the field, previous attempts to scale-up laboratory experiments have not answered definitely the questions about the governing mechanisms and the spatial extent of the influence of small-scale mass transfer processes such as matrix diffusion. The objective of this research is to investigate the effects of multiscale heterogeneity, mechanistic and site model conceptualization, and source term density effect on elucidating and interpreting tracer movement in the field. Tracer release and monitoring information previously obtained in a field campaign of multiple, conservative tracer injection under natural hydraulic gradients at a low-level waste disposal site in eastern Tennessee, United States, is used for the research. A suite of two-pore-domain, or fracture-matrix, groundwater flow and transport models are calibrated and used to conduct model parameter and prediction uncertainty analyses. These efforts are facilitated by a novel nested Latin-hypercube sampling technique. Our results verify, at field scale, a multiple-pore-domain, multiscale mechanistic conceptual model that was used previously to interpret only laboratory observations. The results also suggest that, integrated over the entire field site, mass flux rates attributable to small-scale mass transfer are comparable to that of field-scale solute transport. The uncertainty analyses show that fracture spacing is the most important model parameter and model prediction uncertainty is relatively higher at the interface between the preferred flow path and its parent bedrock. The comparisons of site conceptual models indicate that the effect of matrix diffusion may be confined to the immediate neighborhood of the preferential flow path. Finally, because the relatively large amount of tracer needed for field studies, it is

  9. ALMA OBSERVATIONS OF A HIGH-DENSITY CORE IN TAURUS: DYNAMICAL GAS INTERACTION AT THE POSSIBLE SITE OF A MULTIPLE STAR FORMATION

    SciTech Connect

    Tokuda, Kazuki; Onishi, Toshikazu; Saigo, Kazuya; Kawamura, Akiko; Fukui, Yasuo; Inutsuka, Shu-ichiro; Tachihara, Kengo; Matsumoto, Tomoaki; Machida, Masahiro N.; Tomida, Kengo

    2014-07-01

    Starless dense cores eventually collapse dynamically, forming protostars inside them, and the physical properties of the cores determine the nature of the forming protostars. We report ALMA observations of dust continuum emission and molecular rotational lines toward MC27 or L1521F, which is considered to be very close to the first protostellar core phase. We found a few starless high-density cores, one of which has a very high density of ∼10{sup 7} cm{sup –3}, within a region of several hundred AU around a very low-luminosity protostar detected by Spitzer. A very compact bipolar outflow with a dynamical timescale of a few hundred years was found toward the protostar. The molecular line observation shows several cores with an arc-like structure, possibly due to the dynamical gas interaction. These complex structures revealed in the present observations suggest that the initial condition of star formation is highly dynamical in nature, which is considered to be a key factor in understanding fundamental issues of star formation such as the formation of multiple stars and the origin of the initial mass function of stars.

  10. Lys-63-linked Ubiquitination of γ-Aminobutyric Acid (GABA), Type B1, at Multiple Sites by the E3 Ligase Mind Bomb-2 Targets GABAB Receptors to Lysosomal Degradation*

    PubMed Central

    Zemoura, Khaled; Trümpler, Claudia; Benke, Dietmar

    2016-01-01

    GABAB receptors are heterodimeric G protein-coupled receptors, which control neuronal excitability by mediating prolonged inhibition. The magnitude of GABAB receptor-mediated inhibition essentially depends on the amount of receptors in the plasma membrane. However, the factors regulating cell surface expression of GABAB receptors are poorly characterized. Cell surface GABAB receptors are constitutively internalized and either recycled to the plasma membrane or degraded in lysosomes. The signal that sorts GABAB receptors to lysosomes is currently unknown. Here we show that Mind bomb-2 (MIB2)-mediated Lys-63-linked ubiquitination of the GABAB1 subunit at multiple sites is the lysosomal sorting signal for GABAB receptors. We found that inhibition of lysosomal activity in cultured rat cortical neurons increased the fraction of Lys-63-linked ubiquitinated GABAB receptors and enhanced the expression of total as well as cell surface GABAB receptors. Mutational inactivation of four putative ubiquitination sites in the GABAB1 subunit significantly diminished Lys-63-linked ubiquitination of GABAB receptors and prevented their lysosomal degradation. We identified MIB2 as the E3 ligase triggering Lys-63-linked ubiquitination and lysosomal degradation of GABAB receptors. Finally, we show that sustained activation of glutamate receptors, a condition occurring in brain ischemia that down-regulates GABAB receptors, considerably increased the expression of MIB2 and Lys-63-linked ubiquitination of GABAB receptors. Interfering with Lys-63-linked ubiquitination by overexpressing ubiquitin mutants or GABAB1 mutants deficient in Lys-63-linked ubiquitination prevented glutamate-induced down-regulation of the receptors. These findings indicate that Lys-63-linked ubiquitination of GABAB1 at multiple sites by MIB2 controls sorting of GABAB receptors to lysosomes for degradation under physiological and pathological conditions. PMID:27573246

  11. Dramatic Variability of the Carbonate System at a Temperate Coastal Ocean Site (Beaufort, North Carolina, USA) Is Regulated by Physical and Biogeochemical Processes on Multiple Timescales

    PubMed Central

    Johnson, Zackary I.; Wheeler, Benjamin J.; Blinebry, Sara K.; Carlson, Christina M.; Ward, Christopher S.; Hunt, Dana E.

    2013-01-01

    Increasing atmospheric carbon dioxide (CO2) from anthropogenic sources is acidifying marine environments resulting in potentially dramatic consequences for the physical, chemical and biological functioning of these ecosystems. If current trends continue, mean ocean pH is expected to decrease by ~0.2 units over the next ~50 years. Yet, there is also substantial temporal variability in pH and other carbon system parameters in the ocean resulting in regions that already experience change that exceeds long-term projected trends in pH. This points to short-term dynamics as an important layer of complexity on top of long-term trends. Thus, in order to predict future climate change impacts, there is a critical need to characterize the natural range and dynamics of the marine carbonate system and the mechanisms responsible for observed variability. Here, we present pH and dissolved inorganic carbon (DIC) at time intervals spanning 1 hour to >1 year from a dynamic, coastal, temperate marine system (Beaufort Inlet, Beaufort NC USA) to characterize the carbonate system at multiple time scales. Daily and seasonal variation of the carbonate system is largely driven by temperature, alkalinity and the balance between primary production and respiration, but high frequency change (hours to days) is further influenced by water mass movement (e.g. tides) and stochastic events (e.g. storms). Both annual (~0.3 units) and diurnal (~0.1 units) variability in coastal ocean acidity are similar in magnitude to 50 year projections of ocean acidity associated with increasing atmospheric CO2. The environmental variables driving these changes highlight the importance of characterizing the complete carbonate system rather than just pH. Short-term dynamics of ocean carbon parameters may already exert significant pressure on some coastal marine ecosystems with implications for ecology, biogeochemistry and evolution and this shorter term variability layers additive effects and complexity, including

  12. Site-resolved multiple-quantum filtered correlations and distance measurements by magic-angle spinning NMR: Theory and applications to spins with weak to vanishing quadrupolar couplings.

    PubMed

    Eliav, U; Haimovich, A; Goldbourt, A

    2016-01-14

    We discuss and analyze four magic-angle spinning solid-state NMR methods that can be used to measure internuclear distances and to obtain correlation spectra between a spin I = 1/2 and a half-integer spin S > 1/2 having a small quadrupolar coupling constant. Three of the methods are based on the heteronuclear multiple-quantum and single-quantum correlation experiments, that is, high rank tensors that involve the half spin and the quadrupolar spin are generated. Here, both zero and single-quantum coherence of the half spins are allowed and various coherence orders of the quadrupolar spin are generated, and filtered, via active recoupling of the dipolar interaction. As a result of generating coherence orders larger than one, the spectral resolution for the quadrupolar nucleus increases linearly with the coherence order. Since the formation of high rank tensors is independent of the existence of a finite quadrupolar interaction, these experiments are also suitable to materials in which there is high symmetry around the quadrupolar spin. A fourth experiment is based on the initial quadrupolar-driven excitation of symmetric high order coherences (up to p = 2S, where S is the spin number) and subsequently generating by the heteronuclear dipolar interaction higher rank (l + 1 or higher) tensors that involve also the half spins. Due to the nature of this technique, it also provides information on the relative orientations of the quadrupolar and dipolar interaction tensors. For the ideal case in which the pulses are sufficiently strong with respect to other interactions, we derive analytical expressions for all experiments as well as for the transferred echo double resonance experiment involving a quadrupolar spin. We show by comparison of the fitting of simulations and the analytical expressions to experimental data that the analytical expressions are sufficiently accurate to provide experimental (7)Li-(13)C distances in a complex of lithium, glycine, and water. Discussion

  13. Dramatic variability of the carbonate system at a temperate coastal ocean site (Beaufort, North Carolina, USA) is regulated by physical and biogeochemical processes on multiple timescales.

    PubMed

    Johnson, Zackary I; Wheeler, Benjamin J; Blinebry, Sara K; Carlson, Christina M; Ward, Christopher S; Hunt, Dana E

    2013-01-01

    Increasing atmospheric carbon dioxide (CO2) from anthropogenic sources is acidifying marine environments resulting in potentially dramatic consequences for the physical, chemical and biological functioning of these ecosystems. If current trends continue, mean ocean pH is expected to decrease by ~0.2 units over the next ~50 years. Yet, there is also substantial temporal variability in pH and other carbon system parameters in the ocean resulting in regions that already experience change that exceeds long-term projected trends in pH. This points to short-term dynamics as an important layer of complexity on top of long-term trends. Thus, in order to predict future climate change impacts, there is a critical need to characterize the natural range and dynamics of the marine carbonate system and the mechanisms responsible for observed variability. Here, we present pH and dissolved inorganic carbon (DIC) at time intervals spanning 1 hour to >1 year from a dynamic, coastal, temperate marine system (Beaufort Inlet, Beaufort NC USA) to characterize the carbonate system at multiple time scales. Daily and seasonal variation of the carbonate system is largely driven by temperature, alkalinity and the balance between primary production and respiration, but high frequency change (hours to days) is further influenced by water mass movement (e.g. tides) and stochastic events (e.g. storms). Both annual (~0.3 units) and diurnal (~0.1 units) variability in coastal ocean acidity are similar in magnitude to 50 year projections of ocean acidity associated with increasing atmospheric CO2. The environmental variables driving these changes highlight the importance of characterizing the complete carbonate system rather than just pH. Short-term dynamics of ocean carbon parameters may already exert significant pressure on some coastal marine ecosystems with implications for ecology, biogeochemistry and evolution and this shorter term variability layers additive effects and complexity, including

  14. How multiple episodes of exclusive breastfeeding impact estimates of exclusive breastfeeding duration: report from the eight-site MAL-ED birth cohort study.

    PubMed

    Ambikapathi, Ramya; Kosek, Margaret N; Lee, Gwenyth O; Mahopo, Cloupas; Patil, Crystal L; Maciel, Bruna L; Turab, Ali; Islam, M Munirul; Ulak, Manjeswori; Bose, Anuradha; Paredes Olortegui, Maribel; Pendergast, Laura L; Murray-Kolb, Laura E; Lang, Dennis; McCormick, Benjamin J J; Caulfield, Laura E

    2016-10-01

    The duration of exclusive breastfeeding (EBF) is often defined as the time from birth to the first non-breast milk food/liquid fed (EBFLONG), or it is estimated by calculating the proportion of women at a given infant age who EBF in the previous 24 h (EBFDHS). Others have measured the total days or personal prevalence of EBF (EBFPREV), recognizing that although non-EBF days may occur, EBF can be re-initiated for extended periods. We compared breastfeeding metrics in the MAL-ED study; infants' breastfeeding trajectories were characterized from enrollment (median 7 days, IQR: 4, 12) to 180 days at eight sites. During twice-weekly surveillance, caretakers were queried about infant feeding the prior day. Overall, 101 833 visits and 356 764 child days of data were collected from 1957 infants. Median duration of EBFLONG was 33 days (95% CI: 32-36), compared to 49 days based on the EBFDHS. Median EBFPREV was 66 days (95% CI: 62-70). Differences were because of the return to EBF after a non-EBF period. The median number of returns to EBF was 2 (IQR: 1, 3). When mothers re-initiated EBF (second episode), infants gained an additional 18.8 days (SD: 25.1) of EBF, and gained 13.7 days (SD: 18.1) (third episode). In settings where women report short gaps in EBF, programmes should work with women to return to EBF. Interventions could positively influence the duration of these additional periods of EBF and their quantification should be considered in impact evaluation studies. © 2016 John Wiley & Sons Ltd.

  15. Optimal Siting and Sizing of Multiple DG Units for the Enhancement of Voltage Profile and Loss Minimization in Transmission Systems Using Nature Inspired Algorithms.

    PubMed

    Ramamoorthy, Ambika; Ramachandran, Rajeswari

    2016-01-01

    Power grid becomes smarter nowadays along with technological development. The benefits of smart grid can be enhanced through the integration of renewable energy sources. In this paper, several studies have been made to reconfigure a conventional network into a smart grid. Amongst all the renewable sources, solar power takes the prominent position due to its availability in abundance. Proposed methodology presented in this paper is aimed at minimizing network power losses and at improving the voltage stability within the frame work of system operation and security constraints in a transmission system. Locations and capacities of DGs have a significant impact on the system losses in a transmission system. In this paper, combined nature inspired algorithms are presented for optimal location and sizing of DGs. This paper proposes a two-step optimization technique in order to integrate DG. In a first step, the best size of DG is determined through PSO metaheuristics and the results obtained through PSO is tested for reverse power flow by negative load approach to find possible bus locations. Then, optimal location is found by Loss Sensitivity Factor (LSF) and weak (WK) bus methods and the results are compared. In a second step, optimal sizing of DGs is determined by PSO, GSA, and hybrid PSOGSA algorithms. Apart from optimal sizing and siting of DGs, different scenarios with number of DGs (3, 4, and 5) and PQ capacities of DGs (P alone, Q alone, and P and Q both) are also analyzed and the results are analyzed in this paper. A detailed performance analysis is carried out on IEEE 30-bus system to demonstrate the effectiveness of the proposed methodology. PMID:27057557

  16. The central distribution of a corticotropin-releasing factor (CRF)-binding protein predicts multiple sites and modes of interaction with CRF.

    PubMed Central

    Potter, E; Behan, D P; Linton, E A; Lowry, P J; Sawchenko, P E; Vale, W W

    1992-01-01

    In recent studies to clone and characterize genes coding for the corticotropin-releasing factor-binding protein (CRF-BP), analysis of the tissue distribution of the CRF-BP gene indicated a high level of expression in the rat brain. We have now characterized by immunohistochemical and hybridization histochemical means the cellular localization of CRF-BP protein and mRNA expression, respectively. Results from both approaches converged to indicate that CRF-BP is expressed predominantly in the cerebral cortex, including all major archi-, paleo-, and neocortical fields. Other prominent sites of mRNA and protein expression include subcortical limbic system structures (amygdala, bed nucleus of the stria terminalis), sensory relays associated with the auditory, olfactory, vestibular, and trigeminal systems, severe raphe nuclei, and a number of cell groups in the brainstem reticular core. Expression in the hypothalamus appears largely limited to the ventral premammillary and dorsomedial nuclei; only isolated CRF-BP-stained cells are apparent in neurosecretory cell groups. Dual immunostaining for CRF and CRF-BP revealed a partial colocalization in some of these regions. In addition, prominent CRF-BP-stained terminal fields have been identified in association with CRF-expressing cell groups in circumscribed hypothalamic and limbic structures. In the anterior pituitary, CRF-BP mRNA and immunoreactivity were colocalized with corticotropin-immunoreactivity in a majority of corticotropes. Thus, CRF-BP could serve to modify the actions of CRF by intra- and intercellular mechanisms, in CRF-related pathways in the central nervous system and pituitary. Images PMID:1315056

  17. Optimal Siting and Sizing of Multiple DG Units for the Enhancement of Voltage Profile and Loss Minimization in Transmission Systems Using Nature Inspired Algorithms.

    PubMed

    Ramamoorthy, Ambika; Ramachandran, Rajeswari

    2016-01-01

    Power grid becomes smarter nowadays along with technological development. The benefits of smart grid can be enhanced through the integration of renewable energy sources. In this paper, several studies have been made to reconfigure a conventional network into a smart grid. Amongst all the renewable sources, solar power takes the prominent position due to its availability in abundance. Proposed methodology presented in this paper is aimed at minimizing network power losses and at improving the voltage stability within the frame work of system operation and security constraints in a transmission system. Locations and capacities of DGs have a significant impact on the system losses in a transmission system. In this paper, combined nature inspired algorithms are presented for optimal location and sizing of DGs. This paper proposes a two-step optimization technique in order to integrate DG. In a first step, the best size of DG is determined through PSO metaheuristics and the results obtained through PSO is tested for reverse power flow by negative load approach to find possible bus locations. Then, optimal location is found by Loss Sensitivity Factor (LSF) and weak (WK) bus methods and the results are compared. In a second step, optimal sizing of DGs is determined by PSO, GSA, and hybrid PSOGSA algorithms. Apart from optimal sizing and siting of DGs, different scenarios with number of DGs (3, 4, and 5) and PQ capacities of DGs (P alone, Q alone, and P and Q both) are also analyzed and the results are analyzed in this paper. A detailed performance analysis is carried out on IEEE 30-bus system to demonstrate the effectiveness of the proposed methodology.

  18. Optimal Siting and Sizing of Multiple DG Units for the Enhancement of Voltage Profile and Loss Minimization in Transmission Systems Using Nature Inspired Algorithms

    PubMed Central

    Ramamoorthy, Ambika; Ramachandran, Rajeswari

    2016-01-01

    Power grid becomes smarter nowadays along with technological development. The benefits of smart grid can be enhanced through the integration of renewable energy sources. In this paper, several studies have been made to reconfigure a conventional network into a smart grid. Amongst all the renewable sources, solar power takes the prominent position due to its availability in abundance. Proposed methodology presented in this paper is aimed at minimizing network power losses and at improving the voltage stability within the frame work of system operation and security constraints in a transmission system. Locations and capacities of DGs have a significant impact on the system losses in a transmission system. In this paper, combined nature inspired algorithms are presented for optimal location and sizing of DGs. This paper proposes a two-step optimization technique in order to integrate DG. In a first step, the best size of DG is determined through PSO metaheuristics and the results obtained through PSO is tested for reverse power flow by negative load approach to find possible bus locations. Then, optimal location is found by Loss Sensitivity Factor (LSF) and weak (WK) bus methods and the results are compared. In a second step, optimal sizing of DGs is determined by PSO, GSA, and hybrid PSOGSA algorithms. Apart from optimal sizing and siting of DGs, different scenarios with number of DGs (3, 4, and 5) and PQ capacities of DGs (P alone, Q alone, and  P and Q both) are also analyzed and the results are analyzed in this paper. A detailed performance analysis is carried out on IEEE 30-bus system to demonstrate the effectiveness of the proposed methodology. PMID:27057557

  19. How multiple episodes of exclusive breastfeeding impact estimates of exclusive breastfeeding duration: report from the eight-site MAL-ED birth cohort study.

    PubMed

    Ambikapathi, Ramya; Kosek, Margaret N; Lee, Gwenyth O; Mahopo, Cloupas; Patil, Crystal L; Maciel, Bruna L; Turab, Ali; Islam, M Munirul; Ulak, Manjeswori; Bose, Anuradha; Paredes Olortegui, Maribel; Pendergast, Laura L; Murray-Kolb, Laura E; Lang, Dennis; McCormick, Benjamin J J; Caulfield, Laura E

    2016-10-01

    The duration of exclusive breastfeeding (EBF) is often defined as the time from birth to the first non-breast milk food/liquid fed (EBFLONG), or it is estimated by calculating the proportion of women at a given infant age who EBF in the previous 24 h (EBFDHS). Others have measured the total days or personal prevalence of EBF (EBFPREV), recognizing that although non-EBF days may occur, EBF can be re-initiated for extended periods. We compared breastfeeding metrics in the MAL-ED study; infants' breastfeeding trajectories were characterized from enrollment (median 7 days, IQR: 4, 12) to 180 days at eight sites. During twice-weekly surveillance, caretakers were queried about infant feeding the prior day. Overall, 101 833 visits and 356 764 child days of data were collected from 1957 infants. Median duration of EBFLONG was 33 days (95% CI: 32-36), compared to 49 days based on the EBFDHS. Median EBFPREV was 66 days (95% CI: 62-70). Differences were because of the return to EBF after a non-EBF period. The median number of returns to EBF was 2 (IQR: 1, 3). When mothers re-initiated EBF (second episode), infants gained an additional 18.8 days (SD: 25.1) of EBF, and gained 13.7 days (SD: 18.1) (third episode). In settings where women report short gaps in EBF, programmes should work with women to return to EBF. Interventions could positively influence the duration of these additional periods of EBF and their quantification should be considered in impact evaluation studies. © 2016 John Wiley & Sons Ltd. PMID:27500709

  20. ALMA Observations of a High-density Core in Taurus: Dynamical Gas Interaction at the Possible Site of a Multiple Star Formation

    NASA Astrophysics Data System (ADS)

    Tokuda, Kazuki; Onishi, Toshikazu; Saigo, Kazuya; Kawamura, Akiko; Fukui, Yasuo; Matsumoto, Tomoaki; Inutsuka, Shu-ichiro; Machida, Masahiro N.; Tomida, Kengo; Tachihara, Kengo

    2015-08-01

    It is crucially important to observe dense cores in order to investigate the initial condition of star formation since protostars are formed via dynamical collapse of dense cores, inhering the physical properties from their natal dense cores. Here we present the results of ALMA Cycle 0 and Cycle 1 observations of dust continuum emission and molecular rotational lines toward a dense core, MC27 (aka L1521F), which is considered to be very close to the first protostellar core phase.The Cycle 0 observations revealed complex structures at the center. We found a few starless high-density cores, one of which (MMS2) has a very high density of ~107 cm-3, around the very low-luminousity protostar detected by Spitzer. A very compact bipolar outflow with a dynamical timescale of a few hundred years was found toward the protostar. The HCO+ (3-2) observation shows several cores associated with an arc-like structure whose length is ~2000 AU, possibly due to the dynamical gas interaction. These complex structures suggest that the initial condition of star formation is highly dynamical in nature, which is considered to be a key factor in understanding fundamental issues of star formation such as origins of the stellar multiplicity and the initial mass function. These initial Cycle 0 results were published by Tokuda et al. (2014). Matsumoto et al. (2015) investigated the arc-like structures by performing numerical simulations.Detailed column density distribution with the size from ~100 to ~10000 AU scale are revealed by combining the 12m array data with the 7m array data of the ALMA Compact Array as well as with the single dish MAMBO data. Our preliminary analysis shows that the averaged radial column density distribution of the inner part (r < 2000 AU) is N(H2)~r-0.4, clearly flatter than that of the outer part, ~r-1.3. We detected the above-mentioned complex structure inside the inner flatter region, which may reflect the dynamical status of the dense core. The Cycle 1

  1. Natural-abundance 15N NMR studies of Turkey ovomucoid third domain. Assignment of peptide 15N resonances to the residues at the reactive site region via proton-detected multiple-quantum coherence

    NASA Astrophysics Data System (ADS)

    Ortiz-Polo, Gilberto; Krishnamoorthi, R.; Markley, John L.; Live, David H.; Davis, Donald G.; Cowburn, David

    Heteronuclear two-dimensional 1H{ 15N} multiple-quantum (MQ) spectroscopy has been applied to a protein sample at natural abundance: ovomucoid third domain from turkey ( Meleagris gallopavo), a serine proteinase inhibitor of 56 amino acid residues. Peptide amide 1H NMR assignments obtained by two-dimensional 1H{ 1H} NMR methods (R. Krishnamoorthi and J. L. Markley, unpublished data) led to identification of the corresponding 1H{ 15N} MQ coherence cross peaks. From these, 15N NMR chemical shifts were determined for several specific backbone amide groups of amino acid residues located around the reactive site region of the inhibitor. The results suggest that amide 15N chemical shifts, which are readily obtained in this way, may serve as sensitive probes for conformational studies of proteins.

  2. Analysis of Hydraulic Responses from the ER-6-1 Multiple-Well Aquifer Test, Yucca Flat FY 2004 Testing Program, Nevada Test Site, Nye County, Nevada, Rev. No.: 0

    SciTech Connect

    Greg Ruskauff

    2005-06-01

    This report documents the interpretation and analysis of the hydraulic data collected for the Fiscal Year (FY) 2004 Multiple-Well Aquifer Test-Tracer Test (MWAT-TT) conducted at the ER-6-1 Well Cluster in Yucca Flat Corrective Action Unit (CAU) 97, on the Nevada Test Site (NTS). The MWAT-TT was performed to investigate CAU-scale groundwater flow and transport processes related to the transport of radionuclides from sources on the NTS through the Lower Carbonate Aquifer (LCA) Hydrostratigraphic Unit (HSU). The ER-6-1 MWAT-TT was planned and executed by contractor participants for the Underground Test Area (UGTA) Project of the Environmental Restoration (ER) program of the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO). Participants included Stoller-Navarro Joint Venture (SNJV), the Environmental Engineering Services Contractor; Bechtel Nevada (BN); the Desert Research Institute (DRI); Los Alamos National Laboratory; and the University of Nevada, Las Vegas-Harry Reid Center. The SNJV team consists of the S.M. Stoller Corporation, Navarro Research and Engineering, Battelle Memorial Institute, INTERA Inc., and Weston Solutions, Inc. The MWAT-TT was implemented according to the ''Underground Test Area Project, ER-6-1 Multi-Well Aquifer Test - Tracer Test Plan'' (SNJV, 2004a) issued in April 2004. The objective of the aquifer test was to determine flow processes and local hydraulic properties for the LCA through long-term constant-rate pumping at the well cluster. This objective was to be achieved in conjunction with detailed sampling of the composite tracer breakthrough at the pumping well, as well as with depth-specific sampling and logging at multiple wells, to provide information for the depth-discrete analysis of formation hydraulic properties, particularly with regard to fracture properties.

  3. An integrated map correlation method and multiple-source sites drainage-area ratio method for estimating streamflows at ungauged catchments: A case study of the Western Black Sea Region, Turkey.

    PubMed

    Ergen, Kayra; Kentel, Elcin

    2016-01-15

    Stream gauges measure the temporal variation of water quantity; thus they are vital in managing water resources. The stream gauge network in Turkey includes a limited number of gauges and often streamflow estimates need to be generated at ungauged locations where reservoirs, small hydropower plants, weirs, etc. are planned. Prediction of streamflows at ungauged locations generally relies on donor gauges where flow is assumed to be similar to that at the ungauged location. Generally, donor stream gauges are selected based on geographical proximity. However, closer stream gauges are not always the most-correlated ones. The Map Correlation Method (MCM) enables development of a map that shows the spatial distribution of the correlation between a selected stream gauge and any other location within the study region. In this study, a new approach which combines MCM with the multiple-source site drainage-area ratio (DAR) method is used to estimate daily streamflows at ungauged catchments in the Western Black Sea Region. Daily streamflows predicted by the combined three-source sites DAR with MCM approach give higher Nash-Sutcliffe Efficiency (NSE) values than those predicted using the nearest stream gauge as the donor stream gauge, for most of the trial cases. Hydrographs and flow duration curves predicted using this approach are usually in better agreement with the observed hydrographs and flow duration curves than those predicted using the nearest catchment. PMID:26520038

  4. Multiple Pregnancy

    MedlinePlus

    ... is called multiple pregnancy . If more than one egg is released during the menstrual cycle and each ... fraternal twins (or more). When a single fertilized egg splits, it results in multiple identical embryos. This ...

  5. Multiple myeloma

    MedlinePlus

    Plasma cell dyscrasia; Plasma cell myeloma; Malignant plasmacytoma; Plasmacytoma of bone; Myeloma - multiple ... Multiple myeloma most commonly causes: Low red blood cell count ( anemia ), which can lead to fatigue and ...

  6. Multiple Sclerosis

    MedlinePlus

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the ... attacks healthy cells in your body by mistake. Multiple sclerosis affects women more than men. It often begins ...

  7. Finger Multiplication

    ERIC Educational Resources Information Center

    Simanihuruk, Mudin

    2011-01-01

    Multiplication facts are difficult to teach. Therefore many researchers have put a great deal of effort into finding multiplication strategies. Sherin and Fuson (2005) provided a good survey paper on the multiplication strategies research area. Kolpas (2002), Rendtorff (1908), Dabell (2001), Musser (1966) and Markarian (2009) proposed the finger…

  8. Multiple Sclerosis

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Multiple Sclerosis Information Page Condensed from Multiple Sclerosis: Hope Through ... en Español Additional resources from MedlinePlus What is Multiple Sclerosis? An unpredictable disease of the central nervous system, ...

  9. Tumor-promoting function of single nucleotide polymorphism rs1836724 (C3388T) alters multiple potential legitimate microRNA binding sites at the 3'-untranslated region of ErbB4 in breast cancer.

    PubMed

    Bagheri, Fatemeh; Mesrian Tanha, Hamzeh; Mojtabavi Naeini, Marjan; Ghaedi, Kamran; Azadeh, Mansoureh

    2016-05-01

    ErbB4 can act as either a tumor-suppressor gene or an oncogene in breast cancer. Multiple genetic factors including single nucleotide polymorphisms (SNPs) affect gene expression patterns. Multiple 3'-untranslated region (3'-UTR) SNPs reside within the target binding site of microRNAs, which can strengthen or weaken binding to target genes. The present study aimed to predict potential 3'‑UTR variants of ErbB4 that alter the target binding site of microRNAs (miRNAs) and to clarify the association of the potential variant with the risk of developing breast cancer. In silico prediction was performed to identify potential functional SNPs within miRNA target binding sites in the 3'‑UTR of ErbB4. Thus, 146 patients and controls were genotyped using restriction fragment length polymorphism-polymerase chain reaction. In addition to the Cochran-Armitage test for trend, allele and genotype frequency differences were determined to investigate the association between rs1836724 and the susceptibility to breast cancer. Bioinformatics analysis identified rs1836724 to be a polymorphism in the seed region of four miRNA binding sites (hsa-miR335-5p, hsa-miR-28-5p, has‑miR‑708‑5p and has‑miR‑665), which may participate in the development of breast cancer. Logistic regression data indicated that the T allele of the polymorphism [OR (95% CI)=1.72 (1.056‑2.808), P=0.029] is associated with the risk of breast cancer. Using bioinformatics tools, a correlation was indicated between the presence of the T allele and a reduction in ErbB4 RNA silencing based on miRNA interaction. Furthermore, case subgroup data analysis revealed an association between the C/T genotype and an ER positive phenotype [OR (95% CI)=6.00 (1.082‑33.274), P=0.028] compared with the T/T genotype. ErbB4 and estrogen receptor 1 (ESR1) are regulated by identical miRNAs thus there may be a competition for binding sites. Due to this pattern, if the interaction between miRNAs with one gene is reduced, it

  10. Multiplicity Counting

    SciTech Connect

    Geist, William H.

    2015-12-01

    This set of slides begins by giving background and a review of neutron counting; three attributes of a verification item are discussed: 240Pueff mass; α, the ratio of (α,n) neutrons to spontaneous fission neutrons; and leakage multiplication. It then takes up neutron detector systems – theory & concepts (coincidence counting, moderation, die-away time); detector systems – some important details (deadtime, corrections); introduction to multiplicity counting; multiplicity electronics and example distributions; singles, doubles, and triples from measured multiplicity distributions; and the point model: multiplicity mathematics.

  11. Construction, water-level, and water-quality data for multiple-well monitoring sites and test wells, Fort Irwin National Training Center, San Bernardino County, California, 2009-12

    USGS Publications Warehouse

    Kjos, Adam R.; Densmore, Jill N.; Nawikas, Joseph M.; Brown, Anthony A.

    2014-01-01

    Because of increasing water demands at the U.S. Army Fort Irwin National Training Center, the U.S. Geological Survey in cooperation with the U.S. Army carried out a study to evaluate the water quality and potential groundwater supply of undeveloped basins within the U.S. Army Fort Irwin National Training Center. In addition, work was performed in the three developed basins—Langford, Bicycle, and Irwin—proximal to or underlying cantonment to provide information in support of water-resources management and to supplement monitoring in these basins. Between 2009 and 2012, the U.S. Geological Survey installed 41 wells to expand collection of water-resource data within the U.S. Army Fort Irwin National Training Center. Thirty-four monitoring wells (2-inch diameter) were constructed at 14 single- or multiple-well monitoring sites and 7 test wells (8-inch diameter) were installed. The majority of the wells were installed in previously undeveloped or minimally developed basins (Cronise, Red Pass, the Central Corridor area, Superior, Goldstone, and Nelson Basins) proximal to cantonment (primary base housing and infrastructure). Data associated with well construction, water-level monitoring, and water-quality sampling are presented in this report.

  12. Representing Multiplication

    ERIC Educational Resources Information Center

    Harries, Tony; Barmby, Patrick

    2008-01-01

    In this study, the authors wish to explore the use of visual representations in facilitating the understanding of multiplication. In doing so, they examine the different aspects of multiplication that they can access through different representations. In addition, they draw on a study that they have been carrying out looking at pupils' actual use…

  13. Multiple homicides.

    PubMed

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  14. Multiple granular cell tumor.

    PubMed

    Jones, J K; Kuo, T T; Griffiths, C M; Itharat, S

    1980-10-01

    Eleven cases of granular cell tumor were reviewed. In two of the cases multiple sites of involvement were seen. The tumor occurred in the oral cavity in both of these cases and each was initially wrongly diagnosed as squamous cell carcinoma. The most common site was the subcutaneous tissue (nine patients) and the tongue was involved in three cases. In one patient the parotid gland was involved. Eight of the patients were females and three were males; seven were black and four were white. The importance of differentiating between squamous cell carcinoma and granular cell tumor is stressed, as is the need for a simple wide surgical excision. PMID:7421377

  15. Parenting Multiples

    MedlinePlus

    ... first words, or potty training. If one child lags in a developmental area, consult your doctor to ... site. Note: All information on KidsHealth® is for educational purposes only. For specific medical advice, diagnoses, and ...

  16. Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  17. Phosphorylation of Simian Cytomegalovirus Assembly Protein Precursor (pAPNG.5) and Proteinase Precursor (pAPNG1): Multiple Attachment Sites Identified, Including Two Adjacent Serines in a Casein Kinase II Consensus Sequence

    PubMed Central

    Plafker, Scott M.; Woods, Amina S.; Gibson, Wade

    1999-01-01

    The assembly protein precursor (pAP) of cytomegalovirus (CMV), and its homologs in other herpesviruses, functions at several key steps during the process of capsid formation. This protein, and the genetically related maturational proteinase, is distinguished from the other capsid proteins by posttranslational modifications, including phosphorylation. The objective of this study was to identify sites at which pAP is phosphorylated so that the functional significance of this modification and the enzyme(s) responsible for it can be determined. In the work reported here, we used peptide mapping, mass spectrometry, and site-directed mutagenesis to identify two sets of pAP phosphorylation sites. One is a casein kinase II (CKII) consensus sequence that contains two adjacent serines, both of which are phosphorylated. The other site(s) is in a different domain of the protein, is phosphorylated less frequently than the CKII site, does not require preceding CKII-site phosphorylation, and causes an electrophoretic mobility shift when phosphorylated. Transfection/expression assays for proteolytic activity showed no gross effect of CKII-site phosphorylation on the enzymatic activity of the proteinase or on the substrate behavior of pAP. Evidence is presented that both the CKII sites and the secondary sites are phosphorylated in virus-infected cells and plasmid-transfected cells, indicating that these modifications can be made by a cellular enzyme(s). Apparent compartmental differences in phosphorylation of the CKII-site (cytoplasmic) and secondary-site (nuclear) serines suggest the involvement of more that one enzyme in these modifications. PMID:10516011

  18. Myeloma (multiple)

    PubMed Central

    2006-01-01

    Introduction Multiple myeloma is the most common primary cancer of the bones in adults, representing about 1% of all cancers diagnosed in the US in 2004, and 14% of all haematological malignancies. In the UK, multiple myeloma accounts for 1% of all new cases of cancer diagnosed each year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment in people with asymptomatic early stage multiple myeloma (stage I)? What are the effects of first-line treatments in people with advanced stage multiple myeloma (stages II and III)? What are the effect of salvage treatments, or supportive therapy, in people with advanced stage multiple myeloma (stages II and III)? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2004 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: allogenic transplant (non-myeloablative), autologous stem cell transplant (early or late transplantation, double or single, purging of), bisphosphonates, bone marrow stem cells, bortezomib, chemotherapy (combination, conventional dose, intermediate dose plus stem cell rescue, high-dose plus stem cell rescue), combination chemotherapy plus corticosteroids, deferred treatment (in stage I disease), early chemotherapy plus corticosteroids (in stage I disease), epoetin alpha, first-line treatments, infection prophylaxis, interferon, maintenance therapy (in advanced multiple myeloma), melphalan (normal dose

  19. Smart card multiple function badge

    SciTech Connect

    Nelson, R.A.

    1993-06-01

    Smart cards are credit card-sized computers with integrated data storage, an operating system to manage the data, and built-in security features that protect the data. They are used to distribute information to remote sites, providing the same or greater reliability, data integrity, and information security than a network system. However, smart cards may provide greater functionality at a lower cost than network systems. The US Department of Energy Hanford Site is developing the smart card to be used as a multiple function identification badge that will service various data management requirements on the Site. This paper discusses smart card technology and the proposed Hanford Site applications.

  20. Geospatial optimization of siting large-scale solar projects

    USGS Publications Warehouse

    Macknick, Jordan; Quinby, Ted; Caulfield, Emmet; Gerritsen, Margot; Diffendorfer, James E.; Haines, Seth S.

    2014-01-01

    guidelines by being user-driven, transparent, interactive, capable of incorporating multiple criteria, and flexible. This work provides the foundation for a dynamic siting assistance tool that can greatly facilitate siting decisions among multiple stakeholders.

  1. Multiple Sclerosis

    PubMed Central

    2013-01-01

    Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system. Common manifestations include paresthesias, diplopia, loss of vision, numbness or weakness of the limbs, bowel or bladder dysfunction, spasticity, ataxia, fatigue, and mental changes. Four main patterns of MS are recognized: relapsing remitting, primary progressive, secondary progressive, and progressive relapsing. The cause of MS is unknown, although it appears to be an autoimmune disease. Much of what is known about MS has been learned from an animal model of the disease, experimental allergic encephalomyelitis. PMID:24381825

  2. Multiple Sclerosis.

    PubMed

    Schiess, Nicoline; Calabresi, Peter A

    2016-08-01

    It is estimated that there are 300,000 people with multiple sclerosis (MS) in the United States and 2.3 million worldwide. Each MS attack can affect function in cognitive, emotional, motoric, sensory, or visual domains. Patients are often struck in the prime of their lives as they attempt to move forward with career, and family. Since the previous 2010 Seminars in Neurology Pearls and Pitfalls issue, the world of MS has drastically changed and advanced. Here the authors address the ever-changing MS world in both treatment options and diagnostics, covering easily missed differential diagnoses, newly available immunomodulatory therapy, and the challenges of safely treating patients. PMID:27643903

  3. Multiple myeloma

    PubMed Central

    Rajkumar, S. Vincent

    2008-01-01

    Multiple myeloma is a clonal plasma cell malignancy that accounts for slightly more than 10% of all hematologic cancers. In this paper, we present a historically focused review of the disease, from the description of the first case in 1844 to the present. The evolution of drug therapy and stem-cell transplantation for the treatment of myeloma, as well as the development of new agents, is discussed. We also provide an update on current concepts of diagnosis and therapy, with an emphasis on how treatments have emerged from a historical perspective after certain important discoveries and the results of experimental studies. PMID:18332230

  4. [Multiple myeloma].

    PubMed

    Abe, Masahiro; Miki, Hirokazu; Nakamura, Shingen

    2016-03-01

    Owing to the positive clinical benefits obtained with new agents, complete remission (CR) can be used as a surrogate for overall survival, and should be achieved. Although multiple myeloma is a heterogeneous disease in terms of myeloma cell- and patient-related risk factors, patients should receive the most effective combination therapy based on proteasome inhibitors and/or immunomodulatory drugs (IMiDs) as backbone medication irrespective of the risks encountered in the setting of induction therapy ("one-size-fits-all" therapy), followed by consolidation/maintenance therapy to achieve CR with the ultimate goal of extended survival. Myeloma-defining biomarkers have been established to identify high-risk smoldering myeloma requiring treatment. The development of salvage treatments yielding better outcomes for relapsed/refractory myeloma is urgently needed. Upcoming novel molecular targeting agents with different modes of action and immunotherapeutic agents will be integrated into myeloma treatment regimens with a great therapeutic impact, and further evolution of the treatment paradigm for multiple myeloma is eagerly anticipated. PMID:27076236

  5. Sources and temporal variations of constrained PMF factors obtained from multiple-year receptor modeling of ambient PM2.5 data from five speciation sites in Ontario, Canada

    NASA Astrophysics Data System (ADS)

    Sofowote, Uwayemi M.; Su, Yushan; Dabek-Zlotorzynska, Ewa; Rastogi, Ankit K.; Brook, Jeff; Hopke, Philip K.

    2015-05-01

    The Canadian National Air Pollution Surveillance (NAPS) network operates five fine particulate matter (PM2.5) speciation sites in Ontario. Data from 2005 to 2010 from these sites were subjected to constrained positive matrix factorization (PMF) to obtain factors of particulate matter pollution. Eight factors were found to be common across the sites. These constrained factors were particulate sulfate and nitrate, aged combustion aerosols, biomass/wood combustion, non-ferrous metal smelting, crustal matter, steel works, and road salt. Other factors found at these sites were largely related to local sources in their respective neighbourhoods. Diagnostic results from constraining the PMF factors could be used to select the appropriate post-PMF analyses as they reveal the factors that were expected to have regional or local sources. Interpretation of the spatial trends of factors was guided by the extent of similarity of target ratios across the five sites as determined by their coefficient of variation (C.V.). On average, particulate sulfate had PM2.5 mass contributions that ranged from 7% (Wallaceburg) to 36% (Simcoe) and nitrate species ranged from 7% (Simcoe) to 23% (Windsor). A clear low rural - high urban divide for particulate nitrate was also observed. These non-uniform impacts across the sites indicate that a single representative location is not suitable for studying PM2.5 in Ontario. Temporal variations showed greater abundance of particulate sulfate in the summer and particulate nitrate in the winter respectively. Yearly median values of the sulfate factor that is largely energy-related have been declining for most sites since peaking in 2007. A trajectory ensemble model, simplified quantitative transport bias analysis (sQTBA) was used to identify potential source regions of the constrained sulfate and nitrate factors while radial plots of the conditional probability function (CPF) were used to explore the more locally-sourced factors. The US Midwest, east

  6. [Multiple apheresis].

    PubMed

    Coffe, C

    2007-05-01

    Multiple apheresis makes it possible to obtain at least two labile blood components from a single donor using a cell separator. It can be either multicomponent apheresis leading to the preparation of at least two different blood component types or red blood cell apheresis providing two identical red blood cell concentrates. These techniques available in addition to whole blood donation, are modifying collection strategies in many Etablissements Français du Sang and will contribute to improve stock logistics in the future. In areas with insufficient stock, these procedures will help achieve blood component self-sufficiency. The author first describes the principle underlying different--current or future--techniques as well as their advantages and drawbacks. He finally addresses the potential impact of these processes on the evolution of blood collection and the advantages to be gained. PMID:17521944

  7. Multiple bleeds in haemophilia A.

    PubMed

    Aronstam, A; Painter, M J; Eddey, J V

    1979-01-01

    One hundred and eighty-one bleeding episodes involving two sites simultaneously were noted during a survey of 4935 bleeding episodes, an incidence of 3.7%. Elbows, knees and ankles were the commonest sites involved in double bleeds, while the thigh, upper arm and elbow were the commonest sites involved in the double bleeds needing most transfusions. The overall transfusion requirements were less than for single bleeds. The frequency of multiple bleeds correlated significantly with the overall bleeding frequency, but not with the number of days under observation.

  8. Multiple sclerosis

    PubMed Central

    Boster, Aaron L.; Racke, Michael K.

    2013-01-01

    Summary Preliminary studies have suggested that a high salt diet may play a role in the development of autoimmune disease and possibly multiple sclerosis (MS). Promising clinical trial results for 2 new therapies for MS have been reported. Dimethyl fumarate, also known by its investigational name BG-12, became the third oral disease-modifying therapy for MS to be Food and Drug Administration (FDA)–approved in March 2013. Interestingly, dimethyl fumarate served as the active compound used for the treatment of psoriasis for decades. Alemtuzumab remains under investigation and is not currently FDA-approved for treatment of MS. Other drugs currently approved for alternative indications are being investigated for use in MS. Additionally, an investigation of alternative dosing strategies for glatiramer acetate suggests that patients may benefit from a higher dose formulation and less frequent medication administration. Advances in basic science research have identified another potential autoantigenic target in MS, KIR4.1, which may provide further insight into MS pathophysiology. PMID:24175156

  9. Multiple sclerosis.

    PubMed

    Filippi, Massimo; Preziosa, Paolo; Rocca, Maria A

    2016-01-01

    Due to its sensitivity to the different multiple sclerosis (MS)-related abnormalities, magnetic resonance imaging (MRI) has become an established tool to diagnose MS and to monitor its evolution. MRI has been included in the diagnostic workup of patients with clinically isolated syndromes suggestive of MS, and ad hoc criteria have been proposed and are regularly updated. In patients with definite MS, the ability of conventional MRI techniques to explain patients' clinical status and progression of disability is still suboptimal. Several advanced MRI-based technologies have been applied to estimate overall MS burden in the different phases of the disease. Their use has allowed the heterogeneity of MS pathology in focal lesions, normal-appearing white matter and gray matter to be graded in vivo. Recently, additional features of MS pathology, including macrophage infiltration and abnormal iron deposition, have become quantifiable. All of this, combined with functional imaging techniques, is improving our understanding of the mechanisms associated with MS evolution. In the near future, the use of ultrahigh-field systems is likely to provide additional insight into disease pathophysiology. However, the utility of advanced MRI techniques in clinical trial monitoring and in assessing individual patients' response to treatment still needs to be assessed. PMID:27432676

  10. Value siting

    SciTech Connect

    Ferrar, T.A.; Howes, J.A.

    1995-02-01

    Finding an appropriate site is becoming an increasing challenge in building new power projects. One of the first orders of business in project development is identifying a site that offers the maximum spread between the cost of fuel and net power price. The collection of sites that exhibit an adequate spread - presenting a first-order, acceptable economic expectation - must now be subjected to an ever increasing number of political, societal, technical, and economic exclusion screens. The barriers can include cooling water constraints, community resistance, visual incompatibility, archaeological concerns and endangered species preservation issues. Most power siting difficulties can be substantially mitigated by gaining access to developed, but under-used sites, whose current owners are bound by circumstances - political or financial - that prevent them from using such locations. There are two such categories of sites: Utilities that have sites on which depreciated power production assets rest; and, The federal government, with numerous sites throughout the country, particularly military bases subject to closure under the Base Realignment and Closure (BRAC) proceedings. It is in the interests of developers, as well as consumers, investors and taxpayers, ti undertake a thorough examination of these overlooked pearls of opportunities and develop their potential.

  11. Sports Safety - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Site Map FAQs Contact Us Health Topics Drugs & Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Sports Safety URL of this page: https://medlineplus.gov/ ...

  12. The localization of multiple sites on 16S RNA which are cross-linked to proteins S7 and S8 in Escherichia coli 30S ribosomal subunits by treatment with 2-iminothiolane.

    PubMed

    Wower, I; Brimacombe, R

    1983-03-11

    RNA-protein cross-links were introduced into E. coli 30S ribosomal subunits by reaction with 2-iminothiolane followed by a mild ultraviolet irradiation treatment. After removal of non-reacted protein and partial nuclease digestion of the cross-linked 16S RNA-protein moiety, a number of individual cross-linked complexes could be isolated and the sites of attachment of the proteins to the RNA determined. Protein S8 was cross-linked to the RNA at three different positions, within oligo-nucleotides encompassing positions 629-633, 651-654, and (tentatively) 593-597 in the 16S sequence. Protein S7 was cross-linked within two oligonucleotides encompassing positions 1238-1240, and 1377-1378. In addition, a site at position 723-724 was observed, cross-linked to protein S19, S20 or S21.

  13. Lunar Polar Landing Sites

    NASA Astrophysics Data System (ADS)

    Kamps, Oscar; Foing, Bernard H.; Flahaut, Jessica

    2016-07-01

    An important step for a scientific mission is to assess on where the mission should be conducted. This study on landing site selection focuses on a mission to the poles of the Moon where an in-situ mission should be conducted to answer the questions with respect to volatiles and ices. The European interest for a mission to the poles of the Moon is presented in the mission concept called Heracles. This mission would be a tele-operated, sample return mission where astronauts will controlling a rover from an Orion capsule in cislunar orbit. The primary selection of landing sites was based on the scientific interest of areas near the poles. The maximum temperature map from Diviner was used to select sites where CO^2¬ should always be stable. This means that the maximum temperature is lower than 54K which is the sublimation temperature for CO^2¬ in lunar atmospheric pressure. Around these areas 14 potential regions of interest were selected. Further selection was based on the epoch of the surface in these regions of interest. It was thought that it would be of high scientific value if sites are sampled which have another epoch than already sampled by one of the Apollo or Luna missions. Only 6 sites on both North as South Pole could contain stable CO^2 ¬and were older than (Pre-)Necterian. Before a landing site and rover traverse was planned these six sites were compared on their accessibility of the areas which could contain stable CO^2. It was assumed that slope lower than 20^o is doable to rove. Eventually Amundsen and Rozhdestvenskiy West were selected as regions of interest. Assumptions for selecting landing sites was that area should have a slope lower than 5^o, a diameter of 1km, in partial illuminated area, and should not be isolated but inside an area which is in previous steps marked as accessible area to rove. By using multiple tools in ArcGIS it is possible to present the area's which were marked as potential landing sites. The closest potential landing

  14. Multiple System Atrophy

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Multiple System Atrophy Information Page Condensed from Multiple System Atrophy ... Trials Organizations Publicaciones en Español What is Multiple System Atrophy? Multiple system atrophy (MSA) is a progressive ...

  15. Multiple sclerosis - resources

    MedlinePlus

    Resources - multiple sclerosis ... The following organizations provide information on multiple sclerosis : Multiple Sclerosis Foundation -- www.msfocus.org National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/multiple_sclerosis National ...

  16. Multiple tumours in survival estimates.

    PubMed

    Rosso, Stefano; De Angelis, Roberta; Ciccolallo, Laura; Carrani, Eugenio; Soerjomataram, Isabelle; Grande, Enrico; Zigon, Giulia; Brenner, Hermann

    2009-04-01

    In international comparisons of cancer registry based survival it is common practice to restrict the analysis to first primary tumours and exclude multiple cancers. The probability of correctly detecting subsequent cancers depends on the registry's running time, which results in different proportions of excluded patients and may lead to biased comparisons. We evaluated the impact on the age-standardised relative survival estimates of also including multiple primary tumours. Data from 2,919,023 malignant cancers from 69 European cancer registries participating in the EUROCARE-4 collaborative study were used. A total of 183,683 multiple primary tumours were found, with an overall proportion of 6.3% over all the considered cancers, ranging from 0.4% (Naples, Italy) to 12.9% (Iceland). The proportion of multiple tumours varied greatly by type of tumour, being higher for those with high incidence and long survival (breast, prostate and colon-rectum). Five-year relative survival was lower when including patients with multiple cancers. For all cancers combined the average difference was -0.4 percentage points in women and -0.7 percentage points in men, and was greater for older registries. Inclusion of multiple tumours led to lower survival in 44 out of 45 cancer sites analysed, with the greatest differences found for larynx (-1.9%), oropharynx (-1.5%), and penis (-1.3%). Including multiple primary tumours in survival estimates for international comparison is advisable because it reduces the bias due to different observation periods, age, registration quality and completeness of registration. The general effect of inclusion is to reduce survival estimates by a variable amount depending on the proportion of multiple primaries and cancer site.

  17. Injectable Multiple Sclerosis Medications

    PubMed Central

    Tran, Zung Vu

    2012-01-01

    Although injection-site reactions (ISRs) occur with US Food and Drug Administration–approved injectable disease-modifying therapies (DMTs) for multiple sclerosis, there are currently few reports of real-world data on ISR management strategies or possible correlations between ISRs and patient demographics, disease characteristics, and missed injections. Patient-reported data on the use of DMTs, patient demographic and disease characteristics, missed injections, and ISR reduction strategies were collected via e-mail, a patient registry (www.ms-cam.org), and a Web-based survey. Of the 1380 respondents, 1201 (87%) indicated that they had used injectable DMTs, of whom 377 (31%) had used intramuscular (IM) interferon beta-1a (IFNβ-1a), 172 (14%) had used subcutaneous (SC) IFNβ-1a, 183 (15%) had used SC IFNβ-1b, and 469 (39%) had used glatiramer acetate (GA). The majority of respondents were older (73% were ≥40 years), female (79%), married or living with a partner (72%), white (94%), and nonsmoking (82%). Injection-site reaction incidence, grouped according to severity, varied among DMTs, with IM IFNβ-1a causing significantly (P < .001) fewer mild, moderate, or severe ISRs than the other therapies. Female sex and younger age were significantly (P < .05) associated with more moderate ISRs among users of IM IFNβ-1a, SC IFNβ-1b, and GA. Nonwhites reported severe ISRs more often than whites. For all DMTs injection-site massage and avoidance of sensitive sites were the most frequently used strategies to minimize ISRs. These data may help identify patients with characteristics associated with a higher risk for ISRs, allowing health-care professionals to provide anticipatory guidance to patients at risk for decreased adherence or discontinuation. PMID:24453732

  18. Multiple lifestyle behaviours and overweight and obesity among children aged 9–11 years: results from the UK site of the International Study of Childhood Obesity, Lifestyle and the Environment

    PubMed Central

    Wilkie, Hannah J; Standage, Martyn; Gillison, Fiona B; Cumming, Sean P; Katzmarzyk, Peter T

    2016-01-01

    Objectives The purpose of this study was to explore the independent associations between multiple lifestyle behaviours (physical activity, sleep, screen time (ST) and diet) and overweight and obesity in UK children. The second objective was to compare body mass index (BMI) z-score between children who meet health guidelines for each lifestyle behaviour and those who do not and to explore the impact of interactions between lifestyle behaviours on BMI z-score. Design, setting and participants Cross-sectional study on children aged 9–11 years in the UK (n=374). Outcome measures Participants were classified as overweight or obese using the WHO BMI cut-points. Moderate-to-vigorous intensity physical activity (MVPA) and sleep duration were measured using an ActiGraph GT3X+ accelerometer, whereas ST and dietary habits were assessed using questionnaires. Multilevel multiple logistic regression was employed to analyse associations between lifestyle behaviours and overweight/obesity. Participants were then categorised according to whether or not they met specific health criteria for MVPA, ST, sleep and diet. Multilevel multiple linear regression was used to compare these groupings on the outcome of BMI z-score and interactions were explored. Results MVPA and longer sleep duration were associated with lower odds of overweight or obesity, whereas ST and a healthy diet score were associated with increased odds of overweight/obesity. No association was found for an unhealthy diet score. Meeting MVPA guidelines was significantly associated with a lower BMI z-score in all models, and significant two-way interactions were observed for physical activity and sleep, ST and sleep, and physical activity and diet. Conclusions MVPA, sleep and ST are important lifestyle behaviours associated with overweight/obesity among children. More research is required to confirm the role of diet on adiposity and such work would benefit from objective assessment. Overall, this work suggests that

  19. Evoked potentials in multiple sclerosis.

    PubMed

    Kraft, George H

    2013-11-01

    Before the development of magnetic resonance imaging (MRI), evoked potentials (EPs)-visual evoked potentials, somatosensory evoked potentials, and brain stem auditory evoked responses-were commonly used to determine a second site of disease in patients being evaluated for possible multiple sclerosis (MS). The identification of an area of the central nervous system showing abnormal conduction was used to supplement the abnormal signs identified on the physical examination-thus identifying the "multiple" in MS. This article is a brief overview of additional ways in which central nervous system (CNS) physiology-as measured by EPs-can still contribute value in the management of MS in the era of MRIs.

  20. Multiple protein stationary phases: a review.

    PubMed

    Singh, N S; Habicht, K-L; Dossou, K S S; Shimmo, R; Wainer, I W; Moaddel, R

    2014-10-01

    Cellular membrane affinity chromatography stationary phases have been extensively used to characterize immobilized proteins and provide a direct measurement of multiple binding sites, including orthosteric and allosteric sites. This review will address the utilization of immobilized cellular and tissue fragments to characterize multiple transmembrane proteins co-immobilized onto a stationary phase. This approach will be illustrated by demonstrating that multiple transmembrane proteins were immobilized from cell lines and tissue fragments. In addition, the immobilization of individual compartments/organelles within a cell will be discussed and the changes in the proteins binding/kinetics based on their location. PMID:24780640

  1. The mechanism of synthesis of a mixed-linkage (1{r{underscore}arrow}3), (1{r{underscore}arrow}4) {beta}-D-glucan in maize. Evidence for multiple sites of glucosyl transfer in the synthase complex

    SciTech Connect

    Buckeridge, M.S.; Vergara, C.E.; Carpita, N.C.

    1999-08-01

    The authors examined the mechanism of synthesis in vitro of (1{r{underscore}arrow}3), (1{r{underscore}arrow}4){Beta}-D-glucan ({Beta}-glucan), a growth-specific cell wall polysaccharide round in grasses and cereals. {beta}-Glucan is composed primarily of cellotriosyl and cellotetraosyl units linked by single (1{r{underscore}arrow}3){beta}-linkages. The ratio of cellotriosyl and cellotetraosyl units in the native polymer is strictly controlled at between 2 and 3 in all grasses, whereas the ratios of these units in {Beta}-glucan formed in vitro vary from 1.5 with 5 {micro}M UDP-glucose (GLc) to over 11 with 30 nM substrate. These results support a model in which three sites of glycosyl transfer occur within the synthase complex to produce the cellobiosyl-(1{r{underscore}arrow}3)-D-glucosyl units. The authors propose that failure to fill one of the sites results in the iterative addition of one or more cellobiosyl units to produce the longer cellodextrin units in the polymer. Variations in the UDP-Glc concentration in excised maize (Zea mays) coleoptiles did not result in wide variations in the ratios of cellotriosyl and cellotetraosyl units in {beta}-glucan synthesized in vivo, indicating that other factors control delivery of UDP-Glc to the synthase. In maize sucrose synthase is enriched in Golgi membranes and plasma membranes and may be involved in the control of substrate delivery to {beta}-glucan synthase and cellulose synthase.

  2. Site Construction.

    ERIC Educational Resources Information Center

    Richardson, Eric C.

    1996-01-01

    Presents a guide to planning and building a Web site, with an emphasis on setting up a Web server. Discussion includes hiring a consultant, contracts and payment, assembly of teams, training, development of a business plan, registration of domain name, purchase of hardware and software, local area networks, and types of Internet connection. (JKP)

  3. Commission 26: Double and Multiple Stars

    NASA Astrophysics Data System (ADS)

    Allen, Christine; Docobo, Jose A. D.; Hartkopf, William I.; Balega, Yuri I.; Davis, John; Mason, Brian D.; Oblak, Edouard; Oswalt, Terry D.; Pourbaix, Dimitri; Scarfe, Colin D.

    Although we were happy to welcome over 20 new members at the Prague meeting, Commission 26 is still one of the smallest in the IAU. Notwithstanding its size, it continues to carry on an active and diversified program of activities. Our web site, maintained at the US Naval Observatory, contains further information on the Commission. The site includes links to other relevant sites, to databases and catalogues, an archive of our Information Circulars, a list of upcoming meetings of interest, as well as an extensive bibliography of recently published papers on double and multiple stars. The site can be accessed at .

  4. CONTAMINATION OF PUBLIC GROUND WATER SUPPLIES BY SUPERFUND SITES

    EPA Science Inventory

    Multiple sources of contamination can affect ground water supplies, including municipal landfills, industrial operations, leaking underground storage tanks, septic tank systems, and prioritized uncontrolled hazardous waste sites known as “Superfund” sites. A review of Superfund R...

  5. [Familial multiple cavernomatosis].

    PubMed

    Terriza, F; Amrani, Y; Asencio, J J; Goberna, E; Casado, A; Peralta, J I

    1997-04-01

    We present a family study of multiple cavernomatosis which affected a boy of six, his mother and two brothers. It was seen clinically as epileptic crises, focal neurological defects and frequent headaches. In our case, the condition started as a syndrome of intracranial hypertension with progressive headache and vomiting. During the illness, localizing neurological signs due to bleeding were seen. Amongst these were acute left hemiparesia and paralysis of vertical gaze. Other members of the family remain symptom-free. In a search for angiomas at other sites none were found in the patient or his family. Recently the gene giving rise to the familial cerebral cavernosa malformation has been found to be a locus on chromosome 7. We discuss the findings on neuro-imaging, emphasizing the importance of magnetic resonance (MR) both in diagnosis and finding affected asymptomatic family members, because of its great sensitivity and specificity. Angiography is not a suitable technique for this since they behave as hidden malformations. We also point out its importance as a way of following-up the illness and for evaluation of possible complications due to progressive growth or sudden haemorrhage, which may indicate the need for treatment. Finally we emphasize the different characteristics of MR signals in this type of lesion since cavernomatasa malformations are dynamic lesions. PMID:9172920

  6. Single fibre electromyographic jitter in multiple sclerosis.

    PubMed Central

    Weir, A; Hansen, S; Ballantyne, J P

    1979-01-01

    Recent histological and electrophysiological reports have given evidence for peripheral nervous system (PNS) involvement in multiple sclerosis. We have applied the single fibre electromyography (SFEMG) technique to 15 patients with multiple sclerosis. Six patients had clearly abnormal jitter and two of these had previously undiagnosed coexistent peripheral neuropathy. A further five patients had borderline abnormalities of SFEMG. The mean jitter for each patient was abnormal in 10 patients. This was clear evidence for PNS involvement in this disease. Theoretically, the site of the abnormality could be in the terminal nerve network or at the neuromuscular junction, but this technique cannot distinguish between these sites. PMID:533854

  7. Multiple-Ring Digital Communication Network

    NASA Technical Reports Server (NTRS)

    Kirkham, Harold

    1992-01-01

    Optical-fiber digital communication network to support data-acquisition and control functions of electric-power-distribution networks. Optical-fiber links of communication network follow power-distribution routes. Since fiber crosses open power switches, communication network includes multiple interconnected loops with occasional spurs. At each intersection node is needed. Nodes of communication network include power-distribution substations and power-controlling units. In addition to serving data acquisition and control functions, each node acts as repeater, passing on messages to next node(s). Multiple-ring communication network operates on new AbNET protocol and features fiber-optic communication.

  8. Fatigue and Multiple Sclerosis

    MedlinePlus

    Fatigue - National Multiple Sclerosis Society Skip to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area ... help* daily life for: positive-mom* The National MS Society is Here to Help Need More Information? ...

  9. What Is Multiple Myeloma?

    MedlinePlus

    ... other tissues. If someone has only a single plasma cell tumor, the disease is called an isolated (or solitary ) plasmacytoma . If someone has more than one plasmacytoma, they have multiple myeloma . Multiple myeloma is ...

  10. Challenges of Parenting Multiples

    MedlinePlus

    ... Parenting Multiples There are many psychological, social, and economic issues associated with multiple pregnancies. These issues should ... births can also be helpful during difficult times. ECONOMIC ISSUES • The health care cost for delivery and ...

  11. National Multiple Sclerosis Society

    MedlinePlus

    ... Join the Community Stay Informed Corporate Support National Multiple Sclerosis Society Our Mission: People affected by MS can ... 10.5 Million in New Research to Stop Multiple Sclerosis, Restore Function and End MS Forever October 11, ...

  12. MultipleColposcopyJCO

    Cancer.gov

    Performing multiple biopsies during a procedure known as colposcopy—visual inspection of the cervix—is more effective than performing only a single biopsy of the worst-appearing area for detecting cervical cancer precursors. This multiple biopsy approach

  13. Multiple Endocrine Neoplasia Syndromes

    MedlinePlus

    ... or cancerous (malignant) tumors or grow excessively without forming tumors. Multiple endocrine neoplasia syndromes are caused by ... This Article Generic Name Select Brand Names corticotropin H.P. ACTHAR GEL epinephrine ADRENALIN Multiple Endocrine Neoplasia ...

  14. Mapping fast protein folding with multiple-site fluorescent probes

    PubMed Central

    Prigozhin, Maxim B.; Chao, Shu-Han; Sukenik, Shahar; Pogorelov, Taras V.; Gruebele, Martin

    2015-01-01

    Fast protein folding involves complex dynamics in many degrees of freedom, yet microsecond folding experiments provide only low-resolution structural information. We enhance the structural resolution of the five-helix bundle protein λ6–85 by engineering into it three fluorescent tryptophan–tyrosine contact probes. The probes report on distances between three different helix pairs: 1–2, 1–3, and 3–2. Temperature jump relaxation experiments on these three mutants reveal two different kinetic timescales: a slower timescale for 1–3 and a faster one for the two contacts involving helix 2. We hypothesize that these differences arise from a single folding mechanism that forms contacts on different timescales, and not from changes of mechanism due to adding the probes. To test this hypothesis, we analyzed the corresponding three distances in one published single-trajectory all-atom molecular-dynamics simulation of a similar mutant. Autocorrelation analysis of the trajectory reveals the same “slow” and “fast” distance change as does experiment, but on a faster timescale; smoothing the trajectory in time shows that this ordering is robust and persists into the microsecond folding timescale. Structural investigation of the all-atom computational data suggests that helix 2 misfolds to produce a short-lived off-pathway trap, in agreement with the experimental finding that the 1–2 and 3–2 distances involving helix 2 contacts form a kinetic grouping distinct from 1 to 3. Our work demonstrates that comparison between experiment and simulation can be extended to several order parameters, providing a stronger mechanistic test. PMID:26080403

  15. Mapping fast protein folding with multiple-site fluorescent probes.

    PubMed

    Prigozhin, Maxim B; Chao, Shu-Han; Sukenik, Shahar; Pogorelov, Taras V; Gruebele, Martin

    2015-06-30

    Fast protein folding involves complex dynamics in many degrees of freedom, yet microsecond folding experiments provide only low-resolution structural information. We enhance the structural resolution of the five-helix bundle protein λ6-85 by engineering into it three fluorescent tryptophan-tyrosine contact probes. The probes report on distances between three different helix pairs: 1-2, 1-3, and 3-2. Temperature jump relaxation experiments on these three mutants reveal two different kinetic timescales: a slower timescale for 1-3 and a faster one for the two contacts involving helix 2. We hypothesize that these differences arise from a single folding mechanism that forms contacts on different timescales, and not from changes of mechanism due to adding the probes. To test this hypothesis, we analyzed the corresponding three distances in one published single-trajectory all-atom molecular-dynamics simulation of a similar mutant. Autocorrelation analysis of the trajectory reveals the same "slow" and "fast" distance change as does experiment, but on a faster timescale; smoothing the trajectory in time shows that this ordering is robust and persists into the microsecond folding timescale. Structural investigation of the all-atom computational data suggests that helix 2 misfolds to produce a short-lived off-pathway trap, in agreement with the experimental finding that the 1-2 and 3-2 distances involving helix 2 contacts form a kinetic grouping distinct from 1 to 3. Our work demonstrates that comparison between experiment and simulation can be extended to several order parameters, providing a stronger mechanistic test. PMID:26080403

  16. Air Pollution Monitoring Site Selection by Multiple Criteria Decision Analysis

    EPA Science Inventory

    Criteria air pollutants (particulate matter, sulfur dioxide, oxides of nitrogen, volatile organic compounds, and carbon monoxide) as well as toxic air pollutants are a global concern. A particular scenario that is receiving increased attention in the research is the exposure to t...

  17. Distance Administration: Multiple Perspectives on Multi-Site Institutions

    ERIC Educational Resources Information Center

    Gaskell, Craig; Hayton, Elizabeth

    2015-01-01

    It is becoming increasingly important to understand multi-campus arrangements in the rapidly changing higher education environment. Some attention has been given to the academic perspectives of such arrangements; however, there is limited published work relating to administrative and professional services. Different approaches are evident and…

  18. Multiple Representations as Sites for Teacher Reflection about Mathematics Learning

    ERIC Educational Resources Information Center

    Ryken, Amy E.

    2009-01-01

    This documentary account situates teacher educator, prospective teacher, and elementary students' mathematical thinking in relation to one another, demonstrating shared challenges to learning mathematics. It highlights an important mathematics reasoning skill--creating and analyzing representations. The author examines responses of prospective…

  19. Advanced Multiple Aperture Seeing Profiler

    NASA Astrophysics Data System (ADS)

    Ren, Deqing; Zhao, Gang

    2016-10-01

    Measurements of the seeing profile of the atmospheric turbulence as a function of altitude are crucial for solar astronomical site characterization, as well as the optimized design and performance estimation of solar Multi-Conjugate Adaptive Optics (MCAO). Knowledge of the seeing distribution, up to 30 km, with a potential new solar observation site, is required for future solar MCAO developments. Current optical seeing profile measurement techniques are limited by the need to use a large facility solar telescope for such seeing profile measurements, which is a serious limitation on characterizing a site's seeing conditions in terms of the seeing profile. Based on our previous work, we propose a compact solar seeing profiler called the Advanced Multiple Aperture Seeing Profile (A-MASP). A-MASP consists of two small telescopes, each with a 100 mm aperture. The two small telescopes can be installed on a commercial computerized tripod to track solar granule structures for seeing profile measurement. A-MASP is extreme simple and portable, which makes it an ideal system to bring to a potential new site for seeing profile measurements.

  20. A multiple node software development environment

    SciTech Connect

    Heinicke, P.; Nicinski, T.; Constanta-Fanourakis, P.; Petravick, D.; Pordes, R.; Ritchie, D.; White, V.

    1987-06-01

    Experimenters on over 30 DECnet nodes at Fermilab use software developed, distributed, and maintained by the Data Acquisition Software Group. A general methodology and set of tools have been developed to distribute, use and manage the software on different sites. The methodology and tools are of interest to any group developing and using software on multiple nodes.

  1. Lung Involvement in Multiple Myeloma - Case Study

    PubMed Central

    NIŢU, MIMI; CRIȘAN, EMILIA; OLTEANU, M.; CĂLĂRAŞU, CRISTINA; OLTEANU, MĂDĂLINA; POPESCU, M.R.

    2014-01-01

    Introduction: Mutiple mieloma (MM) cells are rarely found in extramedullary sites. The sites of extramedullary dissemination reported in the literature are spleen, liver, lymph nodes, kidneys, thyroid gland, adrenal gland, ovary, tests, lung, pleura, pericardium, intestinal tract and skin. We report a case in which the myeloma was diagnosed after we discovered the presence of monoclonal plasma cells in the bronchoalveolar lavage fluid (BAL). Matherial and method: a case in which diagnosis was established from bronchoalveolar lavage (BAL) fluid demonstrating the presence of monoclonal plasma cells in Craiova Pneumology Departament. Results: Analysis of BAL fluid for the presence of plasma cells and for cytoplasmic immunoglobulin DNA provides a noninvasive means of establishing the diagnosis. Conclusions: Pulmonary parenchyma is an uncommon site of extramedullary involvement in multiple myeloma. Interstitial lung disease as pulmonary manifestation of multiple myeloma is even rarer; only isolated cases with histological proofs have been reported in the literature. PMID:26788357

  2. Nutrition for Multiples.

    PubMed

    Luke, Barbara

    2015-09-01

    In 2012 there were 135,943 infants of multiple pregnancies born in the United States, nearly a 2-fold increase since 1980, with twins accounting for 96% of all multiple births. To date, most perinatal morbidities associated with multiple births have proven resistant to technological or pharmaceutical interventions. Maternal nutrition can have a profound effect on the course and outcome of multiple pregnancy, with the goal of achieving optimal intrauterine growth and birthweights, and minimizing prenatal and perinatal complications for the mother and her children.

  3. Multisite EPR Oximetry from Multiple Quadrature Harmonics

    PubMed Central

    Ahmad, R.; Som, S.; Johnson, D.H.; Zweier, J.L.; Kuppusamy, P.; Potter, L.C.

    2011-01-01

    Multisite continuous wave (CW) electron paramagnetic resonance (EPR) oximetry using multiple quadrature field modulation harmonics is presented. First, a recently developed digital receiver is used to extract multiple harmonics of field modulated projection data. Second, a forward model is presented that relates the projection data to unknown parameters, including linewidth at each site. Third, a maximum likelihood estimator of unknown parameters is reported using an iterative algorithm capable of jointly processing multiple quadrature harmonics. The data modeling and processing are applicable for parametric lineshapes under nonsaturating conditions. Joint processing of multiple harmonics leads to 2-3 fold acceleration of EPR data acquisition. For demonstration in two spatial dimensions, both simulations and phantom studies on an L-band system are reported. PMID:22154283

  4. A Bistatic Multiple-Doppler Radar Network.

    NASA Astrophysics Data System (ADS)

    Wurman, Joshua; Heckman, Stanley; Boccippio, Dennis

    1993-12-01

    A multiple-Doppler radar network can be constructed using only one, traditional, transmitting pencil-beam radar and one or more passive, low-gain, nontransmitting receivers at remote sites. Radiation scattered from the pencil beam of the transmitting radar as it penetrates weather targets can be detected at the receive-only sites as well as at the active transmitter. The Doppler shifts of the radiation received at all the sites can be used to construct two- and three-dimensional wind fields in a manner similar to that used with traditional Doppler radar networks.There are unique scientific advantages to a bistatic multiple-Doppler network: 1) all radial velocity measurements from individual resolution volumes are collected simultaneously since there is only one source of radiation; 2) the intensity of the obliquely scattered radiation can be compared to Rayleigh scattering predictions and used for hail detection; 3) rapid scanning of localized weather phenomena can be aided by elimination of the need to scan with multiple radars.This type of multiple-Doppler radar network also has significant economic advantages. Passive sites contain no high-voltage transmitting equipment or large rotating antennas. They require no operators and much less maintenance. We estimate initial investment costs, and subsequent operational and maintenance costs are less than one-thirtieth that of conventional radars.There are shortcomings particular to these types of networks: 1) passive, low-gain, receiving sites are more sensitive to contamination from transmitter sidelobes and to secondary scattering from weather echoes; 2) low-gain receiving sites are less sensitive to weak weather echoes; 3) Cartesian (u, v, w) wind fields derived from bistatic network data exhibit about twice the expected error as those constructed from data from traditional monostatic networks containing equal numbers of radars. Multiple scattering and sidelobe contamination levels are acceptable in most situations

  5. Wind Energy Deployment Process and Siting Tools (Presentation)

    SciTech Connect

    Tegen, S.

    2015-02-01

    Regardless of cost and performance, some wind projects cannot proceed to completion as a result of competing multiple uses or siting considerations. Wind energy siting issues must be better understood and quantified. DOE tasked NREL researchers with depicting the wind energy deployment process and researching development considerations. This presentation provides an overview of these findings and wind siting tools.

  6. Multiple density layered insulator

    DOEpatents

    Alger, Terry W.

    1994-01-01

    A multiple density layered insulator for use with a laser is disclosed wh provides at least two different insulation materials for a laser discharge tube, where the two insulation materials have different thermoconductivities. The multiple layer insulation materials provide for improved thermoconductivity capability for improved laser operation.

  7. Multiple density layered insulator

    DOEpatents

    Alger, T.W.

    1994-09-06

    A multiple density layered insulator for use with a laser is disclosed which provides at least two different insulation materials for a laser discharge tube, where the two insulation materials have different thermoconductivities. The multiple layer insulation materials provide for improved thermoconductivity capability for improved laser operation. 4 figs.

  8. Multiple Myeloma Symptoms

    MedlinePlus

    ... it is multiple myeloma . Stay on top of discoveries, trials, research and more. Click here to sign up for the MMRF Newsletter First name Last name E-mail address CLOSE News & Press Multiple Myeloma Knowledge Center Privacy Policy Donor Privacy Policy Terms of ...

  9. Orchestrating Multiple Intelligences

    ERIC Educational Resources Information Center

    Moran, Seana; Kornhaber, Mindy; Gardner, Howard

    2006-01-01

    Education policymakers often go astray when they attempt to integrate multiple intelligences theory into schools, according to the originator of the theory, Howard Gardner, and his colleagues. The greatest potential of a multiple intelligences approach to education grows from the concept of a profile of intelligences. Each learner's intelligence…

  10. Twins, Triplets, Multiple Births

    MedlinePlus

    ... from alone. Multiple births are up in the United States. More women are having babies after age 30 and more are taking fertility drugs. Both boost the chance of carrying more than one baby. A family history of twins also makes multiples more likely. Years ...

  11. Prediction in Multiple Regression.

    ERIC Educational Resources Information Center

    Osborne, Jason W.

    2000-01-01

    Presents the concept of prediction via multiple regression (MR) and discusses the assumptions underlying multiple regression analyses. Also discusses shrinkage, cross-validation, and double cross-validation of prediction equations and describes how to calculate confidence intervals around individual predictions. (SLD)

  12. [Multiple pulmonary hyalinizing granuloma].

    PubMed

    Haro, M; Ruiz, J; Vila, X; Avellanet, M; Izquierdo, J

    1994-01-01

    The causes of multiple pulmonary nodules are many, with metastasis being the most feared. A rare but possible etiology, however, is hyalinizing multiple granuloma. We present a case that allows us to review this condition and its course, as well as a variety of associated immunological changes and possible complications. PMID:8087395

  13. Applying Multiple Intelligences

    ERIC Educational Resources Information Center

    Christodoulou, Joanna A.

    2009-01-01

    The ideas of multiple intelligences introduced by Howard Gardner of Harvard University more than 25 years ago have taken form in many ways, both in schools and in other sometimes-surprising settings. The silver anniversary of Gardner's learning theory provides an opportunity to reflect on the ways multiple intelligences theory has taken form and…

  14. Constraining Multiple Grammars

    ERIC Educational Resources Information Center

    Hopp, Holger

    2014-01-01

    This article offers the author's commentary on the Multiple Grammars (MG) language acquisition theory proposed by Luiz Amaral and Tom Roeper in the present issue. Multiple Grammars advances the claim that optionality is a constitutive characteristic of any one grammar, with interlanguage grammars being perhaps the clearest examples of a…

  15. Current multiplication by using multiple thyristors.

    PubMed

    Liu, Z; Pemen, A J M; Van Heesch, E J M; Winands, G J J

    2008-07-01

    This paper presents a circuit topology to obtain current multiplication by using multiple thyristors. To gain insight into this technique, an equivalent circuit model is introduced. Proper operation of the topology was demonstrated by experiments on a small-scale setup including three thyristors. One thyristor is triggered by a trigger circuit; the other two are autotriggered and require no external trigger circuit. The three thyristors could be synchronized automatically in sequence. During the closing process, the discharging of the energy storage capacitors via the thyristors is prevented. The discharging starts when all thyristors are closed, and the currents through each thyristor are simultaneous and identical. The output current is exactly three times the switching current.

  16. Implementation: Preparing the Site.

    ERIC Educational Resources Information Center

    Epstein, Susan Baerg

    1983-01-01

    Considers site requirements that should be specified by the library and the vendor for a library automated system located at a central site away from the library, including size of site, the environment, cleanliness, electrical power, security/safety (fire, restricted access), site certification, telecommunications, and terminal sites. (EJS)

  17. Modifiable risk factors for surgical site infection.

    PubMed

    Moucha, Calin S; Clyburn, Terry A; Evans, Richard P; Prokuski, Laura

    2011-01-01

    Multiple risk factors for orthopaedic surgical site infection have been identified. Some of these factors directly affect the wound-healing process, whereas others can lead to blood-borne sepsis or relative immunosuppression. Modifying a patient's medications; screening for comorbidities, such as HIV or diabetes mellitus; and advising the patient on options to diminish or eliminate adverse behaviors, such as smoking, should lower the risk for surgical site infections.

  18. Promoting Your Web Site.

    ERIC Educational Resources Information Center

    Raeder, Aggi

    1997-01-01

    Discussion of ways to promote sites on the World Wide Web focuses on how search engines work and how they retrieve and identify sites. Appropriate Web links for submitting new sites and for Internet marketing are included. (LRW)

  19. Correct implementation of the Argonne Expedited Site Characterization (ESC) process for preremedial site investigations.

    SciTech Connect

    Burton, J. C.; Cook, S.; Sedivy, R.; Walker, J. L.

    1997-12-12

    The Argonne Expedited Site Characterization (ANL ESC) methodology, developed by Argonne National Laboratory and popularly known as ESC, is an effective, cost- and time-saving approach for technically successful preremedial site characterizations. The major objective of the ANL ESC is to determine whether a site containing contamination requires remediation. The methodology is equivalent to a CERCLA RI/FS or a RCRA RFI/CMS investigation. The ANL ESC methodology is an interactive, integrated process emphasizing the use of existing data, multiple complementary characterization methods, and on-site decision making to optimize site investigations. The ANL ESC is the basis for the expedited site characterization standard of the ASTM (American Society for Testing and Materials). The methodology has been registered under the service mark QuickSite{trademark} to offer both clients and providers a mechanism for ensuring that they receive the ANL ESC methodology developed by Argonne. The ANL ESC is a flexible process and is neither site nor contaminant dependent. It can be tailored to fit the unique characteristics that distinguish one site from the next, in contrast to the traditional approach of making all sites conform to the same rigid, inflexible investigation regimen. The ANL ESC has been applied successfully to remedial site investigations of landfills with multiple contaminants in the southwestern US for the Department of Interior (DOI), to former grain storage facilities in the Midwest for the Commodity Credit Corporation of the Department of Agriculture (CCC/USDA), to weapons production facilities in Texas for the Department of Energy (DOE), and to closing and active military bases in several locations for the Department of Defense (DOD). The process can be applied both at sites that have seen little investigation and at sites that have undergone numerous previous site characterizations without reaching closure. In the latter case (e.g., at many DOE and DOD sites

  20. Walking in Two Worlds: Master Teachers Serving as Site Coordinators in Partner Schools.

    ERIC Educational Resources Information Center

    Utley, Bonnie L.; Basile, Carole G.; Rhodes, Lynn K.

    2003-01-01

    Describes multiple aspects of the site coordinator's role in K-12/university partnerships where a master teacher was the site coordinator. Interview data highlight multiple themes within the areas of personal and professional benefits and challenges. Overall, site coordinators learned to walk in two worlds nd became an accepted part of the culture…

  1. [Psychoneuroimmunology and multiple sclerosis].

    PubMed

    Mel'nikov, M V; Pashchenkov, M V; Boĭko, A N

    2015-01-01

    In this review, the authors discuss interactions between mental, nervous and immune systems in multiple sclerosis, an impact of psycho-emotional stress on disease development and progression as well as possible mechanisms of these interactions.

  2. Multiple shell fusion targets

    DOEpatents

    Lindl, J.D.; Bangerter, R.O.

    1975-10-31

    Multiple shell fusion targets for use with electron beam and ion beam implosion systems are described. The multiple shell targets are of the low-power type and use a separate relatively low Z, low density ablator at large radius for the outer shell, which reduces the focusing and power requirements of the implosion system while maintaining reasonable aspect ratios. The targets use a high Z, high density pusher shell placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power profile and intershell density results in a low entropy implosion which allows breakeven at low powers. For example, with ion beams as a power source, breakeven at 10-20 Terrawatts with 10 MeV alpha particles for imploding a multiple shell target can be accomplished.

  3. The Multiplicative Situation

    ERIC Educational Resources Information Center

    Hurst, Chris

    2015-01-01

    The relationships between three critical elements, and the associated mathematical language, to assist students to make the critical transition from additive to multiplicative thinking are examined in this article by Chris Hurst.

  4. Pomalidomide for Multiple Myeloma

    Cancer.gov

    A summary of results from a phase III trial that compared the combination of pomalidomide (Pomalyst®) and low-dose dexamethasone versus high-dose dexamethasone alone in patients with multiple myeloma that has progressed despite other treatments.

  5. Hanford Site Development Plan

    SciTech Connect

    Rinne, C.A.; Curry, R.H.; Hagan, J.W.; Seiler, S.W.; Sommer, D.J. ); Yancey, E.F. )

    1990-01-01

    The Hanford Site Development Plan (Site Development Plan) is intended to guide the short- and long-range development and use of the Hanford Site. All acquisition, development, and permanent facility use at the Hanford Site will conform to the approved plan. The Site Development Plan also serves as the base document for all subsequent studies that involve use of facilities at the Site. This revision is an update of a previous plan. The executive summary presents the highlights of the five major topics covered in the Site Development Plan: general site information, existing conditions, planning analysis, Master Plan, and Five-Year Plan. 56 refs., 67 figs., 31 tabs.

  6. Multiple beam ptychography

    NASA Astrophysics Data System (ADS)

    Karl, Robert; Bevis, Charles; Lopez-Rios, Raymond; Reichanadter, Jonathan; Gardner, Dennis F.; Porter, Christina; Shanblatt, Elisabeth; Tanksalvala, Michael; Mancini, Giulia F.; Murnane, Margaret; Kapteyn, Henry; Adams, Daniel

    2016-03-01

    We present an extension to ptychography that allows simultaneous deconvolution of multiple, spatially separate, illuminating probes. This enables an increased field of view and hence, an increase in imaging throughput, without increased exposure times. This technique can be used for any non-interfering probes: demonstrated with multiple wavelengths and orthogonal polarizations. The latter of which gives us spatially resolved polarization spectroscopy from a single scan.

  7. Mobile multiple access study

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Multiple access techniques (FDMA, CDMA, TDMA) for the mobile user and attempts to identify the current best technique are discussed. Traffic loading is considered as well as voice and data modulation and spacecraft and system design. Emphasis is placed on developing mobile terminal cost estimates for the selected design. In addition, design examples are presented for the alternative techniques of multiple access in order to compare with the selected technique.

  8. Multiple stage multiple filter hydrate store

    DOEpatents

    Bjorkman, Jr., Harry K.

    1983-05-31

    An improved hydrate store for a metal halogen battery system is disclosed which employs a multiple stage, multiple filter means or separating the halogen hydrate from the liquid used in forming the hydrate. The filter means is constructed in the form of three separate sections which combine to substantially cover the interior surface of the store container. Exit conduit means is provided in association with the filter means for transmitting liquid passing through the filter means to a hydrate former subsystem. The hydrate former subsystem combines the halogen gas generated during the charging of the battery system with the liquid to form the hydrate in association with the store. Relief valve means is interposed in the exit conduit means for controlling the operation of the separate sections of the filter means, such that the liquid flow through the exit conduit means from each of the separate sections is controlled in a predetermined sequence. The three separate sections of the filter means operate in three discrete stages to provide a substantially uniform liquid flow to the hydrate former subsystem during the charging of the battery system. The separation of the liquid from the hydrate causes an increase in the density of the hydrate by concentrating the hydrate along the filter means.

  9. Trousseau's syndrome: multiple definitions and multiple mechanisms

    PubMed Central

    2007-01-01

    In 1865, Armand Trousseau noted that unexpected or migratory thrombophlebitis could be a forewarning of an occult visceral malignancy. An analysis by Sack and colleagues in 1977 extended the term Trousseau's syndrome to include chronic disseminated intravascular coagulopathy associated with microangiopathy, verrucous endocarditis, and arterial emboli in patients with cancer, often occurring with mucin-positive carcinomas. In recent times the term has been ascribed to various clinical situations, ranging all the way from these classic descriptions to any kind of coagulopathy occurring in the setting of any kind of malignancy. These multiple definitions of Trousseau's syndrome are partly the consequence of multiple pathophysiologic mechanisms that apparently contribute to the hypercoagulability associated with cancer. Even the classic syndrome probably represents a spectrum of disorders, ranging from exaggerated fluid-phased thrombosis dependent on prothrombotic agents such as tissue factor to a platelet- and endotheliumum-based selectin-dependent microangiopathy associated with mucin-producing carcinomas, along with thrombin and fibrin production. Also considered here are recent hypotheses about genetic pathways within tumor cells that might trigger these thrombotic phenomena, and the reasons why therapy with heparins of various kinds remain the preferred treatment, probably because of their salutary actions on several of the proposed pathologic mechanisms. PMID:17496204

  10. Multiple Indicators, Multiple Causes Measurement Error Models

    PubMed Central

    Tekwe, Carmen D.; Carter, Randy L.; Cullings, Harry M.; Carroll, Raymond J.

    2014-01-01

    Multiple Indicators, Multiple Causes Models (MIMIC) are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times however when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this paper are: (1) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model, (2) to develop likelihood based estimation methods for the MIMIC ME model, (3) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. As a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure. PMID:24962535

  11. Multiple stage multiple filter hydrate store

    DOEpatents

    Bjorkman, H.K. Jr.

    1983-05-31

    An improved hydrate store for a metal halogen battery system is disclosed which employs a multiple stage, multiple filter means for separating the halogen hydrate from the liquid used in forming the hydrate. The filter means is constructed in the form of three separate sections which combine to substantially cover the interior surface of the store container. Exit conduit means is provided in association with the filter means for transmitting liquid passing through the filter means to a hydrate former subsystem. The hydrate former subsystem combines the halogen gas generated during the charging of the battery system with the liquid to form the hydrate in association with the store. Relief valve means is interposed in the exit conduit means for controlling the operation of the separate sections of the filter means, such that the liquid flow through the exit conduit means from each of the separate sections is controlled in a predetermined sequence. The three separate sections of the filter means operate in three discrete stages to provide a substantially uniform liquid flow to the hydrate former subsystem during the charging of the battery system. The separation of the liquid from the hydrate causes an increase in the density of the hydrate by concentrating the hydrate along the filter means. 7 figs.

  12. Multiple indicators, multiple causes measurement error models.

    PubMed

    Tekwe, Carmen D; Carter, Randy L; Cullings, Harry M; Carroll, Raymond J

    2014-11-10

    Multiple indicators, multiple causes (MIMIC) models are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times, however, when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this paper are as follows: (i) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model; (ii) to develop likelihood-based estimation methods for the MIMIC ME model; and (iii) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. As a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure. PMID:24962535

  13. Breast-feeding multiples.

    PubMed

    Flidel-Rimon, O; Shinwell, E S

    2002-06-01

    Human breast milk is the best nutrition for human infants. Its advantages over the milk of other species, such as cows, include both a reduced risk for infections, allergies and chronic diseases, together with the full nutritional requirements for growth and development. Breast-feeding is as important for multiples as for singletons. Despite the advantages, multiples receive less breast-feeding than singletons. Common reasons for not breast-feeding multiples include the fear of not fulfilling the infants' needs and the difficulty of coping with the demands on the mother's time. In addition, many multiples are delivered prematurely and by Caesarean section. Maternal pain and discomfort together with anxiety over the infants' condition are not conducive to successful breast-feeding. During lactation, the mother needs to add calories to her daily diet. It has been recommended to add approximately 500-600 kcal/day for each infant. Thus, between eating, nursing and sleeping, life is very busy for the mother of multiples. However, there is evidence that, with appropriate nutrition, one mother can nourish more than one infant. Also, simultaneous breast-feeding can save much time. Combined efforts of parents, close family, friends and the medical team can help to make either full or partial breast-feeding of multiples possible. However, when breast-feeding is not possible, health care workers need to carefully avoid judgmental approaches that may induce feelings of guilt.

  14. Full potential multiple scattering theory

    SciTech Connect

    MacLaren, J.M.

    1994-10-20

    A practical method for performing self-consistent electronic structure calculations based upon full-potential multiple-scattering theory is presented. Solutions to the single site Schroedinger equation are obtained by solving coupled channel integral equations for a potential which is analytically continued out to the circumscribing sphere. This potential coincides with the full cell potential inside each atomic cell. Scattering matrices and wavefunctions for the full cell potential are obtained from surface Wronskian relations. The charge density is obtained from the single particle Green`s function. This Green`s function is computed using the cell scattering matrices and wavefunctions using the layer multiple scattering theory. Self consistent solutions require a solution at each iteration to the Poisson equation. The Poisson equation is solved using a variational cellular method. In the approach a local solution to each cell is augmented by adding a series of regular harmonics (solutions to Laplace`s equation). Minimizing the coulomb energy, subject to continuity of the potential across all cell boundary provides an expression for the coefficients of the regular harmonics. This method is applied to BCC Nb. Calculated properties converge well in angular momentum and show comparable accuracy to full potential linearized muffin-tin orbital calculations.

  15. The dynamics of pain: Evidence for simultaneous site-specific habituation and site-nonspecific sensitization in thermal pain

    PubMed Central

    Jepma, Marieke; Jones, Matt; Wager, Tor D.

    2014-01-01

    Repeated exposure to noxious stimuli changes their painfulness, due to multiple adaptive processes in the peripheral and central nervous system. Somewhat paradoxically, repeated stimulation can produce an increase (sensitization) or a decrease (habituation) in pain. Adaptation processes may also be body-site-specific or operate across body sites, and considering this distinction may help explain the conditions under which habituation vs. sensitization occurs. To dissociate the effects of site-specific and site-nonspecific adaptation processes, we examined reported pain in 100 participants during counterbalanced sequences of noxious thermal stimulation on multiple skin sites. Analysis of pain ratings revealed two opposing sequential effects: repeated stimulations of the same skin site produced temperature-dependent habituation, whereas repeated stimulations across different sites produced sensitization. Stimulation trials were separated by ~20 seconds and sensitization was unrelated to the distance between successively stimulated sites, suggesting that neither temporal nor spatial summation occurred. To explain these effects, we propose a dynamic model with two adaptation processes, one site-specific and one site-nonspecific. The model explains 93% of the variance in the group-mean pain ratings after controlling for current stimulation temperature, with its estimated parameters showing evidence for habituation for the site-specific process and sensitization for the site-nonspecific process. The two pain-adaptation processes revealed in this study, and the ability to disentangle them, may hold keys to understanding multiple pain-regulatory mechanisms and their disturbance in chronic-pain syndromes. Perspective This article presents novel evidence for simultaneous site-specific habituation and site-nonspecific sensitization in thermal pain, which can be disentangled (and the direction and strength of each process estimated) by a dynamic model. The dissociation of site

  16. 2013 BNL Site Environmental Report. Volume 1

    SciTech Connect

    Ratel, K.; Remien, J.; Pohlot, P.; Williams, J.; Green, T.; Paquette, P.; Dorsch, W.; Welty, T.; Burke, J.

    2014-10-01

    A summary of Brookhaven National Laboratory’s (BNL) Site Environmental Report, meant to inform the public, regulators, employees, and other stakeholders of the Laboratory’s environmental performance in the lab’s surrounding area during the calendar year. The review is comprised of multiple volumes relevant to environmental data/environmental management performance and groundwater status report.

  17. Research Supervision: An Important Site of Teaching

    ERIC Educational Resources Information Center

    McMichael, M. Jane; McKee, Margaret

    2008-01-01

    Supervision of students engaged in research projects and theses is an important site of teaching. Schon's (1987) well-known framework-educating for reflective practice-proves aptly suited for this teaching forum, offering insights for research supervision at multiple university levels. Conceptually, a research and writing studio where a practicum…

  18. Hanford Site Development Plan

    SciTech Connect

    Hathaway, H.B.; Daly, K.S.; Rinne, C.A.; Seiler, S.W.

    1993-05-01

    The Hanford Site Development Plan (HSDP) provides an overview of land use, infrastructure, and facility requirements to support US Department of Energy (DOE) programs at the Hanford Site. The HSDP`s primary purpose is to inform senior managers and interested parties of development activities and issues that require a commitment of resources to support the Hanford Site. The HSDP provides an existing and future land use plan for the Hanford Site. The HSDP is updated annually in accordance with DOE Order 4320.1B, Site Development Planning, to reflect the mission and overall site development process. Further details about Hanford Site development are defined in individual area development plans.

  19. Neuromaturation of multiples.

    PubMed

    Allen, Marilee C; Donohue, Pamela K

    2002-06-01

    Etiology of preterm birth and degree of maturation are the primary determinants of a preterm infant's survival and complications. Multiple gestation increases the likelihood of preterm birth but its influence on rate of maturation or complications of prematurity has been controversial, primarily because of confounding variables (e.g. race, aetiology of preterm delivery, degree of prematurity and pregnancy complications). Very low birthweight preterm multiples have virtually the same rates of neonatal mortality, complications and neuromaturation as preterm singletons of the same gestational age. There is no advantage of delivering twins or higher order multiples before 30 weeks gestation, unless a fetus decompensates in utero. Survival improves for near term intermediate-size preterm multiples while intrauterine growth decelerates and placental and fetal neuromaturation accelerate. These data and the high fetal death rate at term support delivery of multiples as soon as there is fetal lung maturity, and consideration of elective delivery of twins at 35-38 weeks gestation and triplets at 33-35 weeks gestation.

  20. MULTIPLE CONTAMINANTS CASE STUDIES

    EPA Science Inventory

    The presentation provides information taken from the arsenic demonstration program projects that have treatment systems removing multiply contaminants from drinking water. The case studies sited in the presentation consist of projects that have arsenic along with either nitrate, ...

  1. SCHOOL SITE STANDARDS AND SITE SELECTION.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany.

    THIS REPORT PRESENTS ELEMENTARY AND SECONDARY SCHOOL SITE DEVELOPMENT DATA COMPILED BY THE DIVISION OF EDUCATIONAL FACILITIES PLANNING, NEW YORK STATE EDUCATION DEPARTMENT. ENROLLMENT FIGURES USED REPRESENT THE ULTIMATE SIZE OF THE SCHOOLS. THE STANDARDS ARE MINIMUM FOR THE STATE OF NEW YORK WITH ELEMENTARY SCHOOL SITES BASED ON THREE ACRES PLUS…

  2. Site-wide seismic risk model for Savannah River Site nuclear facilities

    SciTech Connect

    Eide, S.A.; Shay, R.S.; Durant, W.S.

    1993-09-01

    The 200,000 acre Savannah River Site (SRS) has nearly 30 nuclear facilities spread throughout the site. The safety of each facility has been established in facility-specific safety analysis reports (SARs). Each SAR contains an analysis of risk from seismic events to both on-site workers and the off-site population. Both radiological and chemical releases are considered, and air and water pathways are modeled. Risks to the general public are generally characterized by evaluating exposure to the maximally exposed individual located at the SRS boundary and to the off-site population located within 50 miles. Although the SARs are appropriate methods for studying individual facility risks, there is a class of accident initiators that can simultaneously affect several of all of the facilities, Examples include seismic events, strong winds or tornados, floods, and loss of off-site electrical power. Overall risk to the off-site population from such initiators is not covered by the individual SARs. In such cases multiple facility radionuclide or chemical releases could occur, and off-site exposure would be greater than that indicated in a single facility SAR. As a step towards an overall site-wide risk model that adequately addresses multiple facility releases, a site-wide seismic model for determining off-site risk has been developed for nuclear facilities at the SRS. Risk from seismic events up to the design basis earthquake (DBE) of 0.2 g (frequency of 2.0E-4/yr) is covered by the model. Present plans include expanding the scope of the model to include other types of initiators that can simultaneously affect multiple facilities.

  3. Genetics Home Reference: multiple sclerosis

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions multiple sclerosis multiple sclerosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Multiple sclerosis is a condition characterized by areas of damage ( ...

  4. Multiple noncontiguous spine fractures.

    PubMed

    Henderson, R L; Reid, D C; Saboe, L A

    1991-02-01

    The data from a prospective study of 508 spine injuries were reviewed to determine the incidence of multiple noncontiguous spine fractures. All patients were examined at admission and at 1 and 2 years postinjury. This series identified 77 (15.2%) multilevel fractures. Motor vehicle accidents were the primary cause of these fractures. The incidence of neurologic injury was not significantly different between multiple noncontiguous and single fractures. Failure to use seat belts and ejection from the vehicle were the main factors associated with multiple noncontiguous spine injuries. Seven major fracture patterns were identified, which accounted for 60% of these injuries. The prognosis for multilevel spine fractures was not significantly worse that that for single-level injuries. PMID:2011766

  5. Enhancing multiple disciplinary teamwork.

    PubMed

    Weaver, Terri E

    2008-01-01

    Multiple disciplinary research provides an opportunity to bring together investigators across disciplines to provide new views and develop innovative approaches to important questions. Through this shared experience, novel paradigms are formed, original frameworks are developed, and new language is generated. Integral to the successful construction of effective cross-disciplinary teams is the recognition of antecedent factors that affect the development of the team such as intrapersonal, social, physical environmental, organizational, and institutional influences. Team functioning is enhanced with well-developed behavioral, affective, interpersonal, and intellectual processes. Outcomes of effective multiple disciplinary research teams include novel ideas, integrative models, new training programs, institutional change, and innovative policies that can also influence the degree to which antecedents and processes contribute to team performance. Ongoing evaluation of team functioning and achievement of designated outcomes ensures the continued development of the multiple disciplinary team and confirmation of this approach as important to the advancement of science.

  6. MAVID multiple alignment server.

    PubMed

    Bray, Nicolas; Pachter, Lior

    2003-07-01

    MAVID is a multiple alignment program suitable for many large genomic regions. The MAVID web server allows biomedical researchers to quickly obtain multiple alignments for genomic sequences and to subsequently analyse the alignments for conserved regions. MAVID has been successfully used for the alignment of closely related species such as primates and also for the alignment of more distant organisms such as human and fugu. The server is fast, capable of aligning hundreds of kilobases in less than a minute. The multiple alignment is used to build a phylogenetic tree for the sequences, which is subsequently used as a basis for identifying conserved regions in the alignment. The server can be accessed at http://baboon.math.berkeley.edu/mavid/.

  7. Multiple sort flow cytometer

    DOEpatents

    Engh, G. van den; Esposito, R.J.

    1996-01-09

    A flow cytometer utilizes multiple lasers for excitation and respective fluorescence of identified dyes bonded to specific cells or events to identify and verify multiple events to be sorted from a sheath flow and droplet stream. Once identified, verified and timed in the sheath flow, each event is independently tagged upon separation from the flow by an electrical charge of +60, +120, or +180 volts and passed through oppositely charged deflection plates with ground planes to yield a focused six way deflection of at least six events in a narrow plane. 8 figs.

  8. Multiple origins of life

    NASA Technical Reports Server (NTRS)

    Raup, D. M.; Valentine, J. W.

    1983-01-01

    There is some indication that life may have originated readily under primitive earth conditions. If there were multiple origins of life, the result could have been a polyphyletic biota today. Using simple stochastic models for diversification and extinction, we conclude: (1) the probability of survival of life is low unless there are multiple origins, and (2) given survival of life and given as many as 10 independent origins of life, the odds are that all but one would have gone extinct, yielding the monophyletic biota we have now. The fact of the survival of our particular form of life does not imply that it was unique or superior.

  9. Neutron multiplicity analysis tool

    SciTech Connect

    Stewart, Scott L

    2010-01-01

    I describe the capabilities of the EXCOM (EXcel based COincidence and Multiplicity) calculation tool which is used to analyze experimental data or simulated neutron multiplicity data. The input to the program is the count-rate data (including the multiplicity distribution) for a measurement, the isotopic composition of the sample and relevant dates. The program carries out deadtime correction and background subtraction and then performs a number of analyses. These are: passive calibration curve, known alpha and multiplicity analysis. The latter is done with both the point model and with the weighted point model. In the current application EXCOM carries out the rapid analysis of Monte Carlo calculated quantities and allows the user to determine the magnitude of sample perturbations that lead to systematic errors. Neutron multiplicity counting is an assay method used in the analysis of plutonium for safeguards applications. It is widely used in nuclear material accountancy by international (IAEA) and national inspectors. The method uses the measurement of the correlations in a pulse train to extract information on the spontaneous fission rate in the presence of neutrons from ({alpha},n) reactions and induced fission. The measurement is relatively simple to perform and gives results very quickly ({le} 1 hour). By contrast, destructive analysis techniques are extremely costly and time consuming (several days). By improving the achievable accuracy of neutron multiplicity counting, a nondestructive analysis technique, it could be possible to reduce the use of destructive analysis measurements required in safeguards applications. The accuracy of a neutron multiplicity measurement can be affected by a number of variables such as density, isotopic composition, chemical composition and moisture in the material. In order to determine the magnitude of these effects on the measured plutonium mass a calculational tool, EXCOM, has been produced using VBA within Excel. This

  10. Multiple sort flow cytometer

    DOEpatents

    Van den Engh, Ger; Esposito, Richard J.

    1996-01-01

    A flow cytometer utilizes multiple lasers for excitation and respective fluorescence of identified dyes bonded to specific cells or events to identify and verify multiple events to be sorted from a sheath flow and droplet stream. Once identified, verified and timed in the sheath flow, each event is independently tagged upon separation from the flow by an electrical charge of +60, +120, or +180 volts and passed through oppositely charged deflection plates with ground planes to yield a focused six way deflection of at least six events in a narrow plane.

  11. Site amplifications for generic rock sites

    USGS Publications Warehouse

    Boore, D.M.; Joyner, W.B.

    1997-01-01

    Seismic shear-wave velocity as a function of depth for generic rock sites has been estimated from borehole data and studies of crustal velocities, and these velocities have been used to compute frequency-dependent amplifications for zero attenuation for use in simulations of strong ground motion. We define a generic rock site as one whose velocity at shallow depths equals the average of those from the rock sites sampled by the borehole data. Most of the boreholes are in populated areas; for that reason, the rock sites sampled are of particular engineering significance. We consider two generic rock sites: rock, corresponding to the bulk of the borehole data, and very hard rock, such as is found in glaciated regions in large areas of eastern North America or in portions of western North America. The amplifications on rock sites can be in excess of 3.5 at high frequencies, in contrast to the amplifications of less than 1.2 on very hard rock sites. The consideration of unattenuated amplification alone is computationally convenient, but what matters for ground-motion estimation is the combined effect of amplification and attenuation. For reasonable values of the attenuation parameter K0, the combined effect of attenuation and amplification for rock sites peaks between about 2 and 5 Hz with a maximum level of less than 1.8. The combined effect is about a factor of 1.5 at 1 Hz and is less than unity for frequencies in the range of 10 to 20 Hz (depending on K0). Using these amplifications, we find provisional values of about ???? = 70 bars and K0 = 0.035 sec for rock sites in western North America by fitting our empirically determined response spectra for an M 6.5 event to simulated values. The borehole data yield shear velocities (V??30) of 618 and 306 m/sec for "rock" and "soil" sites, respectively, when averaged over the upper 30 m. From this, we recommend that V??30 equals 620 and 310 m/sec for applications requiring the average velocity for rock and soil sites in

  12. [Multiple bowenoid arsenic keratoses].

    PubMed

    Leyh, F; Rothlaender, J P

    1985-01-01

    Case report of multiple keratoses and chronic lymphatic leukemia after arsenic poisoning 30 years ago during a one-year exposure to copper acetoarsenate in a pesticide factory. Absorption through the skin with local arsenic skin damage is discussed. Etretinate therapy (1 mg/kg b. w.) was ineffective.

  13. Multiple Cutaneous Reticulohistiocytoma

    PubMed Central

    Hemmady, Karishma D; Someshwar, Shylaja S; Jerajani, Hemangi R

    2016-01-01

    Multicentric reticulohistiocytosis is a rare non-Langerhans cell histiocytosis characterized in its full form by severe destructive arthritis, cutaneous nodules, and systemic manifestations. Cutaneous lesions may precede, accompany, or more commonly develop later than other features in this disease. We describe a case of multiple cutaneous reticulohistiocytoma without any systemic associations after thorough investigations. PMID:26955136

  14. Managing Multiple Measures

    ERIC Educational Resources Information Center

    DePascale, Charles A.

    2012-01-01

    Regardless of how one might feel about the recent developments in teacher evaluation systems, No Child Left Behind (NCLB) and adequate yearly progress (AYP), or student assessments for high-stakes promotion decisions, educators overwhelmingly agree that use of multiple measures is better than reliance on a single measure such as a large-scale,…

  15. Automatic multiple applicator electrophoresis

    NASA Technical Reports Server (NTRS)

    Grunbaum, B. W.

    1977-01-01

    Easy-to-use, economical device permits electrophoresis on all known supporting media. System includes automatic multiple-sample applicator, sample holder, and electrophoresis apparatus. System has potential applicability to fields of taxonomy, immunology, and genetics. Apparatus is also used for electrofocusing.

  16. [Smoldering multiple myeloma].

    PubMed

    Fouquet, G; Guidez, S; Herbaux, C; Demarquette, H; Leleu, X

    2014-04-01

    Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell neoplasia, characterized by monoclonal plasma cell proliferation in the absence of end-organ damage, but with a high risk of progression to multiple myeloma. It has therefore to be distinguished from monoclonal gammapathy of undetermined significance (MGUS), which has a much lower risk of progression, but also from multiple myeloma, which remains an incurable disease and requires a specific treatment. The critical question in the management of SMM is whether an early therapeutic strategy could help delaying the progression to multiple myeloma, in order to lower the risk of serious complications related to this progression, or even to cure the disease. This early treatment could not be proposed to all SMM patients, who are indeed asymptomatic, and in whom the risk of toxicity could make it difficult to justify the potential benefit obtained. The challenge is to target early at diagnosis SMM patients with a high risk of progression, using available routine tests sufficiently reliable to warrant the therapeutic sanction which relies on it. Today however, apart from randomized studies, recommendations are to maintain therapeutic abstention in SMM patients. PMID:24050785

  17. Patterns in Multiples.

    ERIC Educational Resources Information Center

    Robold, Alice I.

    1982-01-01

    Activities that allow students to represent patterns concretely before showing the patterns in color on paper are presented. Three basic activities are described, with suggestions made for extensions that allow further pupil exploration of multiples. Student discovery of relationships not found by the teacher is expected. (MP)

  18. Higher-order Multiples.

    PubMed

    Stone, Joanne; Kohari, Katherine S

    2015-09-01

    Higher-order multiple gestations have increased since the advent of advanced reproductive technologies. These pregnancies present unique risks to both mothers and fetuses. It is imperative that early diagnosis of chronicity be determined and that proper counseling is performed, so patients understand the risks, evaluation, and management needed.

  19. Multiple Primary Cancer Monograph

    Cancer.gov

    To identify groups of cancer survivors that are at increased risk for multiple primary cancers, investigators led an effort to provide the first comprehensive population-based analysis of the risk of subsequent cancer in the U.S., resulting in a monograph.

  20. Multiple gap photovoltaic device

    DOEpatents

    Dalal, Vikram L.

    1981-01-01

    A multiple gap photovoltaic device having a transparent electrical contact adjacent a first cell which in turn is adjacent a second cell on an opaque electrical contact, includes utilizing an amorphous semiconductor as the first cell and a crystalline semiconductor as the second cell.

  1. Multiple Grammars and MOGUL

    ERIC Educational Resources Information Center

    Truscott, John

    2014-01-01

    Optionality is a central phenomenon in second language acquisition (SLA), for which any adequate theory must account. Amaral and Roeper (this issue; henceforth A&R) offer an appealing approach to it, using Roeper's Multiple Grammars Theory, which was created with first language in mind but which extends very naturally to SLA. They include…

  2. Mastering the Multiplication Facts

    ERIC Educational Resources Information Center

    D'Ettorre, Jenna

    2009-01-01

    The purpose of this paper is to share the results of a six-week research project (after baseline data was collected) that focused on three different strategies (flashcards, interactive games, and music) and their effectiveness in helping fifth grade students memorize the basic multiplication facts. Many teachers face a serious problem when their…

  3. Multiple Access Trade Study

    NASA Technical Reports Server (NTRS)

    Motamedi, Masoud

    1990-01-01

    The Personal Access Satellite System (PASS) strawman design uses a hybrid Time Division Multiple Access (TDMA)/Frequency Division Multiple Access (FDMA) implementation. TDMA is used for the forward direction (from Suppliers to Users), and FDMA for the return direction (from Users to Suppliers). An alternative architecture is proposed that will require minimal real time coordination and yet provide a fast access method by using random access Code Division Multiple Access (CDMA). The CDMA system issues are addressed such as connecting suppliers and users, both of whom may be located anywhere in the CONUS, when the user terminals are constrained in size and weight; and providing efficient traffic routing under highly variable traffic requirements. It is assumed that bandwidth efficiency is not of paramount importance. CDMA or Spread Spectrum Multiple Access (SSMA) communication is a method in which a group of carriers operate at the same nominal center frequency but are separable from each other by the low cross correlation of the spreading codes used. Interference and multipath rejection capability, ease of selective addressing and message screening, low density power spectra for signal hiding and security, and high resolution ranging are among the benefits of spread spectrum communications.

  4. Multiple Stochastic Point Processes in Gene Expression

    NASA Astrophysics Data System (ADS)

    Murugan, Rajamanickam

    2008-04-01

    We generalize the idea of multiple-stochasticity in chemical reaction systems to gene expression. Using Chemical Langevin Equation approach we investigate how this multiple-stochasticity can influence the overall molecular number fluctuations. We show that the main sources of this multiple-stochasticity in gene expression could be the randomness in transcription and translation initiation times which in turn originates from the underlying bio-macromolecular recognition processes such as the site-specific DNA-protein interactions and therefore can be internally regulated by the supra-molecular structural factors such as the condensation/super-coiling of DNA. Our theory predicts that (1) in case of gene expression system, the variances ( φ) introduced by the randomness in transcription and translation initiation-times approximately scales with the degree of condensation ( s) of DNA or mRNA as φ ∝ s -6. From the theoretical analysis of the Fano factor as well as coefficient of variation associated with the protein number fluctuations we predict that (2) unlike the singly-stochastic case where the Fano factor has been shown to be a monotonous function of translation rate, in case of multiple-stochastic gene expression the Fano factor is a turn over function with a definite minimum. This in turn suggests that the multiple-stochastic processes can also be well tuned to behave like a singly-stochastic point processes by adjusting the rate parameters.

  5. Field site selection

    NASA Technical Reports Server (NTRS)

    Schwarz, D. E.; Ellefsen, R. E.

    1981-01-01

    Several general guidelines should be kept in mind when considering the selection of field sites for teaching remote sensing fundamentals. Proximity and vantage point are two very practical considerations. Only through viewing a broad enough area to place the site in context can one make efficient use of a site. The effects of inclement weather when selecting sites should be considered. If field work is to be an effective tool to illustrate remote sensing principles, the following criteria are critical: (1) the site must represent the range of class interest; (2) the site must have a theme or add something no other site offers; (3) there should be intrasite variation within the theme; (4) ground resolution and spectral signature distinction should be illustrated; and (5) the sites should not be ordered sequentially.

  6. SMARTE'S SITE CHARACTERIZATION TOOL

    EPA Science Inventory

    Site Characterization involves collecting environmental data to evaluate the nature and extent of contamination. Environmental data could consist of chemical analyses of soil, sediment, water or air samples. Typically site characterization data are statistically evaluated for thr...

  7. Multiplicative Calculus and Student Projects.

    ERIC Educational Resources Information Center

    Campbell, Duff

    1999-01-01

    Multiplicative calculus is based on a multiplicative rate of change whereas the usual calculus is based on an additive rate of change. Describes some student investigations into multiplicative calculus, including an original student idea about multiplicative Euler's Method. (Author/ASK)

  8. Appreciating "Thirdspace": An Alternative Way of Viewing and Valuing Site-Specific Dance Performance

    ERIC Educational Resources Information Center

    Munjee, Tara

    2014-01-01

    Site-specific dance performance involves the presentation of choreography in connection with a site. The context of the site combined with a viewer's personal history, beliefs, and identity impact the reading and appreciation of the performance. Although both stage and site dance performance valuing elicit multiple interpretations of artistic…

  9. Core multiplication in childhood.

    PubMed

    McCrink, Koleen; Spelke, Elizabeth S

    2010-08-01

    A dedicated, non-symbolic, system yielding imprecise representations of large quantities (approximate number system, or ANS) has been shown to support arithmetic calculations of addition and subtraction. In the present study, 5-7-year-old children without formal schooling in multiplication and division were given a task requiring a scalar transformation of large approximate numerosities, presented as arrays of objects. In different conditions, the required calculation was doubling, quadrupling, or increasing by a fractional factor (2.5). In all conditions, participants were able to represent the outcome of the transformation at above-chance levels, even on the earliest training trials. Their performance could not be explained by processes of repeated addition, and it showed the critical ratio signature of the ANS. These findings provide evidence for an untrained, intuitive process of calculating multiplicative numerical relationships, providing a further foundation for formal arithmetic instruction. PMID:20537618

  10. Multiple zeros of polynomials

    NASA Technical Reports Server (NTRS)

    Wood, C. A.

    1974-01-01

    For polynomials of higher degree, iterative numerical methods must be used. Four iterative methods are presented for approximating the zeros of a polynomial using a digital computer. Newton's method and Muller's method are two well known iterative methods which are presented. They extract the zeros of a polynomial by generating a sequence of approximations converging to each zero. However, both of these methods are very unstable when used on a polynomial which has multiple zeros. That is, either they fail to converge to some or all of the zeros, or they converge to very bad approximations of the polynomial's zeros. This material introduces two new methods, the greatest common divisor (G.C.D.) method and the repeated greatest common divisor (repeated G.C.D.) method, which are superior methods for numerically approximating the zeros of a polynomial having multiple zeros. These methods were programmed in FORTRAN 4 and comparisons in time and accuracy are given.

  11. Multiple pulse laser

    SciTech Connect

    Hughes, R.S.; Jernigan, J.L.

    1981-02-10

    A multiple pulse laser from a single resonant cavity is disclosed. An acousto-optic cell is used to modulate coherent light from a lasing element. Either multiple chirp signals or a masked mirror are used to provide distinct pulses of light. Through proper choice of materials for the acousto-optic cell and use of divergent optics, a higher power level is obtained. Use of a multi-tapped delay line permits a shorter period between pulses due to the linear superposition principle. When the mask embodiment is used, the acousto-optic cell focuses light which scans across the mask. Whenever the focused light passes through the mask, lasing occurs which generates an output pulse.

  12. Portable multiplicity counter

    DOEpatents

    Newell, Matthew R.; Jones, David Carl

    2009-09-01

    A portable multiplicity counter has signal input circuitry, processing circuitry and a user/computer interface disposed in a housing. The processing circuitry, which can comprise a microcontroller integrated circuit operably coupled to shift register circuitry implemented in a field programmable gate array, is configured to be operable via the user/computer interface to count input signal pluses receivable at said signal input circuitry and record time correlations thereof in a total counting mode, coincidence counting mode and/or a multiplicity counting mode. The user/computer interface can be for example an LCD display/keypad and/or a USB interface. The counter can include a battery pack for powering the counter and low/high voltage power supplies for biasing external detectors so that the counter can be configured as a hand-held device for counting neutron events.

  13. Multiple wavelength diffractive imaging

    NASA Astrophysics Data System (ADS)

    Chen, Bo; Dilanian, Ruben A.; Teichmann, Sven; Abbey, Brian; Peele, Andrew G.; Williams, Garth J.; Hannaford, Peter; van Dao, Lap; Quiney, Harry M.; Nugent, Keith A.

    2009-02-01

    We demonstrate coherent diffraction imaging using multiple harmonics from a high-harmonic generation source. An algorithm is presented that builds the known incident spectrum into the reconstruction procedure with the result that the useable flux is increased by more than an order of magnitude. Excellent images are obtained with a resolution of (165±5)nm and compare very well with images from a scanning electron microscope.

  14. Multiple muons in MACRO

    NASA Technical Reports Server (NTRS)

    Heinz, R.

    1985-01-01

    An analysis of the multiple muon events in the Monopole Astrophysics and Cosmic Ray Observatory detector was conducted to determine the cosmic ray composition. Particular emphasis is placed on the interesting primary cosmic ray energy region above 2000 TeV/nucleus. An extensive study of muon production in cosmic ray showers has been done. Results were used to parameterize the characteristics of muon penetration into the Earth to the location of a detector.

  15. Universality of particle multiplicities

    SciTech Connect

    Goulianos, K. |

    1994-09-01

    We discuss the scaling properties and universality aspects of the rapidity and multiplicity distributions of particles produced in high energy hadronic and e{sup +}e{sup {minus}} interactions. This paper is based on material presented in three lectures on pomeron phenomenology, which included a review of traditional soft pomeron physics and selected topics on hard diffraction processes probing the structure function of the pomeron.

  16. Multiple quantum coherence spectroscopy.

    PubMed

    Mathew, Nathan A; Yurs, Lena A; Block, Stephen B; Pakoulev, Andrei V; Kornau, Kathryn M; Wright, John C

    2009-08-20

    Multiple quantum coherences provide a powerful approach for studies of complex systems because increasing the number of quantum states in a quantum mechanical superposition state increases the selectivity of a spectroscopic measurement. We show that frequency domain multiple quantum coherence multidimensional spectroscopy can create these superposition states using different frequency excitation pulses. The superposition state is created using two excitation frequencies to excite the symmetric and asymmetric stretch modes in a rhodium dicarbonyl chelate and the dynamic Stark effect to climb the vibrational ladders involving different overtone and combination band states. A monochromator resolves the free induction decay of different coherences comprising the superposition state. The three spectral dimensions provide the selectivity required to observe 19 different spectral features associated with fully coherent nonlinear processes involving up to 11 interactions with the excitation fields. The different features act as spectroscopic probes of the diagonal and off-diagonal parts of the molecular potential energy hypersurface. This approach can be considered as a coherent pump-probe spectroscopy where the pump is a series of excitation pulses that prepares a multiple quantum coherence and the probe is another series of pulses that creates the output coherence. PMID:19507812

  17. MULTIPLE OSCILLATION STABILIZING CONTROL.

    SciTech Connect

    YUE,M.; SCHLUETER,R.; AZARM,M.; BARI,R.

    2004-07-23

    This paper presents a strategy that may be used to guide stabilizing control design for multiple oscillations, which are difficult to control using conventional control design procedures. A multiple oscillation phenomena is observed in an example power system. A local bifurcation and an interarea bifurcation develop in an example power system due to multiple bifurcation parameter variations. The dynamic behaviors of the bifurcating system are complex due to the overlapping of the two different bifurcation subsystems and are shown to be difficult to control. The double bifurcations are studied in this paper and in order to stabilize them, three kind of {mu}-synthesis robust controls are designed, (a) {mu}-synthesis power system stabilizer (MPSS); (b) {mu}-synthesis SVC control (MSVC); and (c) a mixed MPSS/MSVC control. Based on the bifurcation subsystem analysis, the measurement signals and locations of the controls are selected. The control performances of three kind of controls are evaluated and compared. The conclusions are given according to the analysis and time simulation results.

  18. Multiple Core Galaxies

    NASA Technical Reports Server (NTRS)

    Miller, R.H.; Morrison, David (Technical Monitor)

    1994-01-01

    Nuclei of galaxies often show complicated density structures and perplexing kinematic signatures. In the past we have reported numerical experiments indicating a natural tendency for galaxies to show nuclei offset with respect to nearby isophotes and for the nucleus to have a radial velocity different from the galaxy's systemic velocity. Other experiments show normal mode oscillations in galaxies with large amplitudes. These oscillations do not damp appreciably over a Hubble time. The common thread running through all these is that galaxies often show evidence of ringing, bouncing, or sloshing around in unexpected ways, even though they have not been disturbed by any external event. Recent observational evidence shows yet another phenomenon indicating the dynamical complexity of central regions of galaxies: multiple cores (M31, Markarian 315 and 463 for example). These systems can hardly be static. We noted long-lived multiple core systems in galaxies in numerical experiments some years ago, and we have more recently followed up with a series of experiments on multiple core galaxies, starting with two cores. The relevant parameters are the energy in the orbiting clumps, their relative.masses, the (local) strength of the potential well representing the parent galaxy, and the number of cores. We have studied the dependence of the merger rates and the nature of the final merger product on these parameters. Individual cores survive much longer in stronger background potentials. Cores can survive for a substantial fraction of a Hubble time if they travel on reasonable orbits.

  19. Site and Facilities: A Resource Book for Camps.

    ERIC Educational Resources Information Center

    Ball, Armand, Ed.; Ball, Beverly, Ed.

    This resource book draws together articles on the development and maintenance of camp sites and facilities. The articles, previously published by "Camping Magazine" and "Journal of Christian Camping," cover (1) site planning and long-range development, including redesigning multiple camp facilities for year-round programs, remodeling and…

  20. Site Environmental Report, 1993

    SciTech Connect

    Not Available

    1994-06-01

    The Site Environmental Report (SER) is prepared annually in accordance with DOE Order 5400.1, ``General Environmental Protection Program.`` This 1993 SER provides the general public as well as scientists and engineers with the results from the site`s ongoing Environmental Monitoring Program. Also included in this report is information concerning the site`s progress toward achieving full compliance with requirements set forth by DOE, US Environmental Protection Agency (USEPA), and Ohio EPA (OEPA). For some readers, the highlights provided in the Executive Summary may provide sufficient information. Many readers, however, may wish to read more detailed descriptions of the information than those which are presented here.

  1. Tomography finds waste sites

    NASA Astrophysics Data System (ADS)

    Bush, Susan M.

    Geophysical diffraction tomography (GDT), a remote sensing method, is being developed for hazardous waste site characterization by researchers at Oak Ridge National Laboratory, Tenn., with the support of the U.S. Army Toxic and Hazardous Materials Agency, Aberdeen Proving Ground, Md.More accurate assessment of hazardous sites translates into more efficient and less costly cleanup efforts by defining parameters such as waste site boundaries, geophysical site characteristics, buried container leakage, and hazardous material migration. Remote sensing devices eliminate the potential for environmental damage, safety hazards, or high costs associated with intrusive site characterization techniques.

  2. Ethylene binding site affinity in ripening apples

    SciTech Connect

    Blankenship, S.M. . Dept. of Horticultural Science); Sisler, E.C. )

    1993-09-01

    Scatchard plots for ethylene binding in apples (Malus domestica Borkh.), which were harvested weekly for 5 weeks to include the ethylene climacteric rise, showed C[sub 50] values (concentration of ethylene needed to occupy 50% of the ethylene binding sites) of 0.10, 0.11, 0.34, 0.40, and 0.57 [mu]l ethylene/liter[sup [minus]1], respectively, for each of the 5 weeks. Higher ethylene concentrations were required to saturate the binding sites during the climacteric rise than at other times. Diffusion of [sup 14]C-ethylene from the binding sites was curvilinear and did not show any indication of multiple binding sites. Ethylene was not metabolized by apple tissue.

  3. Hanford Site Sustainability Program, Richland, Washington - 12464

    SciTech Connect

    Fritz, Lori

    2012-07-01

    In support of implementation of Executive Order (EO) 13514, Federal Leadership in Environmental, Energy and Economic Performance, the Hanford Site Sustainability Plan [1] was developed to implement strategies and activities required to achieve the prescribed goals in the EO as well as demonstrate measurable progress in environmental stewardship at the Hanford Site. The Hanford Site has made significant progress in the area of environmental stewardship through multiple initiatives to reduce energy consumption and GHG emissions, despite increased demands in those areas due to accelerated cleanup work driven by ARRA funding. Future plans, contingent on available funding, include additional enhancements in the areas of fleet management, including installation of additional charging stations and continued acquisition of alternate fueled vehicles, implementation of one or more of the recommendations from the Feasibility Study on reducing GHG emissions from employee commuting, and potential diversion of solid waste from on-site landfills. (author)

  4. Integrating multiple networks for protein function prediction

    PubMed Central

    2015-01-01

    Background High throughput techniques produce multiple functional association networks. Integrating these networks can enhance the accuracy of protein function prediction. Many algorithms have been introduced to generate a composite network, which is obtained as a weighted sum of individual networks. The weight assigned to an individual network reflects its benefit towards the protein functional annotation inference. A classifier is then trained on the composite network for predicting protein functions. However, since these techniques model the optimization of the composite network and the prediction tasks as separate objectives, the resulting composite network is not necessarily optimal for the follow-up protein function prediction. Results We address this issue by modeling the optimization of the composite network and the prediction problems within a unified objective function. In particular, we use a kernel target alignment technique and the loss function of a network based classifier to jointly adjust the weights assigned to the individual networks. We show that the proposed method, called MNet, can achieve a performance that is superior (with respect to different evaluation criteria) to related techniques using the multiple networks of four example species (yeast, human, mouse, and fly) annotated with thousands (or hundreds) of GO terms. Conclusion MNet can effectively integrate multiple networks for protein function prediction and is robust to the input parameters. Supplementary data is available at https://sites.google.com/site/guoxian85/home/mnet. The Matlab code of MNet is available upon request. PMID:25707434

  5. Correct implementation of the Argonne QuickSite{sup SM} process for preremedial site investigations

    SciTech Connect

    Burton, J.C.; Walker, J.L.

    1997-10-01

    Expedited site characterization (ESC), developed by Argonne National Laboratory, is an interactive, integrated process emphasizing the use of existing data of sufficient quality, multiple complementary characterization methods, and on-site decision making to optimize environmental site investigations. The Argonne ESC is the basis for the provisional ESC standard guide of the ASTM (American Society for Testing and Materials). QuickSite{sup SM} is the implementation package developed by Argonne to facilitate ESC of sites contaminated with hazardous wastes. At various sites, Argonne has successfully implemented QuickSite{sup SM} and demonstrated the technical superiority of the ESC process over traditional methodologies guided by statistics and random-sampling approaches. A key feature in the success of QuickSite{sup SM} investigations is achieving an understanding of the subsurface geologic and hydrogeologic controls and processes at a site before extensive sampling efforts begin. The QuickSite{sup SM} investigation at the Tustin Marine Corps Air Station (MCAS) in California will be used to illustrate the importance of understanding these potential controls in minimizing sampling activities and correctly predicting potential contaminant migration patterns for risk assessment.

  6. Hanford Site Comprehensive site Compliance Evaluation Report

    SciTech Connect

    Tollefson, K.S.

    1997-08-05

    This document is the second annual submittal by WHC, ICF/KH, PNL and BHI and contains the results of inspections of the stormwater outfalls listed in the Hanford Site Storm Water Pollution Prevention Plan (SWPPP) (WHC 1993a) as required by General Permit No. WA-R-00-000F (WA-R-00-A17F): This report also describes the methods used to conduct the Storm Water Comprehensive Site Compliance Evaluation, as required in Part IV, Section D, {ampersand} C of the General Permit, summarizes the results of the compliance evaluation, and documents significant leaks and spills.

  7. Simultaneous Removal of Multiple DNA Segments by Polymerase Chain Reactions.

    PubMed

    Krishnamurthy, Vishnu; Zhang, Kai

    2017-01-01

    Precise DNA manipulation is a key enabling technology for synthetic biology. Approaches based on restriction digestion are often limited by the presence of certain restriction enzyme recognition sites. Recent development of restriction-free cloning approaches has greatly enhanced the flexibility and speed of molecular cloning. Most restriction-free cloning methods focus on DNA assembly. Much less work has been dedicated towards DNA removal. Here we introduce a protocol that allows simultaneous removal of multiple DNA segments from a plasmid using polymerase chain reactions (PCR). Our approach will be beneficial to applications in multiple sites mutagenesis, DNA library construction, genetic and protein engineering, and synthetic biology. PMID:27671942

  8. Multiple sclerosis and infections.

    PubMed

    Venkatesan, Arun

    2015-01-01

    The intersection between infections and multiple sclerosis (MS) is complex and bidirectional. Numerous infectious agents have been posited to play a role in the initiation of MS, while emerging evidence suggests a potential relationship between established MS and the gut microbiome. As both systemic and CNS infections are major complications of MS, the clinical manifestations and evolving epidemiology of these infections over the lifespan of the MS patient are examined in this review. Data from animal models and human studies are discussed. PMID:26611265

  9. Multiple-chemical sensitivity.

    PubMed

    Glinton, Gloria J

    2005-12-01

    Multiple-chemical sensitivity (MCS) is a condition in which individuals have an acute hypersensitivity to low levels of chemicals found in everyday substances, such as household cleaning agents, pesticides, fresh paint, new carpeting, synthetic building materials, newsprint, perfume, and numerous other petrochemical products. This condition continues to remain somewhat of a mystery to the medical community, and its true prevalence rate is unknown because many cases are not identified and reported as MCS. This article will inform the reader about the condition of MCS.

  10. Multiple personality disorder.

    PubMed

    Piper, A

    1994-05-01

    Five aspects of the diagnosis and treatment of multiple personality disorder (MPD) were examined. The following five conclusions were made: the contemporary diagnostic criteria are vague and overinclusive; the recent alleged increase in prevalence of the disorder is almost certainly artefactual; legal proceedings involving MPD patients raise disturbing questions about personal responsibility; there is little literature support for the theory that MPD results from childhood trauma; and many of the techniques used to diagnose and treat the condition reinforce its symptoms. A careful revision of diagnostic criteria for the disorder is recommended.

  11. Factorial Invariance in Multiple Populations: A Multiple Testing Procedure

    ERIC Educational Resources Information Center

    Raykov, Tenko; Marcoulides, George A.; Millsap, Roger E.

    2013-01-01

    A multiple testing method for examining factorial invariance for latent constructs evaluated by multiple indicators in distinct populations is outlined. The procedure is based on the false discovery rate concept and multiple individual restriction tests and resolves general limitations of a popular factorial invariance testing approach. The…

  12. CELT site testing program

    NASA Astrophysics Data System (ADS)

    Schoeck, Matthias; Erasmus, D. Andre; Djorgovski, S. George; Chanan, Gary A.; Nelson, Jerry E.

    2003-01-01

    The California Extremely Large Telescope, CELT, is a proposed 30-m telescope. Choosing the best possible site for CELT is essential in order to extract the best science from the observations and to reduce the complexity of the telescope. Site selection is therefore currently one of the most critical pacing items of the CELT project. In this paper, we first present selected results from a survey of the atmospheric transparency at optical and infrared wavelengths over the southwestern USA and northern Mexico using satellite data. Results of a similar study of South America have been reported elsewhere. These studies will serve as the pre-selection criterion of the sites at which we will perform on-site testing. We then describe the current status of on-site turbulence evaluation efforts and the future plans of the CELT site testing program.

  13. A Case of Multiple Spontaneous Keloid Scars

    PubMed Central

    Jfri, Abdulhadi; Rajeh, Nawal; Karkashan, Eman

    2015-01-01

    Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body. PMID:26351423

  14. Pediatric Multiple Sclerosis.

    PubMed

    Lee, Ji Y; Chitnis, Tanuja

    2016-04-01

    Pediatric multiple sclerosis (MS) is a chronic inflammatory neurologic disease that is challenging to diagnose and treat. Although there are many clinical parallels between pediatric-onset MS and adult-onset MS, there is also accumulating evidence of distinguishing clinical features that may, in part, arise from development-specific, neuroimmune processes governing MS pathogenesis in children. Here the authors describe the clinical features, diagnosis, and treatment of pediatric MS, with a particular focus on describing clinical features and highlighting new developments that promise a better understanding of pediatric MS pathogenesis. An important task that lies ahead for pediatric neurologists is better understanding the early gene-environment interaction that precipitates the first demyelinating event in pediatric MS. This area is of particular importance for understanding the MS etiology and the natural history of pediatric MS. Such understanding should in turn inform new developments in diagnostic tools, long-term therapies, and much-needed biomarkers. Such biomarkers are not only valuable for defining the disease onset, but also for monitoring both the treatment response and a disease evolution that spans multiple decades in children with MS. PMID:27116721

  15. Albumin and multiple sclerosis.

    PubMed

    LeVine, Steven M

    2016-04-12

    Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth.

  16. Smoldering multiple myeloma.

    PubMed

    Gao, Minjie; Yang, Guang; Kong, Yuanyuan; Wu, Xiaosong; Shi, Jumei

    2015-01-01

    Smoldering multiple myeloma (SMM) is an asymptomatic precursor stage of multiple myeloma (MM) characterized by clonal bone marrow plasma cells (BMPC) ≥ 10% and/or M protein level ≥ 30 g/L in the absence of end organ damage. It represents an intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and symptomatic MM. The risk of progression to symptomatic MM is not uniform, and several parameters have been reported to predict the risk of progression. These include the level of M protein and the percentage of BMPC, the proportion of immunophenotypically aberrant plasma cells, and the presence of immunoparesis, free light-chain (FLC) ratio, peripheral blood plasma cells (PBPC), pattern of serum M protein evolution, abnormal magnetic resonance imaging (MRI), cytogenetic abnormalities, IgA isotype, and Bence Jones proteinuria. So far treatment is still not recommended for SMM, because several trials suggested that patients with SMM do not benefit from early treatment. However, the Mateos et al. trial showed a survival benefit after early treatment with lenalidomide plus dexamethasone in patients with high-risk SMM. This trial has prompted a reevaluation of early treatment in an asymptomatic patient population. PMID:26000300

  17. Smoldering Multiple Myeloma

    PubMed Central

    Gao, Minjie; Yang, Guang; Kong, Yuanyuan; Wu, Xiaosong; Shi, Jumei

    2015-01-01

    Smoldering multiple myeloma (SMM) is an asymptomatic precursor stage of multiple myeloma (MM) characterized by clonal bone marrow plasma cells (BMPC) ≥ 10% and/or M protein level ≥ 30 g/L in the absence of end organ damage. It represents an intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and symptomatic MM. The risk of progression to symptomatic MM is not uniform, and several parameters have been reported to predict the risk of progression. These include the level of M protein and the percentage of BMPC, the proportion of immunophenotypically aberrant plasma cells, and the presence of immunoparesis, free light-chain (FLC) ratio, peripheral blood plasma cells (PBPC), pattern of serum M protein evolution, abnormal magnetic resonance imaging (MRI), cytogenetic abnormalities, IgA isotype, and Bence Jones proteinuria. So far treatment is still not recommended for SMM, because several trials suggested that patients with SMM do not benefit from early treatment. However, the Mateos et al. trial showed a survival benefit after early treatment with lenalidomide plus dexamethasone in patients with high-risk SMM. This trial has prompted a reevaluation of early treatment in an asymptomatic patient population. PMID:26000300

  18. Smoldering multiple myeloma

    PubMed Central

    Landgren, Ola; Mateos, María-Victoria

    2015-01-01

    Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder. SMM is distinguished from monoclonal gammopathy of undetermined significance by a much higher risk of progression to multiple myeloma (MM). There have been major advances in the diagnosis, prognosis, and management of SMM in the last few years. These include a revised disease definition, identification of several new prognostic factors, a classification based on underlying cytogenetic changes, and new treatment options. Importantly, a subset of patients previously considered SMM is now reclassified as MM on the basis of biomarkers identifying patients with an ≥80% risk of progression within 2 years. SMM has assumed greater significance on the basis of recent trials showing that early therapy can be potentially beneficial to patients. As a result, there is a need to accurately diagnose and risk-stratify patients with SMM, including routine incorporation of modern imaging and laboratory techniques. In this review, we outline current concepts in diagnosis and risk stratification of SMM, and provide specific recommendations on the management of SMM. PMID:25838344

  19. Smoldering multiple myeloma.

    PubMed

    Rajkumar, S Vincent; Landgren, Ola; Mateos, María-Victoria

    2015-05-14

    Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder. SMM is distinguished from monoclonal gammopathy of undetermined significance by a much higher risk of progression to multiple myeloma (MM). There have been major advances in the diagnosis, prognosis, and management of SMM in the last few years. These include a revised disease definition, identification of several new prognostic factors, a classification based on underlying cytogenetic changes, and new treatment options. Importantly, a subset of patients previously considered SMM is now reclassified as MM on the basis of biomarkers identifying patients with an ≥80% risk of progression within 2 years. SMM has assumed greater significance on the basis of recent trials showing that early therapy can be potentially beneficial to patients. As a result, there is a need to accurately diagnose and risk-stratify patients with SMM, including routine incorporation of modern imaging and laboratory techniques. In this review, we outline current concepts in diagnosis and risk stratification of SMM, and provide specific recommendations on the management of SMM. PMID:25838344

  20. Multiple symbol differential detection

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush (Inventor); Simon, Marvin K. (Inventor)

    1991-01-01

    A differential detection technique for multiple phase shift keying (MPSK) signals is provided which uses a multiple symbol observation interval on the basis of which a joint decision is made regarding the phase of the received symbols. In accordance with the invention, a first difference phase is created between first and second received symbols. Next, the first difference phase is correlated with the possible values thereof to provide a first plurality of intermediate output signals. A second difference phase is next created between second and third received symbols. The second difference phase is correlated with plural possible values thereof to provide a second plurality of intermediate output signals. Next, a third difference phase is created between the first and third symbols. The third difference phase is correlated with plural possible values thereof to provide a third plurality of intermediate output signals. Each of the first plurality of intermediate outputs are combined with each of the second plurality of intermediate outputs and each of the third plurality of intermediate outputs to provide a plurality of possible output values. Finally, a joint decision is made by choosing from the plurality of possible output values the value which represents the best combined correlation of the first, second and third difference values with the possible values thereof.

  1. Multiple organ dysfunction syndrome.

    PubMed

    Ramírez, Michelle

    2013-01-01

    Initially known as multiple system organ failure, the term multiple organ dysfunction syndrome (MODS) was first described in the 1960s in adults with bleeding, respiratory failure, and sepsis. It is defined as "the development of potentially reversible physiologic derangement involving two or more organ systems not involved in the disorder that resulted in ICU admission, and arising in the wake of a potentially life threatening physiologic insult."(3) There are many risk factors predisposing to MODS; however, the most common risk factors are shock due to any cause, sepsis, and tissue hypoperfusion. A dysregulated immune response, or immuneparalysis, in which the homeostasis between pro-inflammatory and anti-inflammatory reaction is lost is thought to be key in the development of MODS. The clinical course and evolution of MODS is dependent on a combination of acquired and genetic factors. There are several nonspecific therapies for the prevention and resolution of MODS, mostly care is supportive. Mortality from MODS in septic pediatric patients varies between 11% and 54%.

  2. Multiple capillary biochemical analyzer

    DOEpatents

    Dovichi, Norman J.; Zhang, Jian Z.

    1995-01-01

    A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber. One sideways dimension of the chamber is equal to the diameter of the capillaries and one end to end dimension varies from, at the top of the chamber, slightly greater than the sum of the diameters of the capillaries to, at the bottom of the chamber, slightly smaller than the sum of the diameters of the capillaries. The optical system utilizes optic fibres to deliver light to individual photodetectors, one for each capillary tube. A filter or wavelength division demultiplexer may be used for isolating fluorescence at particular bands.

  3. Multiple capillary biochemical analyzer

    DOEpatents

    Dovichi, N.J.; Zhang, J.Z.

    1995-08-08

    A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber. One sideways dimension of the chamber is equal to the diameter of the capillaries and one end to end dimension varies from, at the top of the chamber, slightly greater than the sum of the diameters of the capillaries to, at the bottom of the chamber, slightly smaller than the sum of the diameters of the capillaries. The optical system utilizes optic fibers to deliver light to individual photodetectors, one for each capillary tube. A filter or wavelength division demultiplexer may be used for isolating fluorescence at particular bands. 21 figs.

  4. Albumin and multiple sclerosis.

    PubMed

    LeVine, Steven M

    2016-01-01

    Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth. PMID:27067000

  5. Site environmental report summary

    SciTech Connect

    Not Available

    1992-12-31

    In this summary of the Fernald 1992 Site Environmental Report the authors will describe the impact of the Fernald site on man and the environment and provide results from the ongoing Environmental Monitoring Program. Also included is a summary of the data obtained from sampling conducted to determine if the site complies with DOE, US Environmental Protection Agency (USEPA), and Ohio EPA (OEPA) requirements. These requirements are set to protect both man and the environment.

  6. Viking landing sites

    NASA Technical Reports Server (NTRS)

    Panagakos, N.

    1973-01-01

    A valley near the mouth of the 20,000-foot-deep Martian Grand Canyon has been chosen by NASA as the site of its first automated landing on the planet Mars. The landing site for the second mission of the 1975-76 Viking spacecraft will probably be an area about 1,000 miles northeast of the first site, where the likelihood of water increases the chances of finding evidence of life.

  7. Site environmental programs

    SciTech Connect

    Schmidt, J.W.; Hanf, R.W.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the site environmental programs. Effluent monitoring and environmental surveillance programs monitor for impacts from operations in several areas. The first area consists of the point of possible release into the environment. The second area consists of possible contamination adjacent to DOE facilities, and the third area is the general environment both on and off the site.

  8. 1994 Site environmental report

    SciTech Connect

    1995-07-01

    The Fernald site is a Department of Energy (DOE)-owned facility that produced high-quality uranium metals for military defense for nearly 40 years. DOE suspended production at the site in 1989 and formally ended production in 1991. Although production activities have ceased, the site continues to examine the air and liquid pathways as possible routes through which pollutants from past operations and current remedial activities may leave the site. The Site Environmental Report (SER) is prepared annually in accordance with DOE Order 5400.1, General Environmental Protection Program. This 1994 SER provides the general public as well as scientists and engineers with the results from the site`s ongoing Environmental Monitoring Program. Also included in this report is information concerning the site`s progress toward achieving full compliance with requirements set forth by DOE, U.S. Environmental Protection Agency (USEPA), and Ohio EPA (OEPA). For some readers, the highlights provided in this Executive Summary may provide sufficient information. Many readers, however, may wish to read more detailed descriptions of the information than those which are presented here. All information presented in this summary is discussed more fully in the main body of this report.

  9. Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

    ERIC Educational Resources Information Center

    Reardon, Sean F.; Raudenbush, Stephen W.

    2013-01-01

    The increasing availability of data from multi-site randomized trials provides a potential opportunity to use instrumental variables methods to study the effects of multiple hypothesized mediators of the effect of a treatment. We derive nine assumptions needed to identify the effects of multiple mediators when using site-by-treatment interactions…

  10. The Functions of Multiple Representations.

    ERIC Educational Resources Information Center

    Ainsworth, Shaaron

    1999-01-01

    Discusses multiple representations and multimedia learning environments; describes a functional taxonomy of MERs (multiple external representations); and considers how MERs are used to support cognitive processes in learning and problem solving with computers. (Contains 41 references.) (Author/LRW)

  11. Predicting Protein Function Using Multiple Kernels.

    PubMed

    Yu, Guoxian; Rangwala, Huzefa; Domeniconi, Carlotta; Zhang, Guoji; Zhang, Zili

    2015-01-01

    High-throughput experimental techniques provide a wide variety of heterogeneous proteomic data sources. To exploit the information spread across multiple sources for protein function prediction, these data sources are transformed into kernels and then integrated into a composite kernel. Several methods first optimize the weights on these kernels to produce a composite kernel, and then train a classifier on the composite kernel. As such, these approaches result in an optimal composite kernel, but not necessarily in an optimal classifier. On the other hand, some approaches optimize the loss of binary classifiers and learn weights for the different kernels iteratively. For multi-class or multi-label data, these methods have to solve the problem of optimizing weights on these kernels for each of the labels, which are computationally expensive and ignore the correlation among labels. In this paper, we propose a method called Predicting Protein Function using Multiple Kernels (ProMK). ProMK iteratively optimizes the phases of learning optimal weights and reduces the empirical loss of multi-label classifier for each of the labels simultaneously. ProMK can integrate kernels selectively and downgrade the weights on noisy kernels. We investigate the performance of ProMK on several publicly available protein function prediction benchmarks and synthetic datasets. We show that the proposed approach performs better than previously proposed protein function prediction approaches that integrate multiple data sources and multi-label multiple kernel learning methods. The codes of our proposed method are available at https://sites.google.com/site/guoxian85/promk.

  12. Multiple stress fractures of the tibia in a healthy adult.

    PubMed

    Lambros, G; Alder, D

    1997-10-01

    Multiple stress fractures in the same bone are a rare occurrence. This paper presents an unusual case of a 19-year-old, healthy man who sustained a pathologic fracture of the proximal tibia through a stress-fracture site. The radiographic examination of the tibia also revealed multiple stress fractures inferior to the pathologic fracture. Magnetic resonance imaging can be used to rule out neoplasm and to confirm the stress-fracture diagnosis. Multiple stress fractures in the same bone can be treated with cast immobilization.

  13. Screening and testing in multiples.

    PubMed

    Evans, Mark I; Andriole, Stephanie

    2010-09-01

    The same principles for diagnosis and screening in singleton pregnancies apply to multiples. However, there can be significant differences in the safety and efficacy of all approaches with multiple gestations. This article deals with specific aspects of screening in multiple pregnancies.

  14. Bayes multiple decision functions.

    PubMed

    Wu, Wensong; Peña, Edsel A

    2013-01-01

    This paper deals with the problem of simultaneously making many (M) binary decisions based on one realization of a random data matrix X. M is typically large and X will usually have M rows associated with each of the M decisions to make, but for each row the data may be low dimensional. Such problems arise in many practical areas such as the biological and medical sciences, where the available dataset is from microarrays or other high-throughput technology and with the goal being to decide which among of many genes are relevant with respect to some phenotype of interest; in the engineering and reliability sciences; in astronomy; in education; and in business. A Bayesian decision-theoretic approach to this problem is implemented with the overall loss function being a cost-weighted linear combination of Type I and Type II loss functions. The class of loss functions considered allows for use of the false discovery rate (FDR), false nondiscovery rate (FNR), and missed discovery rate (MDR) in assessing the quality of decision. Through this Bayesian paradigm, the Bayes multiple decision function (BMDF) is derived and an efficient algorithm to obtain the optimal Bayes action is described. In contrast to many works in the literature where the rows of the matrix X are assumed to be stochastically independent, we allow a dependent data structure with the associations obtained through a class of frailty-induced Archimedean copulas. In particular, non-Gaussian dependent data structure, which is typical with failure-time data, can be entertained. The numerical implementation of the determination of the Bayes optimal action is facilitated through sequential Monte Carlo techniques. The theory developed could also be extended to the problem of multiple hypotheses testing, multiple classification and prediction, and high-dimensional variable selection. The proposed procedure is illustrated for the simple versus simple hypotheses setting and for the composite hypotheses setting

  15. Savannah River Site's Site Specific Plan

    SciTech Connect

    Not Available

    1991-08-01

    This Site Specific Plan (SSP) has been prepared by the Savannah River Site (SRS) in order to show the Environmental Restoration and Waste Management activities that were identified during the preparation of the Department of Energy-Headquarters (DOE-HQ) Environmental Restoration and Waste Management Five-Year Plan (FYP) for FY 1992--1996. The SSP has been prepared in accordance with guidance received from DOE-HQ. DOE-SR is accountable to DOE-HQ for the implementation of this plan. The purpose of the SSP is to develop a baseline for policy, budget, and schedules for the DOE Environmental Restoration and Waste Management activities. The plan explains accomplishments since the Fiscal Year (FY) 1990 plan, demonstrates how present and future activities are prioritized, identifies currently funded activities and activities that are planned to be funded in the upcoming fiscal year, and describes future activities that SRS is considering.

  16. MULTIPLE GALAXY COLLISIONS

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Here is a sampling of 15 ultraluminous infrared galaxies viewed by NASA's Hubble Space Telescope. Hubble's sharp vision reveals more complexity within these galaxies, which astronomers are interpreting as evidence of a multiple-galaxy pileup. These images, taken by the Wide Field and Planetary Camera 2, are part of a three-year study of 123 galaxies within 3 billion light-years of Earth. The study was conducted in 1996, 1997, and 1999. False colors were assigned to these photos to enhance fine details within these coalescing galaxies. Credits: NASA, Kirk Borne (Raytheon and NASA Goddard Space Flight Center, Greenbelt, Md.), Luis Colina (Instituto de Fisica de Cantabria, Spain), and Howard Bushouse and Ray Lucas (Space Telescope Science Institute, Baltimore, Md.)

  17. MULTIPLE SPARK GAP SWITCH

    DOEpatents

    Schofield, A.E.

    1958-07-22

    A multiple spark gap switch of unique construction is described which will permit controlled, simultaneous discharge of several capacitors into a load. The switch construction includes a disc electrode with a plurality of protuberances of generally convex shape on one surface. A firing electrode is insulatingly supponted In each of the electrode protuberances and extends substantially to the apex thereof. Individual electrodes are disposed on an insulating plate parallel with the disc electrode to form a number of spark gaps with the protuberances. These electrodes are each connected to a separate charged capacitor and when a voltage ls applied simultaneously between the trigger electrodes and the dlsc electrode, each spark gap fires to connect its capacitor to the disc electrode and a subsequent load.

  18. Multiple asteroid rendezvous missions

    NASA Technical Reports Server (NTRS)

    Bender, D. F.; Friedlander, A. L.

    1979-01-01

    Asteroid missions, centered on multiple asteroid rendezvous missions to main belt asteroids, are discussed and the required solar electric propulsion for these missions as well as the current performance estimates are examined. A brief statistical analysis involving asteroid availability transfer requirements and propulsion system capabilities is given, leading to a prediction that 5 to 8 asteroids can be encountered with a single launch. Measurement techniques include visual imaging, radio tracking, magnetometry, and in the case of landers, seismometry. The spacecraft will be propelled by a solar electric system with a power level of 25 kW to 40 kW and tour possibilities for 13 different asteroids have been developed. Preliminary estimates of asteroid triaxiality are made to calculate the effect of close orbits.

  19. Multiple-port valve

    DOEpatents

    Doody, Thomas J.

    1978-08-22

    A multiple-port valve assembly is designed to direct flow from a primary conduit into any one of a plurality of secondary conduits as well as to direct a reverse flow. The valve includes two mating hemispherical sockets that rotatably receive a spherical valve plug. The valve plug is attached to the primary conduit and includes diverging passageways from that conduit to a plurality of ports. Each of the ports is alignable wih one or more of a plurality of secondary conduits fitted into one of the hemispherical sockets. The other hemispherical socket includes a slot for the primary conduit such that the conduit's motion along that slot with rotation of the spherical plug about various axes will position the valve-plug ports in respect to the secondary conduits.

  20. Multiple detectors "Influence Method".

    PubMed

    Rios, I J; Mayer, R E

    2016-05-01

    The "Influence Method" is conceived for the absolute determination of a nuclear particle flux in the absence of known detector efficiency and without the need to register coincidences of any kind. This method exploits the influence of the presence of one detector in the count rate of another detector, when they are placed one behind the other and define statistical estimators for the absolute number of incident particles and for the efficiency (Rios and Mayer, 2015a). Its detailed mathematical description was recently published (Rios and Mayer, 2015b) and its practical implementation in the measurement of a moderated neutron flux arising from an isotopic neutron source was exemplified in (Rios and Mayer, 2016). With the objective of further reducing the measurement uncertainties, in this article we extend the method for the case of multiple detectors placed one behind the other. The new estimators for the number of particles and the detection efficiency are herein derived.